bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLAautoimmune risk alleles restrict the hypervariable region of T cell receptors
Authors: Ishigaki Kazuyoshi , Lagattuta Kaitlyn , Luo Yang , James Eddie , Buckner Jane , Raychaudhuri Soumya 
Published: November 2020

ABSTRACTPolymorphisms in thehuman leukocyte antigen(HLA) genes within themajor histocompatibility complex(MHC) locus strongly influence autoimmune disease risk1–5. Two non-exclusive hypotheses exist about the pathogenic role ofHLAalleles; i) the central hypothesis, whereHLArisk alleles influence thymic selection so that the probability of T cell receptors (TCRs) reactive to pathogenic antigens is increased6–8; and ii) the peripheral hypothesis, whereHLArisk alleles increase the affinity for pathogenic antigens9–11. The peripheral hypothesis has been the main research focus in autoimmunity, while human data on the central hypothesis are lacking. Here, we investigated the influence ofHLAalleles on TCR composition at the highly diverse complementarity determining region 3 (CDR3), where TCR recognizes antigens. We demonstrated unexpectedly powerfulHLA-CDR3 associations. The strongest association was found atHLA-DRB1amino acid position 13 (n = 628 subjects, explained variance = 9.4%;P= 4.1 x 10−138). This HLA position mediates genetic risk for multiple autoimmune diseases. In structural analysis of TCR-peptide-MHC complexes, we observed that HLA-DRB1 position 13 does not interact directly with CDR3, but is proximate to antigenic peptide residues that are also close to CDR3. We identified multiple CDR3 amino acid features enriched byHLArisk alleles; for example, the risk alleles of rheumatoid arthritis, type 1 diabetes, and celiac disease all increase the hydrophobicity of CDR3 position 109 (P< 2.1 x 10−5). In the setting of celiac disease, the CDR3 features favored byHLArisk alleles are more enriched among candidate pathogenic TCRs than control TCRs (P= 2.4 × 10−6for gliadin specific TCRs). Together, these results provide novel genetic evidence supporting the central hypothesis.
Cerebellar rTMS in PSP: a double blind sham-controlled study using mobile health technology
Authors: Pilotto Andrea , Rizzetti Maria Cristina , Lombardi Alberto , Hansen Clint , Biggi Michele , Verzeroli G Giacomo , Martinelli Antonella , Romijnders Robbin , Borroni Barbara , Maetzler Walter , Padovani Alessandro 
Published: November 2020

SUMMARYThere are no effective treatments for postural instability and falls in Progressive Supranuclear Palsy (PSP). Objective of the study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty probable PSP patients underwent a session of sham or cerebellar rTMS in a cross-over design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-seconds-trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with longer time without support falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005) and acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS thus showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.
Are women underrepresented in cerebrovascular disease clinical trials? A systematic review using the FDA database
Authors: Zhong Xiaobo , Hao Qing 
Published: November 2020

ABSTRACTBACKGROUND AND PURPOSEClinical trials provide essential evidence in the US Food and Drug Administration (FDA) drug approval process. Women were underrepresented in the enrollment of clinical trials for many medical conditions other than cerebrovascular disease (CVD). We investigated women’s participation in FDA-registered CVD-related interventional clinical trials and assessed whether women CVD patients in the United States were underrepresented. We also evaluated the association between the underrepresentation and the features of design and operation among these trials.METHODSWe systematically reviewed the phase 2 and 3 CVD-related interventional trials started in 2002–2017 in the FDA database. The proportions of women enrolled in these trials and the proportion-to-prevalence ratios (PPRs), defined as the ratios of the proportions of women enrolled in these trials to the proportion of women prevalent among US CVD patients during the same period, were calculated and summarized by a meta-analysis approach. We used boosted regression tree, a machine learning model, to identify the determinants of women’s underrepresentation in CVD-related trials.RESULTSAccording to our selection criteria, we analyzed the data of 145 CVD-related trials, among which 40.9% (95% CI: 38.3–43.5%) of the patients enrolled were women. Their PPR was estimated to be 0.843 (95% CI: 0.796–0.890). We found that four factors substantially influenced women’s underrepresentation in these trials: the number of enrollment sites, the starting year, randomization, and academic institution sponsorship.CONCLUSIONSGenerally, women with CVD in the United States were underrepresented in FDA registered trials started in 2002–2017. In addition, trials with greater numbers of enrollment sites, randomization, and non-academically sponsored trials had a higher risk of underrepresenting women with CVD in the United States. Investigators should take these factors into consideration in clinical trial design in the future, by either increasing women’s participation or stratifying the enrollment by gender.
Automatic Measurements of Smooth Pursuit Eye Movements by Video-Oculography and Deep Learning-Based Object Detection
Authors: Hirota Masakazu , Hayashi Takao , Watanabe Emiko , Mizota Atsushi 
Published: November 2020

AbstractPurposeThe purpose of this study was to develop a technique combining video oculography (VOG) with single shot multibox detector (SSD) to accurately and quantitatively examine eye movements.MethodsEleven healthy volunteers (21.3 ± 0.9 years) participated in this study. Eye movements were recorded while tracking a target using a custom-made eye tracker. The subjects were asked to fixate their focus on the nose of the rabbit-like target (visual angle was 0.1°), which was manually moved to a distance of 1 meter by the examiner during the eye movement test. The test produced 500 images from the VOG external camera and these images were divided into 3 groups (300, 100, and 100) for training, verification, and testing. The performance of the SSD was evaluated with 75% average precision (AP75), and the relationship between the location of the fixated target (calculated by the SSD) and the positions of both eyes (recorded by the VOG) was analyzed.ResultsThe AP75 of the SSD on one class of targets was 97.7%. The horizontal and vertical target locations significantly and positively correlated with the horizontal and vertical both eye positions (adjusted R2 ≥ 0.955, P < 0.001).ConclusionsOur findings suggest that VOG with SSD is suitable for the evaluation of eye version movements in standard clinical assessments.Translational RelevanceThe combination of VOG and SSD can be used to evaluate the SPEM, and this method can be translated into clinical settings without changing the testing methods.
Conflict driven displacement and child health: Evidence from Jordan
Authors: Malik Manzoor Ahmad , Akhtar Saddaf Naaz , Albsoul Rania Ali , Alshyyab Muhammad Ahmed 
Published: November 2020

AbstractBackgroundArmed conflicts result in greater vulnerability and socioeconomic inequality of populations besides risking their health and well-being. Conflict intensifies the health needs and risks the life and well-being of individuals at large through displacement. Therefore, our study aims to apprise the interventions to which children under-five living in Jordan are especially at risk for acute respiratory infections, diarrhea, and fever in the conflict circumstances.MethodsSecondary data analysis is used in the present study. We used a weighted sample of around 9650 children from Jordan Population and Family Health Survey (JPFHS), 2017-18. Bivariate analysis including prevalence rates were used to examine the distribution of socio-demographic characteristics of children. The study has also used multinomial logistic regression model, in order to evaluate the variations in the probability of nationality of under-five children living in Jordan.Results“Syrian nationalist” children have a higher relative risk of ARI (RRR=1.19, [1.08, 1.32]), and “Other-nationalist” children have two times greater risk of ARI compared to “Jordanian children.” The relative risk of diarrhea is lower among “Syrian nationalist” and “Other-nationalist” children compared to “Jordanian children.” Children belong “Other-nationalist” are found to be less relative risk of fever (RRR=0.9, [0.80, 1.01]) than “Jordanian children.”ConclusionsOur study concludes that conflict-driven displacement has an immediate effect on child health through access, availability, and affordability of health care services, resulting in more significant health care risks. Coordinated and effective measures are needed to provide the best health care services among the displaced populations to prevent health risks.
Active ingredient ‘Better gut microbiome function’
Authors: Kadosh Kathrin Cohen , Basso Melissa , Knytl Paul , Johnstone Nicola , Lau Jennifer Y F , Gibson Glenn 
Published: November 2020

SummaryBackgroundThe human gut microbiome and its effect on brain function and mental health is emerging as an area of intensive research. Both animal and human research point towards adolescence as a sensitive period when the gut-brain axis is fine-tuned, and when we can use dietary intervention to change the microbiome, with long-lasting consequences for mental health. Here we report the results of a systematic review/meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, together with a summary of consultation work of youth with lived experience.MethodsSeven databases were searched (no date cut-offs), and controlled trials in clinical and healthy human samples (age range: 10-24) seeking to reduce anxiety were included. All data on between group-differences post intervention and outcomes were extracted as standard mean differences (SMDs) and pooled together based on a random-effects model.Findings5416 studies were identified, 14 were eligible for the qualitative summary, of which 10 were included in the meta-analyses (total of 324 experimental and 293 control subjects). The heterogeneity I2 was12% and the pooled SMD was −0.04 (95% CI: −0.21, 0.14). One study presented with low bias risk whereas 5 with high and 4 with uncertain risk, accounting for that, sensitivities analysis revealed a SMD of −0.16 (95%CI: −0.39, 0.06).InterpretationThere is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding and addressing the wider context.
Impact of public and private sector COVID-19 diagnostics and treatments on US healthcare resource utilization
Authors: Sheinson Daniel , Wong William , Solon Caroline , Cheng Mindy , Elsea David , Meng Yang , Shah Anuj 
Published: November 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19) has imposed a considerable burden on the United States (US) health system, with particular concern over healthcare capacity constraints.MethodsWe modeled the impact of public and private sector contributions to developing diagnostic testing and treatments on COVID-19-related healthcare resource use.ResultsWe estimated that public sector contributions lead to ≥30% reductions in COVID-19-related healthcare resource utilization. Private sector contributions to expanded diagnostic testing and treatments lead to further reductions in mortality (−44%), intensive care unit (ICU) and non-ICU hospital beds (−30% and −28%, respectively), and ventilator use (−29%). The combination of lower diagnostic test sensitivity and proportions of patients self-isolating may exacerbate case numbers, and policies that encourage self-isolating should be considered.ConclusionWhile mechanisms exist to facilitate research, development, and patient access to diagnostic testing, future policies should focus on ensuring equitable patient access to both diagnostic testing and treatments which, in turn, will alleviate COVID-19-related resource constraints.
Patterns of resistance to antibiotics of Enterococcus faecalis in clinical isolates of diabetic foot and presence of culture resistant to linezolid
Authors: Almeida Villegas Jorge Angel , García Fernández Luis Enrique , Estrada Carrillo Iris Mellolzy , Reyes Harold Mondragon , Sánchez Mariana Aguilar , Peña Silvia Patricia 
Published: November 2020

AbstractIntroductionHigh levels of hyperglycemia lead to diabetes, the same levels that if not controlled increase the risk of diabetic neuropathy, which over time translates into loss of sensation and lesions that progress and lead to diabetic foot may occur, microorganisms Mainly Gram positive cocci and Gram negative bacilli, as well as yeasts are those that are mainly found in this metabolic and infectious pathology.MethodsDiabetic foot wounds were studied in patients aged 45-54 years, with a mean age of 50 years, who had different periods of time with a hyperglycemia problem and different complications associated with diabetic foot, and were not considered as exclusion criteria. With a total of 41 cultures, 25 belong to male patients and 16 to female patients. All of these in the Toluca Valley, Mexico. The primary swab was reseeded in chromogenic agar, BHI, Salt and mannitol, calf blood, EMB and MacConkey, after 6 hours after taking the sample. In addition to microbial reseeding, a Gram stain was performed on each of the samples. The Petri dishes were placed in an incubation oven for 18 hours at 35 ° C with ± 2 ° C. Bacterial identification was performed on automated equipment from Beckman Coulter, as well as antibiotic sensitivity tests.Results35 positive cultures were obtained, of which they had a single microbial agent and some cases with two agents, which could be bacteria-bacteria or bacteria-yeast. With 14 positive strains for Enterococcus faecalis, with 100% sensitivity for cell wall inhibitors, and high resistance to tetracycline with 85.71% and 92.86% resistance to the macrolide erythromycin. In addition, there is a strain that was resistant to linezolid, and variable resistance patterns in fluoroquinolones and other antibiotics.
6-month aerobic walking training increases T1w/T2w signal in the white matter of healthy older adults
Authors: Colmenares Andrea Mendez , Voss Michelle W , Fanning Jason , Salerno Elizabeth A , Gothe Neha P , Thomas Michael L , McAuley Edward , Kramer Arthur F , Burzynska Agnieszka Z 
Published: November 2020

AbstractWhite matter (WM) deterioration is an important mechanism of cognitive decline in healthy aging and dementia. Engaging in aerobic exercise to improve cardiorespiratory fitness (CRF) is considered one of the most promising ways to improve cognitive and brain health in aging. Yet, no randomized controlled trials have reported benefits of aerobic exercise interventions on WM microstructure measured with diffusion tensor imaging. Here, we studied the effects of a 6-month exercise intervention (clinical trial NCT01472744) on WM of 180 cognitively healthy older adults (60–79 years) using the ratio of calibrated T1-weighted image to T2-weighted images (T1w/T2w). Participants were randomized to one of four groups including a low intensity activity with complex cognitive demands (Dance), Walking, Walking + nutritional supplement or an active control. Results showed that a 6-month aerobic walking and dance intervention produced positive changes in the T1w/T2w with significant time-by-group interactions in the total WM, the genu and splenium of the corpus callosum, forceps minor, cingulum, relative to an active control condition. In contrast, we observed a decline in T1w/T2w in the majority of WM regions in the active control group. Lastly, a positive change in the T1w/T2w in the genu of the corpus callosum correlated with a positive change in episodic memory in the Walking but not in the control group; however, there were no associations between change in the T1w/T2w and change in CRF. Together, our findings suggest that the T1w/T2w may be a sensitive metric to detect short-term within-person changes in the WM and intervention-induced WM plasticity in the adult human brain.
Patterns of neurodegeneration in dementia reflect a global functional state space
Authors: Jones D. , Lowe V. , Graff-Radford J. , Botha H. , Wiepert D. , Murphy M.C. , Murray M. , Senjem M. , Gunter J. , Wiste H. , Boeve B. , Knopman D. , Petersen R. , Jack C. 
Published: November 2020

AbstractDisruption of mental functions in Alzheimer’s disease (AD) and related disorders is accompanied by selective degeneration of brain regions for unknown reasons. These regions comprise large-scale ensembles of cells organized into networks required for mental functioning. A mechanistic framework does not exist to explain the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and the functional connectome. The association between dementia symptoms and degenerative brain anatomy encodes a mapping between mental functions and neuroanatomy. We isolated this mapping through unsupervised decoding of neurodegeneration in humans. This reflected a simple information processing-based functional description of macroscale brain anatomy, the global functional state space (GFSS). We then linked the GFSS to AD physiology, functional networks, and mental abilities. We extended the GFSS framework to normal aging and seven degenerative diseases of mental functions.One Sentence SummaryA global information processing framework for mental functions links neuroanatomy, cognitive neuroscience and clinical neurology.
Retrospective Analysis of Interventions to Epidemics using Dynamic Simulation of Population Behavior
Authors: Osborn Jenna , Berman Shayna , Bender-Bier Sara , D’Souza Gavin , Myers Matthew 
Published: November 2020

AbstractRetrospective analyses of interventions to epidemics, in which the effectiveness of strategies implemented are compared to hypothetical alternatives, are valuable for performing the cost-benefit calculations necessary to optimize infection countermeasures. SIR (susceptible-infected-removed) models are useful in this regard but are limited by the challenge of deciding how and when to update the numerous parameters as the epidemic changes in response to population behaviors. Behaviors of particular interest include facemasks adoption (at various levels) and social distancing. We present a method that uses a “dynamic spread function” to systematically capture the continuous variation in the population behavior, and the gradual change in infection evolution, resulting from interventions. No parameter updates are made by the user. We use the tool to quantify the reduction in infection rate realizable from the population of New York City adopting different facemask strategies during COVID-19. Assuming a baseline facemask of 67% filtration efficiency, calculations show that increasing the efficiency to 80% could have reduced the roughly 5000 new infections per day occurring at the peak of the epidemic to around 4000. Population behavior that may not be varied as part of the retrospective analysis, such as social distancing in a facemask analysis, are automatically captured as part of the calibration of the dynamic spread function.
Can we predict the severe course of COVID-19 – a systematic review and meta-analysis of indicators of clinical outcome?
Authors: Katzenschlager Stephan , Zimmer Alexandra J. , Gottschalk Claudius , Grafeneder Juergen , Seitel Alexander , Maier-Hein Lena , Benedetti Andrea , Larmann Jan , Weigand Markus A. , McGrath Sean , Denkinger Claudia M. 
Published: November 2020

AbstractBackgroundCOVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19.MethodsWe systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies.ResultsOf 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73).DiscussionThis comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.SummaryIn this systematic review we meta-analyzed 88 articles for risk factors of ICU admission and mortality in COVID-19. We found age, cerebrovascular disease, CRP, LDH and cTnI are the most important risk-factors for ICU admission or mortality.