Explore the vast range of titles available.

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy ( n  = 20) compared with healthy controls ( n  = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T FH ) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T H 1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20. SARS-CoV-2-specific antibodies and memory B cells are significantly reduced, but CD4 + and CD8 + T cells are robustly activated, in patients with multiple sclerosis on anti-CD20 monotherapy versus healthy controls after BNT162b2 or mRNA-1273 mRNA vaccination.

OBJECTIVES/GOALS: The objective of this study was to use NIH RePORTER (Research Portfolio Online Reporting Tools) to analyze K99 funding trends and determine if R00 to R01 or R21 achievement time correlates with the future success of an early-stage NIH-funded investigator. METHODS/STUDY POPULATION: All award data were collected from NIH RePORTER. All K99 awards and funding data in this study were limited to All Clinical Departments (ACD). All researchers (n = 1,148) and awards (n = 2,022) were identified through a K99 search from FY 2007 to FY 2022 across ACD. Historic trends in K99 awards and funding from NIH Fiscal Year (FY) 2007 to FY 2022 were investigated. An R00 dataset was generated from NIH RePORTER. The K99 to R00 achievement statistics from FY 2007 to FY 2022 was investigated. NIH annual datafiles for FY 2007 to FY 2021 were aggregated to generate a master datafile of all R01 (n = 395,505) and R21 awards (n = 61,766). R01 and R21 award data were linked to the researcher previously identified through the K99 search. The connection between K99/R00 awardees and subsequent R01 or R21 awards was focused on. RESULTS/ANTICIPATED RESULTS: From FY 2008 to FY 2022, the number of K99 awards per year increased 123.4%, from 94 to 210. Over the same period, after correcting for inflation, the NIH K99 budget increased 127.0% while the NIH program level budget increased 17.3%. For researchers who achieved their first R01 or R21 0–3 years versus 3–6 years after the start of their R00, their average funding per year since the start of the R00 phase was$467,425 versus $ 290,604, respectively (p < 0.001). In summary, NIH investment in the K99 award pathway has substantially outpaced the NIH program level budget increase, and there is a strong relationship between average funding per year since the start of the R00 phase and time from R00 to R01 or R21. DISCUSSION/SIGNIFICANCE: Our study offers additional evidence of the Matthew effect in science, where previous success generates future success. This analysis may be useful to clinical departments as they evaluate selecting new and retaining current biomedical scientists for independent research positions.

Importance Early-stage and established investigators compete for a limited supply of funds from the National Institutes of Health (NIH). Regardless of their previous funding success, many principal investigators (PIs) encounter a funding gap in which they no longer receive ongoing funding from the NIH. Objective To determine incidence rates of PI-level funding gaps, the mean funding gap length, and whether these 2 metrics are associated with previous funding success. Design, Setting, and Participants This study was conducted using data from NIH RePORTER. Historical datafiles for fiscal year (FY) 2011 to FY 2021 were aggregated to generate 2 master datafiles for this period: all NIH awards and only R01 awards. PIs with no funding in FY 2011 or FY 2021 were removed. PIs were sorted by FY 2011 total funding amounts and grouped by quarter of amount. Results A total of 39 944 unique researchers were awarded 220 131 NIH awards, of which 103 753 were R01 awards. For all NIH awards, there was an overall linear increase from top quarter to bottom quarter in the percentage of PIs who had at least 1 year without funding (from 27% to 75%), percentage of these gap PIs who had at least 2 consecutive years without funding (from 56% to 68%), and mean maximum consecutive years without funding for gap PIs (2.2 years to 3.1 years). For only R01 awards, there was an overall linear increase from top quarter to bottom quarter in the percentage of PIs who had at least 1 year without funding (50% to 74%), percentage of gap PIs who had at least 2 consecutive years without funding (59% to 71%), and mean maximum consecutive years without funding for gap PIs (2.4 years to 3.1 years). Conclusions and Relevance In this cohort study of NIH-funded investigators, PIs with higher NIH funding were less likely to experience a funding gap. Additionally, when these PIs encountered a funding gap, this period without funding was shorter; however, among all PIs, funding gaps typically lasted 2 to 3 years. These associations were found inclusive of all NIH awards and when analysis was limited to only R01 awards. These findings may be useful to PIs and academic institutions as they prepare, structure, and project research resource allocations.

Introduction: We report a rare case of bilateral optic disc edema in a patient found to have severe vitamin A deficiency. While vitamin A deficiency typically presents with optic disc atrophy, this case emphasizes the importance of considering vitamin A deficiency in patients with atypical optic disc edema. Case Presentation: A 39-year-old female with a history of disordered eating habits and extensive psychiatric history presented to the emergency department with acute onset cloudiness and blurring of her vision bilaterally. Physical exam was notable for bilateral optic disc edema in the absence of increased intracranial pressure, as demonstrated by an unremarkable MRI and lumbar puncture opening pressure of 18 cmH2O. Extensive testing on serum and cerebrospinal fluid was notable only for a serum vitamin A level of less than 5 mcg/dL (normal: 38-98 mcg/dL). The patient underwent inpatient hospitalization and was given 100,000 units of intramuscular vitamin A for 3 days with 50,000 units per day for the following two weeks. A follow-up visit one month later revealed resolution of her optic disc edema in the right eye and only mild optic disc edema in the left eye. Conclusion: We describe a case of bilateral optic disc edema in a patient with severe vitamin A deficiency, underscoring the potential for nutritional abnormalities to present in this fashion. We also emphasize a multidisciplinary approach to unveil the underlying causes of atypical presentations of optic disc edema and create an appropriate treatment plan for patients with nutritional deficiencies.

Debate over effective climate change communication must be grounded in rigorous affective science. Rather than treating emotions as simple levers to be pulled to promote desired outcomes, emotions should be viewed as one integral component of a cognitive feedback system guiding responses to challenging decision-making problems.

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection 1 , 2 , but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19. The lungs from individuals with COVID-19 were highly inflamed, with dense infiltration of aberrantly activated monocyte-derived macrophages and alveolar macrophages, but had impaired T cell responses. Monocyte/macrophage-derived interleukin-1β and epithelial cell-derived interleukin-6 were unique features of SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. Alveolar type 2 cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type 1 cells, resulting in impaired lung regeneration. Furthermore, we identified expansion of recently described CTHRC1 + pathological fibroblasts 3 contributing to rapidly ensuing pulmonary fibrosis in COVID-19. Inference of protein activity and ligand–receptor interactions identified putative drug targets to disrupt deleterious circuits. This atlas enables the dissection of lethal COVID-19, may inform our understanding of long-term complications of COVID-19 survivors, and provides an important resource for therapeutic development. Lung samples collected soon after death from COVID-19 are used to provide a single-cell atlas of SARS-CoV-2 infection and the ensuing molecular changes.

How likely is it that someone would approve of using a nuclear weapon to kill millions of enemy civilians in the hope of ending a ground war that threatens thousands of American troops? Ask them how they feel about prosecuting immigrants, banning abortion, supporting the death penalty, and protecting gun rights and you will know. This is the finding from two national surveys of Democrats and Republicans that measured support for punitive regulations and policies across these four seemingly unrelated issues, and a fifth, using nuclear weapons against enemy civilians (in survey 1) or approving of disproportionate killing with conventional weapons (in survey 2). Those who support these various policies that threaten harm to many people tend to believe that the victims are blameworthy and it is ethical to take actions or policies that might harm them. This lends support to the provocative notion of “virtuous violence” put forth by Fiske and Rai [A. P. Fiske, T. S. Rai, Virtuous Violence: Hurting and Killing to Create, Sustain, End, and Honor Social Relationships (2014)], who assert that people commit violence because they believe it is the morally right thing to do. The common thread of punitiveness underlying and connecting these issues needs to be recognized, understood, and confronted by any society that professes to value fundamental human rights and wishes to prevent important decisions from being affected by irrelevant and harmful sociocultural and political biases.

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER +ve ) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.

This study examines the relationship between respondents’ vaccine hesitancy, reported media consumption patterns, ideological leanings, and trust in science. A large-scale survey conducted in the US in 2022 ( N  = 1,646) assessed self-reported COVID-19 vaccination, trust in science, and reported media consumption. Findings show that, regardless of personal ideology, individuals who consumed less conservative media and had a more ideologically diverse media diet were more likely to be fully vaccinated and boosted. Additionally, consuming more conservative media was negatively associated with trust in science, but this relationship was weaker among those with a more ideologically diverse media diet. By incorporating data from an earlier wave of the survey in the summer of 2020, before COVID-19 vaccines were available, we found that a less conservative and more ideologically diverse media diet in 2022 predicted vaccination behavior in 2022, controlling for prior vaccine intentions and media consumption in 2020. A similar survey conducted in the UK in the summer of 2020 paralleled patterns in the US regarding vaccine intentions and media consumption. These results suggest that an ideologically diverse media diet is associated with reduced vaccine hesitancy. Public health initiatives might benefit from encouraging ideologically diverse media consumption.

Compassion shown towards victims often decreases as the number of individuals in need of aid increases, identifiability of the victims decreases, and the proportion of victims helped shrinks. Such “compassion fade” may hamper individual-level and collective responses to pressing large-scale crises. To date, research on compassion fade has focused on humanitarian challenges; thus, it remains unknown whether and to what extent compassion fade emerges when victims are non-human others. Here we show that compassion fade occurs in the environmental domain, but only among non-environmentalists. These findings suggest that compassion fade may challenge our collective ability and willingness to confront the major environmental problems we face, including climate change. The observed moderation effect of environmental identity further indicates that compassion fade may present a significant psychological barrier to building broad public support for addressing these problems. Our results highlight the importance of bringing findings from the field of judgment and decision making to bear on pressing societal issues.