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EDITORIAL article

This article is part of the research topic.

Small non-coding RNAs in Gram negative bacteria

Editorial on the Research Topic: Small non-coding RNAs in Gram negative bacteria Provisionally Accepted

• 1 Long Island University, United States
• 2 Bambino Gesù Children's Hospital (IRCCS), Italy

The final, formatted version of the article will be published soon.

Ongoing efforts to discover and characterize small non-coding RNAs (sncRNAs) in bacteria, often known as microRNA-size small RNAs (msRNAs) or more broadly as bacterial-derived small RNAs (bsRNAs), are deepening our knowledge of how they regulate post-transcriptional process. Although poorly described so far, they play an important role in controlling various biological functions of bacteria such as virulence, biofilm formation, antibiotic resistance, pathogenesis, adaptation to stress, and expression of outer membrane proteins. The objective of this research topic was to pool down the knowledge available so far in addition to attract promising new studies in sRNA regulatory network, which would enable forefront studies in the field of regulatory sRNAs to effectively tackle bacterial pathogens. This research topic includes some original articles that explore how bacteria utilize sRNAs to survive under antibiotic stress conditions as well as their involvement in mediating differences in immune response in the case of respiratory syncytial virus versus rhinovirus bronchiolitis. It also includes valuable review articles that discuss Hfq interactions with sRNAs and how bacterial pathogens produce sRNAs encapsulated in outer membrane vesicles (OMVs). Through this process, sRNAs can be transferred into eukaryotic cells and other bacteria, highlighting their potential as therapeutic agents in the treatment of various diseases. Kim et al. reported how bacteria switch from active aerobic respiration to anaerobic adaptation upon exposure to moderately effective first-generation antibiotics (Kim et al., 2024). The overuse and misuse of antibiotics has led to the emergence of multidrug resistant bacteria, and this situation has worsened with the overuse of antibiotics during Corona Virus Disease (COVID-19) pandemic (Andersson and Hughes, 2014;Rawson et al., 2020). The authors used a transcriptome analysis approach to understand the change in gene expression when the bacteria switch to anaerobic respiration (Kim et al., 2024). It has been noticed that the treatment of sublethal concentrations of antibiotics increased the expression of genes related to anaerobic respiration. In addition, the transition was dependent on the transcriptional regulators, AcrA (aerobic respiratory control) and FMR (fumarate and nitrate reduction) (Kim et al., 2024). It has been reported that the expression of these regulators is modulated by oxygen availability (Levanon et al., 2005). The authors in turn report that the antibiotic stress leads to specific reprogramming of non-coding RNAs including small RNAs FnrS and Tp2 (Kim et al., 2024). It was noticed that FnrS is involved in reducing reactive oxygen species (ROS) levels, thereby increasing cell survival. Overall, the study demonstrates how bacteria strive to maintain cellular homeostasis via sRNA-mediated gene regulation upon sublethal antibiotic exposure. As the authors pointed out, this study provides insights for developing novel antimicrobial compounds targeting sRNAs to combat multi-drug resistance.Another valuable original article in our research topic demonstrates the role of bacterial sRNAs in mediating immune response in Bronchiolitis (Krohmaly et al., 2024). Bronchiolitis is a viral infection caused by many viruses including respiratory syncytial virus (RSV), rhinovirus (RV), and others (Marguet et al., 2009). It has been reported that bronchiolitis caused by RSV is majorly associated with Streptococcus pneumoniae, while bronchiolitis caused by RV is frequently associated with Haemophilus influenzae (Hasegawa et al., 2018;Stewart et al., 2018). In this study, the authors identified many novel sRNAs from different bacterial species and studied their influence on immune response during bronchiolitis (Krohmaly et al., 2024). Through RNA-Seq database, several bacterial sRNAs were found to be associated with RSV and RV-only bronchiolitis in human nasal. They found that some bacterial sRNAs were differently expressed in infants with RSV compare to RV-only bronchiolitis from the MARC-35 cohort. They found that the sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway, compared to those associated with RV-only bronchitis (Krohmaly et al., 2024). This is the first study to report that bacterial sRNAs may be contributing to inflammation differences seen in RSV-and RV-only bronchiolitis.Nowadays, it is known that production and regulation of bacterial sRNAs that are involved in facilitating sRNA-mRNA base-pairing is coordinated through several components, including other sRNAs, mRNAs, and sRNA-binding proteins (sRBPs). Among several sRBPs (e.g., Hfq, ProQ, and CsrA), Hfq is the most extensively studied chaperon that protects sRNAs from degradation and aids in their binding to mRNA. Watkins and Arya have written an interesting review on how the structures of Hfq have defined the difference in interactions of the Gram-negative and Grampositive homologues with RNA (Watkins and Arya, 2023). While it appears that Hfq is a vital virulence factor in Gram-negative bacteria, it remains unclear how this chaperone is involved in mediating sRNA-mRNA interactions, a function that is worth exploring.Another interesting review paper published by Ajam-Hosseini et al. discussed bacterial OMVs that can serve as vehicles for the delivery of sRNAs to target cells (Ajam-Hosseini et al., 2024). It has been shown that sRNAs encapsulated in OMVs can regulate gene expression in recipient cells, leading to changes in cellular behavior and function. Additionally, targeting sRNAs involved in bacterial virulence or antibiotic resistance has the potential to disrupt the pathogenicity of bacteria and improve the effectiveness of antibiotic treatment. This suggests that OMV-encapsulated sRNAs could be used as potential therapeutic strategy in treating various bacterial diseases.In summary, the current Research Topic highlights the importance of regulating bacterial sRNAs in shielding bacterial lifestyle under stress conditions and in modulating the immune response. It also provides valuable insights into the clinical significance of Gram-negative bacterial sRNAs in biomedical applications. Despite its importance, detailed studies on the expression patterns of bacterial sRNAs are scarce. Therefore, we believe that further research could enhance our understating of their role as a versatile toolkit for bacterial adaptation to the host environment. Such studies could also reveal their potential utility as novel therapeutics, including their use in natural or synthetic OMVs.We would like to express our gratitude to the authors and reviewers for their valuable contributions to this research topic. We hope that this collection of reviews, and original articles will be helpful for clinicians, researchers, and students seeking for information about sRNAs in bacterial virulence and communication.

Keywords: Small non-coding RNA (sRNA), Hfq, multidrug resistance, antibiotics, Bronchiolitis, Streptococcus pneumoniae, Outer membrane vesicles (OMVs)

Received: 30 Apr 2024; Accepted: 02 May 2024.

Copyright: © 2024 Subhadra and Sarshar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Bindu Subhadra, Long Island University, Brookville, United States

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Physical Fitness Linked to Better Mental Health in Young People

A new study bolsters existing research suggesting that exercise can protect against anxiety, depression and attention challenges.

By Matt Richtel

Physical fitness among children and adolescents may protect against developing depressive symptoms, anxiety and attention deficit hyperactivity disorder, according to a study published on Monday in JAMA Pediatrics.

The study also found that better performance in cardiovascular activities, strength and muscular endurance were each associated with greater protection against such mental health conditions. The researchers deemed this linkage “dose-dependent,” suggesting that a child or adolescent who is more fit may be accordingly less likely to experience the onset of a mental health disorder.

These findings come amid a surge of mental health diagnoses among children and adolescents, in the United States and abroad, that have prompted efforts to understand and curb the problem.

The new study, conducted by researchers in Taiwan, compared data from two large data sets: the Taiwan National Student Fitness Tests, which measures student fitness performance in schools, and the National Insurance Research Databases, which records medical claims, diagnoses prescriptions and other medical information. The researchers did not have access to the students’ names but were able to use the anonymized data to compare the students’ physical fitness and mental health results.

The risk of mental health disorder was weighted against three metrics for physical fitness: cardio fitness, as measured by a student’s time in an 800-meter run; muscle endurance, indicated by the number of situps performed; and muscle power, measured by the standing broad jump.

Improved performance in each activity was linked with a lower risk of mental health disorder. For instance, a 30-second decrease in 800-meter time was associated, in girls, with a lower risk of anxiety, depression and A.D.H.D. In boys, it was associated with lower anxiety and risk of the disorder.

An increase of five situps per minute was associated with lower anxiety and risk of the disorder in boys, and with decreased risk of depression and anxiety in girls.

“These findings suggest the potential of cardiorespiratory and muscular fitness as protective factors in mitigating the onset of mental health disorders among children and adolescents,” the researchers wrote in the journal article.

Physical and mental health were already assumed to be linked , they added, but previous research had relied largely on questionnaires and self-reports, whereas the new study drew from independent assessments and objective standards.

The Big Picture

The surgeon general, Dr. Vivek H. Murthy, has called mental health “the defining public health crisis of our time,” and he has made adolescent mental health central to his mission. In 2021 he issued a rare public advisory on the topic. Statistics at the time revealed alarming trends: From 2001 to 2019, the suicide rate for Americans ages 10 to 19 rose 40 percent, and emergency visits related to self-harm rose 88 percent.

Some policymakers and researchers have blamed the sharp increase on the heavy use of social media, but research has been limited and the findings sometimes contradictory. Other experts theorize that heavy screen use has affected adolescent mental health by displacing sleep, exercise and in-person activity, all of which are considered vital to healthy development. The new study appeared to support the link between physical fitness and mental health.

“The finding underscores the need for further research into targeted physical fitness programs,” its authors concluded. Such programs, they added, “hold significant potential as primary preventative interventions against mental disorders in children and adolescents.”

Matt Richtel is a health and science reporter for The Times, based in Boulder, Colo. More about Matt Richtel

Understanding A.D.H.D.

The challenges faced by those with attention deficit hyperactivity disorder can be daunting. but people who are diagnosed with it can still thrive..

Millions of children in the United States have received a diagnosis of A.D.H.D . Here is how their families can support them .

The condition is also being recognized more in adults . These are some of the behaviors  that might be associated with adult A.D.H.D.

Since a nationwide Adderall shortage started, some people with A.D.H.D. have said their medication no longer helps with their symptoms. But there could be other factors at play .

Everyone has bouts of distraction and forgetfulness. Here is when psychiatrists diagnose it as something clinical .

The disorder can put a strain on relationships. But there are ways to cope .

Though meditation can be beneficial to those with A.D.H.D., sitting still and focusing on breathing can be hard for them. These tips can help .

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 30, Number 7—July 2024

Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024

Suggested citation for this article

We report highly pathogenic avian influenza A(H5N1) virus in dairy cattle and cats in Kansas and Texas, United States, which reflects the continued spread of clade 2.3.4.4b viruses that entered the country in late 2021. Infected cattle experienced nonspecific illness, reduced feed intake and rumination, and an abrupt drop in milk production, but fatal systemic influenza infection developed in domestic cats fed raw (unpasteurized) colostrum and milk from affected cows. Cow-to-cow transmission appears to have occurred because infections were observed in cattle on Michigan, Idaho, and Ohio farms where avian influenza virus–infected cows were transported. Although the US Food and Drug Administration has indicated the commercial milk supply remains safe, the detection of influenza virus in unpasteurized bovine milk is a concern because of potential cross-species transmission. Continued surveillance of highly pathogenic avian influenza viruses in domestic production animals is needed to prevent cross-species and mammal-to-mammal transmission.

Highly pathogenic avian influenza (HPAI) viruses pose a threat to wild birds and poultry globally, and HPAI H5N1 viruses are of even greater concern because of their frequent spillover into mammals. In late 2021, the Eurasian strain of H5N1 (clade 2.3.4.4b) was detected in North America ( 1 , 2 ) and initiated an outbreak that continued into 2024. Spillover detections and deaths from this clade have been reported in both terrestrial and marine mammals in the United States ( 3 , 4 ). The detection of HPAI H5N1 clade 2.3.4.4b virus in severe cases of human disease in Ecuador ( 5 ) and Chile ( 6 ) raises further concerns regarding the pandemic potential of specific HPAI viruses.

In February 2024, veterinarians were alerted to a syndrome occurring in lactating dairy cattle in the panhandle region of northern Texas. Nonspecific illness accompanied by reduced feed intake and rumination and an abrupt drop in milk production developed in affected animals. The milk from most affected cows had a thickened, creamy yellow appearance similar to colostrum. On affected farms, incidence appeared to peak 4–6 days after the first animals were affected and then tapered off within 10–14 days; afterward, most animals were slowly returned to regular milking. Clinical signs were commonly reported in multiparous cows during middle to late lactation; ≈10%–15% illness and minimal death of cattle were observed on affected farms. Initial submissions of blood, urine, feces, milk, and nasal swab samples and postmortem tissues to regional diagnostic laboratories did not reveal a consistent, specific cause for reduced milk production. Milk cultures were often negative, and serum chemistry testing showed mildly increased aspartate aminotransferase, gamma-glutamyl transferase, creatinine kinase, and bilirubin values, whereas complete blood counts showed variable anemia and leukocytopenia.

In early March 2024, similar clinical cases were reported in dairy cattle in southwestern Kansas and northeastern New Mexico; deaths of wild birds and domestic cats were also observed within affected sites in the Texas panhandle. In > 1 dairy farms in Texas, deaths occurred in domestic cats fed raw colostrum and milk from sick cows that were in the hospital parlor. Antemortem clinical signs in affected cats were depressed mental state, stiff body movements, ataxia, blindness, circling, and copious oculonasal discharge. Neurologic exams of affected cats revealed the absence of menace reflexes and pupillary light responses with a weak blink response.

On March 21, 2024, milk, serum, and fresh and fixed tissue samples from cattle located in affected dairies in Texas and 2 deceased cats from an affected Texas dairy farm were received at the Iowa State University Veterinary Diagnostic Laboratory (ISUVDL; Ames, IA, USA). The next day, similar sets of samples were received from cattle located in affected dairies in Kansas. Milk and tissue samples from cattle and tissue samples from the cats tested positive for influenza A virus (IAV) by screening PCR, which was confirmed and characterized as HPAI H5N1 virus by the US Department of Agriculture National Veterinary Services Laboratory. Detection led to an initial press release by the US Department of Agriculture Animal and Plant Health Inspection Service on March 25, 2024, confirming HPAI virus in dairy cattle ( 7 ). We report the characterizations performed at the ISUVDL for HPAI H5N1 viruses infecting cattle and cats in Kansas and Texas.

Materials and Methods

Milk samples (cases 2–5) and fresh and formalin-fixed tissues (cases 1, 3–5) from dairy cattle were received at the ISUVDL from Texas on March 21 and from Kansas on March 22, 2024. The cattle exhibited nonspecific illness and reduced lactation, as described previously. The tissue samples for diagnostic testing came from 3 cows that were euthanized and 3 that died naturally; all postmortem examinations were performed on the premises of affected farms.

The bodies of 2 adult domestic shorthaired cats from a north Texas dairy farm were received at the ISUVDL for a complete postmortem examination on March 21, 2024. The cats were found dead with no apparent signs of injury and were from a resident population of ≈24 domestic cats that had been fed milk from sick cows. Clinical disease in cows on that farm was first noted on March 16; the cats became sick on March 17, and several cats died in a cluster during March 19–20. In total, >50% of the cats at that dairy became ill and died. We collected cerebrum, cerebellum, eye, lung, heart, spleen, liver, lymph node, and kidney tissue samples from the cats and placed them in 10% neutral-buffered formalin for histopathology.

At ISUVDL, we trimmed, embedded in paraffin, and processed formalin-fixed tissues from affected cattle and cats for hematoxylin/eosin staining and histologic evaluation. For immunohistochemistry (IHC), we prepared 4-µm–thick sections from paraffin-embedded tissues, placed them on Superfrost Plus slides (VWR, https://www.vwr.com ), and dried them for 20 minutes at 60°C. We used a Ventana Discovery Ultra IHC/ISH research platform (Roche, https://www.roche.com ) for deparaffinization until and including counterstaining. We obtained all products except the primary antibody from Roche. Automated deparaffination was followed by enzymatic digestion with protease 1 for 8 minutes at 37°C and endogenous peroxidase blocking. We obtained the primary influenza A virus antibody from the hybridoma cell line H16-L10–4R5 (ATCC, https://www.atcc.org ) and diluted at 1:100 in Discovery PSS diluent; we incubated sections with antibody for 32 minutes at room temperature. Next, we incubated the sections with a hapten-labeled conjugate, Discovery anti-mouse HQ, for 16 minutes at 37°C followed by a 16-minute incubation with the horse radish peroxidase conjugate, Discovery anti-HQ HRP. We used a ChromoMap DAB kit for antigen visualization, followed by counterstaining with hematoxylin and then bluing. Positive controls were sections of IAV-positive swine lung. Negative controls were sections of brain, lung, and eyes from cats not infected with IAV.

We diluted milk samples 1:3 vol/vol in phosphate buffered saline, pH 7.4 (Gibco/Thermo Fisher Scientific, https://www.thermofisher.com ) by mixing 1 unit volume of milk and 3 unit volumes of phosphate buffered saline. We prepared 10% homogenates of mammary glands, brains, lungs, spleens, and lymph nodes in Earle’s balanced salt solution (Sigma-Aldrich, https://www.sigmaaldrich.com ). Processing was not necessary for ocular fluid, rumen content, or serum samples. After processing, we extracted samples according to a National Animal Health Laboratory Network (NAHLN) protocol that had 2 NAHLN-approved deviations for ISUVDL consisting of the MagMax Viral RNA Isolation Kit for 100 µL sample volumes and a Kingfisher Flex instrument (both Thermo Fisher Scientific).

We performed real-time reverse transcription PCR (rRT-PCR) by using an NAHLN-approved assay with 1 deviation, which was the VetMAX-Gold SIV Detection kit (Thermo Fisher Scientific), to screen for the presence of IAV RNA. We tested samples along with the VetMAX XENO Internal Positive Control to monitor the possible presence of PCR inhibitors. Each rRT-PCR 96-well plate had 2 positive amplification controls, 2 negative amplification controls, 1 positive extraction control, and 1 negative extraction control. We ran the rRT-PCR on an ABI 7500 Fast thermocycler and analyzed data with Design and Analysis Software 2.7.0 (both Thermo Fisher Scientific). We considered samples with cycle threshold (Ct) values <40.0 to be positive for virus.

After the screening rRT-PCR, we analyzed IAV RNA–positive samples for the H5 subtype and H5 clade 2.3.4.4b by using the same RNA extraction and NAHLN-approved rRT-PCR protocols as described previously, according to standard operating procedures. We performed PCR on the ABI 7500 Fast thermocycler by using appropriate controls to detect H5-specific IAV. We considered samples with Ct values <40.0 to be positive for the IAV H5 subtype.

We conducted genomic sequencing of 2 milk samples from infected dairy cattle from Texas and 2 tissue samples (lung and brain) from cats that died at a different Texas dairy. We subjected the whole-genome sequencing data to bioinformatics analysis to assemble the 8 different IAV segment sequences according to previously described methods ( 8 ). We used the hemagglutinin (HA) and neuraminidase (NA) sequences for phylogenetic analysis. We obtained reference sequences for the HA and NA segments of IAV H5 clade 2.3.4.4 from publicly available databases, including GISAID ( https://www.gisaid.org ) and GenBank. We aligned the sequences by using MAFFT version 7.520 software ( https://mafft.cbrc.jp/alignment/server/index.html ) to create multiple sequence alignments for subsequent phylogenetic analysis. We used IQTree2 ( https://github.com/iqtree/iqtree2 ) to construct the phylogenetic tree from the aligned sequences. The software was configured to automatically identify the optimal substitution model by using the ModelFinder Plus option, ensuring the selection of the most suitable model for the dataset and, thereby, improving the accuracy of the reconstructed tree. We visualized the resulting phylogenetic tree by using iTOL ( https://itol.embl.de ), a web-based platform for interactive tree exploration and annotation.

Gross Lesions in Cows and Cats

All cows were in good body condition with adequate rumen fill and no external indications of disease. Postmortem examinations of the affected dairy cows revealed firm mammary glands typical of mastitis; however, mammary gland lesions were not consistent. Two cows that were acutely ill before postmortem examination had grossly normal milk and no abnormal mammary gland lesions. The gastrointestinal tract of some cows had small abomasal ulcers and shallow linear erosions of the intestines, but those observations were also not consistent in all animals. The colon contents were brown and sticky, suggesting moderate dehydration. The feces contained feed particles that appeared to have undergone minimal ruminal fermentation. The rumen contents had normal color and appearance but appeared to have undergone minimal fermentation.

The 2 adult cats (1 intact male, 1 intact female) received at the ISUVDL were in adequate body and postmortem condition. External examination was unremarkable. Mild hemorrhages were observed in the subcutaneous tissues over the dorsal skull, and multifocal meningeal hemorrhages were observed in the cerebrums of both cats. The gastrointestinal tracts were empty, and no other gross lesions were observed.

Microscopic Lesions in Cows and Cats

Figure 1 . Mammary gland lesions in cattle in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. A, B) Mammary gland...

The chief microscopic lesion observed in affected cows was moderate acute multifocal neutrophilic mastitis ( Figure 1 ); however, mammary glands were not received from every cow. Three cows had mild neutrophilic or lymphocytic hepatitis. Because they were adult cattle, other observed microscopic lesions (e.g., mild lymphoplasmacytic interstitial nephritis and mild to moderate lymphocytic abomasitis) were presumed to be nonspecific, age-related changes. We did not observe major lesions in the other evaluated tissues. We performed IHC for IAV antigen on all evaluated tissues; the only tissues with positive immunoreactivity were mastitic mammary glands from 2 cows that showed nuclear and cytoplasmic labeling of alveolar epithelial cells and cells within lumina ( Figure 1 ) and multifocal germinal centers within a lymph node from 1 cow ( Table 1 ).

Figure 2 . Lesions in cat tissues in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Tissue sections were stained with...

Both cats had microscopic lesions consistent with severe systemic virus infection, including severe subacute multifocal necrotizing and lymphocytic meningoencephalitis with vasculitis and neuronal necrosis, moderate subacute multifocal necrotizing and lymphocytic interstitial pneumonia, moderate to severe subacute multifocal necrotizing and lymphohistiocytic myocarditis, and moderate subacute multifocal lymphoplasmacytic chorioretinitis with ganglion cell necrosis and attenuation of the internal plexiform and nuclear layers ( Table 2 ; Figure 2 ). We performed IHC for IAV antigen on multiple tissues (brain, eye, lung, heart, spleen, liver, and kidney). We detected positive IAV immunoreactivity in brain (intracytoplasmic, intranuclear, and axonal immunolabeling of neurons), lung, and heart, and multifocal and segmental immunoreactivity within all layers of the retina ( Figure 2 ).

PCR Data from Cows and Cats

We tested various samples from 8 clinically affected mature dairy cows by IAV screening and H5 subtype-specific PCR ( Table 3 ). Milk and mammary gland homogenates consistently showed low Ct values: 12.3–16.9 by IAV screening PCR, 17.6–23.1 by H5 subtype PCR, and 14.7–20.0 by H5 2.3.4.4 clade PCR (case 1, cow 1; case 2, cows 1 and 2; case 3, cow 1; and case 4, cow 1). We forwarded the samples to the National Veterinary Services Laboratory, which confirmed the virus was an HPAI H5N1 virus strain.

When available, we also tested tissue homogenates (e.g., lung, spleen, and lymph nodes), ocular fluid, and rumen contents from 6 cows by IAV and H5 subtype-specific PCR ( Table 3 ). However, the PCR findings were not consistent. For example, the tissue homogenates and ocular fluid tested positive in some but not all cows. In case 5, cow 1, the milk sample tested negative by IAV screening PCR, but the spleen homogenate tested positive by IAV screening, H5 subtype, and H5 2.3.4.4 PCR. For 2 cows (case 3, cow 1; and case 4, cow 1) that had both milk and rumen contents available, both samples tested positive for IAV. Nevertheless, all IAV-positive nonmammary gland tissue homogenates, ocular fluid, and rumen contents had markedly elevated Ct values in contrast to the low Ct values for milk and mammary gland homogenate samples.

We tested brain and lung samples from the 2 cats (case 6, cats 1 and 2) by IAV screening and H5 subtype-specific PCR ( Table 3 ). Both sample types were positive by IAV screening PCR; Ct values were 9.9–13.5 for brain and 17.4–24.4 for lung samples, indicating high amounts of virus nucleic acid in those samples. The H5 subtype and H5 2.3.4.4 PCR results were also positive for the brain and lung samples; Ct values were consistent with the IAV screening PCR ( Table 3 ).

Phylogenetic Analyses

We assembled the sequences of all 8 segments of the HPAI viruses from both cow milk and cat tissue samples. We used the hemagglutinin (HA) and neuraminidase (NA) sequences specifically for phylogenetic analysis to delineate the clade of the HA gene and subtype of the NA gene.

Figure 3 . Phylogenetic analysis of hemagglutinin gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate different...

For HA gene analysis, both HA sequences derived from cow milk samples exhibited a high degree of similarity, sharing 99.88% nucleotide identity, whereas the 2 HA sequences from cat tissue samples showed complete identity at 100%. The HA sequences from the milk samples had 99.94% nucleotide identities with HA sequences from the cat tissues, resulting in a distinct subcluster comprising all 4 HA sequences, which clustered together with other H5N1 viruses belonging to clade 2.3.4.4b ( Figure 3 ). The HA sequences were deposited in GenBank (accession nos. PP599465 [case 2, cow 1], PP599473 [case 2, cow 2], PP692142 [case 6, cat 1], and PP692195 [case 6, cat 2]).

Figure 4 . Phylogenetic analysis of neuraminidase gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate different...

For NA gene analysis, the 2 NA sequences obtained from cow milk samples showed 99.93% nucleotide identity. Moreover, the NA sequences derived from the milk samples exhibited complete nucleotide identities (100%) with those from the cat tissues. The 4 NA sequences were grouped within the N1 subtype of HPAI viruses ( Figure 4 ). The NA sequences were deposited in GenBank (accession nos. PP599467 [case 2, cow 1], PP599475 [case 2, cow 2], PP692144 [case 6, cat 1], and PP692197 [case 6, cat 2]).

This case series differs from most previous reports of IAV infection in bovids, which indicated cattle were inapparently infected or resistant to infection ( 9 ). We describe an H5N1 strain of IAV in dairy cattle that resulted in apparent systemic illness, reduced milk production, and abundant virus shedding in milk. The magnitude of this finding is further emphasized by the high death rate (≈50%) of cats on farm premises that were fed raw colostrum and milk from affected cows; clinical disease and lesions developed that were consistent with previous reports of H5N1 infection in cats presumably derived from consuming infected wild birds ( 10 – 12 ). Although exposure to and consumption of dead wild birds cannot be completely ruled out for the cats described in this report, the known consumption of unpasteurized milk and colostrum from infected cows and the high amount of virus nucleic acid within the milk make milk and colostrum consumption a likely route of exposure. Therefore, our findings suggest cross-species mammal-to-mammal transmission of HPAI H5N1 virus and raise new concerns regarding the potential for virus spread within mammal populations. Horizontal transmission of HPAI H5N1 virus has been previously demonstrated in experimentally infected cats ( 13 ) and ferrets ( 14 ) and is suspected to account for large dieoffs observed during natural outbreaks in mink ( 15 ) and sea lions ( 16 ). Future experimental studies of HPAI H5N1 virus in dairy cattle should seek to confirm cross-species transmission to cats and potentially other mammals.

Clinical IAV infection in cattle has been infrequently reported in the published literature. The first report occurred in Japan in 1949, where a short course of disease with pyrexia, anorexia, nasal discharge, pneumonia, and decreased lactation developed in cattle ( 17 ). In 1997, a similar condition occurred in dairy cows in southwest England leading to a sporadic drop in milk production ( 18 ), and IAV seroconversion was later associated with reduced milk yield and respiratory disease ( 19 – 21 ). Rising antibody titers against human-origin influenza A viruses (H1N1 and H3N2) were later again reported in dairy cattle in England, which led to an acute fall in milk production during October 2005–March 2006 ( 22 ). Limited reports of IAV isolation from cattle exist; most reports occurred during the 1960s and 1970s in Hungary and in the former Soviet Union, where H3N2 was recovered from cattle experiencing respiratory disease ( 9 , 23 ). Direct detection of IAV in milk and the potential transmission from cattle to cats through feeding of unpasteurized milk has not been previously reported.

An IAV-associated drop in milk production in dairy cattle appears to have occurred during > 4 distinct periods and within 3 widely separated geographic areas: 1949 in Japan ( 17 ), 1997–1998 and 2005–2006 in Europe ( 19 , 21 ), and 2024 in the United States (this report). The sporadic occurrence of clinical disease in dairy cattle worldwide might be the result of changes in subclinical infection rates and the presence or absence of sufficient baseline IAV antibodies in cattle to prevent infection. Milk IgG, lactoferrin, and conglutinin have also been suggested as host factors that might reduce susceptibility of bovids to IAV infection ( 9 ). Contemporary estimates of the seroprevalence of IAV antibodies in US cattle are not well described in the published literature. One retrospective serologic survey in the United States in the late 1990s showed 27% of serum samples had positive antibody titers and 31% had low-positive titers for IAV H1 subtype-specific antigen in cattle with no evidence of clinical infections ( 24 ). Antibody titers for H5 subtype-specific antigen have not been reported in US cattle.

The susceptibility of domestic cats to HPAI H5N1 is well-documented globally ( 10 – 12 , 25 – 28 ), and infection often results in neurologic signs in affected felids and other terrestrial mammals ( 4 ). Most cases in cats result from consuming infected wild birds or contaminated poultry products ( 12 , 27 ). The incubation period in cats is short; clinical disease is often observed 2–3 days after infection ( 28 ). Brain tissue has been suggested as the best diagnostic sample to confirm HPAI virus infection in cats ( 10 ), and our results support that finding. One unique finding in the cats from this report is the presence of blindness and microscopic lesions of chorioretinitis. Those results suggest that further investigation into potential ocular manifestations of HPAI H5N1 virus infection in cats might be warranted.

The genomic sequencing and subsequent analysis of clinical samples from both bovine and feline sources provided considerable insights. The HA and NA sequences derived from both bovine milk and cat tissue samples from different Texas farms had a notable degree of similarity. Those findings strongly suggest a shared origin for the viruses detected in the dairy cattle and cat tissues. Further research, case series investigations, and surveillance data are needed to better understand and inform measures to curtail the clinical effects, shedding, and spread of HPAI viruses among mammals. Although pasteurization of commercial milk mitigates risks for transmission to humans, a 2019 US consumer study showed that 4.4% of adults consumed raw milk > 1 time during the previous year ( 29 ), indicating a need for public awareness of the potential presence of HPAI H5N1 viruses in raw milk.

Ingestion of feed contaminated with feces from wild birds infected with HPAI virus is presumed to be the most likely initial source of infection in the dairy farms. Although the exact source of the virus is unknown, migratory birds (Anseriformes and Charadriiformes) are likely sources because the Texas panhandle region lies in the Central Flyway, and those birds are the main natural reservoir for avian influenza viruses ( 30 ). HPAI H5N1 viruses are well adapted to domestic ducks and geese, and ducks appear to be a major reservoir ( 31 ); however, terns have also emerged as an important source of virus spread ( 32 ). The mode of transmission among infected cattle is also unknown; however, horizontal transmission has been suggested because disease developed in resident cattle herds in Michigan, Idaho, and Ohio farms that received infected cattle from the affected regions, and those cattle tested positive for HPAI H5N1 ( 33 ). Experimental studies are needed to decipher the transmission routes and pathogenesis (e.g., replication sites and movement) of the virus within infected cattle.

In conclusion, we showed that dairy cattle are susceptible to infection with HPAI H5N1 virus and can shed virus in milk and, therefore, might potentially transmit infection to other mammals via unpasteurized milk. A reduction in milk production and vague systemic illness were the most commonly reported clinical signs in affected cows, but neurologic signs and death rapidly developed in affected domestic cats. HPAI virus infection should be considered in dairy cattle when an unexpected and unexplained abrupt drop in feed intake and milk production occurs and for cats when rapid onset of neurologic signs and blindness develop. The recurring nature of global HPAI H5N1 virus outbreaks and detection of spillover events in a broad host range is concerning and suggests increasing virus adaptation in mammals. Surveillance of HPAI viruses in domestic production animals, including cattle, is needed to elucidate influenza virus evolution and ecology and prevent cross-species transmission.

Dr. Burrough is a professor and diagnostic pathologist at the Iowa State University College of Veterinary Medicine and Veterinary Diagnostic Laboratory. His research focuses on infectious diseases of livestock with an emphasis on swine.

Acknowledgment

We thank the faculty and staff at the ISUVDL who contributed to the processing and analysis of clinical samples in this investigation, the veterinarians involved with clinical assessments at affected dairies and various conference calls in the days before diagnostic submissions that ultimately led to the detection of HPAI virus in the cattle, and the US Department of Agriculture National Veterinary Services Laboratory and NAHLN for their roles and assistance in providing their expertise, confirmatory diagnostic support, and communications surrounding the HPAI virus cases impacting lactating dairy cattle.

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• Figure 1 . Mammary gland lesions in cattle in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. A, B) Mammary...
• Figure 2 . Lesions in cat tissues in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Tissue sections were stained...
• Figure 3 . Phylogenetic analysis of hemagglutinin gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate...
• Figure 4 . Phylogenetic analysis of neuraminidase gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate...
• Table 1 . Microscopic lesions observed in cattle in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024
• Table 2 . Microscopic lesions observed in cats in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024
• Table 3 . PCR results from various specimens in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024

Suggested citation for this article : Burrough ER, Magstadt DR, Petersen B, Timmermans SJ, Gauger PC, Zhang J, et al. Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Emerg Infect Dis. 2024 Jul [ date cited ]. https://doi.org/10.3201/eid3007.240508

DOI: 10.3201/eid3007.240508

Original Publication Date: April 29, 2024

Table of Contents – Volume 30, Number 7—July 2024

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Eric R. Burrough, Iowa State University Veterinary Diagnostic Laboratory, 1937 Christensen Dr, Ames, IA 50011, USA

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SCIENCE & ENGINEERING INDICATORS

Publications output: u.s. trends and international comparisons.

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Publication Output by Region, Country, or Economy and by Scientific Field

This section of the report outlines trends over time in publication output across regions, countries, or economies and by fields of science. This section also provides insights into the research contributions of different regions, countries, or economies and how the focus of their scientific publications has changed over time. In addition, the section highlights variations in the distribution of publications across scientific fields for different regions, countries, or economies and examines trends over time in closed-access and open-access (OA) publications. This section also summarizes federal funding acknowledgments as a source of data to shed light on published research that received federal funding. (See sidebar Using Funding Acknowledgments to Track Federally Funded Research Over Time .)

Output by Region, Country, or Economy

Total worldwide S&E publication output reached 3.3 million articles in 2022, based on entries in the Scopus database. Indicators 2018 : Bibliometric Data Filters )." data-bs-content="Publication output includes only those indexed in the Scopus database. The publication output discussion uses fractional counting, which credits coauthored publications according to the collaborating institutions or regions, countries, or economies based on the proportion of their participating authors. Country assignments refer to the institutional address of authors, with partial credit given for each international coauthorship. As part of the data analysis, filters were employed on the raw Scopus S&E publication data to remove publications with questionable quality, which appear in what are sometimes called predatory journals (NSB Indicators 2018 : Bibliometric Data Filters )." data-endnote-uuid="a5778137-c92e-4694-991d-a1545bdcca18">​ Publication output includes only those indexed in the Scopus database. The publication output discussion uses fractional counting, which credits coauthored publications according to the collaborating institutions or regions, countries, or economies based on the proportion of their participating authors. Country assignments refer to the institutional address of authors, with partial credit given for each international coauthorship. As part of the data analysis, filters were employed on the raw Scopus S&E publication data to remove publications with questionable quality, which appear in what are sometimes called predatory journals (NSB Indicators 2018 : Bibliometric Data Filters ). Approximately 86% of publications in 2022 came from regions, countries, or economies with high-income and upper-middle-income economies ( Figure PBS-1 ). The number of publications from all income-level groups grew between 2003 and 2022 ( Table SPBS-2 ). Also, the number of publications from upper-middle-income economies grew more quickly than the number from high-income economies during the more recent period between 2010 and 2022.

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S&E publications, by income group: 2003–22

Article counts refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles produced by authors from different regions, countries, or economies, each region, country, or economy receives fractional credit on the basis of the proportion of its participating authors). Data are not directly comparable with data from Science and Engineering Indicators 2022 ; see the Technical Appendix for information on data filters. Low-income regions, countries, or economies are not included in this figure because of their low publication output. Data by region, country, or economy and income group are available in Table SPBS-2 . Regions, countries, or economies are allocated to income groups based on World Bank data, using their current designation. For example, all of China’s publications from 2003 to 2022 are counted as part of the upper-middle-income category because that is China's current designation.

National Center for Science and Engineering Statistics; Science-Metrix; Elsevier, Scopus abstract and citation database, accessed April 2023; World Bank Country and Lending Groups, accessed May 2023.

Science and Engineering Indicators

In 2022, six regions, countries, or economies each produced more than 100,000 articles: China, the United States, India, Germany, the United Kingdom, and Japan. Together, these leading regions, countries, or economies accounted for over 50% of the worldwide total in 2022 ( Figure PBS-2 ; Table PBS-1 ). Figure PBS-2 and Table PBS-1 , or whole counting, as in Table SPBS-17 . There is a slight difference between the United States and China when looking at the whole-counting total production numbers. Using whole counting for 2022, the United States had 605,633 articles, whereas China had 976,141. A whole-counting measure allocates one full count to each region, country, or economy with an author contributing to the article; in fractional counting, each region, country, or economy receives a proportion of the count based on the number of authors from that region, country, or economy. For example, if an article had four authors—two from the United States, one from China, and one from Brazil—the fractional scores would be half for the United States, a quarter for China, and a quarter for Brazil. The difference between whole and fractional counting indicates that the United States has more authors working with Chinese authors than China has working with U.S. authors." data-bs-content="The proportion of output attributable to the large producers is consistent whether using fractional counting, as in Figure PBS-2 and Table PBS-1 , or whole counting, as in Table SPBS-17 . There is a slight difference between the United States and China when looking at the whole-counting total production numbers. Using whole counting for 2022, the United States had 605,633 articles, whereas China had 976,141. A whole-counting measure allocates one full count to each region, country, or economy with an author contributing to the article; in fractional counting, each region, country, or economy receives a proportion of the count based on the number of authors from that region, country, or economy. For example, if an article had four authors—two from the United States, one from China, and one from Brazil—the fractional scores would be half for the United States, a quarter for China, and a quarter for Brazil. The difference between whole and fractional counting indicates that the United States has more authors working with Chinese authors than China has working with U.S. authors." data-endnote-uuid="a3ba485a-d862-4069-8166-933aa601ea66">​ The proportion of output attributable to the large producers is consistent whether using fractional counting, as in Figure PBS-2 and Table PBS-1 , or whole counting, as in Table SPBS-17 . There is a slight difference between the United States and China when looking at the whole-counting total production numbers. Using whole counting for 2022, the United States had 605,633 articles, whereas China had 976,141. A whole-counting measure allocates one full count to each region, country, or economy with an author contributing to the article; in fractional counting, each region, country, or economy receives a proportion of the count based on the number of authors from that region, country, or economy. For example, if an article had four authors—two from the United States, one from China, and one from Brazil—the fractional scores would be half for the United States, a quarter for China, and a quarter for Brazil. The difference between whole and fractional counting indicates that the United States has more authors working with Chinese authors than China has working with U.S. authors. In absolute numbers, the growth in worldwide annual publication output (from 2.0 million in 2010 to 3.3 million in 2022) was driven in particular by two countries: China (42% of additional publications during that period) and India (11%) together accounted for more than half of that increase in publications ( Figure PBS-3 ). Russia, South Korea, Iran, and Brazil made notable contributions to the growth in the number of publications from the rest of the world from 2010 to 2022 ( Figure PBS-3 ; Table SPBS-2 ). Generally, the set of the top 15 producers of S&E articles was the same each year between 2010 and 2022, with the exception of Iran replacing Taiwan in the top 15 beginning in 2014 ( Table PBS-1 ; Table SPBS-2 ).

S&E publications for 10 leading regions, countries, or economies: 2022

Article counts refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles produced by authors from different regions, countries, or economies, each region, country, or economy receives fractional credit on the basis of the proportion of its participating authors). Data by all countries, regions, and economies are available in Table SPBS-2 .

National Center for Science and Engineering Statistics; Science-Metrix; Elsevier, Scopus abstract and citation database, accessed April 2023.

S&E publications in all fields for 15 largest producing regions, countries, or economies: 2012 and 2022

na = not applicable.

The regions, countries, or economies are ranked based on the 2022 total. Article counts refer to publications from conference proceedings and peer-reviewed journal articles in S&E and indexed in Scopus (see Technical Appendix for more details). Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles from multiple regions, countries, or economies, each region, country, or economy receives fractional credit on the basis of the proportion of its participating authors). Detail may not add to total because of regions, countries, or economies that are not shown. Proportions are based on the world total excluding unclassified addresses (data not presented). Details and other regions, countries, or economies are available in Table SPBS-2 .

S&E publications, by selected region, country, or economy and rest of world: 2003–22

Article counts refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles produced by authors from different countries, each country receives fractional credit on the basis of the proportion of its participating authors). Data for all regions, countries, and economies are available in Table SPBS-2 .

The U.S. trend of moderate but increasing publication output varied by state. The National Science Board’s (NSB’s) State Data Tool ( https://ncses.nsf.gov/indicators/states/ ) provides state-level data based on each state’s doctorate population and research and development (R&D) funding. Indicators include academic S&E article output per 1,000 science, engineering, and health doctorate holders in academia (NSB 2021a) and academic S&E article output per $1 million in academic S&E R&D funding (NSB 2021b).

Output by Scientific Field

The distribution of publications by field of science across region, country, or economy may indicate research priorities and capabilities. Health sciences was the field of science in which most articles were published in 2022, representing almost a quarter of all publications ( Table SPBS-2 and Table SPBS-10 ). Other fields with large numbers of publications included engineering (17% of publications in 2022), biological and biomedical sciences (13%), and social sciences (5%) ( Table SPBS-2 , Table SPBS-5 , Table SPBS-8 , and Table SPBS-16 ). In the United States, the European Union (EU-27), and Japan, health sciences publication output in 2022 far exceeded that of any other field. Table SPBS-17 through Table SPBS-31 )." data-bs-content="The use of whole counting or fractional counting to tally the publication output of nations can change the calculated publication count based on the degree to which a region, country, or economy is involved in international collaborations. Under whole counting, a nation receives credit for any publication with an author from that nation. Under fractional counting, the nation’s credit for a publication is prorated based on the share of the publication’s coauthors who are located in that nation ( Table SPBS-17 through Table SPBS-31 )." data-endnote-uuid="05c8023f-5250-4386-96cf-f321c7f293c4">​ The use of whole counting or fractional counting to tally the publication output of nations can change the calculated publication count based on the degree to which a region, country, or economy is involved in international collaborations. Under whole counting, a nation receives credit for any publication with an author from that nation. Under fractional counting, the nation’s credit for a publication is prorated based on the share of the publication’s coauthors who are located in that nation ( Table SPBS-17 through Table SPBS-31 ). Meanwhile, of the other top producers, publications from China were most highly concentrated in engineering (25%), and publications from India were published predominantly in computer and information sciences (21%) ( Figure PBS-4 ).

Distribution of national S&E research portfolios across scientific fields, by selected region, country, or economy: 2022

EU-27 = European Union.

Articles refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles from multiple countries, each country receives fractional credit on the basis of the proportion of its participating authors). See Table SPBS-1 for countries included in the EU; beginning in 2020, the United Kingdom was no longer a member of the EU. See Table SPBS-3 through Table SPBS-16 for data on all regions, countries, and economies by each S&E field.

Fields within life sciences were dominant in the United States in 2022, with more than half of all U.S. publications in health sciences (37%) or biological and biomedical sciences (14%) ( Figure PBS-5 ). There were fewer U.S. publications in engineering (11%), computer and information sciences (7%), and physics (5%). In comparison with the United States, China had a stronger focus on publications in engineering and in the physical sciences and information sciences. In 2022, 25% of China’s publications were in engineering, 11% were in computer and information sciences, and 9% were in physics ( Figure PBS-6 ). Compared with the United States, China had a lower percentage of its publications in health sciences (14%) and biological and biomedical sciences (12%). In 2022, China also had a much lower percentage of its publications in social sciences (1%) when compared with the United States (8%).

U.S. S&E publication portfolio, by field of science: 2022

Articles refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles from multiple countries, each country receives fractional credit on the basis of the proportion of its participating authors). See Table SPBS-3 through Table SPBS-16 for data on all regions, countries, and economies by each S&E field.

S&E publication portfolio from China, by field of science: 2022

Articles refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Articles are credited on a fractional count basis (i.e., for articles from multiple countries, each country receives fractional credit on the basis of the proportion of its participating authors). See Table SPBS-3 through Table SPBS-16 for data on all regions, countries, and economies and by each S&E field.

All the leading regions, countries, or economies saw an increase in their output of health sciences publications between 2010 and 2022. This increase is to be expected, given the context of increasing publication rates in general over that period, with overall number of publications increasing by 71% ( Table SPBS-2 ), while publications in health sciences increased by 66% ( Table SPBS-10 ). Russia had the highest relative growth rate among the 20 leading regions, countries, or economies in health sciences, increasing its publication output by almost 450% between 2010 and 2022 ( Table SPBS-10 ). China and Iran each increased their output of health sciences publications by more than 250% over this period, while India’s health sciences publication output increased by more than 180%. The United States increased its output of health sciences publications by 32% over this period, while Germany, France, the United Kingdom, and Japan had the smallest increases, each with less than 20%.

Leading regions, countries, or economies also saw increases in engineering publications. The fastest growing between 2010 and 2022 were India (up 378%) and Russia (up 230%) ( Table SPBS-8 ). China increased its output of engineering publications by 176% from 2010 to 2022, while France, the United States, and Japan all saw declines in newly published engineering articles per year over this period (3%, 13%, and 26%, respectively).

In the United States, publication output varied from that of other regions, countries, or economies with respect to scientific fields. Of the fields not already mentioned, the fastest growing from 2010 to 2022 were psychology (up 39% from 2010 to 2022) and the social sciences (up 38%) ( Figure PBS-7 ). Meanwhile, fields with the largest decreases in U.S. publications included physics (down 31% from 2010 to 2022) and materials science (down 16%).

Index of U.S. publications, by field: 2010–22

Using funding acknowledgments to track federally funded research over time.

Federally funded research is an important component of the research ecosystem and is often envisioned as a means of supporting science performed for public benefit that may not otherwise be motivated by commercial interest (Bornmann 2013; Stephan 2012; Yin et al. 2022). Federal research funding supports applied and basic research (see Indicators 2022 report “ Research and Development: U.S. Trends and International Comparisons ”) and has long been linked to successful expansions in scientific production—through the increased productivity and impact of individual researchers and laboratories (Ebadi and Schiffauerova 2016) and the national scale (Leydesdorff and Wagner 2009). This sidebar explores funding acknowledgments, as recorded in Scopus, as an emerging source to help illustrate the extent to which published research is supported by federal agencies and the trends in federally funded research. Specifically, the share of published research acknowledging support by federal funding was highest in chemistry and smaller in other fields, such as the social sciences ( Table PBS-A ). These differences may be driven by factors such as the resource costs to conduct research and by field differences, such as the overall frequency of publication, team size, and cultural differences among the disciplines. The time period analyzed in this sidebar is 2018–22, unless otherwise indicated.

Funding acknowledgments can shed light on the ability and priorities of federal funding to support discovery as measured by peer-reviewed journal articles and conference proceedings. However, some benefits and limitations of this emerging data source are important to highlight so as to accurately interpret these trends. Each peer-reviewed journal article and conference proceeding in the Scopus database includes a field for funding acknowledgments that are extracted by algorithmic (software) means. In some cases where the acknowledgments field is incomplete, funding information from agencies is also used to identify funded publications in Scopus. Using this field, it is possible to observe the conversion of federal funds to published research outputs, but a direct linkage between funding inputs and published discoveries remains challenging. First, extraction of this information into a structured field is a relatively new effort and is most complete for the most recent 4 years. Figure SPBS-1 shows how funding acknowledgment sections have grown in coverage since 2003 and that funding information was indexed for 68% of all publications in 2022. * Many factors may have contributed to this growth in addition to improved extraction, including increasing pressure and requirements from funders to include funding acknowledgments, standardization of acknowledgment language, and incentives to demonstrate high publication output—because future funding is tied to past conversion of funds into publications—while receiving funding. † Last, this inquiry helps explore research that acknowledges any federal funding but does not only account for publications that source all their funding from a single source. In practice, a publication may be generated using funding from multiple sources within the federal government, or from additional sources in state government, local government, or the private sector.

U.S. S&E publications with and without acknowledgments of U.S. federal funding: 2003–22

Articles are classified by their year of publication and are assigned to a region, country, or economy on the basis of the institutional address(es) of the author(s) listed in the article. Whole counting is used. An article is considered to be federally funded if the funding information tied with the publication record in Scopus links it with one of the U.S. federal agencies. Not all Scopus publications have funding information available, and coverage has evolved with time. For more information, see Figure SPBS-1 . For a breakdown of federally funded papers by funding agency, see Table SPBS-90 .

National Center for Science and Engineering Statistics; Science-Metrix; Elsevier, Scopus abstract and citation database, accessed April 2023.

Figure PBS-A tracks the growth of federally funded publications relative to the total research production in the United States. Other than a small downturn from 2021 to 2022, every year has seen an increase from the previous year in the number of publications that acknowledge funding support from federal agencies. The most comprehensive data from the past 4 years show variation among subject areas in the percentage of publications that acknowledge federal support. Table PBS-A shows number and share of publications appearing between 2018 and 2022 that acknowledged funding from federal sources and those acknowledging funding from other sources. During this time, more than 50% of publications in the following subject fields acknowledged federal funding support: chemistry (55% of publications), biological and biomedical sciences (53%), astronomy and astrophysics (53%), and physics (52%). Only two subject areas have less than 30% of publications with federal funding acknowledged: agricultural sciences (28%), and social sciences (15%). Otherwise, all other fields had between 30% and 50% of their publications acknowledging federal funding.

U.S. S&E publications, by U.S. federal funding status and field: 2018–22

In conclusion, federal funding plays an important role in the current research environment in the United States. Of the 606,144 articles published in journals and conference proceedings in 2022, 35% acknowledged support from federal agencies ( Figure PBS-A ). Ultimately, acknowledgment of federal funding can help show trends in the conversion of grants into published research over time and show variation at the subject or field level.

* Missing data in funding fields in a Scopus entry may mean that the research did not receive funding, the authors did not cite any funding despite receiving it, or the algorithm was unable to extract the acknowledgment. Of the articles from 2003 that had an entry for funding acknowledgment (27% had text in the funding field in Scopus), around 76% acknowledged a federal funding source. Comparatively, of the publications in 2022 with indexed funding information (68%), 52% acknowledged a federal source. The growth of coverage of funding not being tied to federal funding acknowledgments provides evidence that the data source has become more dependable over time. Data for the percentage of publications with indexed funding sources by year and field can be found in Figure SPBS-1 .

† Table SPBS-90 displays the number of articles and conference proceedings acknowledging federal funding at the agency level and sub-agency level. These counts represent the number of supported articles as acknowledged and attributed in Scopus from 2003 to 2022.

Output and Open Access

There is growing support for the availability of S&E publications through OA sources among government and private funders, institutions, and scientists themselves. Some of these funders have imposed requirements on their grantees to publish their research results in OA journals. In the United States, the Office of Science and Technology Policy announced that all federal agencies should update their public access policies as soon as possible to ensure that results of their funded research are publicly available, with full implementation of these policies by the end of 2025 (Brainard and Kaiser 2022). Meanwhile, restricted access to scientific literature may impede researchers’ ability to stay informed (Larivière and Sugimoto 2018; Piwowar et al. 2018). As alternatives to traditional closed-access journals (where readers must subscribe to gain access or pay per article), articles may be made OA through several avenues, with different levels of availability and durability.

There are four commonly defined types of OA: Gold, Hybrid, Bronze, and Green. Gold OA denotes articles published in journals that are entirely OA as a matter of journal policy. Hybrid OA denotes articles for which the authors have elected to pay a fee for publication as OA rather than as closed access. Bronze OA denotes articles that appear as OA after an embargo period of closed access or articles that appear available as OA despite lacking license information to guarantee OA in the long term. Green OA denotes articles that are self-archived by authors in OA repositories, which are often maintained, curated, and administered by universities or other institutions. The Hybrid and Bronze categories have been combined as Other Journal-Based OA in this report because of their similar structure as journal-hosted types of OA that allow only conditional—and potentially revocable—OA.

The number of articles published annually in closed-access journals increased by 112% between 2003 and 2022 ( Figure PBS-8 ). Over the same period, annual publishing of Green OA articles increased by 228%, while Other Journal-Based OA articles (Hybrid and Bronze OA) increased by 198%. Gold OA articles (which are published in OA journals with no restrictions) had the largest percentage growth, from 19,089 articles in 2003 to 991,805 articles in 2022, an increase of over 5,000%. Hence, although the majority (77%) of S&E articles in 2003 whose access status is known were published in closed-access journals, fewer than half (49%) were in closed-access journals in 2022.

S&E publications, by publication access type: 2003–22

OA = open access.

Articles refer to publications from a selection of conference proceedings and peer-reviewed journals in S&E fields from Scopus. Articles are classified by their year of publication. OA types are mutually exclusive. For articles published under multiple OA types, the article will be counted as part of only the first type it matches in this list: Gold OA, Other Journal-Based OA, or Green OA. Summing all OA and closed-access article counts results in a smaller number of articles than for all S&E because the access status of some articles (e.g., those without digital object identifiers) cannot be reliably ascertained. Green articles are published in toll-access journals but archived in an OA archive, or "repository." These repositories may be discipline specific (like arXiv) or institutional repositories operated by universities or other institutions. Green articles may be published versions or preprints and can have any license or no license. Bronze (Other Journal-Based OA) articles are free to read on the publisher's website, without a license that grants any other rights. There may be a delay between publication and availability to read, and often articles can be removed unilaterally by the publisher. Hybrid (Other Journal-Based OA) articles are free to read at the time of publication, with an open license. These are usually published in exchange for an article processing charge. Gold articles have all the same characteristics as Hybrid articles but are published in all-OA journals, which are in turn called "Gold journals" or just "OA journals."

To conclude this section, the findings of the output analysis reveal the growth in scientific publications over time, with upper-middle-income economies exhibiting particularly large percentage increases. Meanwhile, the distribution of publications across scientific fields shows that life sciences dominated in the United States, Europe, and Japan, whereas publications in engineering and computer sciences dominated in China and India. In OA, the dramatic growth of Gold OA publications and the steady growth of publications in other OA categories show an increased shift toward open science. However, OA can impede the dissemination of some scientific research. Publishing research as OA often requires authors to pay article processing fees, which may be prohibitive for scientists in less-developed nations or whose funders do not subsidize those fees. https://www.elsevier.com/about/policies/pricing . Wiley APCs are at https://authorservices.wiley.com/author-resources/Journal-Authors/open-access/article-publication-charges.html . Springer Nature APCs are at https://www.springernature.com/gp/open-research/journals-books/journals ." data-bs-content="Many publishers make their article processing charges (APCs) known publicly. For example, a list of Elsevier APCs can be found at https://www.elsevier.com/about/policies/pricing . Wiley APCs are at https://authorservices.wiley.com/author-resources/Journal-Authors/open-access/article-publication-charges.html . Springer Nature APCs are at https://www.springernature.com/gp/open-research/journals-books/journals ." data-endnote-uuid="9a612a36-466d-4d60-af1a-57e93bd50e76">​ Many publishers make their article processing charges (APCs) known publicly. For example, a list of Elsevier APCs can be found at https://www.elsevier.com/about/policies/pricing . Wiley APCs are at https://authorservices.wiley.com/author-resources/Journal-Authors/open-access/article-publication-charges.html . Springer Nature APCs are at https://www.springernature.com/gp/open-research/journals-books/journals . The fees can be seen as shifting the costs of accessing research from readers and libraries to authors (Larivière and Sugimoto 2018).

Related Content

When Patients Do Their Own Research

At its best, medicine will be a process of shared decision making, and doctors need to be prepared.

Listen to this article

Produced by ElevenLabs and News Over Audio (NOA) using AI narration.

Miscarriage early in pregnancy is very common—roughly one-fifth of detected pregnancies are thought to end in miscarriage, mostly in the first trimester. After a single miscarriage, patients are typically told that no further testing is needed; most women go on to have healthy pregnancies.

But after multiple miscarriages, doctors and patients begin a process of figuring out what is going on. In these situations, a lot of patients will take information gathering into their own hands. They’ll compile ideas from Google, WebMD, chat boards, support groups, friends, and friends of friends. Patients may arrive at their doctor’s office with file folders of information, a cobbled-together idea of their possibilities. Meanwhile, doctors have clinical knowledge, but they may struggle—especially given their limited time—to engage with their patients’ ideas and guide them.

Medicine wasn’t always this sort of shared process. Not long ago, medical decision making was largely left to doctors. Patients were a passive bunch, arriving at the doctor with their concerns and symptoms, and departing with their doctor’s orders. But today patients have incredible access to information online and elsewhere, and this has prompted a shift to what is sometimes called “shared decision making”: patients and doctors, together, sharing the burden of making consequential health choices.

Emily Oster: Thinking about pregnancy like an economist

This approach sounds great in principle. Shouldn’t patients be involved in decision making about their own health? In the area of obstetrics, the alternative brings to mind deliveries of the 1950s—white-coated doctors smoking cigarettes in their office while women labor in “twilight sleep,” even, in many cases, strapped to the bed. Surely if women had been involved, they would have opted for something a bit more comfortable.

In practice, though, shared decision making can be a source of frustration and confusion, for both sides. From the patient side, it can feel like doctors are either expecting too much engagement— Isn’t it your job to know what to do?— or not listening and not taking the patient’s ideas and preferences seriously. Sometimes it feels like all of this at once. From the medical side, frustration also comes in several forms—with patients who do not want to engage with the decision, and with those who do but are unwilling to listen to expert advice. Why won’t they listen to me? A patient who arrives with her own research can give the impression that she believes her Google search makes her an expert in medicine.

We, the authors of this article, come at this from both angles—one of us is a doctor, and one of us is an expert in statistics who has made a career of helping millions of pregnant people sort through data to make their own best decisions. We both believe that shared decision making in medicine can work, but many doctor-patient interactions today are not working. In our new book, The Unexpected , we try to provide a road map for improving this interaction, focusing on pregnancy. Our idea is simple. Two things are missing from this conversation: some common knowledge, and a script.

First, patients cannot engage with shared decision making if they do not understand the basics of their condition. To return to the example of miscarriage: A very large share of first-trimester miscarriages are a result of chromosomal abnormalities. If a patient does not know how chromosomes work in conception and what might influence them, discussing miscarriage prevention will be difficult. A patient doesn’t possess a doctor’s understanding of their condition—this would be unrealistic—but acquiring basic knowledge will allow patients to most effectively hear and process what is being said.

In particular, patients may benefit from getting a handle on the fundamental medical terminology associated with whatever symptoms they are presenting. Unfamiliar jargon can spark fear far beyond what one would feel if she knew what was being said. “Antiphospholipid antibody syndrome” sounds terrifying if you don’t know that, for many, it’s a treatable condition. When patients do not understand, many will shut down, unable to ask the questions they have or engage with the choices they need to make.

As a result, before doctors ask people to engage with decisions about their health, they need to prepare them. Our book tries to do this for people facing complicated pregnancy conditions. In other cases—cancer treatment, diabetes, other chronic illnesses—different resources exist. Patients should do some homework before they go to the doctor’s office.

The second thing these conversations need is a script. If patients and their doctor had limitless time to talk, then maybe it would be okay to enter the conversation with only a vague idea of the purpose. But time is limited, and that means a script is key, prioritizing questions where the answers matter for decisions.

To return to the miscarriage example, a script might start with the details of what happened. Knowing exactly when in pregnancy a loss occurred, what kind of testing followed it, and how many times it has happened will shape next steps. A second question is whether there are clues as to why it happened, which will inform whether it will happen again. A script might end by talking about what can be done to decrease risk, if anything.

Read: When evidence says no, but doctors say yes

In the best form of this conversation, the doctor brings a deep understanding of what might be going on medically with the patient, the range of possible tests, and what those tests might reveal to the patient. The patient brings a knowledge of their own preferences and their own emotional state. How much information do they want to know? Would they be willing to use more complex medical treatments if they were recommended? Are they even ready to engage emotionally with thinking about trying for pregnancy again?

The central recognition here is that shared decision making isn’t about both sides bringing the same thing to the table and deliberating about it. It’s about two different types of expertise—expertise in medicine on the part of the doctor, and expertise in herself on the part of the patient. Seeing this, in turn, can help the doctors and the patient both recognize when one decision maker should be paramount, or when a decision requires input from both.

An emergency situation—when, say, a person has been in a bike accident, his blood pressure is low, and he is bleeding from his head—isn’t the time for shared decision making. This is when the medical side takes over. No patient needs to be asked whether they think it’s a good idea to scan their head for a skull fracture. At the other end of the spectrum are decisions such as prenatal genetic screening and testing, which are in many cases almost exclusively about patient values and preferences.

Most decisions fall somewhere in between, requiring medical input but with room for patients’ preferences to play a role. Attempting a vaginal birth after a C-section is an example here—both a repeat Cesarean and an attempted vaginal birth have their risks and benefits. The medical expertise comes in explaining these risks and benefits, but the decision for many women here should come down to their own preferences.

With better understanding, clear scripts, and a sense of when different decision makers should dominate, we believe there is space for some decision making to be truly shared. But one more crucial element should be present: trust. Sometimes the desire by patients to play a role in their medical care can seem like a lack of trust in their doctors. And on the flip side, when patients do not feel like their concerns, ideas, or preferences are being listened to, they can lose trust in their provider to find what is best for them . Good decisions require the trust to recognize that we are all rowing in the same direction, and the willingness to engage so we can get there.

​When you buy a book using a link on this page, we receive a commission. Thank you for supporting The Atlantic.

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Peer Review and Scientific Publication at a Crossroads : Call for Research for the 10th International Congress on Peer Review and Scientific Publication

• 1 Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California
• 2 Department of Medicine, Stanford University School of Medicine, Stanford, California
• 3 JAMA and the JAMA Network, Chicago, Illinois
• 4 The BMJ , London, England
• Editorial Three Decades of Peer Review Congresses Drummond Rennie, MD; Annette Flanagin, RN, MA JAMA

The way science is assessed, published, and disseminated has markedly changed since 1986, when the launch of a new Congress focused on the science of peer review was first announced. There have been 9 International Peer Review Congresses since 1989, typically running on an every-4-year cycle, and most recently in 2022 after a 1-year delay due to the COVID-19 pandemic. 1 Here, we announce that the 10th International Congress on Peer Review and Scientific Publication will be held in Chicago, Illinois, on September 3-5, 2025.

The congresses have been enormously productive, incentivizing and publicizing important empirical work into how science is produced, evaluated, published, and disseminated. 2 - 4 However, peer review and scientific publication are currently at a crossroads and their future more difficult than ever to predict. After decades of experience and research in these fields, we have learned a lot about a wide range of aspects of peer review and scientific publication. 2 - 5 We have accumulated a large body of empirical evidence on how systems function and how they can malfunction. There is also growing evidence on how to make peer review, publication, and dissemination processes more efficient, fair, open, transparent, reliable, and equitable. 6 - 15 Experimental randomized evaluations of peer review practices are only a small part of the literature, but their numbers have been growing since the early trials of anonymized peer review. 16 - 22 Research has revealed a rapidly growing list of biases, inefficiencies, and threats to the trustworthiness of published research, some now well recognized, others deserving of more attention. 2 , 3 Moreover, practices continue to change and diversify in response to new needs, tools, and technologies as well as the persistent “publish or perish” pressures on scientists-as-authors.

With the continued evolution of electronic platforms and tools—most recently the emergence and use of large language models and artificial intelligence (AI)—peer review and scientific publication are rapidly evolving to address new opportunities and threats. 23 , 24 Moreover, a lot of money is at stake; scientific publishing is a huge market with one of the highest profit margins among all business enterprises, and it supports a massive biomedical and broader science economy. Many stakeholders try to profit from or influence the scientific literature in ways that do not necessarily serve science or enhance its benefits to society. The number of science journal titles and articles is steadily increasing 25 ; many millions of scientists coauthor scientific papers, and perverse reward systems do not help improve the quality of this burgeoning corpus. Furthermore, principled mandates for immediate and open access to research and data may not be fully understood, accepted, or funded. Many other new, often disruptive, ideas abound on how to improve dissemination of and access to science, some more speculative, utopian, or self-serving than others. In addition, deceptive, rogue actors, such as predatory and pirate publishers, fake reviewers, and paper mills continue to threaten the integrity of peer review and scientific publication. Careful testing of the many proposals to improve peer review and publication and of interventions and processes to address threats to their integrity in a rigorous and timely manner are essential to the future of science and the scholarly publishing enterprise.

Proposed remedies for several of the problems and biases have been evaluated, 4 but many are untested or have inconclusive evidence for or against their use. New biases continue to appear (or at least to be recognized). In addition, there is tension about how exactly to correct the scientific literature, where a large share of what is published may not be replicable or is obviously false. 26 Even outright fraud may be becoming more common—or may simply be recognized and reported more frequently than before. 27 , 28

By their very nature, peer review and scientific publication practices are in a state of flux and may be unstable as they struggle to serve rapidly changing circumstances, technologies, and stakeholder needs and goals. Therefore, some unease would exist even in the absence of major perturbations, even if all the main stakeholders (authors, journals, publishers, funders) simply wanted to continue business as usual. However, the emergence of additional rapid changes further exacerbates the challenges, while also providing opportunities to improve the system at large. The COVID-19 crisis was one major quake that shook the way research is designed, conducted, evaluated, published, disseminated, and accessed. 29 , 30 Advances in AI and large language models may be another, potentially even larger, seismic force, with some viewing the challenge posed by these new developments as another hyped tempest in a teapot and others believing them to be an existential threat to truth and all of humanity. Scientific publication should fruitfully absorb this energy. 23 , 24 Research has never been needed more urgently to properly examine, test, and correct (in essence: peer review) scientific and nonscientific claims for the sake of humanity’s best interests. The premise of all Peer Review Congresses is that peer review and scientific publication must be properly examined, tested, and corrected in the same way the scientific method and its products are applied, vetted, weighted, and interpreted. 2

The range of topics on which we encourage research to be conducted, presented, and discussed at the 10th International Congress on Peer Review and Scientific Publication expands what was covered by the 9 previous iterations of the congress ( Box ). 1 , 2 , 4 We understand that new topics may yet emerge; 2 years until September 2025 is a relatively long period, during which major changes are possible, and even likely. Therefore, we encourage research in any area of work that may be relevant to peer review and scientific publication, including novel empirical investigations of processes, biases, policies, and innovations. The congress has the ambitious goal to cover all branches and disciplines of science. It is increasingly recognized that much can be learned by comparing experiences in research and review practices across different disciplines. While biomedical sciences have had the lion’s share in empirical contributions to research on peer review in the past, we want to help correct this imbalance. Therefore, we strongly encourage the contribution of work from all scientific disciplines, including the natural and physical sciences, social sciences, psychological sciences, economics, computer science, mathematics, and new emerging disciplines. Interdisciplinary work is particularly welcome.

Topics of Interest for the 10th International Congress on Peer Review and Scientific Publication

Efforts to avoid, manage, or account for bias in research methods, design, conduct, and reporting and interpretation

Publication and reporting bias

Bias on the part of researchers, authors, reviewers, editors, funders, commentators, influencers, disseminators, and consumers of scientific information

Interventions to address gender, race and ethnicity, geographic location, career stage, and discipline biases in peer review, publication, research dissemination, and impact

Improving and measuring diversity, equity, and inclusion of authors, reviewers, editors, and editorial board members

Motivational factors for bias related to rewards and incentives

New forms of bias introduced by wider use of large language models and other forms of artificial intelligence (AI)

Editorial and Peer Review Decision-Making

Assessment and testing of models of peer review and editorial decision-making and workflows used by journals, publishers, funders, and research disseminators

Evaluations of the quality, validity, and practicality of peer review and editorial decision-making

Challenges, new biases, and opportunities with mega-journals

Assessment of practices related to publication of special issues with guest editors

Economic and systemic evaluations of the peer review machinery and the related publishing business sector

Methods for ascertaining use of large language models and other forms of AI in authoring and peer review of scientific papers

AI in peer review and editorial decision-making

Quality assurance for reviewers, editors, and funders

Editorial policies and responsibilities

Editorial freedom and integrity

Peer review of grant proposals

Peer review of content for meetings

Editorial handling of science journalism

Role of journals as publishing venues vs peer review venues

COVID-19 pandemic and postpandemic effects

Research and Publication Ethics

Ethical concerns for researchers, authors, reviewers, editors, publishers, and funders

Authorship, contributorship, accountability, and responsibility for published material

Conflicts of interest (financial and nonfinancial)

Research and publication misconduct

Editorial nepotism or favoritism

Paper mills

Citation cartels, citejacking, and other manipulation of citations

Conflicts of interest among those who critique or criticize published research and researchers

Ethical review and approval of studies

Confidentiality considerations

Rights of research participants in scientific publication

Effects of funding and sponsorship on research and publication

Influence of external stakeholders: funders, journal owners, advertisers/sponsors, libraries, legal representatives, news media, social media, fact-checkers, technology companies, and others

Tools and software to detect wrongdoing, such as duplication, fraudulent manuscripts and reviewers, image manipulation, and submissions from paper mills

Corrections and retractions

Legal issues in peer review and correction of the literature

Evaluations of censorship in science

Intrusion of political and ideological agendas in scientific publishing

Science and scientific publication under authoritarian regimes

Improving Research Design, Conduct, and Reporting

Effectiveness of guidelines and standards designed to improve the design, conduct, and reporting of scientific studies

Evaluations of the methodological rigor of published information

Data sharing, transparency, reliability, and access

Research reanalysis, reproducibility, and replicability

Approaches for efficient and effective correction of errors

Curtailing citation and continued spread of retracted science

Innovations in best, fit-for-purpose methods and statistics, and ways to improve their appropriate use

Implementations of AI and related tools to improve research design, conduct, and reporting

Innovations to improve data and scientific display

Quality and reliability of data presentation and scientific images

Standards for multimedia and new content models for dissemination of science

Quality and effectiveness of new formats for scientific articles

Fixed articles vs evolving versions and innovations to support updating of scientific articles and reviews

Models for Peer Review and Scientific Publication

Single-anonymous, double-anonymous, collaborative, and open peer review

Pre–study conduct peer review

Open and public access

Preprints and prepublication posting and release of information

Prospective registration of research

Postpublication review, communications, and influence

Engaging statistical and other technical expertise in peer review

Evaluations of reward systems for authors, reviewers, and editors

Approaches to improve diversity, equity, and inclusion in peer review and publication

Innovations to address reviewer fatigue

Scientific information in multimedia and new media

Publication and performance metrics and usage statistics

Financial and economic models of peer-reviewed publication

Quality and influence of advertising and sponsored publication

Quality and effectiveness of content tagging, markup, and linking

Use of AI and software to improve peer review, decision-making, and dissemination of science

Practices of opportunistic, predatory, and pirate operators

Threats to scientific publication

The future of scientific publication

Dissemination of Scientific and Scholarly Information

New technologies and methods for improving the quality and efficiency of, and equitable access to, scientific information

Novel mechanisms, formats, and platforms to disseminate science

Funding and reward systems for science and scientific publication

Use of bibliometrics and alternative metrics to evaluate the quality and equitable dissemination of published science

Best practices for corrections and retracting fraudulent articles

Comparisons of and lessons from various scientific disciplines

Mapping of scientific methods and reporting practices and of meta-research across disciplines

Use and effects of social media

Misinformation and disinformation

Reporting, publishing, disseminating, and accessing science in emergency situations (pandemics, natural disasters, political turmoil, wars)

The congress is organized under the auspices of JAMA and the JAMA Network, The BMJ , and the Meta-research Innovation Center at Stanford (METRICS) and is guided by an international panel of advisors who represent diverse areas of science and of activities relevant to peer review and scientific publication. 4 The abstract submission site is expected to open on December 1, 2024, with an anticipated deadline for abstract submission by January 31, 2025. Announcements will appear on the congress website ( https://peerreviewcongress.org/ ). 4

Corresponding Author: John P. A. Ioannidis, MD, DSc, Stanford Prevention Research Center, Stanford University, 1265 Welch Rd, MSOB X306, Stanford, CA 94305 ( [email protected] ).

Published Online: September 22, 2023. doi:10.1001/jama.2023.17607

Conflict of Interest Disclosures: All authors serve as directors or coordinators of the Peer Review Congress. Ms Flanagin reports serving as an unpaid board member for STM: International Association of Scientific, Technical, and Medical Publishers. Dr Bloom reports being a founder of medRxiv and a member of the Board of Managers of American Institute of Physics Publishing.

Additional Information: Drs Ioannidis and Berkwits are directors; Ms Flanagin, executive director; and Dr Bloom, European director and coordinator for the International Congress on Peer Review and Scientific Publication.

Note: This article is being published simultaneously in The BMJ and JAMA .

See More About

Ioannidis JPA , Berkwits M , Flanagin A , Bloom T. Peer Review and Scientific Publication at a Crossroads : Call for Research for the 10th International Congress on Peer Review and Scientific Publication . JAMA. 2023;330(13):1232–1235. doi:10.1001/jama.2023.17607

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• 19 April 2024

Do insects have an inner life? Animal consciousness needs a rethink

• Mariana Lenharo

You can also search for this author in PubMed   Google Scholar

You have full access to this article via your institution.

Growing evidence indicates that insects such as bees show some forms of consciousness, according to a new scientific statement. Credit: Phil Savoie/Nature Picture Library

Crows , chimps and elephants : these and many other birds and mammals behave in ways that suggest they might be conscious . And the list does not end with vertebrates. Researchers are expanding their investigations of consciousness to a wider range of animals, including octopuses and even bees and flies.

Armed with such research, a coalition of scientists is calling for a rethink in the animal–human relationship . If there’s “a realistic possibility” of “conscious experience in an animal, it is irresponsible to ignore that possibility in decisions affecting that animal”, the researchers write in a document they call The New York Declaration on Animal Consciousness . Issued today during a meeting in New York City, the declaration also says that there is a “realistic possibility of conscious experience” in reptiles, fish, insects and other animals that have not always been considered to have inner lives, and “strong scientific support” for aspects of consciousness in birds and mammals.

As the evidence has accumulated, scientists are “taking the topic seriously, not dismissing it out of hand as a crazy idea in the way they might have in the past”, says Jonathan Birch, a philosopher at the London School of Economics and Political Science and one of the authors of the declaration.

The document, which had around 40 signatories early today, doesn’t state that there are definitive answers about which species are conscious. “What it says is there is sufficient evidence out there such that there’s a realistic possibility of some kinds of conscious experiences in species even quite distinct from humans,” says Anil Seth, director of the Centre for Consciousness Science at the University of Sussex near Brighton, UK, and one of the signatories. The authors hope that others will sign the declaration and that it will stimulate both more research into animal consciousness and more funding for the field.

Blurry line

The definition of consciousness is complex, but the group focuses on an aspect of consciousness called sentience, often defined as the capacity to have subjective experiences, says Birch. For an animal, such experiences would include smelling, tasting, hearing or touching the world around itself, as well as feeling fear, pleasure or pain — in essence, what it is like to be that animal. But subjective experience does not require the capacity to think about one’s experiences.

The consciousness wars: can scientists ever agree on how the mind works?

Non-human animals cannot use words to communicate their inner states. To assess consciousness in these animals, scientists often rely on indirect evidence, looking for certain behaviours that are associated with conscious experiences, Birch says.

One classic experiment is the mirror test , which investigates an animal’s ability to recognize itself in a mirror. In this experiment, scientists apply a sticker or other visual mark on an animal’s body and place the animal in front of a mirror. Some animals — including chimpanzees ( Pan troglodytes ) 1 , Asian elephants ( Elephas maximus ) 2 and cleaner fishes ( Labroides dimidiatus ) 3 — exhibit curiosity about the mark and even try to remove it. This behaviour suggests the possibility of self-awareness, which might be a sign of consciousness.

In an experiment with crows ( Corvus corone ) 4 , the birds were trained to make a specific head gesture whenever they saw a coloured square on a screen, a task they carried out with high accuracy. While the birds performed the task, scientists measured the activity in a region of their brain associated with high-level cognition. The birds’ brain activity correlated with what the birds were reporting, not with what they were actually shown. This suggests that they were aware of what they were perceiving, another potential marker of consciousness.

Invertebrate inner lives?

Another experiment showed that octopuses ( Octopus bocki ) 5 , when picking between two chambers, avoided one where they had previously received a painful stimulus in favour of one where they were given an anaesthetic. This suggests that they experience and actively avoid pain, which some researchers think indicates conscious experience.

Research shows that octopuses avoid pain, which some scientists take as a sign of consciousness. Credit: Brandon Cole/Nature Picture Library

Investigations of fruit flies ( Drosophila melanogaster ) show that they engage in both deep sleep and ‘active sleep’, in which their brain activity is the same as when they’re awake 6 . “This is perhaps similar to what we call rapid eye movement sleep in humans, which is when we have our most vivid dreams, which we interpret as conscious experiences,” says Bruno van Swinderen, a biologist at the University of Queensland in Brisbane, Australia, who studies fruit flies ’ behaviour and who also signed the declaration.

Some suggest that dreams are key components of being conscious, he notes. If flies and other invertebrates have active sleep, “then maybe this is as good a clue as any that they are perhaps conscious”.

Animal minds

Other researchers are more sceptical about the available evidence on animal consciousness. “I don’t think there is basically any decisive evidence so far,” says Hakwan Lau, a neuroscientist at the Riken Center for Brain Science in Wako, Japan.

Lau acknowledges that there is a growing body of work showing sophisticated perceptual behaviour in animals, but he contends that that’s not necessarily indicative of consciousness. In humans, for example, there is both conscious and unconscious perception. The challenge now is to develop methods that can adequately distinguish between the two in non-humans.

Seth responds that, even in the absence of definitive answers, the declaration might still have a positive influence in shaping policies relating to animal ethics and welfare.

For van Swinderen, the time is right to consider whether most animals might be conscious. “We are experiencing an artificial-intelligence revolution where similar questions are being asked about machines. So it behoves us to ask if and how this adaptive quality of the brain might have evolved in nature.”

Nature 629 , 14-15 (2024)

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