bluuebunny/crossref_metadata_2025_split huggingface dataset:
When “Shelter-in-Place” Isn’t Shelter That’s Safe: A Rapid Analysis of Domestic Violence Case Differences During the COVID-19 Pandemic and Stay-at-Home Orders
Authors: McLay Molly M. 
Published: June 2020

AbstractPurposeThis study explored the COVID-19 pandemic’s impacts on domestic violence (DV) with the following research questions: 1) Did DV occurring during the pandemic differ on certain variables from cases occurring on a typical day the previous year? 2) Did DV occurring after the implementation of shelter-in-place orders differ (on these same variables) from cases occurring prior to shelter-in-place orders?MethodsTwo logistic regression models were developed to predict DV case differences before and during the pandemic. DV reports (N=4618) were collected from the Chicago Police Department. Cases from March 2019 and March 2020 were analyzed based on multiple variables. One model was set to predict case differences since the pandemic began, and another model was set to predict case differences during the shelter-in-place period later that month.ResultsBoth models were significant with multiple significant predictors. During the pandemic period, cases with arrests were 20% less likely to have occurred, and cases at residential locations were 22% more likely to have occurred. During the shelter-in-place period, cases at residential locations were 64% more likely to have occurred, and cases with child victims were 67% less likely to have occurred.ConclusionsThis study offers a rapid analysis of DV case differences since the pandemic and shelter-in-place began. Additional variables and data sources could improve model explanatory power. Research, policy, and practice in this area must pivot to focus on protecting children whose access to mandated reporters has decreased and moving victims out of dangerous living situations into safe spaces.
A comparative evaluation of a dye-based and probe-based RT-qPCR assay for the screening of SARS-CoV-2 using individual and pooled-sample testing
Authors: Verdugo Claudio , Plaza Anita , Acosta-Jamett Gerardo , Castro Natalia , Gutiérrez Josefina , Hernández Carlos , López-Joven Carmen , Loncoman Carlos A. , Navarrete Claudio , Ramírez-Reveco Alfredo , Romero Alex , Silva Andrea , Vega Matías , Verdugo Cristóbal , Vergara-Amado Jonathan 
Published: June 2020

ABSTRACTEffective interventions are mandatory to control the transmission and spread of SARS-CoV-2, a highly contagious virus causing devastating effects worldwide. Cost-effective approaches are pivotal tools required to increase the detection rates and escalate further in massive surveillance programs, especially in countries with limited resources that most of the efforts have focused on symptomatic cases only. Here, we compared the performance of the RT-qPCR using an intercalating dye with the probe-based assay. Then, we tested and compared these two RT-qPCR chemistries in different pooling systems: after RNA extraction (post-RNA extraction) and before RNA extraction (pre-RNA extraction) optimizing by pool size and template volume. We evaluated these approaches in 610 clinical samples. Our results show that the dye-based technique has a high analytical sensitivity similar to the probe-based detection assay used worldwide. Further, this assay may also be applicable in testing by pool systems post-RNA extraction up to 20 samples. However, the most efficient system for massive surveillance, the pre-RNA extraction pooling approach, was obtained with the probe-based assay in test up to 10 samples adding 13.5 µL of RNA template. The low cost and the potential use in pre-RNA extraction pool systems, place of this assays as a valuable resource for scalable sampling to larger populations. Implementing a pool system for population sampling results in an important savings of laboratory resources and time, which are two key factors during an epidemic outbreak. Using the pooling approaches evaluated here, we are confident that it can be used as a valid alternative assay for the detection of SARS-CoV-2 in human samples.
Therapeutic Anticoagulation Is Associated with Decreased Mortality in Mechanically Ventilated COVID-19 Patients
Authors: Trinh Muoi A. , Chang Daniel R. , Govindarajulu Usha S. , Kane Erica , Fuster Valentin , Kohli-Seth Roopa , Ahmed Sanam , Levin Matthew A , Chen Martin D. 
Published: June 2020

AbstractObjectiveTo evaluate differences in morbidity and mortality among mechanically ventilated patients with COVID-19 treated with therapeutic versus prophylactic anticoagulation.MethodsWe performed a retrospective review of 245 COVID-19 positive patients admitted to the ICU requiring mechanical ventilation from March 1, 2020 through April 11, 2020 at Mount Sinai Hospital. Patients either received therapeutic anticoagulation for a minimum of 5 days or prophylactic dose anticoagulation. Morbidity and mortality data were analyzed.ResultsPropensity score (PS) weighted Kaplan-Meier plot demonstrated a survival advantage (57% vs. 25%) at 35 days from admission to the ICU in patients who received therapeutic anticoagulation for a minimum of 5 days compared to those who received prophylactic anticoagulation during their hospital course. A multivariate Cox proportional hazard regression model with PS weights to adjust for baseline differences found a 79% reduction in death in patients who were therapeutically anticoagulated HR 0.209, [95% Cl (0.10, 0.46), p < 0.001]. Bleeding complications were similar between both groups. A 26.7% [95% Cl (1.16, 1.39), p< 0.001] excess mortality was found for each 1 mg/dL rise in serum creatinine over a 21-day period.ConclusionsTherapeutic anticoagulation is associated with a survival advantage among patients with COVID-19 who require mechanical ventilation in the ICU.
Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment
Authors: Iwanami Shoya , Ejima Keisuke , Su Kim Kwang , Noshita Koji , Fujita Yasuhisa , Miyazaki Taiga , Kohno Shigeru , Miyazaki Yoshitsugu , Morimoto Shimpei , Nakaoka Shinji , Koizumi Yoshiki , Asai Yusuke , Aihara Kazuyuki , Watashi Koichi , Thompson Robin N. , Shibuya Kenji , Fujiu Katsuhito , Perelson Alan S. , Iwami Shingo , Wakita Takaji 
Published: June 2020

AbstractDevelopment of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified throughin vitroandin vivomodels, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.One Sentence SummaryStudy design to evaluate antiviral effect.
Venous Access Problems in Sickle Cell Disease Patients: Results of Upper Extremity Thrombolysis in the setting of Catheter Related Thrombosis
Authors: Martin Jonathan G. 
Published: June 2020

AbstractPurposeSickle cell disease is the most common monogenic disorder. All the elements of Virchow’s triad – hypercoagulability, endothelial dysfunction and impaired blood flow – are present in sickle cell disease patients, and can lead to thrombosis and vaso-occlusive crises. Central venous catheters are commonly used in sickle cell disease patients for rapid transfusion to avoid a vaso-occlusive crisis or for treatment after crises onset. However, central venous catheters themselves are an additional source for thrombus formation. We investigate a single day thrombolysis protocol for the treatment of catheter related thrombosis.Materials and MethodsWe present an Institutional Review Board approved retrospective analysis spanning from June 2016 to April 2018 evaluating upper extremity thrombolysis in the setting of catheter related thrombosis. All patients underwent a similar protocol involving peripheral upper extremity access, pharmomechanical thrombolysis, and angioplasty, which is described in detail. In 33% of the procedures, a recalcitrant stenosis was then stented. Maximal balloon size and stent sizes are included for reference.ResultsIn follow up, one patient had a severe complication possibly related to the large thrombus burden, and expired. One patient who did not initially have recalcitrant stenosis and therefor did not have a stent placed during the initial procedure, had recurrent stenosis and thrombosis 6 months after the initial procedure, and had repeat pharmomechanical thrombolysis performed, with stent placement at that time. The other procedures were without complication, and the upper extremity and central venous systems remained patent at most recent follow-up, up to 30 months post procedure.ConclusionsIn the circumstance of severe catheter related thrombosis, we present a protocol which can be considered for therapeutic use without further intervention required in 78% of cases at 2 years.
How Efficient Can Non-Professional Masks Suppress COVID-19 Pandemic?
Authors: Chen Yejian , Dong Meng 
Published: June 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen non-pharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR) γ. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor γ4 with respect to the basic reproduction number R0, if the face masks with 70% < γ < 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.
Impact of social media on knowledge dissemination between physicians during COVID-19 virus outbreak: A cross sectional survey
Authors: Mohamed-Hussein Aliae AR , Makhlouf Nahed A , Yassa Heba A , Makhlouf Hoda A 
Published: June 2020

AbstractBackgroundSocial media became an alternative platform for communicating during medical crisis as COVID-19 pandemic.Aim of the study1- to describe the use of social media by Physicians during Covid-19 outbreak 2- to determine how physicians obtain their medical information about the emerging disease 3- to determine physicians practice and how do they use the information received.MethodsThis is a cross-sectional web-based anonymous survey. Data were collected from Health Care Professional (HCPs) via fulfilling online designed questionnaire. Descriptive statistics with frequencies and percentages are presented. Results: The response rate was 66.2% (232/350). Smart phones was the most commonly used (94.8%) followed by laptops (13.4%). Facebook was used by 65.8% and WhatsApp by 52.8%. The data shared were medical newsletters (68%) and educational movies (52.2%). Source of information were mainly professional local pages (60.8%) then WHO pages (53.7%). Physicians shared trusted information (66.7%) and they confirmed the data were correct before publishing in 55.5%. They shared mainly WHO announcements and alerts (44%), professional lectures (32.1%) and 13.3% shared comics. Overall, 71% perceived lots of data about the cause of disease, clinical picture, daily spread, fatality rate and alert of the countries.ConclusionPhysicians are active users of social media. Facebook and WhatsApp are useful platforms to spread right data about diseases during pandemics. Most physicians are positive towards data published; they watch, read and disseminate trusted informations.
Cortical re-organization after traumatic brain injury elicited using functional electrical stimulation therapy: A case report
Authors: Milosevic Matija , Nakanishi Tomoya , Sasaki Atsushi , Yamaguchi Akiko , Nomura Taishin , Popovic Milos R. , Nakazawa Kimitaka 
Published: June 2020

AbstractFunctional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up. In total, 36 sessions of FEST were applied to enable upper-limb grasping and reaching movements. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), indicating cortical and/or subcortical inhibition after each intervention. At the same time, no changes in motor evoked potentials (MEPs) were observed. Long-term assessments showed increased MEP corticospinal excitability after 12-weeks of FEST, which seemed to remain during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, functional magnetic resonance imaging (fMRI) data showed M1 activations increased during hand grip and finger pinch tasks after 12-weeks of FEST, while gradual reduction of activity compared to after the intervention was seen during follow-ups. Widespread changes were seen not only in the M1, but also sensory, parietal rostroventral, supplementary motor, and premotor areas in both contralateral and ipsilateral hemispheres, especially during the finger pinch task. Drawing test performance showed improvements after the intervention and during follow-ups. Our findings suggest that task-specific and repetitive FEST can effectively increase cortical activations by integrating voluntary motor commands and sensorimotor network through FES. Overall, our results demonstrated cortical re-organization and improved fine motor function in an individual with chronic TBI after FEST.
HumanSYNGAP1Regulates the Development of Neuronal Activity by Controlling Dendritic and Synaptic Maturation
Authors: Llamosas Nerea , Arora Vineet , Vij Ridhima , Kilinc Murat , Bijoch Lukasz , Rojas Camilo , Reich Adrian , Sridharan BanuPriya , Willems Erik , Piper David R. , Scampavia Louis , Spicer Timothy P. , Miller Courtney A. , Holder J. Lloyd , Rumbaugh Gavin 
Published: June 2020

AbstractSYNGAP1is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy.De novoloss-of-function variants in this gene cause a neurodevelopmental disorder defined by cognitive impairment, social-communication disorder, and early-onset seizures. Cell biological studies in mouse and rat neurons have shown thatSyngap1regulates developing excitatory synapse structure and function, with loss-of-function variants driving formation of larger dendritic spines and stronger glutamatergic transmission. However, studies to date have been limited to mouse and rat neurons. Therefore, it remains unknown howSYNGAP1loss-of-function impacts the development and function of human neurons. To address this, we employed CRISPR/Cas9 technology to ablateSYNGAP1protein expression in neurons derived from a human induced pluripotent stem cell line (hiPSC). Reducing SynGAP protein expression in developing hiPSC-derived neurons enhanced dendritic morphogenesis, leading to larger neurons compared to those derived from isogenic controls. Consistent with larger dendritic fields, we also observed a greater number of morphologically defined excitatory synapses in cultures containing these neurons. Moreover, neurons with reduced SynGAP protein had stronger excitatory synapses and expressed synaptic activity earlier in development. Finally, distributed network spiking activity appeared earlier, was substantially elevated, and exhibited greater bursting behavior inSYNGAP1null neurons. We conclude thatSYNGAP1regulates the postmitotic maturation of human neurons made from hiPSCs, which influences how activity develops within nascent neural networks. Alterations to this fundamental neurodevelopmental process may contribute to the etiology ofSYNGAP1-related disorders.
Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles
Authors: Wattiez A-S. , Castonguay W.C. , Gaul O.J. , Waite J.S. , Schmidt C.M. , Reis A. , Rea B.J. , Sowers L.P. , Cintrón-Pérez C.J. , Vázquez-Rosa E. , Pieper A.A. , Russo A.F. 
Published: June 2020

AbstractChronic complications of traumatic brain injury (TBI) represent one of the greatest financial burdens and sources of suffering in society today. A substantial number of these patients suffer from post-traumatic headache (PTH), which is typically associated with tactile allodynia. Unfortunately, this phenomenon has been under-studied, in large part due to the lack of well-characterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of two non-penetrating models of PTH. We show that multifactorial TBI, consisting of aspects of impact, acceleration/deceleration, and blast wave exposure, produces long term tactile hypersensitivity and central sensitization, phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show more severe phenotype with repetitive daily injury for three days, compared to either one or three successive injuries in a single day, providing new insight into patterns of injury that may place patients at greater risk of developing PTH. Importantly, even after recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury had persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide (CGRP) and sodium nitroprusside, a nitric oxide donor. Our results offer new tools for studying PTH, as well as preclinical support for a pathophysiologic role of CGRP in this condition.SummaryTwo models of post-traumatic headache after traumatic brain injury provide novel laboratory tools and insights in relative risks of injury and therapeutic opportunities.
Neuronal Population Models Reveal Specific Linear Conductance Controllers Sufficient to Rescue Preclinical Disease Phenotypes
Authors: Allam Sushmita L. , Rumbell Timothy H. , Trong Tuan Hoang , Parikh Jaimit , Kozloski James R. 
Published: June 2020

AbstractObjectiveDuring the preclinical phase of drug development, potential drug candidates are often screened for their ability to alleviate certainin vitroelectrophysiological features among neurons. This ability is assessed by measuring treatment outcomes using the population mean, both across different cells and different animals. The go/no-go decision for progressing a drug to a clinical trial is then based on ‘average effects’, yet these measures may not be sufficient to mitigate clinical end point risk. Population-based modeling is widely used to represent the intrinsic variability of electrophysiological features among healthy, disease and drug treated neuronal phenotypes. We pursued a method for optimizing therapeutic target design by identifying a single coherent set of ion channel targets for recovery of the healthy (Wild type) cellular phenotype simultaneously across multiple measures. Specifically, we aimed to determine the set of target modulations that best recover a heterogeneous Huntington’s disease (HD) population of model neurons into a multivariate region of phenotypic measurements corresponding to the healthy excitability profile of a heterogenous Wild type (WT) population of model neurons.MethodsOur approach combines mechanistic simulations with populations modeling of striatal neurons using evolutionary algorithms for population optimization to design ‘virtual drugs’. We introduce efficacy metrics to score population of model outcomes and use these to rank our virtual candidates.ResultsWe found that virtual drugs identified using heuristic approaches performed better than single target modulators and those derived from standard classification methods. We compare a real drug to the virtual candidates and demonstrate a novelin silicotriaging method.
FOXA1/2 depletion drives global reprogramming of differentiation state and metabolism in a human liver cell line and inhibits differentiation of human stem cell-derived hepatic progenitor cells
Authors: Warren Iyan , Moeller Michael M. , Guiggey Daniel , Chiang Alexander , Maloy Mitchell , Ogoke Ogechi , Groth Theodore , Mon Tala , Meamardoost Saber , Liu Xiaojun , Thompson Sarah , Szeglowski Antoni , Thompson Ryan , Chen Peter , Paulmurugan Ramasamy , Yarmush Martin L. , Kidambi Srivatsan , Parashurama Natesh 
Published: June 2020

ABSTRACTFOXA factors are critical members of the developmental gene regulatory network (GRN) composed of master transcription factors (TF) which regulate murine cell fate and metabolism in the gut and liver. How FOXA dictates human liver cell fate, differentiation, and simultaneously regulate metabolic pathways is poorly understood. Here, we aimed to determine the role of FOXA2 (and FOXA1 which is believed to compensate for FOXA2) in hepatic differentiation and cell metabolism in a human hepatic cell line (HepG2). siRNA targeting of FOXA1 and FOXA2 in human hepatic (HepG2) cells and during hepatic differentiation significantly downregulated albumin (p < 0.05) and GRN TF gene expression (HNF4A, HEX, HNF1B, TBX3) (p < 0.05) and significantly upregulated endoderm/gut/hepatic endoderm markers (goosecoid (GSC), FOXA3, and GATA4), gut TF (CDX2), pluripotent TF (NANOG), and neuroectodermal TF (PAX6) (p < 0.05), all consistent with a partial/transient cell reprogramming. shFOXA1/2 targeting resulted in similar findings and demonstrated evidence of reversibility. RNA-seq followed by bioinformatic analysis of shFOXA1/2 knockdown HepG2 cells demonstrated 235 significant downregulated genes and 448 upregulated genes, including upregulation of markers for alternate germ layers lineages (cardiac, endothelial, muscle) and neurectoderm (eye, neural). We found widespread downregulation of glycolysis, citric acid cycle, mitochondrial genes, and alterations in lipid metabolism, pentose phosphate pathway, and ketogenesis. Functional metabolic analysis agreed with these findings, demonstrating significantly diminished glycolysis and mitochondrial respiration, and accumulation of lipid droplets. We hypothesized that FOXA1/2 inhibit the initiation of human liver differentiationin vitro. During hPSC-hepatic differentiation, siRNA knockdown demonstrated de-differentiation and unexpectedly, activation of pluripotency factors and neuroectoderm. shRNA knockdown demonstrated similar results and activation of SOX9 (hepatobiliary). These results demonstrate complex effects of FOXA1/2 on hepatic GRN effecting de-differentiation and metabolism with applications in studies of cancer, differentiation, and organogenesis.