bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the systemic and mucosal immune response induced by COVID-19 and the BNT162b2 mRNA vaccine for SARS-CoV-2
Authors: Nickel Olaf , Rockstroh Alexandra , Wolf Johannes , Landgraf Susann , Kalbitz Sven , Kellner Nils , Borte Michael , Fertey Jasmin , Lübbert Christoph , Ulbert Sebastian , Borte Stephan 
Published: January 2022

ABSTRACTBackgroundCurrently used vaccines to protect from COVID-19 mostly focus on the receptor-binding domain (RBD) of the viral spike protein, and induced neutralizing antibodies have shown to be protective. However, functional relevance of vaccine-generated antibodies are poorly understood on variants-of-concern (VOCs) and mucosal immunity.MethodsWe compared specific antibody production against the S1 subunit and the RBD of the spike protein, the whole virion of SARS-CoV-2, and monitored neutralizing antibodies in sera and saliva of 104 BNT162b2 vaccinees and 57 individuals with natural SARS-CoV-2 infection. Furthermore, we included a small cohort of 11 individuals which received a heterologous ChAdOx1-S/BNT162b2 prime-boost vaccination.ResultsVaccinated individuals showed higher S1-IgG antibodies in comparison to COVID-19 patients, followed by a significant decrease 3 months later. Neutralizing antibodies (nAbs) were poorly correlated with initial S1-IgG levels, indicating that these might largely be non-neutralizing. In contrast, RBD IgGAM was strongly correlated to nAbs, suggesting that RBD-IgGAM is a surrogate marker to estimate nAb concentrations after vaccination. The protective effect of vaccine- and infection-induced nAbs was found reduced towards B.1.617.2 and B.1.351 VOCs. NAb titers are significantly higher after third vaccination compared to second vaccination. In contrast to COVID-19 patients, no relevant levels of RBD specific antibodies were detected in saliva samples from vaccinees.ConclusionsOur data demonstrate that BNT162b2 vaccinated individuals generate relevant neutralizing antibodies, which begin to decrease within three months after immunization and show lower neutralizing potential to VOCs as compared to the original Wuhan virus strain. A third booster vaccination provides a stronger nAb antibody response than the second vaccination. The systemic vaccine does not seem to elicit readily detectable mucosal immunity.
Validation of Friedewald, Martin/Hopkins and Sampson Equations in the Low-Density Lipoprotein Cholesterol Estimation with Different Assays
Authors: Zararsız Gözde Ertürk , Bolat Serkan , Cephe Ahu , Kochan Necla , Yerlitaş Serra İlayda , Doğan Halef Okan , Zararsız Gökmen 
Published: January 2022

AbstractBackgroundLow-density lipoprotein cholesterol (LDL-C) is an important biomarker for determining cardiovascular risk and regulating lipid lowering therapy. Therefore, the accurate estimation of LDL-C concentration is essential in cardiovascular disease diagnosis and prognosis. Sampson recently proposed a new formula for the estimation of LDL-C. However, little is known regarding the validation of this formula.ObjectivesThis study aimed to validate this new formula with other well-known formulas in Turkish population, composed of adults.MethodsA total of 88,943 participants above 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included to this study. LDL-C was directly measured by homogeneous assays, i.e., Roche, Beckman and Siemens and estimated by Friedewald’s, Martin/Hopkins’, extended Martin/Hopkins’ and Sampson’s formulas. The accuracies between the estimations obtained by the formulas and the direct measurements were evaluated both in general and separately for the LDL-C, TG and non-HDL-C sublevels. Linear regression analysis was applied and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R2) and mean absolute deviations were also calculated.ResultsThe results showed that the extended Martin/Hopkins approach was the overall most accurate approach for LDL-C estimation. The results also showed that the highest concordances were obtained between the direct assays with the extended Martin/Hopkins formula calculated with the median statistics obtained from our own population. On the other hand, it was observed that the results of the methods may differ in different assays. Although the best performance was obtained by the Sampson formula in patients with “low LDL-C level and hypertriglyceridemia”, the extended Martin/Hopkins approach, calculated from the median statistics of our population, gave the most accurate results in patients with “low LDL-C level or hypertriglyceridemia”.ConclusionsIn conclusion, in patients with a low LDL-C level or hypertriglyceridemia, the extended Martin/Hopkins method; in patients with a low LDL-C level and hypertriglyceridemia, the Sampson method may be preferred. The validity of the Martin Hopkins’ and Sampson’s formulas has to be further investigated in different populations.
Medical student residency preferences and motivational factors: a longitudinal, single-institution perspective
Authors: Ladha Feria A. , Pettinato Anthony M. , Perrin Adam E. 
Published: January 2022

AbstractBackgroundA high proportion of medical school graduates pursue specialties different from those declared at matriculation. While these choices influence the career paths, satisfaction, and potential regret students will experience, they also impact the supply and demand ratio of the shorthanded physician workforce across many specialties. In this study, we investigate how the choice of medical specialty and the factors motivating those choices change between the beginning and end of medical school training.MethodsA questionnaire was administered annually from 2017 to 2020 to a cohort of medical students at the University of Connecticut to determine longitudinal preferences regarding residency choice, motivational factors influencing residency choice, future career path, and demographic information.ResultsThe questionnaire respondent totals were as follows: n=76 (Year 1), n=54 (Year 2), n=31 (Year 3), and n=65 (Year 4). Amongst newly matriculated students, 25.0% were interested in primary care, which increased ∼1.4-fold to 35.4% in the final year of medical school. In contrast, 38.2% of matriculated students expressed interest in surgical specialties, which decreased ∼2.5-fold to 15.4% in the final year. Specialty choices in the final year that exhibited the largest absolute change from matriculation were orthopedic surgery (−9.9%), family medicine (+8.1%), radiology (+7.9%), general surgery (−7.2%), and anesthesiology (+6.2%). Newly matriculated students interested in primary care demonstrated no differences in their ranking of motivational factors compared to students interested in surgery, but many of these factors significantly deviated between the two career paths in the final year. Specifically, students interested in surgical specialties were more motivated by the rewards of salary and prestige compared to primary care students, who more highly ranked match confidence and family/location factors.ConclusionsWe identified how residency choices change from the beginning to the end of medical school, how certain motivational factors change with time, how these results diverge between primary care and surgery specialty choice, and propose a new theory based on risk-reward balance regarding residency choice. Our study promotes awareness of student preferences and may help guide school curricula in developing more student-tailored training approaches. This could foster positive long-term changes regarding career satisfaction and the physician workforce.
Doubtful Clinical Benefit of Casirivimab-Imdevimab Treatment for Disease Severity Outcome of High-Risk Patients with SARS-CoV-2 Delta Variant Infection
Authors: Shopen Noah , Dekel Michal , Mizrahi Michal , Zandberg Efrat , Bishouty Nancy , Talmud Daniel , Vaknin Ben , Haberman Shira , Shalhav Malka Katz , Zeltser David , Cohen Neta 
Published: January 2022

ABSTRACTCasirivimab/Imdevimab therapy reportedly retains neutralization potency against circulating SARS-CoV-2 variants, including Delta (B.1.617.2), but there are sparse data on its clinical benefit against the Delta variant among vaccinated and unvaccinated patients. We explored its therapeutic effect on COVID-19 severity outcome in terms of room air saturation <93% within 14 days of initial presentation and 45-day all-cause mortality among high-risk patients with SARS-CoV-2 Delta variant infection and compared its effect between vaccinated and unvaccinated patients. We conducted a retrospective cohort study at a tertiary care medical center between 6/2021 and 9/2021 and included patients who presented with a positive PCR for SARS-CoV-2 and fulfilled the criteria for Casirivimab/Imdevimab treatment. Of the 359 suitable patients (52% female, median age 63 years), 116 were treated with Casirivimab/Imdevimab and 243 were not. Two-hundred and one (56%) patients had received at least 2 SARS-CoV-2 vaccinations. Casirivimab/Imdevimab treatment was not an independent protective factor of COVID-19 severity outcome (multivariable analysis). Chronic kidney disease (aOR=3.51 [95%CI: 1.34-9.20],P=0.01), lower saturation levels (aOR=0.7 [95%CI: 0.58–0.85],P<0.01), abnormal chest x-ray findings (aOR=2.92, [95%CI: 1.24–6.87,P=0.01), and higher C-reactive protein levels (aOR=1.01 [95%CI: 1.00–1.01],P=0.008) were independent risk factors of COVID-19 severity. Positive immunization status was an independent protective factor (aOR=0.33 [95%CI: 0.14–0.77],P=0.01). A sub analysis of patients treated with Casirivimab/Imdevimab revealed no significant difference in COVID-19 severity between vaccinated and unvaccinated patients. These findings demonstrate no added benefit of Casrivimab/Imdevinab treatment for high-risk patients with the SARS-CoV-2 Delta variant infection, regardless of their vaccination status.
CADM2is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice
Authors: Sanchez-Roige Sandra , Jennings Mariela V , Thorpe Hayley H A , Mallari Jazlene E , van der Werf Lieke C , Bianchi Sevim B , Lee Calvin , Mallard Travis T , Barnes Samuel A , Wu Jin Yi , Barkley-Levenson Amanda M , Boussaty Ely C , Snethlage Cedric E , Schafer Danielle , Babic Zeljana , Winters Boyer D , Watters Katherine E , Biederer Thomas , Mackillop James , Stephens David N , Elson Sarah L , Fontanillas Pierre , Khokhar Jibran Y , Young Jared W , Palmer Abraham A 
Published: January 2022

ABSTRACTImpulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N=123,509-133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N=130,684). Because these GWAS implicated the geneCADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants inCADM2in a multi-ancestral 23andMe cohort (N=3,229,317, European; N=579,623, Latin American; N=199,663, African American). Finally, we producedCadm2mutant mice and used them to perform a Mouse-PheWAS (“MouseWAS”) by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (∼6-11%), and moderate genetic correlations (rg=.20-.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such asTCF4andPTPRF, and also identified nominal associations proximal toDRD2andCRHR1. PheWAS forCADM2variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role ofCADM2in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.
Spatial and Temporal Regulation of Parent-of-Origin Allelic Expression in the Endosperm
Authors: van Ekelenburg Yuri S. , Hornslien Karina S. , Van Hautegem Tom , Fendrych Matyáš , Van Isterdael Gert , Bjerkan Katrine N. , Miller Jason R. , Nowack Moritz K. , Grini Paul E. 
Published: January 2022

AbstractGenomic imprinting promotes differential expression of parental alleles in the endosperm of flowering plants, and is regulated by epigenetic modification such as DNA methylation and histone tail modifications in chromatin. After fertilization, the endosperm develops through a syncytial stage before it cellularizes and becomes a nutrient source for the growing embryo. Both in early and late endosperm development regional compartmentalization has been shown, and different transcriptional domains suggest divergent spatial and temporal regional functions. The analysis of the role of parent-of-origin allelic expression in the endosperm as a whole and also investigation of domain specific functions has been hampered by the availability of the tissue for high-throughput transcriptome analyses and contamination from surrounding tissue. Here we have used Fluorescence-Activated Nuclear Sorting (FANS) of nuclear targeted eGFP fluorescent genetic markers to capture parental specific allelic expression from different developmental stages and specific endosperm domains. This RNASeq approach allows us to successfully identify differential genomic imprinting with temporal and spatial resolution. In a systematic approach we report temporal regulation of imprinted genes in the endosperm as well as region specific imprinting in endosperm domains. Our data identifies loci that are spatially differentially imprinted in one domain of the endosperm while biparentally expressed in other domains. This suggests that regulation of genomic imprinting is dynamic and challenges the canonical mechanisms for genomic imprinting.
LKB1 acts as a critical brake for the glucagon-mediated fasting response
Authors: Acevedo-Acevedo Suehelay , Stefkovich Megan L. , Sophie Kang Sun Woo , Cunningham Rory P. , Cultraro Constance M. , Porat-Shliom Natalie 
Published: January 2022

AbstractAs important as the fasting response is for survival, an inability to shut it down once nutrients become available can lead to exacerbated disease and severe wasting. The liver is central to transitions between feeding and fasting states, with glucagon being a key initiator of the hepatic fasting response. However, the precise mechanisms controlling fasting are not well defined. One potential mediator of these transitions is Liver Kinase B1 (LKB1) given its role in nutrient sensing. Here, we show LKB1 knockout mice have a severe wasting and prolonged fasting phenotype despite increased food intake. By applying RNA sequencing and intravital microscopy we show that loss of LKB1 leads to a dramatic reprogramming of the hepatic lobule through robust upregulation of periportal genes and functions. This is likely mediated through the opposing effect LKB1 has on glucagon pathways and gene expression. Conclusion: our findings show that LKB1 acts as a brake to the glucagon-mediated fasting response resulting in “periportalization” of the hepatic lobule and whole-body metabolic inefficiency. These findings reveal a new mechanism by which hepatic metabolic compartmentalization is regulated by nutrient-sensing.
Pectin cell wall remodeling through PLL12 and callose deposition through polar CALS7 are necessary for long-distance phloem transport
Authors: Kalmbach Lothar , Bourdon Matthieu , Heo Jung-ok , Otero Sofia , Blob Bernhard , Helariutta Ykä 
Published: January 2022

AbstractIn plants, the phloem distributes photosynthetic products for metabolism and storage over long distances. It relies on specialized cells, the sieve elements, which are enucleated and interconnected through large so-called sieve pores in their adjoining cell walls. Reverse genetics identified PECTATE LYASE LIKE 12 (PLL12) as critical for plant growth and development. Using genetic complementation, we establish that PLL12 enzyme activity is required exclusively late during cell differentiation. Physiological assays suggested a role specifically in phloem long distance transport while short distance symplastic transport does not require PLL12. Exploiting CALLOSE SYNTHASE 7 (CALS7) as a polar fluorescent marker, we identified structural defects in sieve pores in pll12. Due to the serial arrangement of sieve elements in the phloem, such defects should affect a plant’s ability specifically for symplastic transport over long distances.
Cannabinoid receptor 1 is required for neurodevelopment of striosome-dendron bouquets
Authors: Crittenden Jill R. , Yoshida Tomoko , Venu Samitha , Mahar Ara , Graybiel Ann M. 
Published: January 2022

AbstractCannabinoid receptor 1 (CB1R) has strong effects on neurogenesis and axon pathfinding in the prenatal brain. Endocannabinoids that activate CB1R are abundant in the early postnatal brain and in mother’s milk, but few studies have investigated their function in newborns. We examined postnatal CB1R expression in the major striatonigral circuit from striosomes of the striatum to the dopamine-containing neurons of the substantia nigra. CB1R enrichment was first detectable between postnatal days 5 and 7, and this timing coincided with the formation of ‘striosome-dendron bouquets’, the elaborate anatomical structures by which striosomal neurons control dopaminergic cell activity through inhibitory synapses. In Cnr1−/− knockouts lacking CB1R expression, striosome-dendron bouquets were markedly disorganized by postnatal day 11 and at adulthood, suggesting a postnatal pathfinding connectivity function for CB1R in connecting striosomal axons and dopaminergic neurons analogous to CB1R’s prenatal function in other brain regions. Our finding that CB1R plays a major role in postnatal wiring of the striatonigral dopamine system, with lasting consequences at least in mice, points to a crucial need to determine whether lactating mothers’ use of CB1R agonists (e.g., in marijuana) or antagonists (e.g., type 2 diabetes therapies) can disrupt brain development in nursing offspring.
Non-identifiability and the Blessings of Misspecification in Models of Molecular Fitness
Authors: Weinstein Eli N. , Amin Alan N. , Frazer Jonathan , Marks Debora S. 
Published: January 2022

AbstractUnderstanding the consequences of mutation for molecular fitness and function is a fundamental problem in biology. Recently, generative probabilistic models have emerged as a powerful tool for estimating fitness from evolutionary sequence data, with accuracy sufficient to predict both laboratory measurements of function and disease risk in humans, and to design novel functional proteins. Existing techniques rest on an assumed relationship between density estimation and fitness estimation, a relationship that we interrogate in this article. We prove that fitness is not identifiable from observational sequence data alone, placing fundamental limits on our ability to disentangle fitness landscapes from phylogenetic history. We show on real datasets that perfect density estimation in the limit of infinite data would, with high confidence, result in poor fitness estimation; current models perform accurate fitness estimation because of, not despite, misspecification. Our results challenge the conventional wisdom that bigger models trained on bigger datasets will inevitably lead to better fitness estimation, and suggest novel estimation strategies going forward.
“Populist Attitude and Conspiracist beliefs contribution to the overconfidence about the risk of Covid-19: implications for Preventive Health Behaviors”
Authors: Agnese Giuliani , Fabio Presaghi 
Published: January 2022

AbstractPopulism and Conspiracy beliefs seem to represent the zeitgeist of people depending on fast and simple information retrieved through social media. The Covid-19 emergency has simply catalyzed this process, not without consequences. Supported by literature review, we hypothesize that the higher the populist attitude the higher the tendency in believing in conspiracies, and that both higher populist attitudes and conspiracist beliefs may induce people in underestimating health related risks that may be reflected in a lowered tendency in adopting preventive health behaviors against Covid-19 spread. Data collected during the quarantine (December 2020, March 2021) mainly supported our hypotheses. Results are discussed in accord with the dramatic consequences it may have overconfidence in undermining the adoption of preventive health behaviors.
Inequalities in access to paid sick leave among workers in England and Wales
Authors: Patel Parth , Beale Sarah , Nguyen Vincent , Braithwaite Isobel , Byrne Thomas E , Erica Fong Wing Lam , Fragaszy Ellen , Geismar Cyril , Hoskins Susan , Navaratnam Annalan M D , Shrotri Madhumita , Kovar Jana , Hayward Andrew C , Aldridge Robert W 
Published: January 2022

AbstractBackgroundIt is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 epidemic given the relationship between presenteeism and infectious disease transmission.MethodThis cross-sectional analysis is nested within a large community cohort study of Covid-19 epidemiology in England and Wales (Virus Watch). An online survey in February 2021 asked participants if they had access to paid sick leave. We use a fixed effect logistic regression model to examine sociodemographic factors associated with lacking access to sick pay.Results8,874 participants in work responded to the survey item about access to sick pay. Of those, 5,864 (66%) report having access to sick pay, 2,218 (25%) report no access to sick pay and 792 (8.9%) were unsure. Workers aged 45-64 (OR 1.72) and over 65 (OR 5.26) are more likely to lack access to sick pay compared to workers aged 25-44. South Asian workers (OR 1.40) and those from Other minority ethnic backgrounds (OR 2.93) are more likely to lack access to sick pay compared to White British workers. Workers in low income households (OR 1.43-2.53) and those with working class occupations (OR 2.04-5.29) are also more likely to lack access to sick pay compared to those in high income households and managerial occupations.DiscussionUnwarranted age and race inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic infectious disease epidemics in the community.