bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of Electronic Health Records for the Assessment of Adiponectin Receptor Autoantibodies during the Progression of Cardio-metabolic Comorbidities
Authors: Pugia Michael J. , Pradhan Meeta , Qi Rong , Eastes Doreen L. , Geisinger Anna , Mills Bradley J. , Baird Zane , Wijeratne Aruna , McAhren Scott M. , Mosley Amber L. , Shekhar Anantha , Robertson Daniel H. 
Published: March 2020

ABSTRACTBACKGROUNDDiabetes is a complex, multi-symptomatic disease that drives healthcare costs through its complications as the prevalence of this disease grows rapidly world-wide. Real-world electronic health records (EHRs) coupled with patient biospecimens, biological understanding, and technologies can lead to identification of new diagnostic markers.METHODSWe analyzed the 20-year EHRs of 1862 participants with midpoint samples (10-year) in an observational study of type 2 diabetes and cardiovascular arterial disease (CVAD) conducted by the Fairbanks Institute to test the diagnostic biomarkers. Participants were assigned to four cohorts (healthy, diabetes, CVAD, CVAD+diabetes) based on EHR data analysis. The immunoassay reference range for circulating autoantibodies against the C-terminal fragment of adiponectin receptor 1 (IgG-CTF) was determined and used to predict outcomes post-sample.RESULTSThe IgG-CTF reference range was determined [75–821 ng/mL] and out-of-range values of IgG-CTF values predicted increased likelihood of additional comorbidities and mortality determined from the EHRs 10 years after sample collection. The probability of mortality was lower in patients with elevated IgG-CTF >821 ng/mL [OR 0.49–0.0] and higher in patients with lowered IgG-CTF <75 ng/mL [OR 3.74–9.64]. Although many patients at the time of sample collection had other conditions (hypertension, hyperlipidemia, or elevated uristatin values), only hypertension correlated with increased likelihood of mortality (OR 4.36–5.34).CONCLUSIONSThis study confirms that retrospective analysis of biorepositories coupled with EHRs can provide insight into novel diagnostic markers and the IgG-CTF marker can predict the likelihood of progressing to additional comorbidities or mortality.
Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2)
Authors: Lei Chong , Su Binxiao , Dong Hailong , Bellavia Andrea , Di Fenza Raffaele , Fakhr Bijan Safaee , Gianni Stefano , Grassi Luigi Giuseppe , Pinciroli Riccardo , Vassena Emanuele , Berra Lorenzo 
Published: March 2020

AbstractIntroductionSevere acute respiratory syndrome (SARS-CoV-2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In has also shown in-vitro and clinical evidence that inhaled nitric oxide gas (iNO) has antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients will be blinded to the treatment.Methods and analysisIntubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not (control group). Treatment will be stopped when patients are free from hypoxemia for more than 24 hours. The primary outcome evaluates levels of oxygenation between the two groups at 48 hours. Secondary outcomes include rate of survival rate at 28 and 90 days in the two groups, time to resolution of severe hypoxemia, time to achieve negativity of SARS-CoV-2 RT-PCR tests.Ethics and disseminationThe study protocol has been approved by the Investigational Review Board of Xijing Hospital (Xi’an, China) and pending the Partners Human Research Committee (Boston, USA). Recruitment will start after approval of both IRBs and local IRBs at other enrolling centers. Results of this study will be published in scientific journals, presented at scientific meetings, reported through flyers and posters, and published on related website or media in combating against this widespread contagious diseases.Trial registrationClinicaltrials.gov. NCT submittedStrengths and limitations of this study— Supplementation with nitric oxide (NO) might improve oxygenation and survival of SARS-CoV-2 patients.— The antiviral activity of NO inhalation will be explored by measuring the time difference between the two groups to reach SARS-CoV-2 RT- PCR negativity.— The spread of the disease worldwide determines the geographic areas of study and the recruitment rate of patients.
Prospective Evaluation of Transpancreatic Sphincterotomy Comparing to Needle-knife Precut in Difficult Biliary Cannulation: Short-and Long-term Outcomes
Authors: Tabak Fatema , Ji Guo-Zhong , Miao Lin 
Published: March 2020

AbstractBackground/AimsTranspancreatic sphincterotomy (TPS) can be an alternative approach of biliary access in difficult cannulation cases. We aimed to prospectively evaluate the efficacy and safety of TPS compared to needle-knife precut (NKP), considering the late consequences of both techniques.MethodsA total of 122 enrolled patients have been divided into three groups based on the applied secondary cannulation techniques. Selective cannulation success, ERCP procedure findings, and immediate adverse events were compared between groups. We investigated the long-term outcomes during six-month after the procedure.ResultsSuccessful selective cannulation was achieved in 92.9% with TPS similarly to other groups. The mean procedure time was shorter in the TPS group without significant difference. Using TPS did not affect the rate of post-ERCP pancreatitis (PEP) with less frequent post-ERCP bleeding and perforation after TPS compared to NKP, without significant difference. Patients who received TPS, NKP, or both had no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period.ConclusionsUsing TPS was useful to achieve success cannulation in difficult cases with an acceptable PEP rate. Furthermore, it was associated with reducing bleeding and perforation rates comparing with NKP and no differences related to the long term consequences within the follow-up period.
Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study
Authors: Li Na , Han Lefei , Peng Min , Lv Yuxia , Ouyang Yin , Liu Kui , Yue Linli , Li Qiannan , Sun Guoqiang , Chen Lin , Yang Lin 
Published: March 2020

AbstractBackgroundThe ongoing epidemics of coronavirus disease 2019 (COVID-19) have caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia.MethodsWe conducted a case-control study to compare clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia.ResultsDuring January 24 to February 29, 2020, there were sixteen pregnant women with confirmed COVID-19 pneumonia and eighteen suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest took cesarean section. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest CT images of COVID-19 pneumonia. Compared to the controls, COVID-19 pneumonia patients had lower counts of white blood cells (WBC), neutrophils, C-reactive protein (CRP), and alanine aminotransferase (ALT) on admission. Increased levels of WBC, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. There were three (18.8%) and two (10.5%) of the mothers with confirmed or suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than the control group. None experienced respiratory failure during hospital stay. COVID-19 infection was not found in the newborns and none developed severe neonatal complications.ConclusionSevere maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal delivery or caesarean section. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.
Dose-dependent oral glucocorticoid cardiovascular risk in people with immune-mediated inflammatory diseases
Authors: Pujades-Rodriguez Mar , Morgan Ann W , Cubbon Richard M , Wu Jianhua 
Published: March 2020

ABSTRACTBackgroundEvidence for the association between glucocorticoid dose and cardiovascular risk is weak for moderate and low doses. To quantify glucocorticoid dose-dependent cardiovascular risk in people with six immune-mediated inflammatory diseases.Methods and FindingsPopulation-based cohort analysis of medical records from 389 primary care practices contributing data to the UK Clinical Practice Research Datalink, linked to hospital admissions and deaths in 1998-2017. There were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (n=25,581), inflammatory bowel disease (n=27,739), rheumatoid arthritis (n=25,324), systemic lupus erythematosus (n=3951), and/or vasculitis (n=5199); and no prior cardiovascular disease (CVD). Mean age was 56 years and 34.1% were men. Median follow-up time was 5.0 years. Time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios of first all-cause and type-specific CVD.We found 13,426 (15.3%) people with incident CVD, including 6,013 atrial fibrillation, 7,727 heart failure and 2,809 acute myocardial infarction events. At 1 and 5 years, the cumulative risks of all-cause CVD increased from 1.5% in periods of non-use to 9.1% for a daily prednisolone-equivalent dose of ≥25.0mg, and from 7.6% to 29.9%, respectively. We found strong dose-dependent estimates for all immune-mediated diseases (hazard ratio [HR] for <5.0mg daily dose vs. non-use=1.74, 95%CI 1.64-1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus), all cardiovascular outcomes, regardless of disease activity level. The highest estimates were for heart failure and acute myocardial infarction.ConclusionsWe estimated glucocorticoid dose-dependent cardiovascular risk in six immune-mediated diseases. Results highlight the importance of prompt and regular monitoring of cardiovascular risk and use of primary prevention treatment at all glucocorticoid doses.
Predicting the cumulative number of cases for the COVID-19 epidemic in China from early data
Authors: Liu Z. , Magal P. , Seydi O. , Webb G. 
Published: March 2020

AbstractWe model the COVID-19 coronavirus epidemic in China. We use early reported case data to predict the cumulative number of reported cases to a final size. The key features of our model are the timing of implementation of major public policies restricting social movement, the identification and isolation of unreported cases, and the impact of asymptomatic infectious cases.
The role of the C2A domain of synaptotagmin 1 in asynchronous neurotransmitter release
Authors: Shields Mallory C. , Bowers Matthew R. , Kramer Hannah L. , Fulcer McKenzie M. , Perinet Lara C. , Metz Marissa J. , Reist Noreen E. 
Published: March 2020

AbstractFollowing nerve stimulation, there are two distinct phases of Ca2+-dependent neurotransmitter release: a fast, synchronous release phase, and a prolonged, asynchronous release phase. Each of these phases is tightly regulated and mediated by distinct mechanisms. Synaptotagmin 1 is the major Ca2+sensor that triggers fast, synchronous neurotransmitter release upon Ca2+binding by its C2A and C2B domains. It has also been implicated in the inhibition of asynchronous neurotransmitter release, as blocking Ca2+binding by the C2A domain of synaptotagmin 1 results in increased asynchronous release. However, the mutation used to block Ca2+binding in the previous experiments (aspartate to asparagine mutations,sytD-N) had the unintended side effect of mimicking Ca2+binding, raising the possibility that the increase in asynchronous release was an artifact of ostensibly constitutive Ca2+binding. To directly test this C2A inhibition hypothesis, we utilized an alternate C2A mutation that we designed to block Ca2+binding without mimicking it (an aspartate to glutamate mutation,sytD-E). Analysis of both the originalsytD-Nmutation and our alternatesytD-Emutation at theDrosophilaneuromuscular junction showed differential effects on asynchronous release, as well as on synchronous release and the frequency of spontaneous release. Importantly, we found that asynchronous release is not increased in thesytD-Emutant. Thus, our work provides new mechanistic insight into synaptotagmin 1 function during Ca2+-evoked synaptic transmission and demonstrates that Ca2+binding by the C2A domain of synaptotagmin 1 does not inhibit asynchronous neurotransmitter releasein vivo.Significance statementThis study provides mechanistic insights into synaptotagmin function during asynchronous neurotransmitter release and supports a dramatically different hypothesis regarding the mechanisms triggering asynchronous vesicle fusion. Using two distinct C2A mutations that block Ca2+binding, we report opposing effects on synchronous, spontaneous, and asynchronous neurotransmitter release. Importantly, our data demonstrate that Ca2+binding by the C2A domain of synaptotagmin does not regulate asynchronous release and thus disprove the current inhibition hypothesis. We propose a spatial competition hypothesis to explain these seemingly discordant results of the differing C2A Ca2+binding mutations.
A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy
Authors: Wisdom Amy J. , Mowery Yvonne M. , Hong Cierra S. , Qin Xiaodi , Zhang Dadong , Himes Jonathon E. , Chen Lan , Fradin Hélène , Muise Eric S. , Xu Eric S. , Carpenter David J. , Kent Collin L. , Smythe Kimberly S. , Williams Nerissa , Luo Lixia , Ma Yan , Owzar Kouros , Bradley Todd , Kirsch David G. 
Published: March 2020

AbstractDespite impressive responses in some patients, immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Nearly all preclinical immunotherapy studies utilize transplant tumor models, but cure rates of transplant tumor models treated with immunotherapy often overestimate patient responses. Here, we show that transplant tumors are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous tumors. We generated a single-cell atlas of tumor-infiltrating immune cells from transplant and primary tumors treated with radiation and immunotherapy, which reveals striking differences in their immune landscapes. Although radiotherapy remodels myeloid cell phenotypes in primary and transplant tumors, only transplant tumors are enriched for CD8+ T cells that mediate tumor clearance while mice with primary sarcomas demonstrate tumor-specific tolerance. These results identify distinct microenvironments in tumors that coevolve with the immune system, which promote tolerance that must be overcome for immune-mediated cancer cures.
Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme inde novopyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2
Authors: Xiong Rui , Zhang Leike , Li Shiliang , Sun Yuan , Ding Minyi , Wang Yong , Zhao Yongliang , Wu Yan , Shang Weijuan , Jiang Xiaming , Shan Jiwei , Shen Zihao , Tong Yi , Xu Liuxin , Yu Chen , Liu Yingle , Zou Gang , Lavillete Dimitri , Zhao Zhenjiang , Wang Rui , Zhu Lili , Xiao Gengfu , Lan Ke , Li Honglin , Xu Ke 
Published: March 2020

AbstractEmerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new viruses because of virus-specificity, and the development of new DAA drugs from the beginning is not timely for outbreaks. Thus, host-targeting antiviral (HTA) drugs have many advantages to fight against a broad spectrum of viruses, by blocking the viral replication and overcoming the potential viral mutagenesis simultaneously. Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacyin vivoand low virus replication in DHODH knocking-out cells. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. Notably, S416 is reported to be the most potent inhibitor with an EC50 of 17nM and SI value >5882 in SARS-CoV-2-infected cells so far. This work demonstrates that both our self-designed candidates and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-repression may have clinical potentials not only to influenza but also to COVID-19 circulating worldwide, no matter such viruses mutate or not.
Effective Assessments of a Short-duration Poor Posture on Upper Limb Muscle Fatigue before Physical Exercise
Authors: Lu Lei , Robinson Mark , Tan Ying , Goonewardena Kusal , Guo Xinliang , Mareels Iven , Oetomo Denny 
Published: March 2020

ABSTRACTA forward head and rounded shoulder posture is a poor posture that is widely seen in everyday life. It is known that sitting in such a poor posture with long hours will bring health issues such as muscle pain. However, it is not known whether sitting in this poor posture for a short period of time will affect human activities. This paper investigates the effects of a shortduration poor posture before some typical physical activities such as push-ups. The experiments are set up as follows. Fourteen male subjects are asked to do push-ups until fatigue with two surface electromyography (sEMG) at the upper limb. Two days later, they are asked to sit in this poor posture for 15 mins with 8 sEMG sensors located at given back muscles. Then they do the push-ups after the short-duration poor posture. The observations from the median frequency of sEMG signals at the upper limb indicate that the short-duration poor posture does affect the fatigue procedure of push-ups. A significant decreasing trend of the performance of push-ups is obtained after sitting in this poor posture. Such effects indicate that some parts of the back muscles indeed get fatigued with only 15 minutes sitting in this poor posture. By further investigating the time-frequency components of sEMG of back muscles, it is observed that the low and middle frequencies of sEMG signals from the infraspinatus muscle of the dominant side are demonstrated to be more prone to fatigue with the poor posture. Although this study focuses only on push-ups, similar experiments can be arranged for other physical exercises as well. This study provides new insights into the effect of a short-duration poor posture before physical activities. These insights can be used to guide athletes to pay attention to postures before physical activities to improve performance and reduce the risk of injury.
Consensus-seeking and conflict-resolving ---an fMRI study on college couples’ shopping interaction
Authors: Jo HanShin , Chen Chiu-Yueh , Chen Der-Yow , Weng Ming-Hung , Kung Chun-Chia 
Published: March 2020

AbstractOne of the typical campus scenes is the social interaction between college couples, and the lesson couples must keep learning is to adapt to each other. This fMRI study investigated the shopping interactions of 30 college couples, one lying inside and the other outside the scanner, beholding the same item from two connected PCs, making preference ratings and subsequent buy/not-buy decisions. The behavioral results showed the clear modulation of significant others’ preferences onto one’s own decisions, and the contrast of the “shop-together vs. shop-alone”, and the “congruent (both liked or disliked the item, 68%) vs. incongruent (one liked but the other disliked, and vice versa)” together trials, both revealed bilateral temporal parietal junction (TPJ) among other reward-related regions, likely reflecting mentalizing during preference harmony. Moreover, when contrasting “own-high/other-low vs. own-low/other-high” incongruent trials, left anterior inferior parietal lobule (l-aIPL) was parametrically mapped, and the “yield (e.g., own-high/not-buy) vs. insist (e.g., own-low/not-buy)” modulation further revealed left lateral-IPL (l-lIPL), together with left TPJ forming a local social decision network that was further constrained by the mediation analysis among left TPJ-lIPL-aIPL. In sum, these results exemplify, via the two-person fMRI, the neural substrate of shopping interactions between couples.
Enhancing biocompatibility of rhodamine fluorescent probes by a neighbouring group effect
Authors: Bucevičius Jonas , Kostiuk Georgij , Gerasimaitė Rūta , Gilat Tanja , Lukinavičius Gražvydas 
Published: March 2020

AbstractFluorescence microscopy is an essential tool for understanding dynamic processes in living cells and organisms. However, many fluorescent probes for labelling cellular structures suffer from unspecific interactions and low cell permeability. Herein, we demonstrate that the neighbouring group effect which results from positioning an amide group next to a carboxyl group in the benzene ring of rhodamines dramatically increases cell permeability of the rhodamine-based probes through stabilizing a fluorophore in a hydrophobic spirolactone state. Based on this principle, we create probes targeting tubulin, actin and DNA. Their superb staining intensity, tuned toxicity and specificity allows long-term 3D confocal and STED nanoscopy with sub-30 nm resolution. As a result, the real microtubule diameter of 23 nm was resolved inside a living cell for the first time. Due to their unrestricted cell permeability and efficient accumulation on tubulin, the new probes produce high contrast images at sub-nanomolar concentrations.
The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
Authors: Matsuyama Shutoku , Kawase Miyuki , Nao Naganori , Shirato Kazuya , Ujike Makoto , Kamitani Wataru , Shimojima Masayuki , Fukushi Shuetsu 
Published: March 2020

AbstractSteroid compounds, which are expected to have dual functions in blocking host inflammation and MERS-CoV replication, were screened from a chemical library. Within this library, ciclesonide, an inhaled corticosteroid, suppressed human coronavirus replication in cultured cells, but did not suppress replication of respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the cause of COVID-19) replication (EC90) was 6.3 μM. After the eleventh consecutive MERS-CoV passage in the presence of ciclesonide, a resistant mutation was generated, which resulted in an amino acid substitution (A25V) in nonstructural protein (NSP) 15, as identified using reverse genetics. A recombinant virus with the mutation was also resistant to ciclesonide suppression of viral replication. These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a candidate drug for treatment of patients suffering MERS or COVID-19.