bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
Authors: Tenthorey Jeannette L. , Young Candice , Sodeinde Afeez , Emerman Michael , Malik Harmit S. 
Published: June 2020

ABSTRACTHost antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving “v1” loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via single adaptive substitutions. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.
Quantifying Numerical and Spatial Reliability of Amygdala and Hippocampal Subdivisions in FreeSurfer
Authors: Kahhale Isabella , Buser Nicholas J , Madan Christopher R. , Hanson Jamie L. 
Published: June 2020

AbstractOn-going, large-scale neuroimaging initiatives can aid in uncovering neurobiological causes and correlates of poor mental health, disease pathology, and many other important conditions. As projects grow in scale with hundreds, even thousands, of individual participants and scans collected, quantification of brain structures by automated algorithms is becoming the onlytrulytractable approach. Here, we assessed the spatial and numerical reliability for newly deployed automated segmentation of hippocampal subfields and amygdala nuclei in FreeSurfer 7. In a sample of participants with repeated structural imaging scans (N=923), we found numerical reliability (as assessed by intraclass correlations, ICCs) was reasonable: ∼95% of hippocampal subfields have “excellent” numerical reliability (ICCs≥0.90), however, only 67% of amygdala subnuclei met this same threshold. Spatial reliability was similarly reasonable, with 58% of hippocampal subfields and 44% of amygdala subnuclei having Dice coefficients≥0.70. Notably, multiple regions had poor numerical and/or spatial reliability. We also examined correlations between spatial reliability and person-level factors (e.g., participant age; T1 image quality). Both sex and image scan quality were related to variations in spatial reliability metrics. Examined collectively, our work suggests caution should be exercised for a few hippocampal subfields and amygdala nuclei with more variable reliability.
Bacteria on steroids: the enzymatic mechanism of an NADH-dependent dehydrogenase that regulates the conversion of cortisol to androgen in the gut microbiome
Authors: Bernardi Rafael C. , Doden Heidi L. , Melo Marcelo C.R. , Devendran Saravanan , Pollet Rebecca M. , Mythen Sean M. , Bhowmik Shiva , Lesley Scott A. , Cann Isaac , Luthey-Schulten Zaida , Koropatkin Nicole M. , Ridlon Jason M. 
Published: June 2020

ABSTRACTThe ability to metabolize both endogenous and exogenous compounds to a variety of metabolic products is not exclusive to our human cells. In fact, the bacterial communities that inhabit our digestive system are responsible for a network of steroid transformations that can produce hormones in the gut, which are then absorbed to act in the host. These communities have been shown to impact our health in numerous ways, affecting disease predisposition, pathogenesis, physical fitness, and dietary responsiveness. Steroid biotransformations by gut bacteria are predicted to impact the host endocrine system. A particular set of transformations facilitated by microbial enzymes has been shown to result in the formation of 11-oxy-androgens from host-derived cortisol. Since androgens have been implicated in disease and immune modulations, understanding the structure and catalytic mechanism of enzymes involved in cortisol metabolism is a key step to hasten the development of strategies that reduce the formation of disease-promoting bioactive steroids in certain individuals. Here, we combine experimental and computational techniques to describe DesC, an enzyme capable of creating 20α-dihydrocortisol and siphoning cortisol away from pathways that produce androgens. DesC diverges significantly from previously described bacterial and eukaryotic counterparts, catalyzing an NADH-dependent 20α-hydroxysteroid dehydrogenase reaction but presenting little sequence and structure similarity to them. The structural information obtained by X-ray crystallography and hybrid QM/MM simulations, validated through mutagenesis studies, show the reaction occurs through a multi-step proton relay mechanism. Free energy calculations were then used to describe the kinetics of the reaction mechanism. The mechanistic information presented here can be employed in the development of therapeutics to divert microbial pathways away from disease-promoting steroids.
Degradation of Lon inCaulobacter crescentus
Authors: Barros Benjamin B , Mahmoud Samar A , Chien Peter , Zeinert Rilee D. 
Published: June 2020

AbstractProtein degradation is an essential process in all organisms. This process is irreversible and energetically costly; therefore, protein destruction must be tightly controlled. While environmental stresses often lead to upregulation of proteases at the transcriptional level, little is known about post-translational control of these critical machines. In this study we show that inCaulobacter crescentuslevels of the Lon protease are controlled through proteolysis. Lon turnover requires active Lon and ClpAP proteases. We show that specific determinants dictate Lon stability with a key carboxy-terminal histidine residue driving recognition. Expression of stabilized Lon variants results in toxic levels of protease that deplete normal Lon substrates such as the replication initiator DnaA to lethally low levels. Taken together, this work demonstrates a feedback mechanism in which ClpAP and Lon collaborate to tune Lon proteolytic capacity for the cell.ImportanceProteases are essential, but unrestrained activity can also kill cells by degrading essential proteins. The quality control protease Lon must degrade many misfolded and native substrates. We show that Lon is itself controlled through proteolysis and that bypassing this control results in toxic consequences for the cell.
Efficacy of cognitive behavioral therapy on non-motor symptoms and quality of life in Parkinson’s disease: A systematic review and meta-analysis
Authors: Luo Fangyi , Ye Mengfei , Lv Tingting , Hu Baiqi , Chen Jiaqi , Yan Junwei , Wang Anzhe , Chen Feng , He Ziyi , Ding Zhinan , Zhang Jian , Gao Hui , Qian Chao , Liu Zheng 
Published: June 2020

AbstractObjectiveThe aim of this study was to perform a quantitative analysis to evaluate the efficacy of cognitive behavioral therapy (CBT) on non-motor symptoms and its impact on quality of life (QOL) in Parkinson’s disease (PD).MethodsWe searched for randomized controlled trials in three electronic databases. Twelve studies, including 358 patients with PD, met the inclusion criteria. We determined the pooled efficacy by standard mean differences and 95% confidence intervals, using I2 to reveal heterogeneity.ResultsThe result showed CBT had a significant effect on depression [-0.94 (95% CI, -1.25 to -0.64, P < 0.001)] and anxiety [-0.78 (95% CI, -1.05 to -0.50, P < 0.001)]. Moderate effect sizes were noted with stress [-0.60 (95% CI, -1.06 to -0.14, P = 0.01)] and sleep disorders [-0.44 (95% CI, -0.74 to -0.15, P = 0.003)]. There was no evident impact of CBT on fatigue or QOL. We found an intervention period > 8 weeks was advantageous compared with < 8 weeks, and CBT intervention was more effective than CBT developmental therapy.ConclusionWe found that CBT in patients with PD was an efficacious therapy for some non-motor symptoms in PD, but not efficacious for fatigue and QOL. These results suggest that CBT results in significant improvement in PD and should be used as a conventional clinical intervention.
Laboratory Testing Implications of Risk-Stratification and Management for Improving Clinical Outcomes of COVID-19 Patients
Authors: Liu Caidong , Wang Ziyu , Li Jie , Xiang Changgang , Wu Lingxiang , Wu Wei , Hou Weiye , Sun Huiling , Wang Youli , Nie Zhenling , Gao Yingdong , Zhang Ruisheng , Xia Xinyi , Wang Qianghu , Wang Shukui 
Published: June 2020

ABSTRACTThe high mortality rate of COVID-19 patients is mainly caused by the progression from mild to critical illness. To identify the key laboratory indicators and stratify high-risk COVID-19 patients with progression to severe/critical illness, we compared 474 moderate patients and 74 severe/critical patients. The laboratory indicators, including lactate dehydrogenase (LDH), monocytes percentage, etc. were significantly higher in the severe/critical patients (P <0.001) and showed a noticeable change at about a week before the diagnosis. Based on these indicators, we constructed a risk-stratification model, which can accurately grade the severity of patients with COVID-19 (accuracy = 0.96, 95% CI: 0.94 - 0.989, sensitivity = 0.98, specificity = 0.84). Also, compared with non-COVID-19 viral pneumonia, we found that COVID-19 had weaker dysfunction to the heart, liver, and kidney. The prognostic model based on laboratory indicators could help to diagnose, monitor, and predict severity at an early stage to those patients with COVID-19.
Vascular brain pathology is more important than neurodegeneration in pathogenesis of pre-stroke cognitive impairment
Authors: Schellhorn T , Zucknick M , Askim T , Munthe-Kaas R , Ihle-Hansen H , Seljeseth YM , Knapskog AB , Næss H , Ellekjær H , Thingstad P , Wyller T Bruun , Saltvedt I , Beyer MK 
Published: June 2020

AbstractIntroductionTo better understand the development of post-stroke cognitive impairment,we explored the association between pre-stroke neuroimaging features and pre-stroke cognitive impairment and investigated possible gender differences. Few previous studies on this topic have been performed.MethodsIn this large prospective longitudinal multicenter brain-MRI cohort study, patients admitted to five stroke units at five different Norwegian hospitals were recruited as part of the Norwegian cognitive impairment after stroke study. Visual radiological assessment of small vessel disease and neurodegenerative changes were performed on brain MRI from 410 patients. Pre-stroke cognition was assessed using the Global Deterioration Scale.ResultsAt least one pathological marker was found in 68% of the patients. The mean age (SD) of the patients with no pathological changes other than the acute stroke, was 70 (± 12.9) and 75 (± 10.2) years for those with pathological scans (p ≤ 0.001). Men were more likely to have at least one pathological brain MRI finding, lacunes, or pathological medial temporal lobe atrophy. The highest percentage of patients with a pathological pre-stroke GDS were found in the “cerebrovascular pathology” group (37.5%) and in the “mixed pathology”-group (44%). In these groups, both men and women had an increased risk of impaired pre-stroke cognition.ConclusionThe majority of patients showed preexisting structural brain pathology. Cerebrovascular pathology was the dominating imaging finding associated with cognitive impairment, thus indicating that the pathogenesis of pre-stroke cognitive impairment might be driven more by small vessel disease (SVD) than neurodegenerative changes. Gender differences exists, with less pathology in women.
Crescentic Glomerulonephritis: What’s different in South Asia? - A Single Center Observational Cohort Study
Authors: Alexander Suceena , Yusuf Sabina , Rajan Gautham , John Elenjickal Elias , Roy Sanjeet , Annamalai VC , Thomas Athul , Eapen Jeethu Joseph , Valson Anna T. , David Vinoi George , Varughese Santosh 
Published: June 2020

ABSTRACTBackgroundThe spectrum and outcomes of crescentic glomerulonephritis in South Asia is vastly different from that reported worldwide and there is a paucity of information.MethodsIt was an observational cohort study of renal biopsies done in the largest tertiary center in South India over a period of 10 years with ≥50% crescents on histology.ResultsA total of 8645 kidney biopsies were done at our center from January 2006 to December 2015, and 200 (2.31%) were crescentic glomerulonephritis. Patients were categorized into three etiological groups - anti-GBM (type I), immune complex (type II) and pauci-immune (type III). The most common was type II (96, 46.5%), followed by type III (73, 38%) and then type I (31, 15.5%). Female preponderance was seen across all three types. About half of all the three types presented with recent onset hypertension. Type II had the highest median proteinuria (4.2 (2.1-6) g/day, p=0.06) and the median eGFR was lowest in type I (5 (4-8) ml/min/1.73m2, p<0.001). Among type III, ANCA associated vasculitis (AAV) was seen only in about half of the patients. Nearly one third patients with type I was also positive for ANCA making them ‘double positive’. Severe glomerular insults like tuft necrosis and chronicity as evidenced by moderate to severe interstitial fibrosis was a predominant feature of type I.ConclusionsANCA negative vasculitis as well as double positive types are reported for the first time from South-Asia. Prevalence of ANCA negative vasculitis (type III subgroup) was much higher in our population. Renal survival was significantly worse in type I & III compared to type II. Types I/III, moderate to severe IFTA, presence of oliguria/anuria and increasing percentage of crescents in renal biopsy were significant predictors of dialysis dependence at index visit or of end stage kidney disease at follow-up in our cohort.
Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomized trial
Authors: Assfalg Robin , Knoop Jan , Hoffman Kristi L. , Pfirrmann Markus , Zapardiel-Gonzalo Jose Maria , Hofelich Anna , Eugster Anne , Weigelt Marc , Matzke Claudia , Reinhardt Julia , Fuchs Yannick , Bunk Melanie , Weiss Andreas , Hippich Markus , Halfter Kathrin , Hauck Stefanie M. , Hasford Jörg , Petrosino Joseph F. , Achenbach Peter , Bonifacio Ezio , Ziegler Anette-Gabriele 
Published: June 2020

AbstractBackgroundOral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes with insulin autoimmunity often appearing in the first years of life. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and actions on immunity and the gut microbiome.MethodsA phase I/II randomized controlled trial was performed in 44 islet autoantibody-negative children aged 6 months to 2 years with genetic risk for type 1 diabetes. Children were randomized 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months. Primary outcome was safety and immune efficacy pre-specified as hypoglycemia and induction of antibody or T cell responses to insulin, respectively.ResultsOral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in both children who received insulin (55%) and placebo (67%), and were modified by theINSULINgene. Among children with type 1 diabetes-susceptibleINSULINgenotype, antibody responses to insulin were more frequent in insulin-treated (cumulative response, 75.8%) as compared to placebo-treated children (18.2%;P=0.0085), and T cell responses to insulin were modified by treatment-independent inflammatory episodes. Changes in the microbiome were related toINSULINgenotype.ConclusionThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe and engaged the adaptive immune system in anINSULINgenotype-dependent manner, and linked inflammatory episodes to the activation of insulin-responsive T cells.Trial registrationClinicaltrials.govNCT02547519FundingGerman Center for Diabetes Research (DZD e.V.), Juvenile Diabetes Research Foundation (JDRF, grant 1-SRA-2018-546-S-B), Federal Ministry of Education and Research (BMBF, grant FKZ01KX1818).
Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing
Authors: Bi Chongwei , Ramos-Mandujano Gerardo , Hala Sharif , Xu Jinna , Mfarrej Sara , Tian Yeteng , Esteban Concepcion Rodriguez , Nuñez Delicado Estrella , Alofi Fadwa S. , Khogeer Asim , Hashem Anwar M. , Almontashiri Naif A.M. , Pain Arnab , Izpisua Belmonte Juan Carlos , Li Mo 
Published: June 2020

AbstractStrategies for monitoring the COVID-19 infection are crucial for combating the pandemic. Here we describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes. It can simultaneously detect SARS-CoV-2 and co-infecting respiratory viruses, and monitor mutations for up to 96 samples in real time. The method, termed NIRVANA for Nanopore sequencing of Isothermal Rapid Viral Amplification for Near real-time Analysis, showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples. It also simultaneously detected other viral pathogens (e.g. influenza A) in clinical and municipal wastewater samples. It provides a rapid field-deployable solution of COVID-19 and cos-infection detection and surveillance of the evolution of pandemic strains.
The gender gap in adolescent mental health: a cross-national investigation of 566,827 adolescents across 73 countries
Authors: Campbell Olympia , Bann David , Patalay Praveetha 
Published: June 2020

AbstractMental ill-health is a leading cause of disease burden worldwide. While women suffer from greater levels of mental health disorders, it remains unclear whether this gender gap differs systematically across regions and/or countries, or across the different dimensions of mental health. We analysed 2018 data from 566,827 adolescents across 73 countries for 4 mental health outcomes: psychological distress, life satisfaction, eudaemonia, and hedonia. We examine average gender differences and distributions for each of these outcomes as well as country-level associations between each outcome and purported determinants at the country level: wealth (GDP per capita), inequality (Gini index), and societal indicators of gender inequality (GII, GGGI, and GSNI). We report four main results: 1) The gender gap in mental health in adolescence is largely ubiquitous cross-culturally, with girls having worse average mental health; 2) There is considerable cross-national heterogeneity in the size of the gender gap, with the direction reversed in a minority of countries; 3) Higher GDP per capita is associated with worse average mental health and a larger gender gap across all mental health outcomes; and 4) more gender equal countries have larger gender gaps, with better mental health in males associated with greater gender equality and inconsistent associations with different mental health outcomes in females. Taken together, our findings suggest that while the gender gap appears largely ubiquitous, its size differs considerably by region, country, and dimension of mental health. Findings point to the hitherto unrealised complex nature of gender disparities in mental health and possible incongruence between expectations and reality in high gender equal countries.
Structural and functional signatures of executive deficits after early use of cocaine depend upon route of administration
Authors: de la Fuente Alethia , Vignaga Sofía Schurmann , Prado Pilar , Figueras Rosario , Lizaso Lucia , Manes Facundo , Cetkovich Marcelo , Tagliazucchi Enzo , Torralva Teresa 
Published: June 2020

AbstractBackgroundThere is growing evidence linking cocaine consumption with a broad spectrum of neurocognitive deficits. Despite of evidence suggesting that the route of administration should be taken into account to assess the short and long term effects of cocaine consumption, to our knowledge no study to date has characterized clinically relevant neuropsychological variables along with physiological variables separately in populations of individuals with histories of smoked cocaine dependence (SCD) and insufflated cocaine hydrochloride dependence (ICD).MethodsThe present study examined a sample of (a) 25 participants who fulfilled criteria for SCD, (b) 22 participants who fulfilled criteria for ICD, and (c) 25 healthy controls matched by age, gender, education, and socioeconomic status. An exhaustive neuropsychological battery was used to assess different cognitive domains (attention, executive functions, fluid intelligence, memory, language and social cognition). We complemented this neuropsychological assessment with the acquisition and analysis of structural (MRI) and functional (fMRI) neuroimaging data.ResultsDifferent routes of administration led to equally different profiles of neurocognitive impairment, with the SCD group being specifically associated with deficits in attention and executive functions. Consistent with risk models, executive function-attention deficit is better explained for age and age onset of consumption initiation. SCD also presented reduced grey matter density relative to ICD in the bilateral caudate, a key area for executive functions and attention. Connectivity between left caudate and inferior frontal regions mediates performance-structure association.ConclusionsCocaine routes of administration are associated to a differential profile that may not be due direct effects of stimulant action but also driven by cognitive and biological differences in key executive functioning and attention areas. This point the critical importance of the routes of administration. This information could inform clinical management and should be taken into account in clinical research.
Improving effectiveness of different deep learning-based models for detecting COVID-19 from computed tomography (CT) images
Authors: Acar Erdi , Şahin Engin , Yılmaz İhsan 
Published: June 2020

AbstractComputerized Tomography (CT) has a prognostic role in the early diagnosis of COVID-19 due to it gives both fast and accurate results. This is very important to help decision making of clinicians for quick isolation and appropriate patient treatment. In this study, we combine methods such as segmentation, data augmentation and the generative adversarial network (GAN) to improve the effectiveness of learning models. We obtain the best performance with 99% accuracy for lung segmentation. Using the above improvements we get the highest rates in terms of accuracy (99.8%), precision (99.8%), recall (99.8%), f1-score (99.8%) and roc acu (99.9979%) with deep learning methods in this paper. Also we compare popular deep learning-based frameworks such as VGG16, VGG19, Xception, ResNet50, ResNet50V2, DenseNet121, DenseNet169, InceptionV3 and InceptionResNetV2 for automatic COVID-19 classification. The DenseNet169 amongst deep convolutional neural networks achieves the best performance with 99.8% accuracy. The second-best learner is InceptionResNetV2 with accuracy of 99.65%. The third-best learner is Xception and InceptionV3 with accuracy of 99.60%.