The impact of US-China tensions on US science: Evidence from the NIH investigations.

Amid the discourse on foreign influence investigations in research, this study examines the impact of NIH-initiated investigations starting in 2018 on U.S. scientists' productivity, focusing on those collaborating with Chinese peers. Using publication data from 2010 to 2021, we analyze over 113,000 scientists and find that investigations coincide with reduced productivity for those with China collaborations compared to those with other international collaborators, especially when accounting for publication impact. The decline is particularly pronounced in fields that received greater preinvestigation NIH funding and engaged more in U.S.-China collaborations. Indications of scientist migration and broader scientific progress implications also emerge. We also offer insights into the underlying mechanisms via qualitative interviews.

Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

The planetary commons: A new paradigm for safeguarding Earth-regulating systems in the Anthropocene.

The Anthropocene signifies the start of a no-analogue trajectory of the Earth system that is fundamentally different from the Holocene. This new trajectory is characterized by rising risks of triggering irreversible and unmanageable shifts in Earth system functioning. We urgently need a new global approach to safeguard critical Earth system regulating functions more effectively and comprehensively. The global commons framework is the closest example of an existing approach with the aim of governing biophysical systems on Earth upon which the world collectively depends. Derived during stable Holocene conditions, the global commons framework must now evolve in the light of new Anthropocene dynamics. This requires a fundamental shift from a focus only on governing shared resources beyond national jurisdiction, to one that secures critical functions of the Earth system irrespective of national boundaries. We propose a new framework-the planetary commons-which differs from the global commons framework by including not only globally shared geographic regions but also critical biophysical systems that regulate the resilience and state, and therefore livability, on Earth. The new planetary commons should articulate and create comprehensive stewardship obligations through Earth system governance aimed at restoring and strengthening planetary resilience and justice.

Cell line authentication: a necessity for reproducible biomedical research.

Immortalized or continuous cell lines are invaluable tools in basic and preclinical research. However, the widespread use of misidentified cell lines is a serious threat to scientific reproducibility. Based on the experiences of mandatory cell line authentication at the International Journal of Cancer (IJC), we provide an overview of the issues pertinent to misidentified cell lines and discuss available solutions. We also summarize the lessons learned, revealing that at least 5% of the human cell lines used in manuscripts considered for peer review are misidentified. About 4% of the considered manuscripts are rejected for severe cell line problems, and most are subsequently published in other journals. In order to diminish such malpractice and its consequences for the scientific record, we postulate that strict multi-layered quality control is essential. Besides journals and publishers, we encourage scientists, research institutions, and funders to take action on the matter and revise their respective policies. Hence, we provide concrete recommendations on introducing regular authentication schemes and staff training, and discuss future steps for enhancing good cell culture practices.

Association of vaccination, international travel, public health and social measures with lineage dynamics of SARS-CoV-2.

Continually emerging SARS-CoV-2 variants of concern that can evade immune defenses are driving recurrent epidemic waves of COVID-19 globally. However, the impact of measures to contain the virus and their effect on lineage diversity dynamics are poorly understood. Here, we jointly analyzed international travel, public health and social measures (PHSM), COVID-19 vaccine rollout, SARS-CoV-2 lineage diversity, and the case growth rate (GR) from March 2020 to September 2022 across 63 countries. We showed that despite worldwide vaccine rollout, PHSM are effective in mitigating epidemic waves and lineage diversity. An increase of 10,000 monthly travelers in a single country-to-country route between endemic countries corresponds to a 5.5% (95% CI: 2.9 to 8.2%) rise in local lineage diversity. After accounting for PHSM, natural immunity from previous infections, and waning immunity, we discovered a negative association between the GR of cases and adjusted vaccine coverage (AVC). We also observed a complex relationship between lineage diversity and vaccine rollout. Specifically, we found a significant negative association between lineage diversity and AVC at both low and high levels but not significant at the medium level. Our study deepens the understanding of population immunity and lineage dynamics for future pandemic preparedness and responsiveness.

"The 10th International MDM2 Workshop": Opening up new avenues for MDM2 and p53 research, the First International MDM2 Workshop in Asia.

The 10th International MDM2 Workshop was held at the National Cancer Center Research Institute (NCCRI) in Tokyo, Japan, from October 15 to 18, 2023. It attracted 166 participants from 12 countries. The meeting featured 52 talks and 41 poster presentations. In the first special session, six invited speakers gave educational and outstanding talks on breakthroughs in MDM2 research. Three keynote speakers presented emerging p53-independent functions of MDM2/MDM4, functional association of MDM2/p53 with cancer immunity, and drug discovery targeting the MDM2/MDM4-p53 pathway. Additionally, 19 invited speakers introduced their new findings. Twenty-one presenters, many of whom were young investigators, postdocs, and students, were selected from submitted abstracts and reported their exciting and unpublished results. For poster presenters, outstanding poster awards were given to the best presenters. There were many inspiring questions and discussions throughout the meeting. Social events like a welcome party, a workshop dinner, and an optional tour enabled further scientific interactions among the participants. The meeting successfully provided an exciting platform for scientific exchange. The experience gained from organizing this meeting will be handed over to the next organizers of the 11th International MDM2 Workshop.

Ambiviricota, a novel ribovirian phylum for viruses with viroid-like properties.

Fungi harbor a vast diversity of mobile genetic elements (MGEs). Recently, novel fungal MGEs, tentatively referred to as 'ambiviruses,' were described. 'Ambiviruses' have single-stranded RNA genomes of about 4-5 kb in length that contain at least two open reading frames (ORFs) in non-overlapping ambisense orientation. Both ORFs are conserved among all currently known 'ambiviruses,' and one of them encodes a distinct viral RNA-directed RNA polymerase (RdRP), the hallmark gene of ribovirian kingdom Orthornavirae. However, 'ambivirus' genomes are circular and predicted to replicate via a rolling-circle mechanism. Their genomes are also predicted to form rod-like structures and contain ribozymes in various combinations in both sense and antisense orientations-features reminiscent of viroids, virusoids, ribozyvirian kolmiovirids, and yet-unclassified MGEs (such as 'epsilonviruses,' 'zetaviruses,' and some 'obelisks'). As a first step toward the formal classification of 'ambiviruses,' the International Committee on Taxonomy of Viruses (ICTV) recently approved the establishment of a novel ribovirian phylum, Ambiviricota, to accommodate an initial set of 20 members with well-annotated genome sequences.

The psychology of separation: Border walls, soft power, and international neighborliness.

This study assesses the impact of international border walls on evaluations of countries and on beliefs about bilateral relationships between states. Using a short video, we experimentally manipulate whether a border wall image appears in a broader description of the history and culture of a little-known country. In a third condition, we also indicate which bordering country built the wall. Demographically representative samples from the United States, Ireland, and Turkey responded similarly to these experimental treatments. Compared to a control group, border walls lowered evaluations of the bordering countries. They also signified hostile international relationships to third-party observers. Furthermore, the government of the country responsible for building the wall was evaluated especially negatively. Reactions were consistent regardless of people's predispositions toward walls in their domestic political context. Our findings have important implications for a country's attractiveness, or "soft power," an important component of nonmilitary influence in international relations.

Disentangling the individual and contextual effects of math anxiety: A global perspective.

Math anxiety is a common affective disorder in students that is characterized by intrusive thoughts that disrupt critical cognitive resources required for math problem-solving. Consistent associations between math anxiety and math achievement have been observed across countries and age groups, placing math anxiety among other important correlates of math achievement, such as socioeconomic status and magnitude representation ability. However, studies examining math anxiety's relation to achievement have largely focused on the effect of students' own math anxiety (individual effect), while little is known regarding the effect of math anxiety in students' educational context (contextual effect). Using three international studies of achievement (n = 1,175,515), we estimated both the individual and contextual effects of math anxiety across the globe. Results suggest that while there are consistent individual effects in virtually all countries examined, the contextual effects are varied, with only approximately half of the countries exhibiting a contextual effect. Additionally, we reveal that teacher confidence in teaching math is associated with a reduction of the individual effect, and country's level of uncertainty avoidance is related to a lessening of the contextual effect. Finally, we uncovered multiple predictors of math anxiety; notably, student perception of teacher competence was negative related with math anxiety, and parental homework involvement was positively related with math anxiety. Taken together, these results suggest that there are significant between-country differences in how math anxiety may be related with math achievement and suggest that education and cultural contexts as important considerations in understanding math anxiety's effects on achievement.

International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

Probabilistic forecasts of international bilateral migration flows.

We propose a method for forecasting global human migration flows. A Bayesian hierarchical model is used to make probabilistic projections of the 39,800 bilateral migration flows among the 200 most populous countries. We generate out-of-sample forecasts for all bilateral flows for the 2015 to 2020 period, using models fitted to bilateral migration flows for five 5-y periods from 1990 to 1995 through 2010 to 2015. We find that the model produces well-calibrated out-of-sample forecasts of bilateral flows, as well as total country-level inflows, outflows, and net flows. The mean absolute error decreased by 61% using our method, compared to a leading model of international migration. Out-of-sample analysis indicated that simple methods for forecasting migration flows offered accurate projections of bilateral migration flows in the near term. Our method matched or improved on the out-of-sample performance using these simple deterministic alternatives, while also accurately assessing uncertainty. We integrate the migration flow forecasting model into a fully probabilistic population projection model to generate bilateral migration flow forecasts by age and sex for all flows from 2020 to 2025 through 2040 to 2045.

How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks: A BARDA Perspective.

Infectious disease outbreaks have become increasingly common and require global partnership for adequate preparedness and response. During outbreaks, medical countermeasures (MCMs)-vaccines, therapeutics, and diagnostics-need to reach patients quickly. BARDA utilizes public-private partnerships to support advanced development of MCMs through U.S. FDA approval against a variety of threats within its mission space. MCM preparedness and response must be approached as an integrated life cycle, not as independent steps. Recent filovirus outbreaks in Africa exemplify that collaborative relationships are critical for emergency response, and products with regulatory approval can expand access and reach patients quicker than investigational products. Unfortunately, insufficient funding globally and differences in funders' prioritization puts gains and future efforts at risk. Of primary concern is a) lack of a feasible regulatory path and clinical capability to achieve regulatory approval for new MCMs for many diseases; and b) the need for partners with the mandate, funding, and capabilities to support the life cycle activities following development-long-term sustainment of manufacturing capability and stockpiling of licensed products to support international outbreaks. Finding partners that complement BARDA's mission and support the MCM life cycle will be a key component in deciding which MCM development efforts can be supported. Without collaboration, the global community runs the risk of losing the capabilities built through years of investment and being underprepared to combat future threats. Synergies between funders that have different roles and responsibilities within the MCM life cycle are critical to MCM availability and create long-term sustainment of products to ensure access.

Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Stroke Risk After Emergency Department Treat-and-Release Visit for a Fall.

BACKGROUND: Previous cohort studies of hospitalized patients with a delayed diagnosis of ischemic stroke found that these patients often had an initial emergency department (ED) diagnosis of a fall. We sought to evaluate whether ED visits for a fall resulting in discharge to home (ie, treat-and-release visits) were associated with increased short-term ischemic stroke risk. METHODS: A case-crossover design was used to compare ED visits for falls during case periods (0-15, 16-30, 31-90, and 91-180 days before stroke) and control periods (equivalent time periods exactly 1 year before stroke) using administrative data from the Healthcare Cost and Utilization Project on all hospital admissions and ED visits across 10 states from 2016 to 2020. To identify ED treat-and-release visits for a fall and patients hospitalized for acute ischemic stroke, we used previously validated International Classification of Diseases, Tenth Revision, Clinical Modification codes. Odds ratios and 95% CIs were calculated using conditional logistic regression. RESULTS: Among 90 592 hospitalized patients with ischemic stroke, 5230 (5.8%) had an ED treat-and-release visit for a fall within 180 days before their stroke. Patients with an ED treat-and-release visit for a fall were older (mean age, 74.7 [SD, 14.6] versus 70.8 [SD, 15.1] years), more often female (61.9% versus 53.4%), and had higher rates of vascular comorbidities than other patients with stroke. ED treat-and-release visits for a fall were significantly more common in the 15 days before stroke compared with the 15-day control period 1 year earlier (odds ratio, 2.7 [95% CI, 2.4-3.1]). The association between stroke and a preceding ED treat-and-release visit for a fall decreased in magnitude with increasing temporal distance from stroke. CONCLUSIONS: ED treat-and-release visits for a fall are associated with significantly increased short-term ischemic stroke risk. These visits may be opportunities to improve stroke diagnostic accuracy and treatment in the ED.

Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023.

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical.

Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

Global Governance of Human Genome Editing: What Are the Rules?

Human gene editing, particularly using the new CRISPR/Cas9 technology, will greatly increase the capability to make precise changes to human genomes. Human gene editing can be broken into four major categories: somatic therapy, heritable gene editing, genetic enhancement, and basic and applied research. Somatic therapy is generally well governed by national regulatory systems, so the need for global governance is less urgent. All nations are in agreement that heritable gene editing should not proceed at this time, but there is likely to be divergence if and when such procedures are shown to be safe and effective. Gene editing for enhancement purposes is not feasible today but is more controversial with the public, and many nations do not have well-developed regulatory systems for addressing genetic enhancement. Finally, different nations treat research with human embryos very differently based on deeply embedded social, cultural, ethical, and legal traditions. Several international governance mechanisms are currently in operation for human gene editing, and several other governance mechanisms have been proposed. It is unlikely that any single mechanism will alone be effective for governing human gene editing; rather, a polycentric or ecosystem approach that includes several overlapping and interacting components is likely to be necessary.

Heart Development and Congenital Structural Heart Defects.

Congenital heart disease is the most frequent birth defect and the leading cause of death for the fetus and in the first year of life. The wide phenotypic diversity of congenital heart defects requires expert diagnosis and sophisticated repair surgery. Although these defects have been described since the seventeenth century, it was only in 2005 that a consensus international nomenclature was adopted, followed by an international classification in 2017 to help provide better management of patients. Advances in genetic engineering, imaging, and omics analyses have uncovered mechanisms of heart formation and malformation in animal models, but approximately 80% of congenital heart defects have an unknown genetic origin. Here, we summarize current knowledge of congenital structural heart defects, intertwining clinical and fundamental research perspectives, with the aim to foster interdisciplinary collaborations at the cutting edge of each field. We also discuss remaining challenges in better understanding congenital heart defects and providing benefits to patients.

Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Highlights from the 2023 International Meeting on the Molecular Biology of Hepatitis B virus.

Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.