bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced antibody acquisition with increasing age following vaccination with BNT162b2: results from a large study performed in the general population aged 12 to 92 years
Authors: van den Hoogen Lotus L. , Boer Mardi C. , Postema Abigail , de Rond Lia , de Zeeuw-Brouwer Mary-lène , Pronk Inge , Wijmenga-Monsuur Alienke J. , Bijvank Elske , Kruiper Caitlyn , Beckers Lisa , Maurik Marjan Bogaard-van , Zutt Ilse , van Vliet Jeffrey , van Bergen Rianne , Kuijer Marjan , Smits Gaby , Monique Verschuren W. M. , Picavet H. Susan J. , van der Klis Fiona R.M. , den Hartog Gerco , van Binnendijk Robert S. , Buisman Anne-Marie
Published: May 2022

Vaccine-induced protection of the population against severe COVID-19, hospitalization and death is of utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post BNT162b2 vaccination. 1·735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female and the median vaccination interval was 35 days (interquartile range, IQR: 35-35). All participants had seroconverted to S1 one month after two doses of vaccine. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4·535 BAU/ml, IQR: 2·341-7·205) compared to infection-naïve persons (1·842 BAU/ml, 1·019-3·116) after two doses, p<0.001. In infection-naïve persons, linear mixed effects regression showed a strong negative association between age and S1 IgG one month after the first vaccination (p<0.001) across the entire age range. The association was still present after the second vaccination, but less pronounced. Females had higher S1 IgG than males after both the first and second vaccination (p<0.001); although this difference was lower after the second dose. In persons with an infection history, age nor sex was associated with peak S1 IgG. As IgG decreased with age and time since vaccination, older persons may become at risk of infection, especially with escape variants such as Omicron.
Bias-adjusted predictions of county-level vaccination coverage from the COVID-19 Trends and Impact Survey
Authors: Reitsma Marissa B. , Rose Sherri , Reinhart Alex , Goldhaber-Fiebert Jeremy D. , Salomon Joshua A.
Published: May 2022

The potential for bias in non-representative, large-scale, low-cost survey data can limit their utility for population health measurement and public health decision-making. We developed a multi-step regression framework to bias-adjust vaccination coverage predictions from the large-scale US COVID-19 Trends and Impact Survey that included post-stratification to the American Community Survey and secondary normalization to an unbiased reference indicator. As a case study, we applied this framework to generate county-level predictions of long-run vaccination coverage among children ages 5 to 11 years. Our vaccination coverage predictions suggest a low ceiling on long-term national coverage (46%), detect substantial geographic heterogeneity (ranging from 11% to 91% across counties in the US), and highlight widespread disparities in the pace of scale-up in the three months following Emergency Use Authorization of COVID-19 vaccination for 5 to 11 year-olds. Generally, our analysis demonstrates an approach to leverage differing strengths of multiple sources of information to produce estimates on the time-scale and geographic-scale necessary for proactive decision-making. The utility of large-scale, low-cost survey data for improving population health measurement is amplified when these data are combined with other representative sources of data.
Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies
Authors: Mirzakhani Mohammad , Tahmasebi Safa , Dashti Mohammadreza , Mohammadi Mohammad Reza , Faghih Manizhe , Mohammadnia-Afrouzi Mousa , Gouvarchin Ghaleh Hadi Esmaeili , Amani Jafar
Published: May 2022

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. SARS-CoV-2 transmit among the people fast and infected thousands of people daily around the world. Because of rapid transmission of SARS-CoV-2 among the people, there is an urgent need to prevent people from infection or hospitalization and control the disease.

Methods

We will search electronic databases such as PubMed, Web of Science, Cochrane (CENTRAL), Scopus, Google scholar, the key journals (vaccine and vaccines). Moreover, trial registry including clinicalTrials.gov, WHO ICTRP, and ISRCTN will be searched. We will only select all clinical trial studies in any phases of evaluation (i.e. phase I, II, II, IV). For anti-spike glycoprotein antibody (IgG) response and neutralizing antibody response, we will report Ratio of Geometric Mean (RoGM), Ratio of Mean (RoM) or standardized mean difference (SMD) depends on type of articles.

Discussion

Various vaccine platforms have been developed to increase the resistance to the SARS-CoV2 virus and reduce hospitalization and mortality rates. The comprehensive data gathering and analysis of results will guide scientists about the best available evidence. Moreover, the current study results may indicate which of the vaccine platforms are more effective and safe for COVID-19.
Population health impact, cost-effectiveness, and affordability of community-based HIV treatment and monitoring in South Africa: a health economics modelling study
Authors: Sahu Maitreyi , Bayer Cara J. , Roberts D. Allen , van Rooyen Heidi , van Heerden Alastair , Shahmanesh Maryam , Asiimwe Stephen , Sausi Kombi , Sithole Nsika , Ying Roger , Rao Darcy W. , Krows Meighan L. , Shapiro Adrienne E. , Baeten Jared M. , Celum Connie , Revill Paul , Barnabas Ruanne V. ,   for the Delivery Optimization of Antiretroviral Therapy (DO ART) Study Team
Published: May 2022

Introduction

Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy.

Methods and Findings

We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. We evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. Sensitivity analyses varied costs of ART, hospitalisation, and testing. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3–31.5) of incident HIV infections, 27.8% (26.8–28.8) of HIV-related deaths, and 18.7% (17.9–19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15–24 years experienced the greatest reduction in incident HIV (30.7%, 27.1–34.7). In the first five years (2020–2024), community ART required an additional $44.9 million (35.8–50.1) annually, representing 14.3% (11.4–16.0) of the current HIV budget. The cost per DALY averted was $102 (85–117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9–92.8). Cost-effectiveness was robust to sensitivity analyses.

Conclusions

In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring for people not already virally suppressed can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.
Levels and determinants of COVID-19 vaccine hesitancy among sub-Saharan African adolescents
Authors: Wang Dongqing , Chukwu Angela , Mwanyika-Sando Mary , Abubakari Sulemana Watara , Assefa Nega , Madzorera Isabel , Hemler Elena C , Ismail Abbas , Lankoande Bruno , Mapendo Frank , Millogo Ourohiré , Workneh Firehiwot , Azemraw Temesgen , Febir Lawrence G , James Christabel , Tinkasimile Amani , Asante Kwaku Poku , Baernighausen Till , Berhane Yemane , Killewo Japhet , Oduola Ayoade M.J. , Sie Ali , Smith Emily R , Soura Abdramane Bassiahi , Tajudeen Raji , Vuai Said , Fawzi Wafaie W
Published: May 2022

COVID-19 vaccine hesitancy among adolescents poses a challenge to the global effort to control the pandemic. This multi-country survey aimed to assess the levels and determinants of COVID-19 vaccine hesitancy among adolescents in sub-Saharan Africa between July and December 2021. The survey was conducted using computer-assisted telephone interviewing among adolescents in five sub-Saharan African countries, Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania. A rural area and an urban area were included in each country (except Ghana, which only had a rural area), with approximately 300 adolescents in each area and 2803 in total. Sociodemographic characteristics and perceptions and attitudes on COVID-19 vaccines were measured. Vaccine hesitancy was defined as definitely not getting vaccinated or being undecided on whether to get vaccinated if a COVID-19 vaccine were available. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for associations between potential determinants and COVID-19 vaccine hesitancy. The percentage of COVID-19 vaccine hesitancy was 15% in rural Kersa, 24% in rural Ibadan, 31% in rural Nouna, 33% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 64% in urban Lagos, 76% in urban Dar es Salaam, and 88% in rural Dodoma. Perceived low necessity, concerns about vaccine safety, and concerns about vaccine effectiveness were the leading reasons for hesitancy. Healthcare workers, parents or family members, and schoolteachers had the greatest impacts on vaccine willingness. Perceived lack of safety (aPR: 3.61; 95% CI: 3.10, 4.22) and lack of effectiveness (aPR: 3.59; 95% CI: 3.09, 4.18) were associated with greater vaccine hesitancy. The levels of COVID-19 vaccine hesitancy among adolescents are alarmingly high across the five sub-Saharan African countries, especially in Tanzania. COVID-19 vaccination campaigns among sub-Saharan African adolescents should address their concerns and misconceptions about vaccine safety and effectiveness.
Annual prevalence of non-communicable diseases and identification of vulnerable populations following the Fukushima disaster and COVID-19 pandemic
Authors: Murakami Michio , Nomura Shuhei
Published: May 2022

Disasters, pandemics, and their response measures can have secondary effects on the physical and psychological health of affected populations. Identifying populations vulnerable to these effects is beneficial for promoting effective health and prevention strategies. Using health insurance receipt data from 2009 to 2020, we assessed changes in prevalence of major non-communicable diseases (NCDs), including hypertension, hyperlipidemia, diabetes, and mental disorders, among affected populations before and after the Fukushima disaster and coronavirus disease (COVID-19) outbreak in Japan. Furthermore, age and sex groups with the largest increases in prevalence after these events were identified. The participants of this study were members of the Employees’ Health Insurance scheme, including employees of companies and their dependent family members. The dataset was provided by JMDC Inc. The annual age-adjusted prevalence of each disease was used to calculate the ratio of disease prevalence before and after the events. After the Fukushima disaster, hypertension, hyperlipidemia, and diabetes generally increased over a 9-year period in Fukushima Prefecture. The increase in the prevalence rate of these three NCDs and mental disorders were the highest among females aged 40–74 years compared to males and the other age groups. The prevalence of all four diseases increased after the COVID-19 outbreak in Japan, with marked increase in males aged 0–39 years. Populations that have experienced secondary health effects such as NCDs are unique to each disaster or pandemic, and it is important to provide tailor-made public health support among populations in accordance to the type of disasters and pandemic.

Highlights

We assessed secondary health effects of Fukushima disaster and COVID-19 pandemic

Non-communicable diseases increased after the disaster and COVID-19 pandemic

The increase rates were higher among females aged 40–74 years after the disaster

The increase rates were higher among males aged 0–39 years after COVID-19 pandemic

It is important to provide tailor-made public health support among populations
Computational conjugate adaptive optics for longitudinal through-skull imaging of cortical myelin
Authors: Kwon Yongwoo , Hong Jin Hee , Yoon Seokchan , Kang Sungsam , Lee Hojun , Jo Yonghyeon , Kim Ki Hean , Choi Wonshik
Published: May 2022

We present a 1.3-μm reflection matrix microscope and computational conjugate adaptive optics algorithm for label-free longitudinal imaging of cortical myelin through an intact mouse skull. The myelination processes of the same mice were observed from 3 to 10 postnatal weeks down to cortical layer 4 with a near-diffraction-limited resolution of 0.79 µm. Our system will expedite the investigations on the role of myelination in learning, memory, and brain disorders.
Intelligibility improves perception of timing changes in speech
Authors: Zoefel Benedikt , Gilbert Rebecca A. , Davis Matthew H.
Published: May 2022

Auditory rhythms are ubiquitous in music, speech, and other everyday sounds. Yet, it is unclear how perceived rhythms arise from the repeating structure of sounds. For speech, it is unclear whether rhythm is solely derived from acoustic properties (e.g., rapid amplitude changes), or if it is also influenced by the linguistic units (syllables, words, etc.) that listeners extract from intelligible speech. Here, we present three experiments in which participants were asked to detect an irregularity in rhythmically spoken speech sequences. In each experiment, we reduce the number of possible stimulus properties that differ between intelligible and unintelligible speech sounds and show that these acoustically-matched intelligibility conditions nonetheless lead to differences in rhythm perception. In Experiment 1, we replicate a previous study showing that rhythm perception is improved for intelligible (16-channel vocoded) as compared to unintelligible (1-channel vocoded) speech – despite near-identical broadband amplitude modulations. In Experiment 2, we use spectrally-rotated 16-channel speech to show the effect of intelligibility cannot be explained by differences in spectral complexity. In Experiment 3, we compare rhythm perception for sine-wave speech signals when they are heard as non-speech (for naïve listeners), and subsequent to training, when identical sounds are perceived as speech. In all cases, detection of rhythmic regularity is enhanced when participants perceive the stimulus as speech compared to when they do not. Together, these findings demonstrate that intelligibility enhances the perception of timing changes in speech, which is hence linked to processes that extract abstract linguistic units from sound.
Prelimbic cortex neural encoding dynamically tracks expected outcome value
Authors: Niedringhaus Mark , West Elizabeth A.
Published: May 2022

Animals must modify their behavior based on updated expected outcomes in a changing environment. Prelimbic cortex (PrL) neural encoding during learning predicts and is necessary for appropriately altering behavior based on new expected outcome value following devaluation. We aimed to determine how PrL neural activity encodes reward predictive cues after the expected outcome value of those cues is decreased following conditioned taste aversion. In one post- devaluation session, rats were tested under extinction to determine their ability alter their behavior to the expected outcome values (i.e., extinction test). In a second post-devaluation session, rats were tested with the newly devalued outcome delivered so that the rats experienced the updated outcome value within the session (i.e., re-exposure test). We found that PrL neural encoding to the cue associated with the devalued reward predicted the ability of rats to suppress behavior in the extinction test session, but not in the re-exposure test session. While all rats were able to successfully devalue the outcome during conditioned taste aversion, a subset of rats continued to consume the devalued outcome in the re-exposure test session. We found differential patterns of PrL neural encoding in the population of rats that did not avoid the devalued outcome during the re-exposure test compared to the rats that successfully avoided the devalued outcome. Our findings suggest that PrL neural encoding dynamically tracks expected outcome values, and differential neural encoding in the PrL to reward predictive cues following expected outcome value changes may contribute to distinct behavioral phenotypes.
Can machine learning with data from wearable devices distinguish disease severity levels and generalise across patients? A pilot study in Mania and Depression
Authors: Li Bryan M. , Corponi Filippo , Anmella Gerard , Mas Ariadna , Sanabra Miriam , Pacchiarotti Isabella , Valentí Marc , Giménez-Palomo Anna , Garriga Marina , Agasi Isabel , Bastidas Anna , Fernández-Plaza Tabatha , Arbelo Néstor , Cavero Myriam , García-Rizo Clemente , Bioque Miquel , Verdolini Norma , Madero Santiago , Murru Andrea , Grande Iria , Amoretti Silvia , Ruiz Victoria , Fico Giovanna , De Prisco Michele , Oliva Vincenzo , Vieta Eduard , Hidalgo-Mazzei Diego
Published: May 2022

Abstract

Mood disorders are severe and chronic mental conditions exacting high costs from society. The lack of reliable biomarkers to aid clinicians in tailoring pharmacotherapy based on distinguishable patient-specific traits means that the current prescribing paradigm is largely one of trial and error. Previous studies showed that different biological signatures, such as patterns of heart rate variability or electro-dermal reactivity, are associated with clinically meaningful outcomes. Against this backdrop, the advances in machine learning and the spread of wearable devices capable of providing continuous and ecological monitoring of patients may unlock great opportunities in mental healthcare. We herewith present a pilot study on mania and depression where we moved beyond the simple disease state binary classification but pursued the more informative and clinically meaningful task of differentiating between levels of disease severity. While most previous similar endeavours used recording segments extracted from the same subjects for both training and testing, we explicitly carried out model development and evaluation on segments from different groups of patients, in order to have a fair assessment of the model out-of-sample generalisation. This illustrated how individuals heterogeneity and non-disease-related dimensions of variations (e.g. sex, age, physical fitness) may dominate the signal so that in low sample size regimes a model might learn and overfit subject-specific patterns rather than capturing disease-relevant traits generalisable across disorders. Lastly, we developed a viable baseline for pre-processing raw data from wristband recordings and compared three classical and two deep-learning models to identify levels of disease severity.
Emergence of a Pseudomonas aeruginosa Hypermutator Strain During the Course of Ventilator-Associated Pneumonia
Authors: Nozick Sophie , Ozer Egon A. , Medernach Rachel , Kumar Rebecca , Mills Jori O. , Wunderink Richard G. , Qi Chao , Hauser Alan R.
Published: May 2022

Hypermutator lineages of Pseudomonas aeruginosa arise frequently during the years of lung infection seen in patients with cystic fibrosis and bronchiectasis but are rare in the absence of structural lung disease. Since the onset of the COVID-19 pandemic, large numbers of patients have remained mechanically ventilated for extended periods of time. These patients are prone to acquire bacterial pathogens that persist for many weeks and have the opportunity to evolve within the pulmonary environment. However, little is known about what types of adaptations occur in these bacteria and whether these adaptations mimic those described in chronic infections. We describe a COVID-19 patient with a secondary Pseudomonas aeruginosa lung infection in which the causative bacterium persisted for >90 days. During the course of this infection, a hypermutator lineage of P. aeruginosa emerged and co-existed with a non-hypermutator lineage. Compared to the parental lineage, the hypermutator lineage evolved to be more extensively resistant to antibiotics, to change its type III secretion profile, and to grow more slowly. Genomic analyses of the hypermutator lineage identified numerous mutations, including in the mismatch repair gene mutL and other genes frequently mutated in individuals with cystic fibrosis. Together, these findings demonstrate that hypermutator phenotypes can emerge when clearance of P. aeruginosa fails to occur in typically acute infections such as ventilator-associated pneumonia and suggest that hypermutator lineages can affect patient treatments and outcomes.
Extensive acquisition of carbapenem-resistant Acinetobacter baumannii in Intensive Care Unit patients is driven by widespread environmental contamination
Authors: Doughty Emma L. , Liu Haiyang , Moran Robert A. , Hua Xiaoting , Ba Xiaoliang , Guo Feng , Chen Xiangping , Zhang Linghong , Holmes Mark , van Schaik Willem , McNally Alan , Yu Yunsong
Published: May 2022

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major public health concern globally. Often studied in the context of hospital outbreaks, little is known about the persistence and evolutionary dynamics of endemic CRAB populations. A three-month prospective observational study was conducted in a 28-bed intensive care unit (ICU) in Hangzhou, China. A total of 3985, 964 and 119 samples were collected from the hospital environment, patients and staff, respectively. CRAB were isolated from 10.75% of collected samples (n = 551) and whole-genome sequenced. The ICU CRAB population was dominated by OXA-23-producing global clone 2 isolates (99.27 % of all isolates) that could be divided into 20 distinct clusters. CRAB was persistently present in the ICU, driven by regular introductions of distinct clusters. The hospital environment was heavily contaminated, with CRAB isolated from bed units on 183/335 (54.63 %) sampling occasions but from patients on only 72/299 (24.08 %) occasions. CRAB was spread to adjacent bed units and rooms and following re-location of patients within the ICU. We also observed that, over the course of this study, three different plasmids had transferred between CRAB strains in the ICU. The epidemiology of CRAB in this setting contrasted with previously described clonal outbreaks in high-income countries, highlighting the importance of environmental CRAB reservoirs in ICU epidemiology. There is an urgent need for targeted infection prevention and control interventions in endemic settings that can address the global threat posed by this against this multidrug-resistant opportunistic pathogen.
A Functional Genomics Pipeline to Identify High-Value Asthma and Allergy CpGs in the Human Methylome
Authors: Morin Andréanne , Thompson Emma E. , Helling Britney A. , Shorey-Kendrick Lyndsey E. , Faber Pieter , Gebretsadik Tebeb , Bacharier Leonard B. , Kattan Meyer , O’Connor George T. , Rivera-Spoljaric Katherine , Wood Robert A. , Barnes Kathleen C. , Mathias Rasika A. , Altman Matthew C. , Hansen Kasper , McEvoy Cindy T. , Spindel Eliot R. , Hartert Tina , Jackson Daniel J. , Gern James E. , McKennan Chris G. , Ober Carole
Published: May 2022

Background

DNA methylation of cytosines at CpG dinucleotides is a widespread epigenetic mark; but genome-wide variation has been relatively unexplored due to the limited representation of variable CpGs on commercial high-throughput arrays.

Objective

To explore this hidden portion of the epigenome, we combined whole-genome bisulfite sequencing (WGBS) with in silico evidence of gene regulatory regions to design a custom array of high-value CpGs. We focused these studies in airway epithelial cells from children with and without allergic asthma because these cells mediate the effects of inhaled microbes, pollution, and allergens on asthma and allergic disease risk.

Methods

We identified differentially methylated regions (DMRs) from WGBS in nasal epithelial cell (NEC) DNA from 39 children with and without allergic asthma of both European and African ancestries. We selected CpGs from DMRs, previous allergy or asthma Epigenome-Wide Association Studies (EWAS), or Genome-Wide Association Study (GWAS) loci, and overlapped them with functional annotations for inclusion on a custom Asthma&Allergy array. Using both the Custom and EPIC arrays, we performed EWAS of allergic sensitization (AS) in NEC DNA from children in the URECA birth cohort and using the Custom array in the INSPIRE birth cohort. We assigned each CpG on the arrays to its nearest gene and its promotor capture Hi-C interacting gene and performed expression quantitative trait methylation (eQTM) studies for both sets of genes.

Results

Custom array CpGs were enriched for intermediate methylation (IM) levels compared to EPIC CpGs. IM CpGs were further enriched among those associated with AS and for eQTMs on both arrays.

Conclusions

Our study revealed signature features of high-value CpGs and evidence for epigenetic regulation of genes at AS EWAS loci that are robust to race/ethnicity, ascertainment, age, and geography.

Clinical Implications

These studies identified allergic sensitization-associated differentially methylated CpGs and their target genes in airway epithelium, providing potential epigenetic mechanisms in the development of allergic diseases and suggesting novel drug targets.

Capsule Summary

This study of previously unexplored regions of the airway epithelial methylome revealed novel epigenetic mechanisms regulating genes previously implicated in the pathogenesis of asthma and allergic diseases.
Estimating Vaccine-Preventable COVID-19 Deaths Under Counterfactual Vaccination Scenarios in the United States
Authors: Zhong Ming , Kshirsagar Meghana , Johnston Richard , Dodhia Rahul , Glazer Tammy , Kim Allen , Michael Divya , Nair-Desai Sameer , Tsai Thomas C. , Friedhoff Stefanie , Lavista Ferres Juan M.
Published: May 2022

Importance

With an abundant supply of COVID-19 vaccines becoming available in spring and summer 2021, the major barrier to high vaccination rates in the United States has been a lack of vaccine demand. This has contributed to a higher rate of deaths from SARS-CoV-2 infections amongst unvaccinated individuals as compared to vaccinated individuals. It is important to understand how low vaccination rates directly impact deaths resulting from SARS-CoV-2 infections in unvaccinated populations across the United States.

Objective

To estimate a lower bound on the number of vaccine-preventable deaths from SARS-CoV-2 infections under various scenarios of vaccine completion, for every state of the United States.

Design, Setting, and Participants

This counterfactual simulation study varies the rates of complete vaccination coverage under the scenarios of 100%, 90% and 85% coverage of the adult (18+) population of the United States. For each scenario, we use U.S. state-level demographic information in conjunction with county-level vaccination statistics to compute a lower bound on the number of vaccine-preventable deaths for each state.

Exposures

COVID-19 vaccines, SARS-CoV-2 infection

Main Outcomes and Measures

Death from SARS-CoV-2 infection

Results

Between January 1st, 2021 and April 30th, 2022, there were 641,305 deaths due to COVID-19 in the United States. Assuming each state continued peak vaccination capacity after initially achieving its peak vaccination rate, a vaccination rate of 100% would have led to 322,324 deaths nationally, that of 90% would have led to 415,878 deaths, and that of 85% would have led to 463,305 deaths. As a comparison, using the state with the highest peak vaccination rate (per million population each week) for all the states, a vaccination rate of 100% would have led to 302,344 deaths nationally, that of 90% would have led to 398,289 deaths, and that of 85% would have led to 446,449 deaths.

Conclusions and Relevance

Once COVID-19 vaccine supplies peaked across the United States, if there had been 100% COVID-19 vaccination coverage of the over 18+ population, a conservative estimate of 318,981 deaths could have been potentially avoided through vaccination. For a 90% vaccination coverage, we estimate at least 225,427 deaths averted through vaccination, and at least 178,000 lives saved through vaccination for an 85% vaccination coverage.
Sex differences in the change in cardiorespiratory fitness and additional physical and mental health outcomes after exercise training in adults with atrial fibrillation: a systematic review protocol
Authors: Vidal-Almela Sol , Marçal Isabela R. , Terada Tasuku , O’Neill Carley D. , Reed Jennifer L.
Published: May 2022

Background

Patients with atrial fibrillation (AF), the most common sustained cardiac arrhythmia, often have a low cardiorespiratory fitness (CRF) and poor physical and mental health due to disabling AF symptoms. This is more pronounced in females, who also report worse AF symptoms and quality of life (QoL) than males. Improving CRF through exercise training is an important AF management target associated with lower hospitalization and mortality rates. Emerging research suggests smaller CRF improvements in females than males following the same exercise training program. Yet, this has not been systematically reviewed in the AF population. The primary purpose of this systematic review is to compare changes in CRF following exercise training between females and males with AF. Secondary aims will compare changes in AF symptoms, QoL and additional physical and mental health outcomes between sexes.

Methods

We will adhere to the reporting guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Five electronic bibliographic databases are being searched to identify studies with prospective cohort and experimental designs, implementing exercise training of any form (e.g. aerobic, strength) for at least 4 weeks, in adults (≥18 years old) with an AF diagnosis. Eligible studies must report a baseline and follow-up measure of at least one primary or secondary outcome. CRF (primary outcome) can be estimated or directly measured as peak oxygen consumption (VO2peak). When eligible results are not segregated by sex, authors will be contacted to obtain sex-specific data. Study quality and risk of bias will be assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) scale and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analyses will be conducted to synthesize the measures of effect in studies with sufficient homogeneity.

Discussion

This review will address the lack of sex-based analyses in exercise studies in the AF population. By using a sex lens, we will provide evidence on the physical and mental health effects of exercise training in females and males with AF. Our findings will be of value to patients with AF, researchers and healthcare providers involved in AF management.

Systematic review registration

PROSPERO #CRD42022302310
An Optimized Buffer for Repeatable Multicolor STORM
Authors: Abdelsayed Vaky , Boukhatem Hadjer , Olivier Nicolas
Published: May 2022

STORM microscopy is one of the most popular method of super-resolution microscopy, due to moderate requirements on the optical setup, and high achievable resolution. However, since its inception more than 15 years ago, protocols have barely evolved, and despite some recent progress, multicolor imaging can still be complex without the right equipment. We decided to optimize the buffer composition to improve the blinking of the most popular red dye CF-568 while maintaining good performance for far-red fluorophores such as Alexa-647 using the concentration of three chemicals and the pH as 4 optimization parameters. We developed a simple, cheap and stable buffer, that can be stored several weeks and frozen for longer term storage that allow high quality 3-color STORM imaging.
Direct and indirect phenotypic effects on sociability indicate potential to evolve
Authors: Fisher David N.
Published: May 2022

The decision to leave or join a group is important as group size influences many aspects of organisms’ lives and their fitness. This tendency to socialise with others, sociability, should be influenced by genes carried by focal individuals (direct genetic effects) and by genes in partner individuals (indirect genetic effects), indicating the trait’s evolution could be slower or faster than expected. However, estimating these genetic parameters is difficult. Here, in a laboratory population of the cockroachBlaptica dubia, I estimate phenotypic parameters for sociability: repeatability (R) and repeatable influence (RI), that indicate whether direct and indirect genetic effects respectively are likely. I also estimate the interaction coefficient (Ψ), which quantifies how strongly a partner’s trait influences the phenotype of the focal individual and is key in models for the evolution of interacting phenotypes. Focal individuals were somewhat repeatable for sociability across a three-week period (R= 0.083), and partners also had marginally consistent effects on focal sociability (RI= 0.055). The interaction coefficient was non-zero, although in opposite sign for the sexes; males preferred to associate with larger individuals (Ψmale= −0.129) while females preferred to associate with smaller individuals (Ψfemale= 0.068). Individual sociability was consistent between dyadic trials and in social networks of groups. These results provide phenotypic evidence that direct and indirect genetic effects have limited influence on sociability, with perhaps most evolutionary potential stemming from heritable effects of the body mass of partners. Sex-specific interaction coefficients may produce sexual conflict and the evolution of sexual dimorphism in social behaviour.
Insular holobionts: persistence and seasonal plasticity of the Balearic wall lizard (Podarcis lilfordi) gut microbiota
Authors: Baldo Laura , Tavecchia Giacomo , Rotger Andreu , Igual José Manuel , Riera Joan Lluís
Published: May 2022

Integrative studies of animals and associated microbial assemblages (i.e., the holobiont) are rapidly changing our perspectives on organismal ecology and evolution. Islands provide ideal natural systems to understand the biogeographic patterns that shape these symbiotic associations, their resilience and plasticity over temporal and spatial scales, and ultimately their role in the host ecological adaptation. Here we used the Balearic wall lizard Podarcis lilfordi to address the diversification of the holobiont in an insular context by dissecting the drivers of the gut microbiota diversity within and across host allopatric populations. By extensive fecal sampling of individually identified lizards from three closed populations/islets in the South of Mallorca (Na Moltona, Na Guardis and En Curt) along two years and two seasons (spring and autumn), we sorted out the effect of islet, year, season, sex and partly life stage on the microbiota composition. We further related microbiota distances to host genetics and trophic ecology. Overall, the three populations showed a remarkable conservation of the major microbial taxonomic profile, while carrying their unique microbial signature at finer level of taxonomic resolution (Amplicon Sequence Variants (ASVs)). Microbiota distances across populations were compatible with both host genetics (as inferred by microsatellites) and trophic niche distances (as inferred by stable isotopes and fecal content). Within populations, a large proportion of ASVs (30-50%) persisted along the four sampling dates. Microbial diversity was driven by life stage and season, with no annual or sex effect. Seasonal changes within islets were mainly associated with fluctuations in the relative abundances of few bacterial taxa (mostly families Lachnospiraceae and Ruminococcaceae), consistently in both sampled years and without any major compositional turnover. These results support a large resilience of the major compositional aspects of the P. lilfordi gut microbiota over the short-term evolutionary divergence of their host allopatric populations (<10,000 years), but also suggest an undergoing process of parallel diversification of the holobiont. The cyclic seasonal fluctuations in gut microbiota composition hint to an important plasticity of these bacterial communities in response to the host annual physiological/metabolic shifts. The importance of these microbial community dynamics in the host ecology and dietary flexibility remains to be investigated.
Hindlimb Muscle Representations in Mouse Motor Cortex Defined by Viral Tracing
Authors: Maurer Lauren , Brown Maia , Saggi Tamandeep , Kolarcik Christi L.
Published: May 2022

Descending pathways from the cortex to the spinal cord are involved in the control of natural movement. Although mice are widely used in the study of the neurobiology of movement and as models of neurodegenerative disease, an understanding of motor cortical organization is lacking, particularly for hindlimb muscles. In this study, we used the retrograde transneuronal transport of rabies virus to compare the organization of descending cortical projections to fast- and slow-twitch hindlimb muscles surrounding the ankle joint in mice. Although the initial stage of virus transport from the soleus muscle (predominantly slow-twitch) appeared to be more rapid than that associated with the tibialis anterior muscle (predominantly fast-twitch), the rate of further transport of the virus to cortical projection neurons in layer V was equivalent for the two injected muscles. After appropriate survival times, dense concentrations of layer V projection neurons were identified in three cortical areas: the primary motor cortex (M1), secondary motor cortex (M2), and primary somatosensory cortex (S1). The origin of the cortical projections to each of the two injected muscles overlapped almost entirely within these cortical areas. This organization suggests that cortical projection neurons maintain a high degree of specificity, even when they are involved in controlling muscles with different functional roles (fast-versus slow-twitch, extensor versus flexor). Our results represent an important addition to the understanding of the mouse motor system and lay the foundation for future studies investigating the mechanisms underlying motor system dysfunction and degeneration in diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.
Coordination of Pickpocket ion channel delivery and dendrite growth in Drosophila sensory neurons
Authors: Mitchell Josephine W. , Midillioglu Ipek , Schauer Ethan , Wang Bei , Han Chun , Wildonger Jill
Published: May 2022

Sensory neurons enable an organism to perceive external stimuli, which is essential for survival. The sensory capacity of a neuron depends on the elaboration of its dendritic arbor and the delivery of sensory ion channels to the dendritic membrane. However, it is not well understood how ion channels are trafficked to sensory dendrites and whether their delivery is coordinated with dendrite growth. We investigated the trafficking of the DEG/ENaC/ASIC ion channel Pickpocket (Ppk) in peripheral sensory neurons in fruit fly larvae. We used CRISPR-Cas9 genome engineering to tag endogenous Ppk1 and visualize it live, including monitoring Ppk1 membrane localization via a novel secreted split-GFP approach. Strikingly, Ppk1 is present throughout the membrane of actively growing dendrites, and Ppk1 density scales in proportion to the dendritic membrane, even when dynein-mediated transport to dendrites is disrupted. Our data suggest that Ppk1 is integral to the membrane of growing dendrites and implicate the recycling endosome GTPase Rab11 in the forward trafficking of Ppk1 to dendrites. Together, our results suggest that Ppk channel transport is coordinated with dendrite morphogenesis, thus ensuring proper ion channel levels and distribution in sensory dendrites.

Author Summary

Peripheral sensory neurons are essential for an organism to interact with its environment. Neurons are composed of signal-receiving dendrites and a signal-sending axon. Ion channels distributed throughout sensory dendrites transduce external stimuli into chemical signals, however the mechanisms that localize ion channels to sensory dendrites are not well understood. Both the composition of ion channels in the dendrites and the structure of a sensory neuron’s dendritic arbor are important for how it functions to sense external stimuli. Using live imaging and genomic engineering, we have discovered that the localization of a sensory ion channel, Pickpocket, in fruit fly sensory neurons is coordinated with growth of the dendritic arbor and that Pickpocket levels scale in proportion to dendrite length, even when transport to dendrites is disrupted. We also developed a novel genetically encoded approach to visualize the membrane expression of proteins in a living organism utilizing the split-GFP system. We found that both the secretory and endosomal networks mediate the forward trafficking of Pickpocket during neuronal morphogenesis, thus coordinating membrane growth with ion channel delivery. Our findings reveal that actively growing sensory dendrites are equipped with the ion channels needed for sensing external stimuli.
Gpr88deletion impacts motivational control independently of striatal dopamine function
Authors: Spark Daisy L. , Vermeulen Michela H. , Rueda Patricia , de la Fuente Gonzalez Rocío , Sepehrizadeh Tara , De Veer Michael , la Cour Clotilde Mannoury , Fornito Alex , Langiu Monica , Stewart Gregory D. , Nithianantharajah Jess , Langmead Christopher J.
Published: May 2022

Background

Disrupted motivational control is a common—but poorly treated—feature of psychiatric disorders. Aberrant mesolimbic dopamine signalling is implicated in motivational symptoms, however direct manipulations to these pathways have yielded suboptimal therapeutic effects. GPR88 is an orphan G protein-coupled receptor highly expressed in the striatum on medium spiny neurons, and therefore well-placed to modulate striatal signalling. While the phenotype ofGpr88knockout mice supports a disruption of motivational pathways, it is unclear whether GPR88 is involved in reward valuation and/or effort-based decision making in a sex-dependent manner, and if this involves altered dopamine function.

Methods

In male and femaleGpr88knockout mice, we used touchscreen-based progressive ratio, with and without reward devaluation, and effort-related choice tasks to assess motivation and cost/benefit decision making, respectively. To explore whether these motivational behaviours were related to altered striatal dopamine, we quantified expression of dopamine-related genes and/or proteins, and used [18F]DOPA PET and GTPγ[35S] binding to assess pre- and postsynaptic dopamine function, respectively.

Results

We show that male and femaleGpr88knockout mice display greater motivational drive than wild-type mice, which was maintained following reward devaluation. Further, we show that cost/benefit decision making is impaired in male, but not female,Gpr88knockout mice. Surprisingly, we found thatGpr88deletion had no effect on striatal dopamine by any of the measures assessed.

Conclusion

Our results highlight that GPR88 regulates motivational control of behaviour through a dopaminergic-independent mechanism, providing further support for GPR88 as target for mood symptoms in psychiatric disorders.
Whole-transcriptomic profiling of human cerebral cortex tissues reveals microglia-associated molecular subtypes
Authors: Zhuang Jiali
Published: May 2022

Microglia is one of the major immune cell types in the human brain and plays pivotal roles in regulating inflammatory and immune response in healthy as well as disease states. By analyzing whole transcriptomic data derived from a large cohort of postmortem cortex tissues, we identified two distinct microglial subtypes within the population. The main difference between the two subtypes lies in the differential expression levels of the C1q complex components, Fc γ receptor (CD16) components and CD14. We validated our discovery in independent cohorts of brain autopsy tissues as well as in RNA-seq data generated from isolated microglia. Future investigations into the causes and physiological implications of these subtypes may shed more light on the homeostasis and regulation of the immune related processes in the brain.
Strength of selection potentiates distinct adaptive responses in an evolution experiment with outcrossing yeast
Authors: Phillips Mark A. , Briar Rupinderjit K. , Scaffo Marcus , Zhou Shenghao , Sandoval-Powers Megan , Burke Molly K.
Published: May 2022

Experimental evolution studies with sexually-reproducing populations consistently find that adaptation is highly polygenic and fueled by standing genetic variation. However, studies vary substantially with respect to other evolutionary dynamics. Resolving these discrepancies is a crucial next step as we move toward extrapolating findings from laboratory systems to natural populations. Differences in experimental parameters between studies can perhaps answer these questions, and here we assess how one such parameter - selection intensity - influences outcomes. We subject populations of outcrossingSaccharomyces cerevisiaeto zero, moderate, and high ethanol stress for ∼200 generations and ask: 1) does stronger selection lead to greater changes in allele frequencies at adaptive sites; and 2) do targets of selection vary with intensity? With respects to sites with large effects, we find some evidence for positive correlations between selection intensity and allele frequency change. While we observe shared genomic responses across treatments, we also identify treatment-specific responses. Combined with evidence of phenotypic trade-offs between treatments, our findings support the hypothesis that selection intensity influences evolutionary outcomes due to pleiotropic and epistatic interactions. We conclude that it should be a major consideration when attempting to generalize inferences across studies; in other words, we argue that different intensities of selection effectively create distinct environments and genotype-by-environment interactions. Lastly, our results demonstrate the importance of clearly-defined controls in experimental evolution. Despite working with a presumably lab-adapted model system, without this element we would not have been able to distinguish genomic responses to ethanol stress from those associated with laboratory conditions.