bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China
Authors: Zhu Siyi , Gao Qiang , Yang Lin , Yang Yonghong , Xia Wenguang , Cai Xiguo , Hui Yanping , Zhu Di , Zhang Yanyan , Zhang Guiqing , Wu Shuang , Wang Yiliang , Zhou Zhiqiang , Liu Hongfei , Zhang Changjie , Zhang Bo , Yang Jianrong , Feng Mei , Ni Zhong , Chen Baoyu , Du Chunping , He Hongchen , Qu Yun , Wei Quan , He Chengqi , Reinhardt Jan D. 
Published: September 2020

AbstractObjectiveTo estimate the prevalence of disability and anxiety in Covid-19 survivors at discharge from hospital and analyze relative risk by exposures.DesignMulti-center retrospective cohort study.SettingTwenty-eight hospitals located in eight provinces of China.MethodsA total of 432 survivors with laboratory-confirmed SARS CoV-2 infection participated in this study. At discharge, we assessed instrumental activities of daily living (IADL) with Lawton’s IADL scale, dependence in activities of daily living (ADL) with the Barthel Index, and anxiety with Zung’s self-reported anxiety scale. Exposures included comorbidity, smoking, setting (Hubei vs. others), disease severity, symptoms, and length of hospital stay. Other risk factors considered were age, gender, and ethnicity (Han vs. Tibetan).ResultsPrevalence of at least one IADL problem was 36.81% (95% CI: 32.39-41.46). ADL dependence was present in 16.44% (95% CI: 13.23-20.23) and 28.70% (95% CI: 24.63-33.15) were screened positive for clinical anxiety. Adjusted risk ratio (RR) of IADL limitations (RR 2.48, 95% CI: 1.80-3.40), ADL dependence (RR 2.07, 95% CI 1.15-3.76), and probable clinical anxiety (RR 2.53, 95% CI 1.69-3.79) were consistently elevated in survivors with severe Covid-19. Age was an additional independent risk factor for IADL limitations and ADL dependence; and setting (Hubei) for IADL limitations and anxiety. Tibetan ethnicity was a protective factor for anxiety but a risk factor for IADL limitations.ConclusionA significant proportion of Covid-19 survivors had disability and anxiety at discharge from hospital. Health systems need to be prepared for an additional burden resulting from rehabilitation needs of Covid-19 survivors.
On Statistical Power for Case-Control Host Genomic Studies of COVID-19
Authors: Lin Yu-Chung , Brooks Jennifer D. , Bull Shelley B. , Gagnon France , Greenwood Celia M.T. , Hung Rayjean J. , Lawless Jerald , Paterson Andrew , Sun Lei , Strug Lisa 
Published: September 2020

AbstractThe identification of genetic variation that directly impacts infection susceptibility and disease severity of COVID-19 is an important step towards risk stratification, personalized treatment plans, therapeutic and vaccine development and deployment. Given the importance of study design in infectious disease genetic epidemiology, we use simulation and draw on current estimates of exposure, infectivity and test accuracy of COVID-19 to demonstrate the feasibility of detecting host genetic factors associated with susceptibility and severity with published COVID-19 study designs. We demonstrate why studying susceptibility to SARS-CoV-2 infection could be futile at the early stages of the pandemic. Our insights can aid in the interpretation of genetic findings emerging in the literature and guide the design of future host genetic studies.
Overexpression of HIF-2α in Protected Regions of Alzheimer’s disease Resilient Cases
Authors: Mitri Vivianne 
Published: September 2020

ABSTRACTAlzheimer’s disease (AD) Resilient individuals are characterized by having a degree of amyloid plaques at level with that of demented individuals, but a reduced amount of abnormal neurofibrillary protein “tangles” (NFTs). NFTs, also known to be upregulated under hypoxic conditions, become clinically relevant when involved in the stratum radiatum. In this paper, we show this region and more to have significant increases of hypoxic adaptive protein, HIF-2α, within AD resilient cases. Pericyte staining was present in the stratum lacunosum and radiatum of all cases affected by AD pathology (n = 4) but in AD resilient cases were increased by 12-fold (n=3) p<.0001. No staining was detected in normal cases (n=2). HIF-2α was also only present in hippocampal neuronal nuclei of AD resilient cases, including the dentate gyrus and CA1. Cytoplasmic staining of pyramidal neurons within the subiculum was seen in all cases affected by AD pathology. The intensity of HIF-2α appears to be specific to known regions of protection in AD resilience and to increase on a gradient that corresponds to protection against dementia. These results also highlight the stratum lacunosum and radiatum as regions critically impacted by hypoxic insult among AD cases.SignificanceHIF-2α directly regulates expression of erythropoietin (EPO), a neuroprotective glycoprotein that in brain pericytes is completely dependent upon activation of HIF-2α. To date, only indirect evidence exists that shows that brain pericyte-derived EPO can reach the bloodstream via HIF-2α expression (Urrutia et al, 2016). In this study, we provide novel preliminary findings that directly show HIF-2α expression in pericytes of human brains. Additionally, its localization is specific to the CA1 of the hippocampus, a region critical for hypoxic adaptation and the progression of Alzheimer’s disease. Finally, we present evidence of neuronal expression of HIF-2α in other critical regions of protection within AD resilient cases.
The Potential Role of Extracellular Vesicles in COVID-19 Associated Endothelial injury and Pro-inflammation
Authors: Krishnamachary Balaji , Cook Christine , Spikes Leslie , Chalise Prabhakar , Dhillon Navneet K. 
Published: September 2020

ABSTRACTCOVID-19 infection caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic with the number of deaths growing exponentially. Early evidence points to significant endothelial dysfunction, micro-thromboses, pro-inflammation as well as a dysregulated immune response in the pathogenesis of this disease. In this study, we analyzed the cargo of EVs isolated from the plasma of patients with COVID-19 for the identifiction of potential biomarkers of disease severity and to explore their role in disease pathogenesis. Plasma-derived EVs were isolated from 53 hospitalized patients with COVID infection and compared according to the severity of the disease. Analysis of inflammatory and cardiovascular protein cargo of large EVs revealed significantly differentially expressed proteins for each disease sub-group. Notably, members of the TNF superfamily and IL-6 family were up-regulated in patients on oxygen support with severe and moderate disease. EVs from the severe group were also enhanced with pro-thrombotic/endothelial injury factors (TF, t-PA, vWF) and proteins associated with cardiovascular pathology (MB, PRSS8, REN, HGF). Significantly higher levels of TF, CD163, and EN-RAGE were observed in EVs from severe patients when compared to patients with a moderate disease requiring supplemental O2. Importantly, we also observed increased caspase 3/7 activity and decreased cell survival in human pulmonary microvascular endothelial cells exposed to EVs from the plasma of patients with severe disease compared to asymptomatic group. In conclusion, our findings indicate alterations in pro-inflammatory, coagulopathy, and endothelial injury protein cargo in large EVs in response to SARS-CoV-2 infection that may be a causative agent in severe illness.
Analysis and validation of a highly sensitive one-step nested quantitative real-time polymerase chain reaction assay for specific detection of severe acute respiratory syndrome coronavirus 2
Authors: Zhang Yang , Dai Chunyang , Wang Huiyan , Gao Yong , Li Tuantuan , Fang Yan , Shen Zuojun , Chen Lichang , Chen Zhaowu , Ma Xuejun , Li Ming 
Published: September 2020

ABSTRACTCoronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is posing a serious threat to global public health. Reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. Due to technical limitations, the reported positive rates of qRT-PCR assay of throat swab samples vary from 30%–60%. Therefore, the evaluation of alternative strategies to overcome the limitations of qRT-PCR is required. A previous study reported that one-step nested (OSN)-qRT-PCR revealed better suitability for detecting SARS-CoV-2. However, information on the analytical performance of OSN-qRT-PCR is insufficient. In this study, we aimed to analyze OSN-qRT-PCR by comparing it with droplet digital PCR (ddPCR) and qRT-PCR by using a dilution series of SARS-CoV-2 pseudoviral RNA and a quality assessment panel. The clinical performance of OSN-qRT-PCR was also validated and compared with ddPCR and qRT-PCR using specimens from COVID-19 patients. The LoD (copies/ml) of qRT-PCR, ddPCR, and OSN-qRT-PCR were 520.1 (95% CI): 363.23–1145.69) for ORF1ab and 528.1 (95% CI: 347.7–1248.7) for N, 401.8 (95% CI: 284.8–938.3) for ORF1ab and 336.8 (95% CI: 244.6–792.5) for N, and 194.74 (95% CI: 139.7–430.9) for ORF1ab and 189.1 (95% CI: 130.9–433.9) for N, respectively. Of the 34 clinical samples from COVID-19 patients, the positive rates of OSN-qRT-PCR, ddPCR, and qRT-PCR were 82.35% (28/34), 67.65% (23/34), and 58.82% (20/34), respectively. In conclusion, the highly sensitive and specific OSN-qRT-PCR assay is superior to ddPCR and qRT-PCR assays, showing great potential as a technique for detection of SARS-CoV-2 in patients with low viral loads.
Aerosols created by dental procedures in a primary care setting
Authors: Hobson R S , Pabary S B , Alamani K , Badminton K 
Published: September 2020

AbstractThe study was undertaken to record the amount of dental aerosol created using 3-in-1 syringe, air rotor, and ultrasonic scaler using high volume suction (HVS) in 5 primary care dental surgeries. The time for the aerosol to dissipate following completion of the procedure was also recorded. The amount of aerosol created above the background level for the surgery corresponding to the operating positions of the nurse, dentist, and patient was recorded using particle meters measuring the number of 2.5µm (PM2.5) and 10µm (PM10) particles respectively. The procedures were recorded in triplicate for each surgery and average change calculated for each procedure, lasting 90 seconds.PM2.5 remained at or very near background readings during all procedures, whereas PM10 increased with use of the air rotor and to a much lower extent with both 3-in-1, and ultrasonic scaler. The means time to return to background reading level was 2.5 minutes.It was concluded that PM2.5 levels did not rise and although PM10 increased for all procedures the increase was low and with a return to background readings within 2m:50s (95% CI: 2:34 to 3:37) of completing the procedures that a minimum fallow period of 5minutes would allow be more than ample to be safe.
Acute kidney injury in patients with severe COVID-19
Authors: Casas-Aparicio Gustavo A. , León-Rodríguez Isabel , González-Navarro Mauricio , Alvarado-de la Barrera Claudia , Ávila-Ríos Santiago , Peralta-Prado Amy , Luna-Villalobos Yara , Velasco-Morales Alejandro , Calderón-Dávila Natalia 
Published: September 2020

ABSTRACTIntroductionSome patients with COVID-19 pneumonia present systemic disease involving multiple systems. There is limited information about the clinical characteristics and events leading to acute kidney injury (AKI). We described the factors associated with the development of AKI and explored the relation of AKI and mortality in Mexican population with severe COVID-19.MethodsWe retrospectively reviewed the medical records of individuals with severe pneumonia caused by SARS-CoV-2 hospitalized at the largest third-level reference institution for COVID-19 care in Mexico between March and April 2020. Demographic information, comorbidities, clinical and laboratory data, dates of mechanical ventilation and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded.ResultsOf 99 patients studied, 58 developed AKI (58.6%). The group with AKI had higher body mass index (p=0.0003) and frequency of obesity (p=0.001); a higher requirement of invasive mechanical ventilation (p=0.008) and vasoactive drugs (p=0.004); greater levels of serum creatinine (p<0.001) and D-dimer on admission (p<0.001); and lower lymphocyte counts (p=0.001) than the non-AKI group. The multivariate analysis indicated that risk factors for AKI were obesity (adjusted hazard ratio (HR)=2.71, 95% confidence interval (CI)=1.33-5.51, p=0.005); higher serum creatinine (HR=1.44, CI=1.02- 2.02, p=0.035) and D-dimer levels on admission (HR=1.14, CI=1.06-1.23, p<0.001). Inhospital mortality was higher in the AKI group than in the non-AKI group (65.5% vs. 14.6%; p=0.001).ConclusionsAKI was common in our cohort of patients with severe COVID-19 and it was associated with mortality. The risk factors for AKI were obesity, elevated creatinine levels and higher D-dimer levels on admission.
Inactivation of posterior but not anterior dorsomedial caudate-putamen impedes learning with self-administered nicotine stimulus
Authors: Robison Christopher L. , Kazan Theodore , Miller Rikki , Cova Nicole , Charntikov Sergios 
Published: September 2020

ABSTRACTThe rodent caudate-putamen is a large heterogeneous neural structure with distinct anatomical connections that differ in their control of learning processes. Previous research suggests that the anterior and posterior dorsomedial caudate-putamen (a- and p-dmCPu) differentially regulate associative learning with a non-contingent nicotine stimulus. The current study used bilateral NMDA-induced excitotoxic lesions to the a-dmCPu and p-dmCPu to determine the functional involvement of a-dmCPu and p-dmCPu in appetitive learning with contingent nicotine stimulus. Rats with a-dmCPu, p-dmCPu, or sham lesions were trained to lever-press for intravenous nicotine (0.03 mg/kg/inf) followed by access to sucrose 30 s later. After 1, 3, 9, and 20 nicotine-sucrose training sessions, appetitive learning in the form of a goal-tracking response was assessed using a non-contingent nicotine-alone test. All rats acquired nicotine self-administration and learned to retrieve sucrose from a receptacle at equal rates. However, rats with lesions to p-dmCPu demonstrated blunted learning of the nicotine-sucrose association. Our primary findings show that rats with lesions to p-dmCPu had a blunted goal-tracking response to a non-contingent nicotine administration after 20 consecutive days of nicotine-sucrose pairing. Our findings extend previous reports to a contingent model of nicotine self-administration and show that p-dmCPu is involved in associative learning with nicotine stimulus using a paradigm where rats voluntarily self-administer nicotine infusions that are paired with access to sucrose—a paradigm that closely resembles learning processes observed in humans.
The Contribution of Brain Structural and Functional Variance in Predicting Age, Sex and Treatment
Authors: Chen Ning-Xuan , Fu Gui , Chen Xiao , Li Le , Milham Michael P. , Lui Su , Yan Chao-Gan 
Published: September 2020

AbstractStructural and functional neuroimaging have been widely used to track and predict demographic and clinical variables, including treatment outcomes. However, it is often difficult to directly establish and compare the respective weights and contributions of brain structure and function in prediction studies. The present study aimed to directly investigate respective roles of brain structural and functional indices, along with their contributions in the prediction of demographic variables (age/sex) and clinical changes of schizophrenia patients. The present study enrolled 492 healthy people from Southwest University Adult Lifespan Dataset (SALD) for demographic variables analysis and 42 patients with schizophrenia from West China Hospital for treatment analysis. We conducted a model fit test with two variables (one voxel-based structural metric and another voxel-based functional metric) and then performed a variance partitioning on the voxels that can be predicted sufficiently. Permutation tests were applied to compare the contribution difference between each pair of structural and functional measurements. We found that voxel-based structural indices had stronger predictive value for age and sex, while voxel-based functional metrics showed stronger predictive value for treatment. Therefore, through variance partitioning, we could clearly and directly explore and compare the voxel-based structural and functional indices on particular variables. In sum, for long-term change variable (age) and constant biological feature (sex), the voxel-based structural metrics would contribute more than voxel-based functional metrics; but for short-term change variable (schizophrenia treatment), the functional metrics could contribute more.
Positive association of Angiotensin II Receptor Blockers, not Angiotensin-Converting Enzyme Inhibitors, with an increased vulnerability to SARS-CoV-2 infection in patients hospitalized for suspected COVID-19 pneumonia
Authors: Georges Jean-Louis , Gilles Floriane , Cochet Hélène , Bertrand Alisson , De Tournemire Marie , Monguillon Victorien , Pasqualini Maeva , Prevot Alix , Roger Guillaume , Saba Joseph , Soltani Joséphine , Koukabi-Fradelizi Mehrsa , Beressi Jean-Paul , Laureana Cécile , Prost Jean-François , Livarek Bernard 
Published: September 2020

ABSTRACTBackgroundAngiotensin converting enzyme (ACE) type 2 is the receptor of SARS-CoV-2 for entry into lungs cells. Because ACE-2 may be modulated by ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk for COVID-19 infection.AimThis study sought to analyze the association of COVID-19 with previous treatment with ACEI and ARB.MethodsWe retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by PCR. Patients were split into 2 groups, whether (group 1, n=484) or not (group 2, n=250) COVID-19 was confirmed. Multivariate adjusted comparisons included a propensity score analysis.ResultsAge was 63.6±18.7 years, and 302(44%) were female. Hypertension was present in 42.6% and 38.4% patients of group 1 and 2, respectively (P=0.28). A treatment with ARBs (20.7% versus 12.0%, respectively, OR 1.92, 95% confidence interval [1.23-2.98], p=0.004) was more frequent in patients of group 1 than in group 2. No difference was found for treatment with ACEIs (12.7% vs 15.7%, respectively, OR 0.81 [0.52-1.26], p=0.35). Propensity score matched multivariate logistic regression confirmed a significant association between COVID-19 and a previous treatment with ARBs (adjusted OR 2.18 [1.29-3.67], p=0.004). Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged>60, women, and hypertensive patients.ConclusionThis study suggests that ACEIs and ARBs are not similarly associated with the COVID-19. In this retrospective series, patients with COVID-19 pneumonia received more frequently a previous treatment with ARBs, than patients without COVID-19.
Social Perception of Young Adults Prolongs the Lifespan of Aged Drosophila
Authors: Cho Li-Chun , Yu Chih-Chieh , Kao Chih-Fei 
Published: September 2020

AbstractLifespan is modulated at distinct levels by multiple factors, including genetic backgrounds, the environment, behavior traits, the metabolic status, and more interestingly, the sensory perceptions. However, the effects of social perception between individuals living in the same space remain less clear. Here, we used the Drosophila model to study the influences of social perception on the lifespan of aged fruit flies. We found the mean lifespan of aged Drosophila is markedly prolonged after being co-housed with young adults of the same gender. Moreover, the changes of lifespan were affected by several experimental contexts: (1) the ratios of aged and young adults co-housed, (2) the chronological ages of two populations, and (3) the integrity of sensory modalities. Together, we hypothesize the chemical/physical stimuli derived from the interacting young adults are capable of interfering with the physiology and behavior of aged flies, ultimately leading to the alteration of lifespan.
APOE2promotes longevity independent of Alzheimer’s disease
Authors: Shinohara Mitsuru , Kanekiyo Takahisa , Tachibana Masaya , Kurti Aishe , Shinohara Motoko , Fu Yuan , Zhao Jing , Han Xianlin , Sullivan Patrick M. , Rebeck William G , Fryer John D. , Heckman Michael G. , Bu Guojun 
Published: September 2020

AbstractObjectiveAlthough apolipoprotein E (APOE) allele associates with longevity, its mechanism is not understood. The protective effects ofAPOE2 and the deleterious effects ofAPOE4on Alzheimer’s disease (AD) risk may confoundAPOEeffects on longevity.MethodsWe analyzed a large number of subjects from the National Alzheimer’s Coordinating Center (NACC), and animal models expressing human apoE isoforms in the absence of AD.ResultsClinically, theAPOE2allele was associated with longer lifespan, whileAPOE4associated with shorter lifespan, compared to the commonAPOE3allele. This effect was also seen irrespective of clinical AD status, and in subjects with little amyloid pathology or after adjustment for AD-related pathologies. In animal studies, apoE2-TR mice also exhibited longer lifespan, while apoE4 showed some trends of shorter lifespan. Notably, old apoE2-TR mice kept activity measured by open field assay, associated with longer lifespan. Evidence of preserved activity inAPOE2carrier was also obtained in clinical records. In animal studies, higher levels of apoE2 in brain and plasma were correlated with activity. Moreover, lower levels of total cholesterol in the brain and higher levels of high-density lipoprotein cholesterol and triglycerides in the plasma of apoE2-TR mice were associated with apoE levels and more activity.InterpretationAPOE2can contribute to longevity independent of AD. Preserved activity would be an early-observable feature of apoE2-mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved.