bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nontraumatic In-Custody Homicidal Deaths in Harris County, Texas (2015–2019)
Authors: Wolf Dwayne A. 
Published: May 2021

Abstract
A subset of in-custody deaths, typically occurring in the precustody phase, arise from a combination of mechanisms, rather than a single anatomically or circumstantially demonstrable cause. This case series examined nontraumatic in-custody deaths that occurred over a 5-year period (2015–2019) in Harris County, Texas. Cases were identified as “in custody” or “during police intervention,” with a homicide manner; traumatic causes of death (eg, police shootings) were excluded.
Sixteen cases were identified. The median age was 40 years, with an interquartile range of 35 to 50.5 years. All but one were male, and there were 8 (50%) Black, 5 (31%) White, and 1 (6%) Hispanic cases. Intoxicants were detected in all except 1 death that occurred after a prolonged hospitalization; stimulants were identified in 12 (75%). The cause of death for each was descriptive, representing the complex interplay of external forces with physiologic/toxicologic and disease-related mechanisms.
This series is used as a backdrop for a discussion regarding the inadequacy of the current 5-category manner of death classification scheme and to suggest an alternative category of manner. This alternative category, specifically “legal intervention,” would be most useful for this subset of nontraumatic in-custody deaths but may have applicability for other types of in-custody deaths.
Isolated Atrial Neutrophilic Myocarditis
Authors: Duffy Michael , O'Connor Kate , Milne David , Ondruschka Benjamin , Tse Rexson , Garland Jack 
Published: May 2021

Abstract
Myocarditis can focally or diffusely involve the myocardium and is associated with arrhythmia, cardiac failure, and sudden death. The majority of cases of myocarditis are lymphocytic in etiology, and neutrophilic myocarditis is relatively uncommon. Although reported in lymphocytic myocarditis, isolated/focal neutrophilic myocarditis of the atrium causing death is not reported in the postmortem literature, and its postmortem computed tomography correlation is not documented. We report a fatal case of isolated neutrophilic atrial myocarditis affecting only the left atrium in a 33-year-old woman presenting as a sudden unexpected death. Microscopy of the left atrium, a not commonly sampled area of the heart, showed florid neutrophilic myocarditis with the remaining right atrium, conduction system, and both ventricles uninvolved. Similar to previously reported fatal isolated atrial lymphocytic myocarditis, postmortem computed tomography was unable to detect any atrial abnormalities. This case highlights a potential “blind spot” for both routine postmortem imaging and examination.
Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence
Authors: Moody Sarah , Senkin Sergey , Islam S M Ashiqul , Wang Jingwei , Nasrollahzadeh Dariush , Penha Ricardo Cortez Cardoso , Fitzgerald Stephen , Bergstrom Erik N , Atkins Joshua , He Yudou , Khandekar Azhar , Smith-Byrne Karl , Carreira Christine , Gaborieau Valerie , Latimer Calli , Thomas Emily , Abnizova Irina , Bucciarelli Pauline E , Jones David , Teague Jon W , Abedi-Ardekani Behnoush , Serra Stefano , Scoazec Jean-Yves , Saffar Hiva , Azmoudeh-Ardelan Farid , Sotoudeh Masoud , Nikmanesh Arash , Eden Michael , Richman Paul , Campos Lia S , Fitzgerald Rebecca C , Ribeiro Luis Felipe , Dzamalala Charles , Mmbaga Blandina Theophil , Shibata Tatsuhiro , Menya Diana , Goldstein Alisa M , Hu Nan , Malekzadeh Reza , Fazel Abdolreza , McCormack Valerie , McKay James , Perdomo Sandra , Scelo Ghislaine , Chanudet Estelle , Humphreys Laura , Alexandrov Ludmil B , Brennan Paul , Stratton Michael R 
Published: May 2021

AbstractEsophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. The mutational profiles of ESCC were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.
Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient: a source of immune escape variants
Authors: Weigang Sebastian , Fuchs Jonas , Zimmer Gert , Schnepf Daniel , Kern Lisa , Beer Julius , Luxenburger Hendrik , Ankerhold Jakob , Falcone Valeria , Kemming Janine , Hofmann Maike , Thimme Robert , Neumann-Haefelin Christoph , Ulferts Svenja , Grosse Robert , Hornuss Daniel , Tanriver Yakup , Rieg Siegbert , Wagner Dirk , Huzly Daniela , Schwemmle Martin , Panning Marcus , Kochs Georg 
Published: May 2021

AbstractThe recent emergence of SARS-CoV-2 variants showing increased transmissibility and immune escape is a matter of global concern. Their origin remains unclear, but intra-host virus evolution during persistent infections could be a contributing factor. Here, we studied the long-term SARS-CoV-2 infection in an immunosuppressed organ transplant recipient. Frequent respiratory specimens were tested for variant viral genomes by RT-qPCR, next-generation sequencing (NGS), and virus isolation. Late in infection, several virus variants emerged which escaped neutralization by COVID-19 convalescent and vaccine-induced antisera and had acquired genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil. Importantly, infection of susceptible hACE2-transgenic mice with one of the patient’s escape variants elicited protective immunity against re-infection with either the parental virus, the escape variant or the South African variant of concern, demonstrating broad immune control. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results indicate that immunocompromised patients are an alarming source of potentially harmful SARS-CoV-2 variants and open up new avenues for the updating of COVID-19 vaccines.
Investigating the relationship between serum ACE 2 level and COVID-19 patients’ prognosis: a cross-sectional study
Authors: Mohammadi Parsa , Varpaei Hesam Aldin , Seifi Arash , Miandoab Sepideh Zahak , Beiranvand Saba , Mobaraki Sahar , Mohammadi Mostafa 
Published: May 2021

AbstractBackgroundThe only known receptor for this virus in the human body is ACE2, the same known receptor for the SARS virus.Material and MethodIn this single-center cross-sectional study, 38 hospitalized adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the infectious disease ward in Imam Khomeini hospital complex. The study also has been approved in ethics committee of Tehran University of medical sciences with ethic code: 99/11/101/16529. Data were analyzed using SPSS 25. p < 0.05 was considered statistically significant when a two-tailed test was performed.ResultAmong the 38 patients, the mean age was 64.13 years, 52.6% were male, 42% were PCR test positive and 39.5% was expired. The most common presenting symptoms were cough (80%), fever (75.5%), dyspnea (60.5%), myalgias (35.8%), diarrhea (20%), and nausea and vomiting (15%). There were not any significant differences between expired and discharged group in terms of serum ACE2 level. Results were similar between discharged and expired patients in the subgroup analysis of 38 patients.ConclusionIt seems that serum ACE 2 level is not correlated with COVID-19 patients’ prognosis. However, it seems that more researches are required to confirm supposed association between serum ACE2 level and inflammatory biomarkers, clinical outcome, and patient’s survival.
An Audit of Use and Monitoring of ACE-inhibitors in General Practice
Authors: Coffey Fíona , Bradley Colin , Curran Tadhg-Iarla 
Published: May 2021

AbstractIntroductionACE-inhibitors are one of the most widely prescribed drugs in general practice for the treatment of hypertension. They are also one of the most frequent drugs associated with preventable drug-related morbidity incidents and guidelines are in place regarding the monitoring of renal function during treatment with these drugs.AimTo assess the pattern of prescribing and monitoring of ACE-inhibitors in a general practice setting.MethodsA retrospective medical records review was undertaken in a general practice in the Kerry region. Data collected included the indication for the ACE-inhibitor and whether blood pressure, electrolytes, renal function and glomerular filtration rate were measured within three months after initiation and in the period from January 2010 to June 2011. Data was entered into Microsoft Excel and analysed using SPSS.ResultsData on 285 patients was analysed and showed that 78.2% of patients were on ACE-inhibitors for treatment of blood pressure. Following initiation of the ACE-inhibitor, 94.8% of patients had their blood pressure checked within 3 months, while 37.1% of patients had electrolytes checked, 51% of patients had their renal function checked and 31% of people had their glomerular filtration rate checked in the same time period. In the months from January 2010 to June 2011, 91.2% of patients had their blood pressure checked with 73% having electrolytes checked, 80.4% having their renal function checked and 54.7% had their glomerular filtration rate checked. Of those who had their renal function checked 26.1% had an abnormal creatinine level.ConclusionFollow up of monitoring blood pressure, renal function, electrolytes and glomerular filtration rate within 3 months initiation of the ACE-inhibitor was poor but annual check up scored highly. Having a recall system in place within the practice for reminding patients to get their blood levels checked may help to increase all percentages to 100%.
Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination
Authors: Gonçalves Juliana , Juliano A. Margarida , Charepe Nádia , Alenquer Marta , Athayde Diogo , Ferreira Filipe , Archer Margarida , João Amorim Maria , Serrano Fátima , Soares Helena 
Published: May 2021

AbstractIn view of data scarcity to guide decision-making in breastfeeding women, we evaluated how mRNA vaccines impact immune response of lactating health care workers (HCW) and the effector profile of breast milk transferred immune protection. We show that upon BNT162b2 vaccination, immune transfer via milk to suckling infants occurs through secretory IgA (SIgA) and T cells. Functionally, spike-SIgA was non-neutralizing and its titers were unaffected by vaccine boosting, indicating that spike-SIgA is produced in a T-cell independent manner by mammary gland. Even though their milk was devoid of neutralizing antibodies, we found that lactating women had higher frequencies of RBD-reactive circulating memory B cells and more RBD-IgG antibodies, when compared to controls. Nonetheless, blood neutralization titers in lactating and non-lactating HCW were similar. Further studies are required to determine transferred antibodies and spike-T cells complete functional profile and whether they can mediate protection in the suckling infant.HighlightsMilk and blood responses to BNT162b2 vaccine are initially isotype discordantImmune transfer via milk to suckling infants occurs by spike-reactive SIgA and T cellsSpike-reactive SIgA in the breastmilk is non-neutralizing and T-cell independentLactating vs non-lactating HCW had distinct cellular responses, despite similar NT50
Association between high serum favipiravir concentrations and drug-induced liver injury
Authors: Kawasuji Hitoshi , Tsuji Yasuhiro , Ogami Chika , Takegoshi Yusuke , Kaneda Makito , Murai Yushi , Kimoto Kou , Ueno Akitoshi , Miyajima Yuki , Fukui Yasutaka , Nagaoka Kentaro , Sakamaki Ippei , Morinaga Yoshitomo , Yamamoto Yoshihiro 
Published: May 2021

AbstractObjectivesThis study aimed to evaluate the incidence and pattern of favipiravir-induced liver injury and the potential association between serum concentrations in hospitalized COVID-19 patients.Patients and methodsWe retrospectively reviewed laboratory-confirmed patients with COVID-19 for whom serum favipiravir trough concentration (Cmin) was measured under steady-state conditions during treatment. All patients were administered 1800 mg of favipiravir twice daily on the first day and 800 mg twice daily from the second day.ResultsThirty observed favipiravir concentrations were collected from nine patients. Of these, favipiravir-induced liver injury developed in three patients after 13 (11–14) days from the initiation of therapy, with two classified as cholestatic and one hepatocellular injury, with a score of four (possible), seven (probable), and three (possible) based on the CIMOS/RUCAM scoring system. Median (range) favipiravir Cmin at steady state was found to be significantly higher in patients with liver injury at 66.4 (47.8–72.4) mg/L than in those without injury at 12.8 (9.4–21.8) mg/L (P = 0.028).ConclusionsHigher favipiravir serum concentrations were observed in patients who developed favipiravir-induced liver injury than in those who did not. As the variations in favipiravir concentrations between patients were large, personalized optimal dosing strategies may be needed for safe use.
Impaired everyday executive functions and cognitive strategy use on the Weekly Calendar Planning Activity in individuals with stroke undergoing acute inpatient rehabilitation
Authors: Jaywant Abhishek , Arora Catherine , Lussier Alexis , Toglia Joan 
Published: May 2021

AbstractExecutive dysfunction is common in stroke patients undergoing acute inpatient rehabilitation. However, comprehensive neuropsychological evaluation of executive functions is often not feasible in this setting. Objective, standardized, and performance-based measures of cognitively-based instrumental activities of daily living (C-IADL) can capture everyday executive functions and inform rehabilitation planning and interventions. The goal of this study was to compare performance of individuals with stroke to healthy age-matched adults in performance on the 10-item Weekly Calendar Planning Activity (WCPA). 77 stroke inpatients undergoing rehabilitation and 77 healthy control participants completed the WCPA, a C-IADL measure involving scheduling appointments that requires planning, working memory, shifting, and inhibitory control. Compared to the control group, stroke patients had significantly worse accuracy, made more errors, used fewer cognitive strategies, followed fewer rules, took more time to complete the task, and were less efficient. 83% of stroke patients were less accurate than predicted by their age, and 64% used less strategies than their age prediction. Among 28 participants who screened as having “normal” cognitive function on the Montreal Cognitive Assessment, the majority had deficits on the WCPA. Our results indicate that the WCPA is sensitive to executive dysfunction in stroke patients undergoing acute inpatient rehabilitation and underscores deficits in C-IADL accuracy, efficiency, and strategy use at this stage of stroke recovery. The WCPA may be a useful measure to ascertain executive dysfunction and to incorporate in cognitive rehabilitation.
Roles of generation-interval distributions in shaping relative epidemic strength, speed, and control of new SARS-CoV-2 variants
Authors: Park Sang Woo , Bolker Benjamin M. , Funk Sebastian , Metcalf C. Jessica E. , Weitz Joshua S. , Grenfell Bryan T. , Dushoff Jonathan 
Published: May 2021

AbstractInferring the relative strength (i.e., the ratio of reproduction numbers, ℛvar/ℛwt) and relative speed (i.e., the difference between growth rates,rvar−rwt) of new SARS-CoV-2 variants compared to their wild types is critical to predicting and controlling the course of the current pandemic. Multiple studies have estimated the relative strength of new variants from the observed relative speed, but they typically neglect the possibility that the new variants have different generation intervals (i.e., time between infection and transmission), which determines the relationship between relative strength and speed. Notably, the increasingly predominant B.1.1.7 variant may have a longer infectious period (and therefore, a longer generation interval) than prior dominant lineages. Here, we explore how differences in generation intervals between a new variant and the wild type affect the relationship between relative strength and speed. We use simulations to show how neglecting these differences can lead to biases in estimates of relative strength in practice and to illustrate how such biases can be assessed. Finally, we discuss implications for control: if new variants have longer generation intervals then speed-like interventions such as contact tracing become more effective, whereas strength-like interventions such as social distancing become less effective.
Implementation of SARS-CoV2 Screening in K-12 Schools using In-School Pooled Molecular Testing and Deconvolution by Rapid Antigen Test
Authors: Pollock Nira R. , Berlin David , Smole Sandra C. , Madoff Lawrence C. , Henderson Kelsey , Larsen Elizabeth , Hay Jeremiah , Gabriel Stacey , Gawande Atul A. , Lennon Niall J. 
Published: May 2021

SummaryWhat is already known about this topic?SARS-CoV2 testing is a key component of a multi-layered mitigation strategy to enable safe return to in-person school for the K-12 population. However, costs, logistics, and uncertainty about effectiveness are potential barriers to implementation.What is added by this report?Over three months, 259,726 individual swabs were tested across 50,636 pools from 582 schools. Pool positivity rate was 0.8%; 98.1% of pools tested negative and 0.3% inconclusive, and 0.8% of pools submitted could not be tested. In reflex testing, 92.5% of fully deconvoluted pools with N1 or N2 target Ct ≤30 yielded a positive individual using the BinaxNOW antigen rapid diagnostic test (Ag RDT) performed 1-3 days later. With sufficient staffing support and low pool positivity rates, pooled sample collection and reflex testing were feasible for schools.What are the implications for public health practice?Screening testing for K-12 students and staff is achievable at scale and at low cost with a scheme that incorporates in-school pooling, RT-PCR primary testing, and Ag RDT reflex/deconvolution testing. Staffing support is a key factor for program success.
Pregnancy pharmacoepidemiology: How often are key methodological elements reported in publications?
Authors: Margulis Andrea V , Kawai Alison T , Anthony Mary S , Rivero-Ferrer Elena 
Published: May 2021

ABSTRACTPurposePublications are an important information source for clinicians, researchers, and patients. Key methodological elements must be reported for maximum transparency. We identified key methodological elements necessary for fully understanding pharmacoepidemiological research in pregnancy and quantified the proportion of studies that report these elements in a sample of publications.MethodsKey methodological elements were identified from guidelines from regulatory agencies, literature, and subject-matter knowledge: source of information to determine pregnancy start; mother- or father-infant linkages (process, success rate); unit of analysis; and whether non-live births and fetuses with various anomalies were included in the study population.We conducted a literature review for recent observational studies on medical product utilization or safety during pregnancy and estimated the prevalence of reporting these elements.ResultsData were extracted from a random sample of 100 publications; 8% were published in epidemiology/pharmacoepidemiology journals; 85% were medical product–safety studies.Of included publications, 43% reported the source for determining pregnancy start; 57% reported whether the study population included multifetal pregnancies; 39%, whether it included more than 1 pregnancy per woman; 27%, whether it included fetuses with chromosomal abnormalities; 60%, fetuses with major congenital malformations; and 93%, non-live births. Of the 20 studies with mother-infant linkage, 35% described the process; 21% reported the linkage success rate. Among studies with more than one pregnancy/offspring per woman, 22% reported methods addressing sibling correlation.ConclusionsIn this sample of pregnancy-related pharmacoepidemiology publications, completeness of reporting can be improved. A pregnancy-specific checklist would help to increase transparency in the dissemination of study results.Key points▪Publications on the utilization or safety of medical products in pregnancy (pregnancy pharmacoepidemiology) are fully understandable when all key methodological elements are presented to the reader.▪We identified 17 methodological elements from guidelines, literature, and subject-matter knowledge that we felt were crucial for understanding publications on pregnancy pharmacoepidemiology.▪In a random sample of 100 publications, completeness of reporting varied across elements, with almost perfect reporting on whether non-live births were included in the study population to a 21% completeness on mother-infant linkage success rate.▪A pregnancy-specific checklist would help to increase transparency in the dissemination of study results.
The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy
Authors: van der Grein Susanne G. , Defourny Kyra A.Y. , Rabouw Huib H. , Goerdayal Soenita S. , van Herwijnen Martijn J.C. , Wubbolts Richard W. , Altelaar Maarten , van Kuppeveld Frank J.M. , Nolte-‘t Hoen Esther N.M. 
Published: May 2021

SummaryNaked viruses can escape host cells before the induction of lysis via release in extracellular vesicles (EVs). These nanosized EVs cloak the secreted virus particles in a host-derived membrane, which alters virus-host interactions that affect infection efficiency and antiviral immunity. Currently, little is known about the viral and host factors regulating this form of virus release. Here, we assessed the role of picornavirus security proteins by studying the encephalomyocarditis virus (EMCV) Leader protein. EV release upon infection with wildtype virus or a Leader-deficient mutant was characterized at the single particle level using high-resolution flow cytometry. Inactivation of the Leader abolished EV induction during infection and strongly reduced EV-enclosed virus release. We demonstrate that the Leader promotes the release of virions within EVs by stimulating a secretory arm of autophagy. This newly discovered role of the EMCV Leader adds to the variety of mechanisms via which this protein affects virus-host interactions. Moreover, these data provide first evidence for a crucial role of non-structural viral proteins in the non-lytic release of picornaviruses via packaging in EVs.