bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in the care of lipodystrophies
Authors: Shamsudeen Isabel , Hegele Robert A. 
Published: November 2021

Purpose of review
Lipodystrophies are a group of rare, heterogeneous disorders characterized by a lack or maldistribution of adipose tissue. Treatment focusses on the management of complications, including hypertriglyceridemia, which can be severe. Patients are predisposed to early atherosclerotic cardiovascular disease and acute pancreatitis. This review summarizes the recent advances in the treatment of lipodystrophies, with a particular focus on the treatment of hypertriglyceridemia in familial partial lipodystrophy (FPLD).

Recent findings
Treatment of dyslipidemia in FPLD requires management of secondary exacerbating factors, particularly insulin resistance and diabetes, together with modification of atherosclerotic cardiovascular disease risk factors. In addition, specific lipid-lowering therapies are usually needed, starting with statins and fibrates. Leptin therapy improves triglycerides. Several emerging treatments for hypertriglyceridemia include apo C-III antagonists (volanesorsen, AKCEA-APOCIII-LRx and ARO-APOC3) and angiopoietin-like 3 antagonists (evinacumab, vupanorsen and ARO-ANG3); efficacy observed in clinical trials of these agents in nonlipodystrophic patients with severe hypertriglyceridemia suggests that they may also be helpful in lipodystrophy.

Summary
Emerging therapies for dyslipidemia show promise in advancing the care of patients with lipodystrophy. However, these treatments are not yet approved for use in lipodystrophy. Further study of their efficacy and safety in this patient population is needed.
Deep Learning-Based Image Conversion Improves the Reproducibility of Computed Tomography Radiomics Features
Authors: Lee Seul Bi , Cho Yeon Jin , Hong Youngtaek , Jeong Dawun , Lee Jina , Kim Soo-Hyun , Lee Seunghyun , Choi Young Hun 
Published: November 2021

Objectives
This study aimed to evaluate the usefulness of deep learning–based image conversion to improve the reproducibility of computed tomography (CT) radiomics features.

Materials and Methods
This study was conducted using an abdominal phantom with liver nodules. We developed an image conversion algorithm using a residual feature aggregation network to reproduce radiomics features with CT images under various CT protocols and reconstruction kernels. External validation was performed using images from different scanners, consisting of 8 different protocols. To evaluate the variability of radiomics features, regions of interest (ROIs) were drawn by targeting the liver parenchyma, vessels, paraspinal area, and liver nodules. We extracted 18 first-order, 68 second-order, and 688 wavelet radiomics features. Measurement variability was assessed using the concordance correlation coefficient (CCC), compared with the ground-truth image.

Results
In the ROI-based analysis, there was an 83.3% improvement of CCC (80/96; 4 ROIs with 3 categories of radiomics features and 8 protocols) in synthetic images compared with the original images. Among them, the 56 CCC pairs showed a significant increase after image synthesis. In the radiomics feature–based analysis, 62.0% (3838 of 6192; 774 radiomics features with 8 protocols) features showed increased CCC after image synthesis, and a significant increase was noted in 26.9% (1663 of 6192) features. In particular, the first-order feature (79.9%, 115/144) showed better improvement in terms of the reproducibility of radiomics feature than the second-order (59.9%, 326/544) or wavelet feature (61.7%, 3397/5504).

Conclusions
Our study demonstrated that a deep learning model for image conversion can improve the reproducibility of radiomics features across various CT protocols, reconstruction kernels, and CT scanners.
White Matter Hyperintensity Distribution Differences in Aging and Neurodegenerative Disease Cohorts
Authors: Dadar Mahsa , Mahmoud Sawsan , Zhernovaia Maryna , Camicioli Richard , Maranzano Josefina , Duchesne Simon ,   For the CCNA Group
Published: November 2021

AbstractIntroductionWhite matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders.MethodsData included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimer’s dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinson’s disease (PD-CIE), cognitively impaired Parkinson’s disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women.ResultsAll cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH loads than the left.ConclusionsThere were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.
Emergence and Spread of the SARS-CoV-2 Variant of Concern Delta Across Different Brazilian Regions
Authors: Arantes Ighor , Naveca Felipe Gomes , Gräf Tiago ,   COVID-19 Fiocruz Genomic Surveillance Network, Miyajima Fábio , Faoro Helisson , Wallau Gabriel Luz , Delatorre Edson , Appolinario Luciana Reis , Pereira Elisa Cavalcante , Martins Venas Taina Moreira , Rocha Alice Sampaio , Lopes Renata Serrano , Siqueira Marilda Mendonça , Bello Gonzalo , Resende Paola Cristina 
Published: November 2021

ABSTRACTThe SARS-CoV-2 Variant of Concern (VOC) Delta was first detected in India in October 2020. The first imported cases of the Delta variant in Brazil were identified in April 2021 in the Southern region, followed by more cases in different country regions during the following months. By early September 2021, Delta was already the dominant variant in the Southeastern (87%), Southern (73%), and Northeastern (52%) Brazilian regions. This work aimed to understand the spatiotemporal dissemination dynamics of Delta in Brazil. To this end, we employed a combination of Maximum Likelihood (ML) and Bayesian methods to reconstruct the evolutionary relationship of 2,264 of VOC Delta complete genomes (482 from this study) recovered across 21 out of 27 Brazilian federal units. Our phylogeographic analyses identified three major transmission clusters of Delta in Brazil. The clade BR-I (n= 1,560) arose in Rio de Janeiro in late April 2021 and was the major cluster behind the dissemination of the VOC Delta in the Southeastern, Northeastern, Northern, and Central-Western regions. The clade BR-II (n= 207) arose in the Paraná state in late April 2021 and aggregated the largest fraction of sampled genomes from the Southern region. Lastly, the clade BR-III emerged in the São Paulo state in early June 2021 and remained mostly restricted to this state. In the rapid turnover of viral variants characteristic of the SARS-CoV-2 pandemic, Brazilian regions seem to occupy different stages of an increasing prevalence of the VOC Delta in their epidemic profiles. This process demands continuous genomic and epidemiological surveillance toward identifying and mitigating new introductions, limiting their dissemination, and preventing the establishment of more significant outbreaks in a population already heavily affected by the COVID-19 pandemic.
Development and Implementation of Dried Blood Spot-based COVID-19 Serological Assays for Epidemiologic Studies
Authors: Wong Marcus P , Meas Michelle A , Adams Cameron , Hernandez Samantha , Green Valerie , Montoya Magelda , Hirsch Brett M , Horton Mary , Quach Hong L , Quach Diana L , Shao Xiaorong , Fedrigo Indro , Zermeno Alexandria , Huffaker Julia , Montes Raymond , Madden Alicia , Cyrus Sherri , McDowell David , Williamson Phillip , Contestable Paul , Stone Mars , Coloma Josefina , Busch Michael P , Barcellos Lisa F , Harris Eva 
Published: November 2021

AbstractSerological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at- home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months post-infection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an eight-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible.
A cross-sectional survey of burnout in a sample of resident physicians in Sudan
Authors: Mohamed Elhadi Yasir Ahmed , Ahmed Abdelmuniem , Salih Elhadi B. , Abdelhamid Osman S. , Hamid Ahmed Mohamed Hayder , El Dabbah Noha Ahmed 
Published: November 2021

AbstractBackgroundResident physicians in Sudan suffer multiple physical and psychological stressors. Nevertheless, the prevalence of burnout among this critical population remains unknown. The purpose of this study was to estimate the prevalence of burnout and its related factors in a sample of Sudanese resident physicians.MethodsA cross-sectional design was used to assess burnout among resident physicians at the teaching hospitals of Wad-Medani, Gezira state in Sudan. All resident physicians across nine hospitals were asked to join the study. The Arabic version of Maslach Burnout Inventory was distributed to respondents from July to October 2021.ResultsOut of 300 resident physicians 69.3% responded. The study population had a mean age of 29.99 ± 3.01 years, more than half were females (56.7%) and single (59.6%). In total, 86.1% met the criteria for burnout in at least one dimension, and 13.9 % in all three dimensions.70.7% suffer from a high level of burnout on the dimension of emotional exhaustion (EE), while 44.2% reported a high level on depersonalization (DP) and 73.1% experienced a sense of decreased professional accomplishment (PA). There were significant differences in the levels of burnout, EE and DP among different specialties. Burnout syndrome was associated with working hours per single duty; with participants working for more than 24 hours had experienced higher levels of burnout, EE and DP.ConclusionsHigh prevalence of burnout syndrome was found in this sample of resident physicians in Sudan. Stakeholders should urgently implement effective remedies to protect the mental health of resident physicians.
Relationships among High School Student-Athletes’ Mental Health, Stressors, and Social Support during the COVID-19 Pandemic in Japan
Authors: Yamaguchi Kaori , Katagami Eriko , Shinohara Ryoji , Tsuji Taishi , Yamagata Zentaro , Tsuchiya Hironobu 
Published: November 2021

AbstractObjectivesThe impact of the spread of COVID-19 on the mental health and its mitigating factors of high school athletes is not fully understood. The aims of this study were 1) to describe the psychological distress and stressors experienced by high school athletes during the COVID-19 pandemic and to elucidate the relationships between them and 2) to determine the relationship between psychological distress and social support.MethodsParticipants of this cross-sectional study were recruited from public high schools in East Japan. We conducted either an online or paper-based questionnaire survey from July 12 to 31, 2020, and used data collected from 3017 high school student athletes (valid response rate: 88.7%) for the analyses. We evaluated psychological distress (K6 ≥10), stressors to athletes during the COVID-19 pandemic (SAC-19), and perceived social support from others. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for developing psychological distress.ResultsAmong the participants, 764 (25.3%) experienced psychological distress. Among the five factors extracted from the SAC-19, self-restraint requests (OR = 1.03, 95% CI: 1.01– 1.04), pressure from the surrounding environment (OR = 1.15, 95% CI: 1.12–1.18), and difficulties in maintaining athletic activities (OR = 1.16, 95% CI: 1.12–1.21) increased the risk of psychological distress. On the other hand, participants who were satisfied with the support from family members (OR = 0.77, 95% CI: 0.67–0.90), teammates (the same grade) (OR = 0.81, 95% CI: 0.67–0.98), and coaches and instructors (OR = 0.77, 95% CI: 0.65–0.91) showed lower psychological distress.ConclusionsDuring the COVID-19 pandemic, high school athletes experienced more psychological distress than usual. Stressors such as self-restraint requests, pressure from the surrounding environment, and difficulties in maintaining athletic activities increased the risk. On the other hand, social support from family members, teammates (the same grade), and coaches and instructors can help alleviate these stressors.
Single-cell generalized trend model (scGTM): a flexible and interpretable model of gene expression trend along cell pseudotime
Authors: Cui Elvis Han , Song Dongyuan , Wong Weng Kee , Li Jingyi Jessica 
Published: November 2021

AbstractMotivationModeling single-cell gene expression trends along cell pseudotime is a crucial analysis for exploring biological processes. Most existing methods rely on nonparametric regression models for their flexibility; however, nonparametric models often provide trends too complex to interpret. Other existing methods use interpretable but restrictive models. Since model interpretability and flexibility are both indispensable for understanding biological processes, the single-cell field needs a model that improves the interpretability and largely maintains the flexibility of nonparametric regression models.ResultsHere we propose the single-cell generalized trend model (scGTM) for capturing a gene’s expression trend, which may be monotone, hill-shaped, or valley-shaped, along cell pseudotime. The scGTM has three advantages: (1) it can capture non-monotonic trends that are still easy to interpret, (2) its parameters are biologically interpretable and trend informative, and (3) it can flexibly accommodate common distributions for modeling gene expression counts. To tackle the complex optimization problems, we use the particle swarm optimization algorithm to find the constrained maximum likelihood estimates for the scGTM parameters. As an application, we analyze several single-cell gene expression data sets using the scGTM and show that it can capture interpretable gene expression trends along cell pseudotime and reveal molecular insights underlying the biological processes.Availability and implementationThe Python package scGTM is open-access and available athttps://github.com/ElvisCuiHan/scGTM.Contactjli@stat.ucla.edu
Analytical sensitivity and effectiveness of different SARS-CoV-2 testing options
Authors: Lelie Nico , Koppelman Marco , van Drimmelen Harry , Bruisten Sylvia 
Published: November 2021

AbstractWe prepared severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) working standards and reference panels from a pool of swab fluid samples before and after inactivation by beta-propiolactone and quantified viral load in nucleic acid amplification technology (NAT) detectable RNA copies/mL using limiting dilution analysis. The following 50% lower limits of detection (LOD) were estimated by probit analysis as compared to detection limits of rapid antigen tests on 1.5 fold dilutions of the native material: Roche cobas PCR 1.8 (1.0-3.3), Hologic Aptima TMA 6.6 (4.4-9.9), DRW SAMBA 15 (7-30), Molgen LAMP 23 (13-42), Fluorecare antigen 50,000, Abbott Panbio antigen 75,000 and Roche antigen 100,000 copies/mL. One 50% Tissue Culture Infectious Dose (TCID50)/mL of culture fluid was estimated to be equivalent to approximately 1000 RNA copies/mL (2700-4300 International Units) in our working standard. When assuming this level as start of contagiousness in a log-linear ramp up viremia model with 10-fold rise of viral load per day for the B.1 (Wuhan) type we estimated relative time points of first detectability of early infection by the different SARS-CoV-2 assays from the LODs mentioned above. The four NAT assays would be able to detect early viremia 40-66 hours earlier than the 1000 copies/mL infectivity threshold, whereas the three antigen tests would become positive 41-48 hours later. Our modeling of analytical sensitivity data was found to be compatible with clinical sensitivity data of rapid antigen tests and confirms that NAT assays are more reliable than antigen assays for identifying early infected asymptomatic individuals who are potentially infectious.
Mendelian randomization analysis identifies blood tyrosine levels as a biomarker of non-alcoholic fatty liver disease
Authors: Gobeil Émilie , Maltais-Payette Ina , Taba Nele , Brière Francis , Ghodsian Nooshin , Abner Erik , Bourgault Jérôme , Gagnon Éloi , Manikpurage Hasanga D. , Couture Christian , Mitchell Patricia L. , Mathieu Patrick , Julien François , Corbeil Jacques , Vohl Marie-Claude , Thériault Sébastien , Esko Tõnu , Tchernof André , Arsenault Benoit J. 
Published: November 2021

AbstractNon-alcoholic fatty liver disease (NAFLD) is a complex cardiometabolic disease associated with premature mortality. The diagnosis of NAFLD is challenging and the identification of biomarkers causally influenced by NAFLD may be clinically useful. We aimed at identifying blood metabolites causally impacted by NAFLD using two-sample Mendelian randomization (MR) with validation in a population-based biobank and a cohort of patients undergoing bariatric surgery. Our instrument for genetically-predicted NAFLD (the study exposure) included all independent genetic variants (n=7 SNPs) from a recent genome-wide association study on NAFLD. The study outcomes included 123 blood lipids, lipoproteins and metabolites measured in 24,925 individuals from 10 European cohorts. After correction for multiple testing, we identified a positive effect of NAFLD on plasma tyrosine levels but not on other metabolites. The association between NAFLD and tyrosine levels was consistent across MR methods and robust to outliers and pleiotropy. In observational analyses performed in the Estonian Biobank (10,809 individuals including 359 patients with NAFLD), after multivariable adjustment, tyrosine levels were positively associated with the presence of NAFLD (odds ratio per 1-SD increment = 1.23 (95% confidence interval = 1.12-1.36, p = 2.19e-05). In a sample of 138 patients undergoing bariatric surgery, compared to patients without NAFLD, blood tyrosine levels were higher in those with NAFLD, but were comparable among patients with or without non-alcoholic steatohepatitis. This analysis revealed a potentially causal effect of NAFLD on blood tyrosine levels, suggesting that blood tyrosine levels may represent a new biomarker of NAFLD.Graphical abstract
The relationship of COVID-19 related stress and media consumption with schizotypy, depression and anxiety
Authors: Daimer Sarah , Mihatsch Lorenz , Neufeld Sharon A.S. , Murray Graham K. , Knolle Franziska 
Published: November 2021

AbstractStudies report a strong impact of the COVID-19 pandemic and related stressors on the mental wellbeing of general population. In this paper, we investigated whether COVID-19 related concerns and social adversity affected schizotypal traits, anxiety and depression using structural equational modelling. In mediation analyses, we furthermore explored whether these associations were mediated by healthy (sleep and physical exercise) or unhealthy behaviours (drug and alcohol consumption, excessive media use).We assessed schizotypy, depression and anxiety as well as, healthy and unhealthy behaviours and a wide range of sociodemographic scores using online surveys from residents of Germany and the United Kingdom over one year during the COVID-19 pandemic. Four independent samples were collected (April/ May 2020: N=781, September/ October 2020: N=498, January/ February 2021: N=544, May 2021: N= 486). The results revealed that COVID-19 related life concerns were significantly associated with schizotypy in the autumn 2020 and spring 2021 surveys, and with anxiety and depressive symptoms in all surveys; and social adversity significantly affected the expression of schizotypal traits in all but the spring 2020 survey, and depressive and anxiety symptoms in all samples. Importantly, we found that excessive media consumption (>4h per day) fully mediated the relationship of COVID-19 related life concerns and schizotypal traits in the winter 2021 survey. Furthermore, several of the surveys showed that excessive media consumption was associated with increased depressive and anxiety- related symptoms in people burdened by COVID-19 related life.The ongoing uncertainties of the pandemic and the restrictions on social life have a strong impact on mental well-being and especially the expression of schizotypal traits. The negative impact is further boosted by excessive media consumption, which is especially critical for people with high schizotypal traits.