bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vigilance for Medical Products of Human Origin—Progress on the Notify Library’s Global Effort to Share Information and Learning
Authors: Petrisli Evangelia , Carella Claudia , Navarro Aurora , Fehily Deirdre , Strong Douglas Michael , Cardillo Massimo 
Published: January 2021

Background.
World Health Assembly Resolution 63.22 mandated World Health Organization to facilitate Member State access to appropriate information on medical products of human origin (MPHO), including collecting data on serious adverse events and reactions. To meet this challenge, the Italian National Transplant Center, with a mandate from World Health Organization, has built and maintained an open-access searchable database of instructive records on disease transmission and other MPHO adverse occurrences.

Methods.
One record in the Notify Library describes a specific type of adverse occurrence in 1 type of MPHO and might be linked with 1 or multiple different references. The record inclusion criteria are that it has been reliably documented in a published article or official vigilance reporting system and that it has instructive value for the fields of transfusion, transplantation, or assisted reproduction. The selection and review of references for publication is performed by international experts who collaborate in 5 topic-specific editorial groups: infection transmission, malignancy transmission, living-donor reactions, process-related incidents, and clinical complications. New relevant references are identified through systematic searches and proactive communication by the experts.

Results.
The Library contains 1733 records, quoting 2632 references. Of the records, 41.8% are related to organs, 20.8% to blood and blood components, 16.5% to hematopoietic progenitor cells, 15.2% to tissues, 4.2% to reproductive tissues and cells, and 1.5% to other MPHO.

Conclusions.
Notify Library is the first open-access, searchable database of systematically identified reports of disease transmission and other adverse occurrences arising from the donation and clinical application of MPHO.
Incidence and Risk Factors for Fatal Graft-versus-host Disease After Liver Transplantation
Authors: Kitajima Toshihiro , Henry Matthew , Ivanics Tommy , Yeddula Sirisha , Collins Kelly , Rizzari Michael , Yoshida Atsushi , Abouljoud Marwan S. , Nagai Shunji , Moonka Dilip 
Published: January 2021

Background.Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD).Methods.Using data from the Organ Procurement and Transplantation Network and United Network for Organ Sharing registry, 77 416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens.Results.The incidence of fatal GVHD was 0.2% (121 of 77 416), of whom 105 (87%) died within 180 d and 13 (11%) died between 181 d and 1 y. Median survival after LT was 68.0 (49.5–125.5) d. Recipient age minus donor age >20 y (hazard ratio [HR], 2.57;P< 0.001) and basiliximab induction (HR, 1.69;P= 0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR, 0.51;P= 0.001). In an increased risk cohort of patients with recipient-donor age discrepancy >20 y, MMF use was associated with a 50% decline in fatal GVHD (HR, 0.50;P< 0.001).Conclusions.Recipient age minus donor age >20 y remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age >20 y. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD.
Changes in Functional Status Among Kidney Transplant Recipients: Data From the Scientific Registry of Transplant Recipients
Authors: Chu Nadia M. , Chen Xiaomeng , Bae Sunjae , Brennan Daniel C. , Segev Dorry L. , McAdams-DeMarco Mara A. 
Published: January 2021

Background.With stressors of dialysis prekidney transplantation (KT) and restoration of kidney function post-KT, it is likely that KT recipients experience a decline in functional status while on the waitlist and improvements post-KT.Methods.We leveraged 224 832 KT recipients from the national registry (SRTR, February 1990–May 2019) with measured Karnofsky Performance Status (KPS, 0%–100%) at listing, KT admission, and post-KT. We quantified the change in KPS from listing to KT using generalized linear models. We described post-KT KPS trajectories using adjusted mixed-effects models and tested whether those trajectories differed by age, sex, race, and diabetes status using a Wald test among all KT recipients. We then quantified risk adverse post-KT outcomes (mortality and all-cause graft loss [ACGL]) by preoperative KPS and time-varying KPS.Results.Mean KPS declined from listing (83.7%) to admission (78.9%) (mean = 4.76%, 95% confidence interval [CI]: −4.82, −4.70). After adjustment, mean KPS improved post-KT (slope = 0.89%/y, 95% CI: 0.87, 0.91); younger, female, non-Black, and diabetic recipients experienced greater post-KT improvements (Pinteractions< 0.001). Lower KPS (per 10% decrease) at admission was associated with greater mortality (adjusted hazard ratio [aHR] = 1.11, 95% CI: 1.10, 1.11) and ACGL (aHR = 1.08, 95% CI: 1.08, 1.09) risk. Lower post-KT KPS (per 10% decrease; time-varying) were more strongly associated with mortality (aHR = 1.93, 95% CI: 1.92, 1.94) and ACGL (aHR = 1.84, 95% CI: 1.83, 1.85).Conclusions.Functional status declines pre-KT and improves post-KT in the national registry. Despite post-KT improvements, poorer functional status at KT and post-KT are associated with greater mortality and ACGL risk. Because of its dynamic nature, clinicians should repeatedly screen for lower functional status pre-KT to refer vulnerable patients to prehabilitation in hopes of reducing risk of adverse post-KT outcomes.
Traumatic subarachnoid hemorrhage: a scoping review
Authors: Griswold Dylan P , Fernandez Laura , Rubiano Andres M 
Published: January 2021

AbstractSixty-nine million people suffer from traumatic brain injury (TBI) each year, and TBI is the most common cause of subarachnoid hemorrhage (SAH). Traumatic SAH (tSAH) has been described as an adverse prognostic factor leading to progressive neurological deterioration and increased morbidity and mortality. However, a limited number of studies evaluate recent trends in the diagnostic and management of SAH in the context of trauma. The objective of this scoping review was to understand the extent and type of evidence concerning the diagnostic criteria and management of traumatic subarachnoid hemorrhage. This scoping review was conducted following the JBI methodology for scoping reviews. The review included adults who suffered SAH secondary to trauma. Data extracted from each study included study aim, country, methodology, population characteristics, outcome measures, a summary of findings, and future directives. Thirty studies met inclusion criteria. Studies were grouped into five categories by topic: tSAH associated with mild TBI (n=13), and severe TBI (n=3); clinical management and diagnosis (n=9); imaging (n=3); and 5) aneurysmal tSAH (n=1). Of the 30 studies, two came from a low-and middle-income country (LMIC); excluding China, nearly a high-income country. Patients with tSAH associated with mTBI have a very low risk of clinical deterioration and surgical intervention and should be managed conservatively when considering ICU admission. The Helsinki and Stockholm CT scoring systems, in addition to the AIS, Cr, age decision tree, may be valuable tools to use when predicting outcome and mortality.
Lack of evidence for interactions between APOE and Klotho genotypes on cognitive, dementia and brain imaging metrics in UK Biobank
Authors: Tank Rachana , Ward Joey , Smith Daniel J. , Flegal Kristin E. , Lyall Donald M. 
Published: January 2021

AbstractImportanceRecent research has suggested that genetic variation in the Klotho (KL) locus may modify the association between apolipoprotein e (APOE) e4 genotype and cognitive impairment.ObjectiveLarge-scale testing for associations and interactions between KL and APOE genotypes vs. risk of dementia (n=1,570 cases), cognitive abilities (n=174,513) and brain structure (n = 13,158) in older (60+ years) participants.Design, setting and participantsCross-sectional and prospective data (UK Biobank).Main outcomes and measuresKL status was indexed with heterozygosity of the rs9536314 polymorphism (vs. not), in unrelated people with vs. without APOE e4 genotype, using regression and interaction tests. We assessed non-demented cognitive scores (processing speed; reasoning; memory; executive function), multiple structural brain imaging, and clinical dementia outcomes. All tests were corrected for age, sex, assessment centre, eight principal components for population stratification, genotypic array, smoking history, deprivation, and self-reported medication history.ResultsAPOE e4 presence (vs. not) was associated with increased risk of dementia, worse cognitive abilities and brain structure differences. KL heterozygosity was associated with less frontal lobe grey matter. There were no significant APOE/KL interactions for cognitive, dementia or brain imaging measures (all P>0.05).Conclusions and relevanceWe found no evidence of APOE/KL interactions on cognitive, dementia or brain imaging outcomes. This could be due to some degree of cognitive test imprecision, generally preserved participant health potentially due to relatively young age, type-1 error in prior studies, or indicative of a significant age-dependent KL effect only in the context of marked AD pathology.Key pointsQuestion: Klotho genotype has been previously shown to ‘offset’ a substantial amount of the APOE e4/cognitive impairment association. Is this modification effect apparent in large-scale independent data, in terms of non-demented cognitive abilities, brain structure and dementia prevalence?Findings: In aged 60 years and above participants from UK Biobank, we found significant associations of APOE and Klotho genotypes on cognitive, structural brain and dementia outcomes, but no significant interactions.Meaning: This could reflect somewhat healthy participants, prior type 1 error or cognitive/dementia ascertainment imprecision, and/or that Klotho genotypic effects are age and neuropathology dependent.
An optimised protocol for detection of SARS-CoV-2 in stool
Authors: Li T , Garcia-Gutierrez E , Scadden J , Davies J , Hutchins C , Aydin A , Romano S , Sayavedra L , O’Grady J , Narbad A 
Published: January 2021

AbstractAimSARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples.MethodsStool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100 mg stool. Debris was removed via centrifugation and supernatants were concentrated by ultrafiltration. RNA was then extracted from the concentrated material using a commercial kit and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes.ResultsThe RNA extraction procedure we used allowed the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100 mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool.ConclusionsHere we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as faecal microbiota transplant (FMT).
Delayed bystander CD8 T cell activation, early immune pathology and persistent dysregulation characterise severe COVID-19
Authors: Bergamaschi Laura , Mescia Federica , Turner Lorinda , Hanson Aimee , Kotagiri Prasanti , Dunmore Benjamin J. , Ruffieux Hélène , De Sa Aloka , Huhn Oisín , Morgan Michael D , Gerber Pehuen Pereyra , Wills Mark R. , Baker Stephen , Calero-Nieto Fernando J , Doffinger Rainer , Dougan Gordon , Elmer Anne , Goodfellow Ian G , Gupta Ravindra K. , Hosmillo Myra , Hunter Kelvin , Kingston Nathalie , Lehner Paul J. , Matheson Nicholas J. , Nicholson Jeremy K. , Petrunkina Anna M. , Richardson Sylvia , Saunders Caroline , Thaventhiran James E.D. , Toonen Erik J. M. , Weekes Michael P. ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens Berthold , Toshner Mark , Hess Christoph , Bradley John R. , Lyons Paul A. , Smith Kenneth G.C. 
Published: January 2021

SummaryIn a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust bystander CD8 T cell immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed bystander responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune defects may have clinical implications.
A Viral Fragmentation Signature for SARS-CoV-2 in Clinical Samples Correlating with Contagiousness
Authors: Choudhury Yukti , Cher Chae Yin , Wan Zi Yi , Xie Chao , Lim Jing Shan , Virk Ramandeep Kaur , Tan Min Han , Jing Teo Alvin Kuo , Hsu Li Yang 
Published: January 2021

AbstractThe viral load of SARS-CoV-2 in clinical samples as measured by the primary diagnostic tool of RT-PCR is an imperfect readout for infection potential as most targeted assays designed for sensitivity, indiscriminately detect short and long RNA fragments, although infectivity is embodied only in the whole virus and its intact genome. Here, we used next-generation sequencing (NGS) to characterize 155 clinical samples and show sensitive and quantitative detection of viral RNA which confirmed subgenomic RNA in 57.6% of samples and provided a novel method to determine relative integrity of viral RNA in samples. The relative abundance of long fragments quantified as a viral fragmentation score was positively associated with viral load and inversely related to time from disease onset. An empirically determined score cut-off for presence of substantially fragmented RNA was able to identify 100% of samples collected after 8 days of illness with poor infection potential in line with current clinical understanding of infectiousness of SARS-CoV-2. The quantification of longer fragments in addition to existing short targets in an NGS or RT-PCR-based assay could provide a valuable readout of infection potential simultaneous to the detection of any fragments of SARS-CoV-2 RNA in test samples.
Rates and predictors of uptake of formal and informal mental health support during the COVID-19 pandemic: an analysis of 26,740 adults in the UK in lockdown
Authors: Bu Feifei , Mak Hei Wan , Fancourt Daisy 
Published: January 2021

AbstractPurposeThe coronavirus disease 2019 (COVID-19) pandemic has put a great strain on people’s mental health. A growing number of studies have shown worsening mental health measures globally during the pandemic. However, there is a lack of empirical study on how people support their mental health during the COVID-19 pandemic. This study aimed to examine a number of formal and informal mental health supports. Further, it explored factors that might be associated with the use of different types mental health support.MethodData from 26,740 adults in the UCL COVID -19 Social Study were analysed between 13thApril, 2020 and 3rdJuly, 2020. Data were analysed using logistic and Poisson regression models.ResultsAbout 45% of people reported talking to friends or family members to support their mental health, 43% engaging in self-care activities, 20% taking medication, 9% speaking to mental health professionals, 8% talking to a GP or other health professional, and another 8% using helpline or online services. Gender, education, living status, loneliness, pre-existing mental health conditions, general depression and anxiety, coping and personality were found to be associated with the use of mental health support.ConclusionWhile the negative impacts caused by the COVID-19 pandemic are inevitable, people can play an active role in managing their mental health. Understanding the patterns and predictors of various kinds of mental health support during the pandemic is crucial for future service planning and delivery through recognising potential barriers to mental health care faced by certain groups.
Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes
Authors: Murley Alexander G , Tsvetanov Kamen A , Rouse Matthew A , Jones P Simon , Sværke Katrine , Li Win , Carpenter T Adrian , Rowe James B 
Published: January 2021

AbstractObjectiveTo measure cortical metabolite deficitsin vivoin syndromes associated with frontotemporal lobar degeneration, in relation to cognitive and behavioral change.MethodsSixty patients were recruited with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n=11, progressive supranuclear palsy n=26, corticobasal syndrome n=11, primary progressive aphasias n=12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex using 3T semi-laser magnetic resonance spectroscopy. Metabolite concentrations were corrected for age, sex, and partial volume. We related corrected metabolite concentrations to cognitive and behavioral measures using canonical correlation analysis.ResultsMetabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64)=1.73, p<0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R=0.95, p<0.001).ConclusionMagnetic resonance spectroscopy confirms behaviourally relevant metabolite deficits including glutamate, in syndromes associated with frontotemporal lobar degeneration. Magnetic resonance spectroscopy may be a useful index of neurodegeneration, and highlight candidates for pharmacological treatment.
Integrative Omics Reveal Novel Protein Targets For Chronic Obstructive Pulmonary Disease Biomarker Discovery
Authors: Cordero Ana I Hernandez , Milne Stephen , Yang Chen Xi , Li Xuan , Shi Henry , Sin Don D. , Obeidat Ma’en 
Published: January 2021

AbstractBackgroundLarge genome-wide association studies (GWAS) and other genetic studies have revealed genetic loci that are associated with chronic obstructive pulmonary disease (COPD). However, the proteins responsible for COPD pathogenesis remain elusive. We used integrative-omics by combining genetics of lung function and COPD with genetics of proteome to identify proteins underlying lung function variation and COPD risk.MethodsWe used summary statistics from the GWAS of human plasma proteome from the INTERVAL cohort (n=3,301) and integrated these data with lung function GWAS results from the UK Biobank cohorts (n=400,102) and COPD GWAS results from the ICGC cohort (35,735 cases and 222,076 controls). We performed in parallel: a proteome-wide Bayesian colocalization, and a proteome-wide Mendelian Randomization (MR) analyses. Next, we selected proteins that colocalized with lung function and/or COPD risk and explored their causal association with lung function and/or COPD using MR analysis (P<0.05).ResultsWe found 537, 607, and 250 proteins that colocalized with force expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), or COPD risk, respectively. Of these, 1,051 were unique proteins. The sRAGE protein demonstrated the strongest colocalization with FEV1/FVC and COPD risk, while QSOX2, FAM3D and F177A proteins had the strongest associations with FEV1. Of these, 37 proteins that colocalized with lung function and/or COPD, also had a significant causal association. These included proteins such as PDE4D, QSOX2 and RGAP1, amongst others.ConclusionIntegrative-omics reveals new proteins related to lung function. These proteins may play important roles in the pathogenesis of COPD.
A heritable androgenic mechanism of female intrasexual competition in cooperatively breeding meerkats
Authors: Drea Christine M. , Davies Charli S. , Greene Lydia K. , Mitchell Jessica , Blondel Dimitri V. , Shearer Caroline L. , Feldblum Joseph T. , Dimac-Stohl Kristin A. , Smyth-Kabay Kendra N. , Clutton-Brock Tim H. 
Published: January 2021

AbstractFemale intrasexual competition can be intense in cooperatively breeding species, with the dominant breeder or matriarch limiting reproduction in subordinates via aggression, eviction or infanticide. In males, these tendencies bidirectionally link to testosterone, but in females, there has been no systematic investigation of androgen-mediated behaviour within and across generations. In 22 wild meerkat (Suricata suricatta) clans, we show that matriarchs 1) express peak androgen concentrations during late gestation, 2) when displaying peak feeding competition, dominance, and evictions, and 3) relative to subordinates, produce offspring that are more aggressive in early development. Late-gestation, antiandrogen treatment of matriarchs 4) reduced their dominance behaviour, was associated with infrequent evictions, decreased social centrality within the clan, 5) increased aggression in cohabiting subordinate dams, and 6) reduced their offspring’s aggression. These effects implicate androgen-mediated aggression in the operation of female sexual selection, and intergenerational transmission of ‘masculinised’ phenotypes in the evolution of meerkat cooperative breeding.