bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivoimaging of individual islets across the mouse pancreas reveals a heterogeneous insulin secretion response to glucose
Authors: Frikke-Schmidt Henriette , Arvan Peter , Seeley Randy J , Cras-Méneur Corentin 
Published: May 2020

AbstractWhile numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretionin vivoare typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows thein vivoimaging of insulin secretion from individual islets after a glucose challenge, in live, anesthetized mice, addressing secretion from the pancreas as a whole. Imaging the whole pancreas at high resolution in live mice includes numerous technical challenges. Using rapid-fire imaging in high dynamic range and tiling combined with computer-assisted masked morphometry, we have developed a method to overcome motion blur, and the effects of anesthesia, to be able to monitor and quantify insulin (CpepSfGFP) content simultaneously and longitudinally for the first time in hundreds of individual islets, throughout a glucose challenge.Through this approach we demonstrate that while isolated islets respond homogeneously to glucose in culture, their response profile differs significantlyin vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreasin vivo.
Targeted Genome Mining Discovery of the Ramoplanin Congener Chersinamycin from the Dynemicin-ProducerMicromonospora chersinaDSM 44154
Authors: Morgan Kelsey T. , Zheng Jeffrey , McCafferty Dewey G. 
Published: May 2020

ABSTRACTThe availability of genome sequence data combined with bioinformatic genome mining has accelerated the identification of biosynthetic gene clusters (BGCs). Ramoplanins and enduracidins are lipodepsipeptides produced byActinoplanes ramoplaniniferATCC 33076 andStreptomyces fungicidicusB-5477, respectively, that exhibit excellent in vitro activity against a broad spectrum of Gram-positive pathogens. To explore if ramoplanin/enduracidin-like BGCs exist within genomes of organisms sequenced to date, we devised a targeted genome mining strategy that employed structure-activity relationships to identify conserved, essential biosynthesis genes from the ramoplanin and enduracidin BGCs. Five microorganisms were found to contain ramoplanin-like BGCs: the enediyne antibiotic producerMicromonospora chersinastrain DSM 44151(dynemycin); the glycopeptide antibiotic producersAmycolatopsis orientalisstrain B-37 (norvancomycin),Amycolatopsis orientalisstrain DSM 40040 (vancomycin), andAmycolatopsis balhimycinaFH1894 strain DSM 44591 (balhimycin); andStreptomycessp. TLI_053. A single compound from fermentation ofM. chersinawas purified to homogeneity and found to possess good antibiotic activity against several Gram-positive bacterial test strains (1-2 μg/mL), comparing favorably to ramoplanin family members. We named this compoundchersinamycinand elucidated its covalent structure, which differs distinctly from ramoplanins and enduracidins. Further, the chersinamycin BGC was validated through insertional gene inactivation using CRISPR-Cas9 gene editing. In addition to the information gained by comparing and contrasting the sequence and organization of these five new BGCs, the amenability ofM. chersinato genetic manipulation provides a much-needed tool to investigate the fundamental aspects of lipodepsipeptide biosynthesis and to facilitate metabolic engineering efforts for the production of novel antibiotics capable of combating antibiotic-resistant infections.
Use of High Flow Nasal Therapy to Treat Moderate to Severe Hypoxemic Respiratory Failure in COVID-19
Authors: Patel Maulin , Gangemi Andrew , Marron Robert , Chowdhury Junad , Yousef Ibraheem , Zheng Matthew , Mills Nicole , Tragesser Lauren , Giurintano Julie , Gupta Rohit , Gordon Matthew , Rali Parth , D’Alonzo Gilbert , Fleece David , Zhao Huaqing , Patlakh Nicole , Criner Gerard J. ,   for the Temple University COVID-19 Research Group
Published: May 2020

AbstractInvasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of High flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.MethodsThis was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to April 24, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). Primary outcome was prevention of intubation.ResultsOf the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (±13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. SF and chest Xray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital/ventilator associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of VAP/HAP was statistically higher in the progressed to intubation group.ConclusionHFNT use is associated with a reduction in the rate of Invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.Key PointsKey QuestionWhat is the utility of High Flow Nasal Therapy (HFNT) in COVID-19 related Hypoxemic Respiratory Failure?Bottom LineIn this retrospective analysis of moderate to severe hypoxic respiratory failure for COVID 19 patients, 67 patients (65.4%) were able to avoid intubation despite severely low SF ratio (Mean 121.9).Why Read onHFNT has a significant role in COVID-19 for reducing rate of intubations and associated mortality
IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY
Authors: Fernández Cruz Ana , Ruiz-Antorán Belén , Gómez Ana Muñoz , Sancho López Aránzazu , Sánchez Patricia Mills , Soto Gustavo Adolfo Centeno , Alonso Silvia Blanco , Garachana Laura Javaloyes , Gómez Amy Galán , Alijo Ángela Valencia , Irusta Javier Gómez , Payares-Herrera Concepción , Torre Ignacio Morrás , Chica Enrique Sánchez , de Cepeda Laura Delgado Téllez , Díaz Alejandro Callejas , Ramos Martínez Antonio , Rubio Elena Múñez , Avendaño-Solá Cristina 
Published: May 2020

ABSTRACTObjectiveWe aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.DesignWe performed a single-centre retrospective cohort study.SettingA University hospital in Madrid, Spain, during March 2020.ParticipantsPatients admitted with SARS-CoV-2 pneumonia.ExposuresPatients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score.Main Outcomes and MeasuresTo determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test.ResultsDuring the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).ConclusionsOur results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.SummaryWe investigated in-hospital mortality of patients with SARS-CoV-2 pneumonia in a large series of patients treated with steroids compared to controls, and adjusted using a propensity score. Our results show a beneficial impact of steroid treatment in SARS-CoV-2 pneumonia.
Dragon III- Phase 1: Feasibility and safety of neoadjuvant chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) for locally-advanced gastric cancer patients in China
Authors: Sah Birendra Kumar , Xu Wei , Zhang Benyan , Zhang Huan , Yuan Fei , Li Jian , Liu Wentao , Yan Chao , Li Chen , Yan Min , Zhu Zhenggang 
Published: May 2020

AbstractBackgroundNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of FLOT regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received 4 cycles of neoadjuvant chemotherapy (NAC) and 4 cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities and pathological tumor regression were analyzed. The two-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed 4 cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and 3 patients had complete or subtotal pathological tumor regression. Nine patients completed 4 cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, 8 patients achieved the overall survival endpoint, and 7 patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort.The trial is registered with ClinicalTrials.gov (number NCT03646591).
Multiplexing of EEG signatures for temporal and spatial distance estimates
Authors: Robinson Eva Marie , Wiener Martin 
Published: May 2020

AbstractThe perception and measurement of spatial and temporal dimensions have been widely studied. However, whether these two dimensions are processed independently is still being debated. Additionally, whether EEG components are uniquely associated with time or space, or whether they reflects a more general measure of magnitude remains unknown. While undergoing EEG, subjects traveled a randomly predetermined spatial or temporal interval and were then instructed to reproduce the interval traveled. In the task, the subject’s travel speed varied for the estimation and reproduction phases of each trial, so that one dimension could not inform the other. Behaviorally, subject performance was more variable when reproducing time than space, but overall, just as accurate; notably, behavior was not correlated between tasks. EEG data revealed during estimation the contingent negative variation (CNV) tracked the probability of the upcoming interval, regardless of dimension. However, during reproduction, the CNV exclusively oriented to the upcoming temporal interval at the start of reproduction. Further, a dissociation between relatively early frontal beta and late posterior alpha oscillations was observed for time and space reproduction, respectively. Our findings indicate that time and space are neurally separable dimensions, yet are hierarchically organized across task contexts within the CNV signal.
Explainable machine learning models to understand determinants of COVID-19 mortality in the United States
Authors: Mathur Piyush , Sethi Tavpritesh , Mathur Anya , Maheshwari Kamal , Cywinski Jacek B , Khanna Ashish K , Dua Simran , Papay Frank 
Published: May 2020

AbstractBackgroundCOVID-19 is now one of the leading causes of mortality amongst adults in the United States for the year 2020. Multiple epidemiological models have been built, often based on limited data, to understand the spread and impact of the pandemic. However, many geographic and local factors may have played an important role in higher morbidity and mortality in certain populations.ObjectiveThe goal of this study was to develop machine learning models to understand the relative association of socioeconomic, demographic, travel, and health care characteristics of different states across the United States and COVID-19 mortality.MethodsUsing multiple public data sets, 24 variables linked to COVID-19 disease were chosen to build the models. Two independent machine learning models using CatBoost regression and random forest were developed. SHAP feature importance and a Boruta algorithm were used to elucidate the relative importance of features on COVID-19 mortality in the United States.ResultsFeature importances from both the categorical models, i.e., CatBoost and random forest consistently showed that a high population density, number of nursing homes, number of nursing home beds and foreign travel were strongest predictors of COVID-19 mortality. Percentage of African American amongst the population was also found to be of high importance in prediction of COVID-19 mortality whereas racial majority (primarily, Caucasian) was not. Both models fitted the data well with a training R2 of 0.99 and 0.88 respectively. The effect of median age,median income, climate and disease mitigation measures on COVID-19 related mortality remained unclear.ConclusionsCOVID-19 policy making will need to take population density, pre-existing medical care and state travel policies into account. Our models identified and quantified the relative importance of each of these for mortality predictions using machine learning.
Association of age, sex, comorbidities, and clinical symptoms with the severity and mortality of COVID-19 cases: a meta-analysis with 85 studies and 67299 cases
Authors: Islam Mohammad Safiqul , Barek Md. Abdul , Aziz Md. Abdul , Aka Tutun Das , Jakaria Md. 
Published: May 2020

AbstractBackgroundA new pathogenic disease named COVID-19 became a global threat, first reported in Wuhan, China, in December 2019. The number of affected cases growing exponentially and now, more than 210 countries confirmed the cases.ObjectiveThis meta-analysis aims to evaluate risk factors, the prevalence of comorbidity, and clinical characteristics in COVID-19 death patients compared to survival patients that can be used as a reference for further research and clinical decisions.MethodsPubMed, Science Direct, SAGE were searched to collect data about demographic, clinical characteristics, and comorbidities of confirmed COVID-19 patients from January 1, 2020, to May 17, 2020. Meta-analysis was performed with the use of Review Manager 5.3ResultsEighty-five studies were included in Meta-analysis, including a total number of 67,299 patients with SARS-CoV-2 infection. Males are severely affected or died than females (OR = 2.26, p < 0.00001; OR = 3.59, p < 0.00001) are severely affected, or died by COVID-19 and cases with age ≥50 are at higher risk of death than age <50 years (OR=334.23). Presence of any comorbidity or comorbidities like hypertension, cardiovascular disease, diabetes, cerebrovascular disease, respiratory disease, kidney disease, liver disease, malignancy significantly increased the risk of death compared to survival (OR = 3.46, 3.16, 4.67, 2.45, 5.84, 2.68, 5.62, 2.81,2.16). Among the clinical characteristics such as fever, cough, myalgia, diarrhea, abdominal pain, dyspnea, fatigue, sputum production, chest tightness headache and nausea or vomiting, only fatigue (OR = 1.31, 95%) and dyspnea increased the death significantly (OR= 1.31, 4.57). The rate of death of COVID-19 cases is 0.03-times lower than the rate of survival (OR = 0.03).ConclusionOur result indicates that male patients are affected severely or died, the rate of death is more in the age ≥50 group, and the rate of death is affected by comorbidities and clinical symptoms.
The impact of thermal pasteurization on viral load in human milk and other matrices: A rapid review
Authors: Pitino Michael A. , O’Connor Deborah L. , McGeer Allison J. , Unger Sharon 
Published: May 2020

AbstractHolder pasteurization (62.5°C, 30 min) of human milk (HM) is thought to reduce the risk of transmitting viruses to an infant. Some viruses may be secreted into milk – others may be contaminants. The effect of thermal pasteurization on viruses in HM has yet to be rigorously reviewed. The objective of this study is to characterize the effect of commonly used pasteurization techniques on viruses in HM and non-HM matrices. Databases (MEDLINE, Embase, Web of Science) were searched from inception to April 20th, 2020 for primary research articles assessing the impact of pasteurization on viral load or detection of live virus. Reviews were excluded, as were studies lacking quantitative measurements or those assessing pasteurization as a component of a larger process. Overall, 65,131 reports were identified, and 108 studies included. Pasteurization of HM at a minimum temperature of 56°C-60°C is effective at reducing detectable live virus. In cell culture media or plasma, coronaviruses (e.g., SARS-CoV, SARS-CoV-2, MERS) are highly susceptible to heating at ≥56°C. Although pasteurization parameters and matrices reported vary, all viruses studied, with the exception of parvoviruses, were susceptible to thermal killing. Future research important for the study of novel viruses should standardize pasteurization protocols and should test viral inactivation using a human milk matrix.Novelty bulletsIn all matrices, including human milk, pasteurization at temperatures of 62.5°C was generally sufficient to reduce surviving viral load by several logs or to below the limit of detection.Holder pasteurization (62.5°C, 30 min) of human donor milk should be sufficient to inactivate non-heat resistant viruses, including coronaviruses, if present.
Association of Renin Angiotensin System Blockers with Outcomes in Patients with Covid-19: A Systematic Review and Meta-analysis
Authors: Garg Aakash , Rout Amit , Sharma Abhishek , Fiorello Brittany , Kostis John B. 
Published: May 2020

ABSTRACTBackgroundPatients with cardiovascular disease are at increased risk of critical illness and mortality from Covid-19 disease. Conflicting findings have raised concerns regarding the association of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) use with likelihood or severity of infection during this pandemic.ObjectiveTo study the cumulative evidence for association of ACEI/ARB use with outcomes among patients with confirmed Covid-19.MethodsThe MEDLINE and EMBASE databases were thoroughly searched from November 01, 2019 to May 15, 2020 for studies reporting on outcomes based on ACEI/ARB use in patients with confirmed Covid-19. Preferred reporting items for systematic review and meta-analysis guidelines were used for the present study. Relevant data was collected and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects model.Main Outcome measuresIn-hospital mortality was the primary end of interest. Second end-point was severe or critical illness defined as either need for intensive care unit, invasive mechanical ventilation, or mortality.ResultsFifteen studies with total of 23,822 patients (N ACEI/ARB=6,650) were included in the present analysis. Overall, prevalence of ACEI/ARB use ranged from 7.7% to 46.2% across studies. Among 10 studies, patients using ACEI/ARB had similar odds of mortality [OR 1.03 (0.69-1.55)] and severe or critical illness [1.18 (0.91-1.54)] compared to those not on ACEI/ARB. In an analysis restricted to patients with hypertension, ACEI/ARB use was associated with significantly lower mortality [0.64 (0.45-0.89)], while the odds of severe/critical illness [0.76(0.52-1.12); p=0.16] remained non-significant compared with non-ACEI/ARB users.ConclusionThere is no evidence for increased risk of severe illness or mortality in patients using ACEI/ARB compared with non-users. In patients with hypertension, ACE/ARB use might be associated with reduced mortality, however these findings need to be confirmed in prospective randomized controlled trials.
Enveloped Virus Inactivation on Personal Protective Equipment by Exposure to Ozone
Authors: Blanchard Emmeline L. , Lawrence Justin D. , Noble Jeffery A. , Xu Minghao , Joo Taekyu , Ng Nga Lee , Schmidt Britney E. , Santangelo Philip J. , Finn M.G. 
Published: May 2020

AbstractOzone is a highly oxidizing gas easily generated from atmospheric oxygen with inexpensive equipment and is commonly used for the disinfection of municipal water, foods, and surfaces. We report tests of the ability of ozone to inactivate enveloped respiratory viruses (influenza A virus and respiratory syncytial virus), chosen as more easily handled surrogates for SARS-CoV-2, on N95 respirators and other personal protective equipment (PPE) commonly used in hospitals. At 20 ppm, an ozone concentration easily achieved by standard commercial equipment, the viruses were inactivated with high efficiency as long as the relative humidity was above a threshold value of approximately 50%. In the absence of humidity control, disinfection is more variable and requires considerably longer exposure under relatively dry conditions. This report extends the observations of a previous publication (http://doi.org/10.1080/01919510902747969) to hospital-relevant materials and provides additional details about the relationship of humidity to the antiviral activity of ozone. Home CPAP disinfection devices using ozone can provide effective results for individuals. Ozone did not appear to degrade any of the materials tested except for elastic bands if strained during treatment (such as by the pressure exerted by stapled attachment to N95 respirators). The filtration efficiency of N95 respirator material was not compromised. Overall, we recommend exposures of at least 40 minutes to 20 ppm ozone and >70% relative humidity at ambient temperatures (21-24°C) for 4-log (99.99%) reduction of viral infectivity on a variety of PPE, including gowns, face shields, and respirators. Shorter exposure times are likely to be effective under these conditions, but at the risk of some variability for different materials. Higher ozone concentrations and higher humidity levels promoted faster inactivation of viruses. Our work suggests that ozone exposure can be a widely accessible method for disinfecting PPE, permitting safer re-use for healthcare workers and patients alike in times of shortage.