bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Post-GWAS Analysis Identifies Potential Risk Genes and Causal Variants for Alzheimer’s Disease, Providing New Insights Into Its Disease Mechanisms
Authors: WANG ZHEN , Zhang Quanwei , Lin Jhih-Rong , Jabalamel M.Reza , Mitra Joydeep , Nguyen Nha , Zhang Zhengdong 
Published: October 2020

Abstract
Background: Alzheimer’s disease (AD) is a genetically complex, multifactorial neurodegenerative disease. It affects more than 45 million people worldwide and currently remains untreatable. Although genome-wide association studies (GWAS) have identified many AD-associated common variants, only about 25 genes are currently known to affect the risk of developing AD, despite its highly polygenic nature. Moreover, the causal variants underlying GWAS AD-association signals remain unknown.Methods: We developed a computational pipeline that integrates 936 AD-associated SNPs, linkage disequilibrium and genomic data from multiple sources – e.g., disease genes databases, functional annotation of genetic variants, GTEx, and the 1000 Genomes Project – to predict both AD risk genes and their causal variants.Results: We identified 342 putative AD risk genes in 203 risk regions spanning 502 AD-associated common variants. 246 AD risk genes have not been identified as AD risk genes by previous GWAS, and 115 of them are outside the risk regions, likely under the regulation of transcriptional regulatory elements contained therein. Even more significantly, for 109 AD risk genes, we predicted 150 causal variants, of both coding and regulatory (in promoters or enhancers) types, and 85 (57%) of them are supported by functional annotation. In-depth functional analyses showed that AD risk genes were overrepresented in AD-related pathways or GO terms – e.g., the complement and coagulation cascade and phosphorylation and activation of immune response – and their expression was relatively enriched in microglia, endothelia, and pericytes of the human brain. We found nine AD risk genes – e.g., IL1RAP, PMAIP1, LAMTOR4 – as predictors for the prognosis of AD survival and genes such as ARL6IP5 with altered network connectivity between AD patients and normal individuals involved in AD progression.Conclusions: Our findings provide novel biological insights into the genetic architecture, expression profiles, functional pathways involved in the AD etiology, and open new strategies for developing therapeutics targeting AD risk genes or causal variants to influence AD pathogenesis.
Unusual Urticaria Pigmentosa in an Asian Man With Indolent Systemic Mastocytosis: A Case Report
Authors: Wongsa Chamard , Sompornrattanaphan Mongkhon , Thongngarm Torpong , Owattanapanich Weerapat , Sitthinamsuwan Panitta , Sukpanichnant Sanya , Sukakul Thanisorn 
Published: October 2020

Abstract
Background: The diagnosis of mastocytosis remains challenging. Given that the disease has a low prevalence and its clinical presentations range from asymptomatic to severe life-threatening conditions, physicians’ lack of awareness of mastocytosis is the main barrier to its diagnosis. Skin involvement is common. In adults, skin lesions are highly suggestive of systemic mastocytosis; however, clinical demonstration of lesions is difficult if they are minimal in number. In Asian, who had dark brown skin color, urticaria pigmentosa was not easy to identify. Here we present the case of indolent systemic mastocytosis with an unusual urticaria pigmentosa. Case presentation: A 48-year-old man had had recurrent severe honeybee anaphylaxis since he was 23. He had small, subtle, brownish skin lesions on his chest and abdomen, which he and previous physicians had not recognized. The skin lesions were compatible with urticaria pigmentosa, also known as maculopapular cutaneous mastocytosis. His clinical findings and an elevated baseline tryptase level triggered a thorough systemic mastocytosis investigation. The skin and bone marrow were infiltrated by abnormal, spindle-shaped mast cells, and KIT and TET2 mutations were in the patient’s serum. The honeybee anaphylaxis mechanism in this patient was IgE mediated, supported by a positive result of specific IgE to honeybee. The final diagnosis was indolent systemic mastocytosis with IgE-mediated honeybee anaphylaxis. As venom immunotherapy is unavailable in Thailand, we prescribed treatment with a regular, oral, nonsedating H1-antihistamine and an epinephrine self-injector. At the 2-year follow-up, the patient had not progressed to advanced systemic mastocytosis nor experienced any anaphylactic episodes.Conclusion: Urticaria pigmentosa is a small, round, brown, or red maculopapular lesion. In the Asian population with dark brown skin color, physician should be exclusively careful examination, particularly in a hidden area and in anaphylaxis cases. Early recognition of urticaria pigmentosa in the adult patient might reduce the delay in diagnosis of indolent systemic mastocytosis.
Predictive Model of Multiple Emergency Department Visits Among Adults: Analysis of the Data from the National Survey of Drug Use and Health (NSDUH)
Authors: Bobashev Georgiy , Warren Lauren , Wu Li-Tzy 
Published: October 2020

Abstract
Objective. In this methodological paper, we use a novel, predictive approach to examine how demographics, substance use, mental and other health indicators predict multiple visits (≥3) to emergency departments (ED) within a year. Methods. State-of-the-art predictive methods were used to evaluate predictive ability and factors predicting multiple visits to ED within a year and to identify factors that influenced the strength of the prediction. The analysis used public-use datasets from the 2015-2018 National Surveys on Drug Use and Health (NSDUH), which used the same questionnaire on the variables of interest. Analysis focused on adults aged ≥18 years. Several predictive models (regressions, trees, and random forests) were validated and compared on independent datasets. Results. Predictive ability on a test set for multiple ED visits (≥3 times within a year) measured as the area under the receiver operating characteristic (ROC) was 0.79, which is good for a national survey. Models revealed consistency in predictive factors across the 4 survey years. The most influential variables for predicting ≥3 ED visits per year were fair/poor self-rated health, having a lower income, asthma, heart condition/disease, having chronic obstructive pulmonary disease (COPD), African-American race, female sex, having diabetes, being restless/fidgety, and being of younger age (18-25). Conclusions. The findings reveal the need to address behavioral and mental health contributors to ED visits and reinforce the importance of developing integrated care models in primary care settings to improve mental health for medically vulnerable patients. Presented modeling approach can be broadly applied to national and other large surveys.
Mesenchymal Stem Cell-conditioned Medium Alleviates High Fat-induced Hyperglucagonemia&nbsp;via miR-181a-5p and its Target PTEN/AKT Signaling
Authors: Song Jia , He Qin , Guo Xinghong , Wang Lingshu , Wang Jinbang , Cui Chen , Hu Huiqing , Yang Mengmeng , Cui Yixin , Yan Fei , Qin Jun , Sun Zheng , Hou Xinguo , Li Wenjuan , Chen Li 
Published: October 2020

Abstract
Background: Pancreatic α-cells are critical to glucose homeostasis because they release glucagon and stimulate the liver to produce glucose. Dysregulation of α-cells gives rise to fasting and postprandial hyperglycemia in type 2 diabetes mellitus(T2DM). Mesenchymal stem cells (MSCs) or their conditioned medium can improve islet function and enhance insulin sensitivity in target tissues. However, studies showing the direct effect of MSCs on islet α-cell dysfunction are limited. Methods: In this study, we used high-fat diet (HFD)-induced mice and α-cell line exposure to palmitate (PA) to determine the effects of bone marrow-derived MSC-conditioned medium (bmMSC-CM) involved in glucagon secretion. To investigate the potential signaling pathways, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) , AKT and phosphorylated AKT(p-AKT) were assessed by Western blotting.Results: In vivo, bmMSC-CM infusion protected against HFD-induced hyperglycemia and hyperglucagonemia. Consistently, bmMSC-CM decreased PA-induced glucagon secretion in α-cells and isolated islets. Additionally, bmMSC-CM reduced intracellular PTEN expression and rescued AKT signaling. Previous studies and the TargetScan database indicate that miR-181a and its target PTEN play vital roles in ameliorating α-cell dysfunction. We observed that miR-181a-5p is highly expressed in BM-MSCs but prominently lower in αTC1-6 cells. Overexpression or downregulation of miR-181a-5p respectively alleviates or aggravates glucagon secretion in αTC1-6 cells via the PTEN/AKT signaling pathway. Conclusions: Our observations suggest that MSC-secreted miR-181a-5p mitigates glucagon secretion of α-cells by regulating PTEN/AKT signaling. These findings might provide a novel understanding of MSC-based treatment.
A Machine Learning Model to Predict Death Outcome in Severe COVID-19 Patients
Authors: Yang Qiao , Li Jixi , Zhang Zhijia , Wu Xiaocheng , Liao Tongquan , Yu Shiyong , You Zaichun , Hou Xianhua , Ye Jun , Liu Gang , Ma Siyuan , Xie Ganfeng , Zhou Yi , Li Mengxia , Wu Meihui , Feng Yimei , Wang Weili , Li Lufeng , Xie Dongjing , Hu Yunhui , Liu Xi , Wang Bin , Zhao Songtao , Li Li , Luo Chunmei , Tang Tang , Wu Hongmei , Hu Tianyu , Yang Guangrong , Luo Bangyu , Li Lingchen , Yang Xiu , Li Qi , Xu Zhi , Wu Hao , Sun Jianguo 
Published: October 2020

Abstract
BackgroundThe novel coronavirus disease 2019 (COVID-19) spreads rapidly among people and causes a global pandemic. It is of great clinical significance to identify COVID-19 patients with high risk of death.MethodsA total of 2,169 adult COVID-19 patients were enrolled from Wuhan, China between February 10th and April 15th, 2020. Difference analyses of medical records were performed between severe and non-severe groups as well as between survivors and non-survivors. In addition, we developed a decision tree classifier to identify risk factors for death outcome.ResultsOf the 2,169 COVID-19 patients, the median age was 61 years and male patients accounted for 48%. A total of 646 patients were diagnosed with severe illness, and 75 patients died. The most common system symptoms were respiratory, systemic and digestive symptoms. Obvious differences in demographics, clinical characteristics and laboratory examinations were found between severe and non-severe groups, as well as between survivors and non-survivors. A machine learning model was developed to predict death outcome in severe patients. The decision tree classifier included three biomarkers, neutrophil-to-lymphocyte ratio, C-reactive protein and lactic dehydrogenase. The area under the curve of the receiver operating characteristic of this model was 0.96. This model performed well both in train dataset and test dataset. The accuracy of this model was 0.98 and 0.98, respectively.ConclusionThe machine learning model was robust and effective in predicting the death outcome in severe COVID-19 patients.
WITHDRAWN: Prevalence and Correlates of Secondhand Smoking Exposure Among Pregnant and Postnatal Chinese Women
Authors: YANG YUAN , Zhang Meng , Bo Haixin , Zhang Dongying , Ma Liangkun , Wang PeiHong , Liu XiaoHua , Ge LiNa , Lin WenJuan , Xu Yang , Zhang YaLan , Li FengJuan , Xu XuJuan , Wu HongHe , Jackson Todd , Ungvari Gabor , Chueng Teris , Meng LiRong , Xiang YuTao 
Published: October 2020

Abstract
BackgroundInhalation of secondhand smoke during pregnancy and postnatal period is detrimental to developing infants and increases risk for health problems throughout the lifespan. This study examined the prevalence of exposure to secondhand smoke, its correlates, and its association with QOL among pregnant and postnatal Chinese women.MethodsThis multicenter, cross-sectional study was conducted between February and October 2019 in China. Participants were pregnant and postnatal women. We assessed associations of frequency and location of secondhand smoking with sample characteristics as well as depression and quality of life based on EPDS and WHOQOL-BREF, respectively.ResultsA total of 992 women participated in the study, of whom, 211 (21.3%, 95%CI=18.7-23.8%) had been exposed to secondhand smoking. Secondhand smoking was most common in public areas (56.4%), and residential homes (20.5%), while workplaces had the lowest rate of secondhand smoking (13.7%). Women with physical comorbidities were more likely to report secondhand smoking exposure, while younger women, women living in urban areas, and those with college or higher education level were less likely to report exposure to secondhand smoking.ConclusionThe prevalence of exposure to secondhand smoking is becoming lower among pregnant and postnatal women in China compared to findings reported in previous studies. Due to the detrimental impact of secondhand smoking on physical health, legal legislation should be promptly enforced to establish smoke-free environments in both public and private urban/rural areas for protection of pregnant and postnatal women, especially those who are physically vulnerable and less educated.
Chromosome Y as A Marker for Sex Discrepancies in Patients With Organ Transplants: A Case Report
Authors: Balaguer Nuria , Mateu-Brull Emilia , Naja Roy Pascal , Nagi Jara Ben , Milán Miguel 
Published: October 2020

Abstract
Background: Organ transplantations cause discrepancy in results from cell-free DNA (cfDNA) testing, but scientific literature is scarce.Case: A 33-year old gravida underwent cfDNA testing, which showed high levels of Y chromosome (ChrY) in the maternal bloodstream. The ChrY pattern was comparable to an adult male reference. As a result, cfDNA testing was only informative for autosomes. Routine 20-week ultrasound scan showed no structural alterations and the presence of female external genitalia. Post-clinical research revealed that the patient received a bone marrow transplant from a male donor several years before. Fluorescence in situ hybridization showed that 100% of nuclei analysed from the patient’s lymphocytes presented a ChrY.Conclusion: This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.
Emergency Medicine Matters: Epidemiology of Medical Pathology and Changes in Patient Outcomes after Implementation of a Post-graduate Training Program at a Tertiary Teaching Hospital in Kigali, Rwanda
Authors: Moretti Katelyn , Uwamahoro Doris Lorette , Naganathan Sonya , Uwamahoro Chantal , Karim Naz , Nkeshimana Menelas , Aluisio Adam R. 
Published: October 2020

Abstract
Background: Emergency care is a new but growing specialty across Africa where medical conditions have been estimated to account for 92% of all disability-adjusted life years. This study describes the epidemiology of medical emergencies and the impact of formalized emergency care training on patient outcomes for medical conditions in Rwanda.Methods: A retrospective cohort study was performed using a database of randomly sampled patients presenting to the emergency center (EC) at the University Teaching Hospital of Kigali. All patients, > 15 years of age treated for medical emergencies pre- and post-implementation of an Emergency Medicine (EM) residency training program were eligible for inclusion. Patient characteristics and final diagnosis were described by time period (January 2013 - September 2013 versus September 2015 - June 2016). Univariate chi-squared analysis was performed for diagnoses, EC interventions, and all cause EC and inpatient mortality stratified by time period. Results: A random sample of 1,704 met inclusion with 929 patients in the pre-residency time period and 775 patients in the post-implementation period. Demographics, triage vital signs, and shock index were not different between time periods. Most frequent diagnoses included: gastrointestinal, infectious disease and neurologic pathology. Differences by time period in EC management included: antibiotic use (37.2% vs. 42.2%, p=0.04), vasopressor use (1.9% vs. 0.5%, p=0.01), IV crystalloid fluid (IVF) use (55.5% vs. 47.6%, p=0.001) and mean IVF administration (2,057 ml vs. 2,526 ml, p<0.001). EC specific mortality fell from 10.0% to 1.4% (p<0.0001) across time periods.Conclusions: Mortality rates fell across top medical diagnoses after implementation of an EM residency program. Changes in resuscitation care may explain, in part, this mortality decrease. This study demonstrates that committing to emergency care can potentially have large effects on reducing mortality.
Clinical Features and Disease Severity in Patients With Mosaic Neurofibromatosis Type 1: A Single-Center Study and Literature Review
Authors: Raundahl Maj , Gregersen Pernille Axel , Handrup Mette Møller , Ejerskov Cecilie 
Published: October 2020

Abstract
Background The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications.Method A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed.Results We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. Conclusion Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.
Procalcitonin Expression in Patients with Large Cell Neuroendocrine Carcinoma of the Lung
Authors: Itoga Masamichi , Tanaka Hisashi , Taima Kageaki , Ishioka Yoshiko , Sakamoto Hiroaki , Takanashi Shingo , Kurose Akira , Tasaka Sadatomo 
Published: October 2020

Abstract
ObjectiveProcalcitonin (PCT) has received much attention as a serum marker for bacterial infection. Elevated serum PCT is occasionally seen in severe trauma, heatstroke, and neoplastic diseases, including lung cancer with neuroendocrine component. ResultsIn the present study, we evaluated PCT expression in the specimen of pulmonary neuroendocrine tumors, comparing large cell neuroendocrine carcinoma (LCNEC), carcinoid, and small cell lung carcinoma (SCLC). Pathological specimens of 10 LCNEC, 4 carcinoid, and 7 SCLC cases were evaluated with immunochemical staining of PCT. Clinical characteristics and serum levels of PCT and C-reactive protein were also evaluated. We observed positive PCT expression in 5 (50%) LCNEC and 2 (50%) carcinoid specimens that were surgically resected. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease progression. In patients with SCLC, PCT was not detected in the tumor or serum. This is the first immunohistochemical study of the PCT expression in the lung tumor specimens. We concluded that, in patients with LCNEC, high serum PCT levels may be indicative of disease activity and serve as a biomarker.
Distribution of β-lactamase Gene and Genetic Context of blaKPC-2 in Clinical Carbapenemase-producing Klebsiella Pneumoniae Isolates
Authors: Liu Hongmao , Lin Hailong , Sun Zhewei , Zhu Xinyi , Zhang Xueya , Li Qiaoling , Lu Junwan , Lin Xi , Lin Li , Li Kewei , Zhu Mei , Bao Qiyu , Xu Teng , Hu Yunliang , Zhang Hailin 
Published: October 2020

Abstract
Background: This study is designed to characterize the dissemination mechanism and genetic context of Klebsiella pneumoniae carbapenemase (KPC) genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates.Methods: A retrospective analysis was performed on CRKP isolates from a teaching hospital of Wenzhou Medical University from 2015-2017. Polymerase chain reaction (PCR)-based amplification and whole-genome sequencing (WGS) were used to analyze the genetic context of the blaKPC-2 gene. Conjugation experiments were performed to evaluate the transferability of blaKPC-2-bearing plasmids. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to investigate the clonal relatedness of blaKPC-2-producing strains.Results: The blaKPC-2 gene was identified in 13.61% (40/294) of clinical K. pneumoniae isolates. Three different sequence types (ST11, ST15 and ST656) and 5 PFGE subtypes (A to E) were classified among them. ST11 was the dominant sequence type (92.50%, 37/40). Plasmid-oriented antibiotic resistance genes such as extended spectrum-β-lactamases (ESBLs) and other antimicrobial resistance genes were also found in KPC-positive K. pneumoniae (KPC-Kp). Mapping PCR and genomic sequencing revealed that the blaKPC-2-bearing sequence regions related to different mobile elements, including Tn1721- and IS26-based transposons, were mainly located in but not restricted to IncFII-like plasmids and were structurally divergent.Conclusions: The blaKPC-2 genes related to divergent mobile genetic elements encoded on transferable plasmids may transfer easily and widely, resulting in the spread of resistance among bacteria of different species or genera. Co-infection of KPC-Kp plasmids carrying additional non-β-lactam antibiotic resistance genes simultaneously further limits the antibiotics available to treat infections with KPC-producing pathogens.