bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remnant Cystic Duct Disease After Cholecystectomy: A Case Series
Authors: Xu Suqin , Zou Shubing 
Published: June 2020

Background:
Remnant cystic duct (RCD) may be responsible for postcholecystectomy syndrome. We present our experience with the management of remnant cystic duct disease (RCDD) after cholecystectomy.

Methods:
Over a period of 5 years, 10 patients underwent reoperation for RCDD in our hospital. Cystic duct was identified by intraoperative exploration.

Results:
There were 4 men and 6 women ranging in age from 37 to 76 years (median, 60.40 y). All 10 had biliary pain, 5 had jaundice, and 2 had pancreatitis. The time from initial cholecystectomy to reoperation ranged from 4 to 28 years (median, 12.22 y). Eight patients had an abnormal liver function. Six of these 8 patients (75%) were diagnosed by magnetic resonance cholangiopancreatography. In 7 patients treated by completed cholecystectomy (6 by laparoscopy and 1 by laparotomy), pathology proved the presence of an RCD and chronic cholecystitis. The other 3 patients were treated by removing stones. All patients had 6- to 14-day hospital stays after reoperation, except for 1 patient with a 3-day stay.

Conclusions:
RCDD may be a more reasonable explanation for a source of postcholecystectomy syndrome. Magnetic resonance cholangiopancreatography has a role in the diagnosis of RCDD. We believe that excision of diseased RCD is necessary and that laparoscopic surgery is feasible.
Effectiveness of mepolizumab in a real-life cohort of patients with severe refractory eosinophilic asthma and multiple comorbidities
Authors: Crimi Claudia , Campisi Raffaele , Cacopardo Giulia , Intravaia Rossella , Nolasco Santi , Porto Morena , Pelaia Corrado , Crimi Nunzio 
Published: June 2020

AbstractBACKGROUNDPatients with severe asthma often suffer from comorbidities whose impact on the course of biological therapy has not been elucidated yet.OBJECTIVETo evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities who received mepolizumab (MEPO) for the treatment of severe eosinophilic asthma (EA).METHODSHealth records of 31 patients were retrospectively analyzed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 second (FEV1), FEV1% of predicted and FEV1/FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), nine (T6) and 12 months (T12). A clinical response was defined as: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV1 increase ≥ 200 mL.RESULTSAt T12 blood eosinophil level decreased by 89.89% (p>0.0001), an improvement in ACT of 3 points from baseline was recorded in 80.65% of patients (p>0.0001) and 96.77% of patients reduced by minimum 30% the number of exacerbations (p>0.0001). 84% of patients discontinued OCS (p>0.0001). FEV1 increased by 0.22 (p=0.0224) while FEV1/FVC was statistically significant only at T1. No significant differences were generally found among patients with a specific comorbidity. The number of comorbidities did not influence treatment response. Neither the comorbidities nor other characteristics (sex, BMI, age, smoking, baseline eosinophil level) influenced treatment response.CONCLUSIONSMEPO in patients with severe EA is effective regardless of the presence of one or more comorbidities.
Diagnostic accuracy of a host response point-of-care test in patients with suspected COVID-19
Authors: Clark Tristan W , Brendish Nathan J , Poole Stephen , Naidu Vasanth V , Mansbridge Christopher , Norton Nicholas , Wheeler Helen , Presland Laura , Ewings Sean 
Published: June 2020

AbstractRationaleManagement of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 minutes, but its accuracy for the detection of COVID-19 is unknown.ObjectivesTo evaluate the diagnostic accuracy of FebriDx in hospitalised patients during the first wave of the pandemicMethodsMeasures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of PCR, and stratified by duration of symptoms. A multivariable predictive model was developed and underwent internal validation.ResultsFebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model diagnosis of COVID-19 was not significantly influenced by clinical symptoms and signs, and FebriDx accuracy was not improved by restricting testing to those with duration of symptoms of less than seven days.ConclusionsDuring the first wave of the pandemic, FebriDx had high sensitivity for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool.Trial registrationISRCTN14966673
SARS-CoV-2 genetic variations associated with COVID-19 severity
Authors: Aiewsakun Pakorn , Wongtrakoongate Patompon , Thawornwattana Yuttapong , Hongeng Suradej , Thitithanyanont Arunee 
Published: June 2020

AbstractHerein, we performed a genome-wide association study on SARS-CoV-2 genomes to identify genetic variations that might be associated with the COVID-19 severity. 152 full-length genomes of SARS-CoV-2 that were generated from original clinical samples and whose patient status could be determined conclusively as either “asymptomatic” or “symptomatic” were retrieved from the GISAID database. We found that nucleotide variations at the genomic position 11,083, locating in the coding region of non-structural protein 6, were associated with the COVID-19 severity. While the 11083G variant (i.e. having G at the position 11,083) was more commonly found in symptomatic patients, the 11083T variant appeared to associate more often with asymptomatic infections. We also identified three microRNAs that differentially target the two variants, namely miR-485-3p, miR-539-3p, and miR-3149. This may in part contribute to the differential association of the two SARS-CoV-2 variants with the disease severity.
Effectiveness of Growth Hormone–Releasing Hormone Agonists (GHRH-A) in Chronic Kidney Disease-Induced Heart Failure with Preserved Ejection Fraction
Authors: Rieger Angela C. , Bagno Luiza L , Salerno Alessandro , Florea Victoria , Rodriguez Jose , Rosado Marcos , Turner Darren , Takeuchi Lauro M. , Dulce Raul , Balkan Wayne , Schulman Ivonne H. , Schally Andrew , Hare Joshua M. 
Published: June 2020

ABSTRACTBackgroundTherapies that improve morbidity and mortality in heart failure with preserved ejection fraction (HFpEF) are lacking. Growth hormone releasing hormone analogues (GHRH-A) reverse fibrosis and improve cardiac function in ischemic and non-ischemic animal models. We tested the hypothesis that GHRH-A treatment ameliorates chronic kidney disease (CKD)-induced HFpEF in a large animal model.MethodsFemale Yorkshire pigs (n=16) underwent 5/6 nephrectomy via renal artery embolization, which induced HFpEF, and 12-weeks later received daily subcutaneous injections of GHRH-A (n=8) or placebo (n=8). Kidney function, renal and cardiac MRI, pressure-volume loops, and electrical stimulation were assessed at baseline, 12-weeks, and 16-18 weeks post-embolization.ResultsThe CKD model was confirmed by increased creatinine and BUN. HFpEF was demonstrated at 12 weeks by maintenance of ejection fraction associated with increased left ventricular mass, relative wall thickening, end-diastolic pressure (EDP), end-diastolic pressure-volume relationship (EDPVR), and tau. After 6 weeks of treatment, diastolic function improved in the GHRH-A group, evidenced by normalization of EDP (p=0.03) associated with improved diastolic compliance as measured by EDP/EDV ratio (p=0.018).ConclusionA beneficial effect of GHRH-A in diastolic function was observed in a CKD large animal model that manifests the characteristics of HFpEF. These findings have important therapeutic implications for the HFpEF syndrome.
Pharmacogenetics at scale: An analysis of the UK Biobank
Authors: McInnes Greg , Lavertu Adam , Sangkuhl Katrin , Klein Teri E. , Whirl-Carrillo Michelle , Altman Russ B. 
Published: June 2020

AbstractPharmacogenetics (PGx) studies the influence of genetic variation on drug response. Clinically actionable associations inform guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), but the broad impact of genetic variation on entire populations is not well-understood. We analyzed PGx allele and phenotype frequencies for 487,409 participants in the U.K. Biobank, the largest PGx study to date. For fourteen CPIC pharmacogenes known to influence human drug response, we find that 99.5% of individuals may have an atypical response to at least one drug; on average they may have an atypical response to 12 drugs. Non-European populations carry a greater frequency of variants that are predicted to be functionally deleterious; many of these are not captured by current PGx allele definitions. Strategies for detecting and interpreting rare variation will be critical for enabling broad application of pharmacogenetics.
Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia - challenges, strengths, and opportunities in a global health emergency
Authors: Davide Ferrari , Jovana Milic , Roberto Tonelli , Francesco Ghinelli , Marianna Meschiari , Sara Volpi , Matteo Faltoni , Giacomo Franceschi , Vittorio Iadisernia , Dina Yaacoub , Giacomo Ciusa , Erica Bacca , Carlotta Rogati , Marco Tutone , Giulia Burastero , Alessandro Raimondi , Marianna Menozzi , Erica Franceschini , Gianluca Cuomo , Luca Corradi , Gabriella Orlando , Antonella Santoro , Margherita Di Gaetano , Cinzia Puzzolante , Federica Carli , Andrea Bedini , Riccardo Fantini , Luca Tabbì , Ivana Castaniere , Stefano Busani , Enrico Clini , Massimo Girardis , Mario Sarti , Andrea Cossarizza , Cristina Mussini , Federica Mandreoli , Paolo Missier , Giovanni Guaraldi 
Published: June 2020

ABSTRACTAimsThe aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia.MethodsThis was an observational study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients’ medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome.ResultsA total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth “boosted mixed model” included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example.ConclusionThis study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.
Risk factors for mortality in pregnant women with SARS-CoV-2 infection
Authors: Martinez-Portilla Raigam J. , Sotiriadis Alexandros , Torres-Torres Johnatan , Christos Chatzakis , Hawkins-Villarreal Ameth , Villafan-Bernal Jose R. , Gurrola-Ochoa Rodolfo A. , Figueras Francesc 
Published: June 2020

Since the first case of pneumonia was described, SARS-CoV-2 infection (coronavirus disease [COVID]-19) rapidly spread worldwide With 94,288 infections and more than 10,000 deaths, Mexico is the third Latin-American country in number of confirmed cases and second in mortality1. A major risk factor for adverse outcome in COVID-19 infection is the presence of advance age, co-morbidities including diabetes, hypertension and obesity among other non-communicable diseases2. Epidemiological data from high-prevalence countries reveal that compared to men, women are less likely to die or to require hospital admission to intensive care. This may suggest that pregnant women are not more susceptible to infection or to experience serious complications. However, whether the presence of co-morbidities or advanced maternal age confers a higher risk of adverse outcome in pregnant women with COVID-19 is unknown3.In this research letter, we aimed at evaluating the risk factor associated with maternal mortality secondary to COVID-19 infection in a middle-income country.Advanced maternal age is linked to an increased risk of mortality, while diabetes is the most important risk factor for maternal death. This is partly explained by an increasing incidence of non-communicable diseases in women of advanced age which is a common feature in most countries4. In the last decades, low- and middle-income countries have experienced accelerated socio-cultural changes associated with its incorporation into the international economic community, which have increased the number of obese and diabetic population, including pregnant women5. This has caused an increased risk for complications and fatality among COVID-19 positive population2,3. Thus, policies for reducing obesity and diabetes in low- and middle-income countries are most needed to reduce the mortality of COVID-19 in pregnant women.
Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration
Authors: Devadoss Dinesh , Singh Shashi P. , Acharya Arpan , Do Kieu Chinh , Periyasamy Palsamy , Manevski Marko , Mishra Neerad , Tellez Carmen , Ramakrishnan Sundaram , Belinsky Steve , Byrareddy Siddappa , Buch Shilpa , Chand Hitendra S. , Sopori Mohan 
Published: June 2020

ABSTRACTIn the era of highly active anti-retroviral therapy (HAART), obstructive lung diseases (OLDs) are common among the people living with HIV (PLWH); however, the mechanism by which HIV induces OLDs is unclear. Although human bronchial epithelial cells (HBECs) express HIV coreceptors and are critical in regulating lung immune responses, their role in transmitting HIV remains unclear. Herein, we present evidence that HIV-1 infects normal HBECs and the viral DNA is integrated in the genome to establish the viral latency. To prove that HIV productively infects HBECs, we demonstrate: (a) along with CXCR4, HBECs express the HIV-receptor CD4, and are induced to express CCR5 by IL-13 treatment; (b) following infection with HIV, HBECs produce HIV-p24 and contain the latent HIV provirus, which is activated by endotoxin and/or vorinostat; (c) DNA from HIV-1 infected HBECs contains the HIV-specificgagandnefgenes, along withAlusequences, confirming the integration of HIV in the host DNA; (d) the lung epithelial cells of HIV-infected subjects and SHIV-infected cynomolgus macaques are positive for HIV-specific transcripts. Thus, these studies suggest that HIV establishes latency in lung epithelial cells, making them potential HIV reservoirs. The long-living lung epithelial cells, activated by commonly encountered lung infections, might represent an ideal HIV target/reservoir, contributing to OLDs and other HIV-associated lung comorbidities.
Short chain fatty acids enhance expression and activity of the umami taste receptor in enteroendocrine cells via a Gαi/opathway
Authors: Shackley Matilda , Tate Edward W. , Brown Alastair J.H. , Frost Gary , Hanyaloglu Aylin C. 
Published: June 2020

AbstractThe short chain fatty acids (SCFAs) acetate, butyrate and propionate, are produced by the fermentation of non-digestible carbohydrates by the gut microbiota. SCFAs are of interest because they regulate appetite, adiposity, metabolism, glycemic control and immunity. SCFAs act at two distinct G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. These are expressed in intestinal enteroendocrine cells (EECs), where they mediate SCFA-driven anorectic gut hormone release. EECs also express other GPCRs that act as nutrient sensors, in a manner that is plastic and adaptable to the environment. SCFAs may elicit some of their health-promoting effects by altering levels of GPCRs in EECs, thus, enhancing gut sensitivity to dietary molecules. Here, we identified that exposure of the murine EEC STC-1 cell-line to a concentration of SCFAs found in the colon, specifically enhances mRNA levels of the umami taste receptors TASR1 and TASR3, without altering levels of the SCFA GPCRs, FFAR2 and FFAR3. Interestingly, treatment of EECs with propionate or butyrate, but not acetate, increased levels of umami receptor transcripts. This phenomenon was reversed by inhibiting Gαi/osignaling with pertussis toxin, suggesting that SCFAs act through FFAR2/3 to alter gene expression. Surprisingly, neither a FFAR3-nor a FFAR2-selective synthetic ligand could increase TASR1/TASR3 mRNA levels. We assessed the functional impact of increases in TASR1/TASR3 expression using unique pharmacological properties of the umami taste receptor; namely, the potentiation of signaling by inosine monophosphate. We found that the umami taste receptor induced inosine-1-phosphate and calcium signaling in response to L-alanine and L-monosodium glutamate, and that butyrate pretreatment significantly enhanced such signaling. Our study reveals that SCFAs may contribute to EEC adaptation and alter EEC sensitivity to bioactive nutrients.
The knowledge and practice towards COVID-19 pandemic prevention among residents of Ethiopia: An Online Cross-Sectional Study
Authors: Bekele Daniel , Tolossa Tadesse , Tsegaye Reta , Teshome Wondesen 
Published: June 2020

AbstractBackgroundThe Novel coronavirus disease-2019 (COVID-19) is now the international concerns and a pandemic, since the World Health Organization declared as the outbreaks. The objective of this study to assess the prevention knowledge and practices towards the COVID-19 among the residents of Ethiopia.MethodsAn online cross-sectional study was conducted among the sample of Ethiopian residents via social platforms of the author’s network with the popular media such as Facebook, in Ethiopia from the April 15-22, 2020 and successfully recruited 341 responses. The snowball sampling was employed to recruit the participants. The data were analyzed using STATA version 14. Descriptive statistics were used to summarize the level of knowledge and practices.ResultsThe majority of the respondents (80.35%) were male. The overall prevention knowledge of the participants towards the novel coronavirus (COVID-19) was high. About 91.2% of the participant was heard about the novel coronavirus disease and Social Medias’ were the main source of the information. About 90% of the participants had a good prevention knowledge of maintaining social distance and frequent hand washing. The practices of the participants towards the COVID-19 prevention were very low. Out of 341 participants, only 61% and 84% of the participants were practicing social distance and frequent hand washing, respectively.ConclusionsMajority of the participants had knew the ways of protecting themselves from the novel coronavirus. But, there was deficiencies of changing these prevention knowledge to practice. This indicates that there was gap between knowledge and implementation of prevention strategies in the community. The concerned body should focus on providing education for the community regarding the implementation of the prevention knowledge to practice.
Biological Network Growth in Complex Environments: a Computational Framework
Authors: Paul Torsten Johann , Kollmannsberger Philip 
Published: June 2020

AbstractSpatial biological networks are abundant on all scales of life, from single cells to ecosystems, and perform various important functions including signal transmission and nutrient transport. These biological functions depend on the architecture of the network, which emerges as the result of a dynamic, feedback-driven developmental process. While cell behavior during growth can be genetically encoded, the resulting network structure depends on spatial constraints and tissue architecture. Since network growth is often difficult to observe experimentally, computer simulations can help to understand how local cell behavior determines the resulting network architecture. We present here a computational framework based on directional statistics to model network formation in space and time under arbitrary spatial constraints. Growth is described as a biased correlated random walk where direction and branching depend on the local environmental conditions and constraints, which are presented as 3D multilayer grid. To demonstrate the application of our tool, we perform growth simulations of a dense network between cells and compare the results to experimental data from osteocyte networks in bone. Our generic framework might help to better understand how network patterns depend on spatial constraints, or to identify the biological cause of deviations from healthy network function.Author summaryWe present a novel modeling approach and computational implementation to better understand the development of spatial biological networks under the influence of external signals. Our tool allows us to study the relationship between local biological growth parameters and the emerging macroscopic network function using simulations. This computational approach can generate plausible network graphs that take local feedback into account and provide a basis for comparative studies using graph-based methods.
Reproducible functional connectivity endophenotype confers high risk of ASD diagnosis in a subset of individuals
Authors: Urchs Sebastian GW. , Nguyen Hien Duy , Moreau Clara , Dansereau Christian , Tam Angela , Evans Alan C. , Bellec Pierre 
Published: June 2020

AbstractFunctional connectivity (FC) analyses of individuals with autism spectrum disorder (ASD) have established robust alterations of brain connectivity at the group level. Yet, the translation of these imaging findings into robust markers of individual risk is hampered by the extensive heterogeneity among ASD individuals. Here, we report an FC endophenotype that confers a greater than 7-fold risk increase of ASD diagnosis, yet is still identified in an estimated 1 in 200 individuals in the general population. By focusing on a subset of individuals with ASD and highly predictive FC alterations, we achieved a greater than 3-fold increase in risk over previous predictive models. The identified FC risk endophenotype was characterized by underconnectivity of transmodal brain networks and generalized to independent data. Our results demonstrate the ability of a highly targeted prediction model to meaningfully decompose part of the heterogeneity of the autism spectrum. The identified FC signature may help better delineate the multitude of etiological pathways and behavioural symptoms that challenge our understanding of the autism spectrum.