bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymptotic analysis of extended two-dimensional narrow capture problems
Authors: Bressloff P. C. 
Published: February 2021

In this paper, we extend our recent work on two-dimensional diffusive search-and-capture processes with multiple small targets (narrow capture problems) by considering an asymptotic expansion of the Laplace transformed probability flux into each target. The latter determines the distribution of arrival or capture times into an individual target, conditioned on the set of events that result in capture by that target. A characteristic feature of strongly localized perturbations in two dimensions is that matched asymptotics generates a series expansion in
ν
= −1/ln
ϵ
rather than
ϵ
, 0 <
ϵ
≪ 1, where
ϵ
specifies the size of each target relative to the size of the search domain. Moreover, it is possible to sum over all logarithmic terms non-perturbatively. We exploit this fact to show how a Taylor expansion in the Laplace variable
s
for fixed
ν
provides an efficient method for obtaining corresponding asymptotic expansions of the splitting probabilities and moments of the conditional first-passage-time densities. We then use our asymptotic analysis to derive new results for two major extensions of the classical narrow capture problem: optimal search strategies under stochastic resetting and the accumulation of target resources under multiple rounds of search-and-capture.
Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals
Authors: Markmann Alena J. , Giallourou Natasa , Bhowmik D. Ryan , Hou Yixuan J. , Lerner Aaron , Martinez David R. , Premkumar Lakshmanane , Root Heather , van Duin David , Napravnik Sonia , Graham Stephen D. , Guerra Quique , Raut Rajendra , Petropoulos Christos J. , Wrin Terri , Cornaby Caleb , Schmitz John , Kuruc JoAnn , Weiss Susan , Park Yara , Baric Ralph , de Silva Aravinda M. , Margolis David M. , Bartelt Luther A. 
Published: February 2021

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.
Changes in Characteristics of Drug Overdose Death Trends during the COVID-19 Pandemic
Authors: DiGennaro Catherine , Garcia Gian-Gabriel P. , Stringfellow Erin J. , Wakeman Sarah , Jalali Mohammad S. 
Published: February 2021

AbstractBackgroundReports analyzing drug overdose (OD) mortality data during the COVID-19 pandemic are limited. Outcomes across states are heterogenous, necessitating assessments of associations between COVID-19 and OD deaths on a state-by-state level. This report aims to analyze trends in OD deaths in Massachusetts during COVID-19.MethodsAnalyzing 3,924 death records, we characterize opioid-, cocaine-, and amphetamine-involved OD mortality and substance co-presence trends from March 24-November 8 in 2020 as compared to 2018 and 2019.ResultsOD deaths involving amphetamines increased by 85% from 2019 to 2020 (61 vs. 113; P<0.001) but were steady from 2018 to 2019. Heroin’s presence continued to decrease (341 in 2018, 247 in 2019, 157 in 2020; P<0.001); however, fentanyl was present in more than 85% of all OD deaths across all periods. Among OD deaths, alcohol involvement consistently increased, present in 250 deaths in 2018, 299 in 2019 (P=0.02), and 350 in 2020 (P=0.04). In 2019, 78% of OD decedents were White and 7% were Black, versus 73% and 10% in 2020 (P=0.02).ConclusionIncreased deaths involving stimulants, alcohol, and fentanyl reflect concerning trends in the era of COVID-19. Rising OD death rates among Black residents underscore that interventions focused on racial equity are necessary.
Recognition of Diabetes in a Multi-ethnic Population: Results from a Nationally Representative Population-Based Study
Authors: Roystonn Kumarasan , Lau Jue Hua , AshaRani PV , Kumar Fiona Devi Siva , Wang Peizhi , Fang Sum Chee , Lee Eng Sing , Ann Chong Siow , Subramaniam Mythily 
Published: February 2021

ABSTRACTBackgroundThe prevalence of diabetes is on the rise in developed countries. Yet discrepancies exist in reports regarding the level of knowledge of diabetes. This study evaluates the recognition of diabetes among residents in the Singapore population. Sociodemographic characteristics associated with the ability to correctly recognise diabetes were also examined.MethodsThis was a nationwide cross-sectional vignette-based study. Data were collected from 2895 residents aged 18 years and above through face-to-face interviews, of which 436 are persons with diabetes. Descriptive statistics, chi-square tests, and binary logistic regression were used in the analyses.ResultsIn total, 82.7% (2418/2895) of respondents recognised diabetes correctly. In adjusted models, correct recognition was significantly higher among respondents aged 35-49 years (OR, 1.85; 95% CI, 1.15 to 2.98; P= 0.01), 50-64 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.19 to 3.56; P= 0.01), ethnic Malays (OR, 1.39; 95% CI, 1.02 to 1.89; P= 0.04) (vs. Chinese) and persons with diagnosed diabetes (OR, 2.64; 95% CI, 1.38 to 5.08; P < 0.01). Being male (OR, 0.64; 95% CI, 0.46 to 0.90; P < 0.01), ethnic Others (OR, 0.59; 95% CI, 0.37 to 0.93; P < 0.01), and being unemployed (OR, 0.48; 95% CI, 0.25 to 0.92; P= 0.03), were significantly associated with poor recognition of diabetes.ConclusionOverall public recognition of diabetes is high, but the significant gaps in knowledge in certain demographic groups are of concern. Public health interventions aimed at preventing and controlling diabetes should continue to target all members of the population with accurate and appropriate information. Ongoing efforts of diabetes awareness and educational programs need to be improved, particularly for young adults, males, and the unemployed.
Deleterious effects of SARS-CoV-2 infection on human pancreatic cells
Authors: Shaharuddin Hanan , Wang Victoria , Santos Roberta S. , Gross Andrew , Wang Yizhou , Jawanda Harneet , Zhang Yi , Hasan Wohaib , Garcia Gustavo , Arumugaswami Vaithilingaraja , Sareen Dhruv 
Published: February 2021

SUMMARYCOVID-19 pandemic has infected more than 46 million people worldwide and caused more than 1.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, SARS-CoV-2 is capable of infecting iPSC-derived pancreatic cells, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key inflammatory cytokine, CXCL12, known to be involved in pancreas dysfunction. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas is confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate for the first time that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.
Clozapine metabolism is associated with Absolute Neutrophil Count in individuals with treatment-resistant schizophrenia
Authors: Willcocks Isabella , Legge Sophie E. , Nalmpanti Mariana , Mazzeo Lucy , King Adrian , Jansen John , Helthuis Marinka , Owen Michael J. , O’Donovan Michael C. , Walters James T.R. , Pardiñas Antonio F. 
Published: February 2021

AbstractAIMTo investigate the relationship between clozapine concentration and neutrophils in a European cohort of long-term clozapine users.METHODSPearson’s Correlation and Linear Regression analyses were applied to a subset of the CLOZUK2 dataset (N = 208) to assess the association between Absolute Neutrophil Count (ANC) and plasma clozapine concentration. Norclozapine and the metabolic ratio between clozapine and norclozapine were also investigated, along with SNPs associated with clozapine metabolismRESULTSAssociation between ANC and plasma clozapine concentration was found to be significant in a linear regression model (β = −1.41, p = 0.009), with a decrease in ANC of approximately 141 cells/mm3 for every 0.1 mg/litre increase in clozapine concentration. This association was attenuated by the addition of the metabolic ratio, which was significantly negatively correlated with ANC (β=-0.69, p=0.021). In a further regression model, three SNPs previously associated with norclozapine plasma concentrations and clozapine/norclozapine ratio were also found to be significantly associated with ANC: rs61750900 (β=-0.410, p=0.048), rs2011425 (β=0.450, p=0.026) and rs1126545 (β=0.330, p=0.039)CONCLUSIONANC was found to be significantly negatively associated with plasma clozapine concentration. Further investigation has suggested that the relationship is mediated by the clozapine/norclozapine ratio, and potentially moderated by genetic variants with effects on clozapine metabolism
Limited specificity of SARS-CoV-2 antigen-detecting rapid diagnostic tests at low temperatures
Authors: Haage Verena , Moreira-Soto Andres , Sacks Jilian A. , Corman Victor , Drosten Christian , Drexler Felix 
Published: February 2021

AbstractSARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are available within and outside of health care settings to enable increased access to COVID-19 diagnosis. These environments include provisional testing facilities, lacking temperature control; as outside temperatures fall, recommended testing temperatures cannot be guaranteed. We report impaired specificity in two out of six Ag-RDTs when used at 2-4°C, indicating that testing in cold settings might cause false-positive results potentially entailing unwarranted quarantine assignments and incorrect incidence estimates.
COVID-19 among bartenders and waiters before and after pub lockdown
Authors: Methi Fredrik , Telle Kjetil , Magnusson Karin 
Published: February 2021

AimTo study how different bans on serving alcohol in Norwegian bars and restaurants were related to the detection of SARS-CoV-2 in bartenders and waiters.MethodsIn 24,276 bartenders and waiters and 1,287,970 persons with other occupations (mean [SD] age 41.7 [12.8] years and 51.7% men), we examined the weekly rates of workers tested and detected with SARS-CoV-2, one to five weeks before and one to five weeks after implementation of different degrees of bans on serving alcohol in pubs and restaurants, across 56 Norwegian municipalities with: 1) full blanket ban, 2) partial ban with hourly restrictions (e.g. from 10 pm), or 3) no ban, adjusted for age, sex and testing behavior.ResultsIn municipalities introducingfull ban, COVID-19 among bartenders and waiters had been reduced by 65% by three weeks (from 3.4 [95%CI=2.5-4.3] to 1.2 [95%CI=0.7-1.7] per 1000), i.e. to the same levels as that for persons with other occupations (1.8 [95%CI=1.7-1.9] vs 1.2 [95%CI=1.1-1.3] per 1000). Similarly, in municipalities introducingpartial ban, COVID-19 among bartenders and waiters had been reduced by 68% by three weeks (from 2.5 [95%CI=1.4-3.6] to 0.8 [95%CI=0.0-1.5] per 1000). However, there was more uncertainty to the estimated reduction for partial bans.ConclusionMunicipalities with higher levels of confirmed COVID-19 among bartenders and waiters implemented stricter bans on serving of alcohol than other municipalities. Contraction of COVID-19 among bartenders and waiters declined similarly in municipalities with full and partial bans.
A survey of International Health Regulations National Focal Points experiences in carrying out their functions
Authors: Packer Corinne , Halabi Sam F. , Hollmeyer Helge , Mithani Salima S. , Wilson Lindsay , Ruckert Arne , Labonté Ronald , Fidler David P. , Gostin Lawrence O. , Wilson Kumanan 
Published: February 2021

AbstractBackgroundThe 2005 International Health Regulations (IHR (2005)) require States Parties to establish National Focal Points (NFPs) responsible for notifying the World Health Organization (WHO) of potential events that might constitute public health emergencies of international concern (PHEICs), such as outbreaks of novel infectious diseases. Given the critical role of NFPs in the global surveillance and response system supported by the IHR, we sought to assess their experiences in carrying out their functions.MethodsIn collaboration with WHO officials, we administered a voluntary online survey to all 196 States Parties to the IHR (2005) in Africa, Asia, Europe, and South and North America, from October to November 2019. The survey was available in six languages via a secure internet-based system.ResultsIn total, 121 NFP representatives answered the 56-question survey; 105 in full, and an additional 16 in part, resulting in a response rate of 62% (121 responses to 196 invitations to participate). The majority of NFPs knew how to notify the WHO of a potential PHEIC, and believed they have the content expertise to carry out their functions. Respondents found training workshops organized by WHO Regional Offices helpful on how to report PHEICs. NFPs experienced challenges in four critical areas: 1) insufficient intersectoral collaboration within their countries, including limited access to, or a lack of cooperation from, key relevant ministries; 2) inadequate communications, such as deficient information technology systems in place to carry out their functions in a timely fashion; 3) lack of authority to report potential PHEICs; and 4) inadequacies in some resources made available by the WHO, including a key tool – the NFP Guide. Finally, many NFP representatives expressed concern about how WHO uses the information they receive from NFPs.ConclusionOur study, conducted just prior to the COVID-19 pandemic, illustrates key challenges experienced by NFPs that can affect States Parties and WHO performance when outbreaks occur. In order for NFPs to be able to rapidly and successfully communicate potential PHEICs such as COVID-19 in the future, continued measures need to be taken by both WHO and States Parties to ensure NFPs have the necessary authority, capacity, training, and resources to effectively carry out their functions as described in the IHR.
Microglia control glutamatergic synapses in the adult mouse hippocampus
Authors: Basilico Bernadette , Ferrucci Laura , Ratano Patrizia , Golia Maria T. , Grimaldi Alfonso , Rosito Maria , Ferretti Valentina , Reverte Ingrid , Marrone Maria C. , Giubettini Maria , De Turris Valeria , Salerno Debora , Garofalo Stefano , St-Pierre Marie-Kim , Carrier Micael , Renzi Massimiliano , Pagani Francesca , Raspa Marcello , Scavizzi Ferdinando , Gross Cornelius T. , Marinelli Silvia , Tremblay Marie E. , Caprioli Daniele , Maggi Laura , Limatola Cristina , Di Angelantonio Silvia , Ragozzino Davide 
Published: February 2021

ABSTRACTMicroglial cells are active players in regulating synaptic development and plasticity in the brain. However, how these cells influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological depletion of microglia, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features accompanied by higher levels of plasticity. In addition, microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. Remarkably, microglial repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in synaptic organization and activity of glutamatergic synapses.
The ATF6β-calreticulin axis promotes neuronal survival under endoplasmic reticulum stress and excitotoxicity
Authors: Nguyen Dinh Thi , Le Thuong Manh , Hattori Tsuyoshi , Takarada-Iemata Mika , Ishii Hiroshi , Roboon Jureepon , Tamatani Takashi , Kannon Takayuki , Hosomichi Kazuyoshi , Tajima Atsushi , Taniuchi Shusuke , Miyake Masato , Oyadomari Seiichi , Saito Shunsuke , Mori Kazutoshi , Hori Osamu 
Published: February 2021

AbstractWhile ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of ATF6β is largely unknown. Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin, a molecular chaperone in the ER with a high Ca2+-binding capacity. Calreticulin expression was reduced to ~50% in the central nervous system ofAtf6b−/−mice, and restored by ATF6β. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+stores in the ER and enhanced ER stress-induced death, which was rescued by ATF6β, calreticulin, Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and ER stress inhibitor salubrinal.In vivo, kainate-induced neuronal death was enhanced in hippocampi ofAtf6b−/−andCalr+/−mice, and restored by 2-APB and salubrinal. These results suggest that the ATF6β-calreticulin axis plays a critical role in the neuronal survival by improving Ca2+homeostasis under ER stress.
Mechanisms of speed encoding in the human middle temporal cortex measured by 7T fMRI
Authors: Gaglianese Anna , Fracasso Alessio , Fernandes Francisco G. , Harvey Ben , Dumoulin Serge O. , Petridou Natalia 
Published: February 2021

AbstractPerception of dynamic scenes in our environment results from the evaluation of visual features such as the fundamental spatial and temporal frequency components of a moving object. The ratio between these two components represents the object’s speed of motion. The human middle temporal cortex hMT+ has a crucial biological role in the direct encoding of object speed. However, the link between hMT+ speed encoding and the spatiotemporal frequency components of a moving object is still under explored. Here, we recorded high resolution 7T blood oxygen level-dependent BOLD responses to different visual motion stimuli as a function of their fundamental spatial and temporal frequency components. We fitted each hMT+ BOLD response with a 2D Gaussian model allowing for two different speed encoding mechanisms: 1) distinct and independent selectivity for the spatial and temporal frequencies of the visual motion stimuli 2) pure tuning for the speed of motion. We show that both mechanisms occur but in different neuronal groups within hMT+, with the largest subregion of the complex showing separable tuning for the spatial and temporal frequency of the visual stimuli. Both mechanisms were highly reproducible within participants, reconciling single cell recordings from MT in animals that have showed both encoding mechanisms. Our findings confirm that a more complex process is involved in the perception of speed than initially thought and suggest that hMT+ plays a primary role in the evaluation of the spatial features of the moving visual input.
Pseudogenization oftrnT-GGUin chloroplast genomes of the plant family Asteraceae
Authors: Abdullah  , Mehmood Furrukh , Heidari Parviz , Ahmed Ibrar , Poczai Peter 
Published: February 2021

AbstractThe chloroplast genome evolves through the course of evolution. Various types of mutational events are found within the chloroplast genome, including insertions-deletions (InDels), substitutions, inversions, gene rearrangement, and pseudogenization of genes. The pseudogenization of thetrnT-GGUgene was previously reported in theCryptomeria japonica(Cupressaceae), Pelargonium x hortorum (Geraniaceae), and in the two species of the tribe Gnaphalieae (Asteroideae, Asteraceae). Here, we performed a broad analysis of thetrnT-GGUgene among the species of twelve subfamilies of Asteraceae and found pseudogenization of this gene is not limited to the two species of Gnaphalieae or the tribe Gnaphalieae. We report for the first time that this gene is pseudo in the species of three subfamilies of Asteraceae, including Gymnarrhenoideae, Cichorioideae and Asteroideae. The analyses of the species of 78 genera of Asteroideae revealed that this pseudogenization event is linked to the insertion within the 5′ acceptor stem and not linked to the habit, habitat, and geographical distribution of the plant.