bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum bilirubin level correlates with mortality in patients with traumatic brain injury
Authors: Wang Ruoran , He Min , Xu Jianguo 
Published: June 2020

Abstract
As a catabolic product of hemoglobin, bilirubin has been confirmed playing an important role in the development of various central nervous system disease. The aim of this study is to explore the correlation between serum bilirubin level and mortality in patients with traumatic brain injury (TBI).
Patients admitted with traumatic brain injury (TBI) in our hospital between January 2015 and January 2018 were enrolled in this study. Clinical and laboratory data of 361 patients were retrospectively collected to explore the independent risk factors of mortality.
The comparison of baseline characteristics showed that non-survivors had lower Glasgow Coma Scale (GCS) (P < .001) and higher level of serum total bilirubin (TBIL) (P < .001) and direct bilirubin (DBIL) (P < .001). We found that only GCS (P < .001), glucose (P < .001), lactate dehydrogenase (LDH) (P = .042) and DBIL (P = .005) were significant risk factors in multivariate logistic regression analysis. GCS and DBIL had comparable AUC value (0.778 vs 0.750, P > .05) on predicting mortality in TBI patients. The AUC value of the combination of GCS and DBIL is higher than the single value of these two factors (P < .05). Moreover, predictive model 1 consisted of GCS, glucose, LDH and DBIL had the highest AUC value of 0.894.
DBIL is a significant risk factor of mortality in TBI patients. Assessing the level of DBIL is beneficial for physicians to evaluate severity and predict outcome for TBI patients.
Use sonoelastography to predict the reparability of large-to-massive rotator cuff tears
Authors: Tseng Yu-Hsuan , Chou Wen-Yi , Wu Kuan-Ting , Chang Ching-Di , Chen Yi-Cun , Huang Yu-Chi , Lin Wei-Che , Chen Po-Cheng 
Published: June 2020

Abstract

Introduction:
Most symptomatic large-to-massive rotator cuff tears (RCTs) should be operated, but the surgical reparability depended on the degree of rotator cuff muscle atrophy or fatty infiltration. The orthopedic surgeons will decide whether the teared stump is reparable during the surgery, but preoperative evaluation can be done by some assessment tools. Magnetic resonance imaging (MRI) was used in recent studies to predict the reparability of large-to-massive RCTs, but the clinical availability was not as good as ultrasound. We hypothesize that the ultrasound elastography can predict the reparability of large-to-massive RCTs.

Methods:
This is a prospective observational study and participants with large-to-massive RCTs who are going to have surgeries will be included. Out investigators will evaluate the shoulder passive range of motion (ROM) and strength of all participants. Participants’ degree of shoulder pain and activities of daily living (ADLs) will be assessed by American Shoulder and Elbow Surgeons (ASES) score. The ultrasound elastography will be used to evaluate the tissue quality of supraspinatus muscle and infraspinatus muscle. To test the reliability of the ultrasound elastography, two physicians will perform the ultrasound elastography independently and twenty participants will be selected for the reliability test. Besides, MRI will be used to evaluate the size of tear, the degree of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, the orthopedic surgeons will perform surgeries and decide whether the teared stump can be completely repaired intraoperatively. The primary analysis is the predictive validity of ultrasound elastography for the reparability of large-to-massive RCTs. Before the predictive validity of ultrasound elastography is measured, our investigators will assess the reliability of ultrasound elastography when administered to cases with large-to-massive RCTs, and we will check the correlations between the findings of ultrasound elastography and MRI.

Discussion:
The outcome will provide the evidence of ultrasound elastography for preoperative evaluation of large-to-massive RCTs. The relationships between the findings of ultrasound elastography and MRI will also be examined for further analysis.

Trial registration:
Clinicaltrials.gov NCT03682679. Date of Registration: 25 September 2018, https://clinicaltrials.gov/ct2/show/NCT03682679?cond=rotator+cuff&cntry=TW&draw=2&rank=1.
Does Tc-99m ECD ictal brain SPECT have incremental value in localization of epileptogenic zone and predicting postoperative seizure freedom in cases with discordant video electroencephalogram and MRI findings?
Authors: Pawar Shwetal Uday , Ravat Sangeeta Hasmukh , Muzumdar Dattatraya Prakash , Sankhe Shilpa Sushilkumar , Chheda Akash Harakchand , Manglunia Ashmi Shyam , Maldar Arnaaz Noormohamed 
Published: June 2020

Objective
Localization of epileptogenic focus in drug-refractory epilepsy using Tc-99m ethylene cystine dimer (ECD) brain single photon emission computed tomography (SPECT) is less studied in patients with discordant findings on video electroencephalogram (VEEG) and MRI. The study was done to evaluate brain SPECT for epileptogenic focus localization and postoperative seizure freedom.

Methods
Epilepsy patients with discordant VEEG and MRI findings underwent brain SPECT at ictal and interictal phases. Various groups unilateral/bilateral mesial temporal sclerosis (MTS), solitary and multifocal lesional, nonlesional epilepsy were studied for localization of epileptogenic focus and postoperative seizure freedom (>2 years) using Engels classification. Reasons for nonoperability was evaluated in nonoperated group.

Results
SPECT could localize epileptogenic focus in 49/67 (73.13%) and guided surgery in 19/33 (57.57%) patients in operated group. SPECT was useful in 12 (46.12%) of unilateral (2)/bilateral (10) MTS. Postoperative seizure freedom of Engels Class I and II in 22 (66.67%), III in six (18.2%) and IV in one patient based on SPECT findings (P = 0.0086). Overall sensitivity and specificity were 79.3% and 85.7%, respectively. SPECT could localize epileptogenic focus in 23/34 (67.64%) patients in nonoperated group; 10 (29.41%) patients refused for surgery and no epileptogenic focus was localized in the rest of 14 (41.2%).

Conclusion
Ictal SPECT showed incremental value and was found necessary for epileptogenic focus localization and subsequent surgery in unilateral/bilateral MTS in this study. Seizure freedom in patients undergoing epilepsy surgery based on ictal SPECT assistance was comparable to the surgical group not requiring ictal SPECT.
STEMI, Cardiogenic Shock, and Mortality in Patients Admitted for Acute Angiography: Associations and Predictions from Plasma Proteome Data
Authors: Debrabant Birgit , Halekoh Ulrich , Soerensen Mette , Møller Jacob Eifer , Hassager Christian , Frydland Martin , Palstrøm Nicolai , Hjelmborg Jacob , Beck Hans Christian , Rasmussen Lars Melholt 
Published: June 2020

ABSTRACT

Aim:
Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity, and cardiogenic shock (CS) a major cause of hospital mortality after AMI. Especially for ST elevation myocardial infarction (STEMI) patients, fast intervention is essential.
Few proteins have proven clinically applicable for AMI. Most proposed biomarkers are based on a priori hypothesis-driven studies of single proteins, not enabling identification of novel candidates. For clinical use, the ability to predict AMI is important; however, studies of proteins in prediction models are surprisingly scarce.
Consequently, we applied proteome data for identifying proteins associated with definitive STEMI, CS, and all-cause mortality after admission, and examined the ability of the proteins to predict these outcomes.

Methods and Results:
Proteome-wide data of 497 patients with suspected STEMI were investigated; 381 patients were diagnosed with STEMI, 35 with CS, and 51 died during the first year. Data analysis was conducted by logistic and Cox regression modeling for association analysis, and by multivariable LASSO regression models for prediction modeling.
Association studies identified 4 and 29 proteins associated with definitive STEMI or mortality, respectively. Prediction models for CS and mortality (holding two and five proteins, respectively) improved the prediction ability as compared with protein-free prediction models; AUC of 0.92 and 0.89, respectively.

Conclusion:
The association analyses propose individual proteins as putative protein biomarkers for definitive STEMI and survival after suspected STEMI, while the prediction models put forward sets of proteins with putative predicting ability of CS and survival. These proteins may be verified as biomarkers of potential clinical relevance.
SWELL1-LRRC8 complex regulates skeletal muscle cell size, intracellular signalling, adiposity and glucose metabolism
Authors: Kumar Ashutosh , Xie Litao , Ta Chau My , Hinton Antentor J. , Gunasekar Susheel K. , Minerath Rachel A. , Shen Karen , Maurer Joshua M. , Grueter Chad E. , Abel E. Dale , Meyer Gretchen , Sah Rajan 
Published: June 2020

AbstractMaintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism, however the molecular mechanosensor remains unknown. Here, we show that SWELL1 (LRRC8a) functionally encodes a swell-activated anion channel that regulates PI3K-AKT, ERK1/2, mTOR signaling, muscle differentiation, myoblast fusion, cellular oxygen consumption, and glycolysis in skeletal muscle cells. SWELL1 over-expression in SWELL1 KO myotubes boosts PI3K-AKT-mTOR signaling to supra-normal levels and fully rescues myotube formation. Skeletal muscle targeted SWELL1 KO mice have smaller myofibers, generate less forceex vivo, and exhibit reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet, compared to WT mice. These results reveal that the SWELL1-LRRC8 complex regulates insulin-PI3K-AKT-mTOR signalling in skeletal muscle to influence skeletal muscle differentiationin vitroand skeletal myofiber size, muscle function, adiposity and systemic metabolismin vivo.
Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology
Authors: Bussani Rossana , Schneider Edoardo , Zentilin Lorena , Collesi Chiara , Ali Hashim , Braga Luca , Secco Ilaria , Volpe Maria Concetta , Colliva Andrea , Zanconati Fabrizio , Berlot Giorgio , Silvestri Furio , Zacchigna Serena , Giacca Mauro 
Published: June 2020

ABSTRACTCOVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.
Phylogenomics and phylodynamics of SARS-CoV-2 retrieved genomes from India
Authors: Farah Sameera , Atkulwar Ashwin , Praharaj Manas Ranjan , Khan Raja , Gandham Ravikumar , Baig Mumtaz 
Published: June 2020

AbstractThe ongoing SARS-CoV-2 pandemic is one of the biggest outbreaks after the Spanish flu of 1918. Understanding the epidemiology of viral outbreaks is the first step towards vaccine development programs. This is the first phylodynamics study attempted on of SARS-CoV-2 genomes from India to infer its current evolution in the context of an ongoing pandemic. Out of 286 retrieved SARS-CoV-2 whole genomes from India, 138 haplotypes were generated and analyzed. Median-joining network was built to investigate the relatedness of SARS-CoV-2 haplotypes in India. The BDSIR package of BEAST2 was used to calculate the reproduction number (R0) and the infectious rate of the virus. Past and current population trend was investigated using the stamp date method in coalescent Bayesian skyline plot, implemented in BEAST2 and by exponential growth prior in BEAST 1.10.4. Median-joining network reveals two distinct ancestral clusters A and B showing genetic affinities with Wuhan outbreak sample. The network also illustrates the autochthonous development of isolates in a few instances. High basic reproduction number of SARS-nCoV-2 in India points towards the phase of active community transmission. The Bayesian skyline plot revel exponential rise in the effective population size (Ne) of Indian isolates from the first week of January to the first week of April 2020. More genome sequencing and analyses of the virus will be required in coming days to monitor COVID19 after the upliftment of lock down in India.
Novel coronavirus (COVID-19) Outbreak in Iraq: The First Wave and Future Scenario
Authors: Sarhan Adil R. , Flaih Mohammed H. , Hussein Thaer A. , Hussein Khwam R. 
Published: June 2020

AbstractThe first patient with COVID-19 was reported in Iraq on 24 February 2020 for the Iranian student came from Iran. As of 24 May 2020, the confirmed cases of COVID-19 infections reached 4469, with 160 deaths and 2738 patients were recovered from the infection. Significant public health strategies have been implemented by the authorities to contain the outbreak nationwide. Nevertheless however, the number of cases is still rising dramatically. Here, we aim to describe a comprehensive and epidemiological study of all cases diagnosed in Iraq by 24 May 2020. Most of the cases were recorded in Baghdad followed by Basra and Najaf. About 45% of the patients were female (with 31% deaths of the total cases) and 55% were male (with 68% deaths of the total cases). Most cases are between the ages of (20-59) years old, and (30-39) years are the most affected range (19%) Approximately (8%) of cases are children under 10 years old. Iraq has shown a cure rate lower than those reported by Iran, Turkey and Jordan; and higher than Saudi Arabia and Kuwait. Healthcare workers represented about (5%) of the total confirmed cases. These findings enable us to understand COVID-19 epidemiology and prevalence in Iraq that can alert the our community to the risk of this novel coronavirus and serve as a baseline for future studies.
Household finished flooring and soil-transmitted helminth and Giardia infections among children in rural Bangladesh and Kenya: a prospective cohort study
Authors: Benjamin-Chung Jade , Crider Yoshika S. , Mertens Andrew , Ercumen Ayse , Pickering Amy J. , Lin Audrie , Steinbaum Lauren , Swarthout Jenna , Rahman Mahbubur , Parvez Sarker M. , Haque Rashidul , Njenga Sammy M. , Kihara Jimmy , Null Clair , Luby Stephen P. , Colford John M. , Arnold Benjamin F. 
Published: June 2020

AbstractBackgroundSoil-transmitted helminths (STH) and Giardia duodenalis are responsible for a large burden of disease globally. In low-resource settings, household finished floors (e.g., concrete floors) may reduce transmission of STH and G. duodenalis.MethodsIn a prospective cohort of children nested within two randomised trials in rural Bangladesh and Kenya, we estimated associations between household finished flooring and STH and G. duodenalis prevalence. In 2015-2016, we collected stool samples from children aged 2-16 years in rural Bangladesh and Kenya. We detected STH infection using qPCR (Bangladesh N=2,800; Kenya N=3,094) and detected G. duodenalis using qPCR in Bangladesh (N=6,894) and ELISA in Kenya (N=8,899). We estimated adjusted prevalence ratios (aPRs) using log-linear models adjusted for potential confounders.FindingsAt enrolment, 10% of households in Bangladesh and 5% in Kenya had finished floors. In both countries, household finished flooring was associated with lower Ascaris lumbricoides prevalence (Bangladesh aPR: 0.33, 95% CI 0.14, 0.78; Kenya aPR: 0.62, 95% CI 0.39, 0.98) and any STH (Bangladesh aPR: 0.73, 95% CI 0.52, 1.01; Kenya aPR: 0.57, 95% CI 0.37, 0.88). Household finished floors were also associated with lower Necator americanus prevalence in Bangladesh (aPR: 0.52, 95% CI 0.29, 0.94) and G. duodenalis prevalence in both countries (Bangladesh aPR: 0.78, 95% CI 0.64, 0.95; Kenya: aPR: 0.82, 95% CI 0.70, 0.97).InterpretationIn low-resource settings, living in households with finished floors over a two-year period was associated with lower prevalence of G. duodenalis and certain STH in children.FundingBill & Melinda Gates Foundation grant OPPGD759
Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication
Authors: Garcia Gustavo , Sharma Arun , Ramaiah Arunachalam , Sen Chandani , Kohn Donald , Gomperts Brigitte , Svendsen Clive N. , Damoiseaux Robert D , Arumugaswami Vaithilingaraja 
Published: June 2020

ABSTRACTEmergence of a highly contagious novel coronavirus, SARS-CoV-2 that causes COVID-19, has precipitated the current global health crisis with over 479,000 deaths and more than 9.3 million confirmed cases. Currently, our knowledge of the mechanisms of COVID-19 disease pathogenesis is very limited which has hampered attempts to develop targeted antiviral strategies. Therefore, we urgently need an effective therapy for this unmet medical need. Viruses hijack and dysregulate cellular machineries in order for them to replicate and infect more cells. Thus, identifying and targeting dysregulated signaling pathways that have been taken over by viruses is one strategy for developing an effective antiviral therapy. We have developed a high-throughput drug screening system to identify potential antiviral drugs targeting SARS-CoV-2. We utilized a small molecule library of 430 protein kinase inhibitors, which are in various stages of clinical trials. Most of the tested kinase antagonists are ATP competitive inhibitors, a class of nucleoside analogs, which have been shown to have potent antiviral activity. From the primary screen, we have identified 34 compounds capable of inhibiting viral cytopathic effect in epithelial cells. Network of drug and protein relations showed that these compounds specifically targeted a limited number of cellular kinases. More importantly, we have identified mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-Damage Response (DDR) pathways as key cellular signaling pathways critical for SARS-CoV-2 infection. Subsequently, a secondary screen confirmed compounds such as Berzosertib (VE-822), Vistusertib (AZD2014), and Nilotinib with anti SARS-CoV-2 activity. Finally, we found that Berzosertib, an ATR kinase inhibitor in the DDR pathway, demonstrated potent antiviral activity in a human epithelial cell line and human induced pluripotent stem cell (hIPSC)-derived cardiomyocytes. These inhibitors are already in clinical trials of phase 2 or 3 for cancer treatment, and can be repurposed as promising drug candidates for a host-directed therapy of SARS-CoV-2 infection. In conclusion, we have identified small molecule inhibitors exhibiting anti SARS-CoV-2 activity by blocking key cellular kinases, which gives insight on important mechanism of host-pathogen interaction. These compounds can be further evaluated for the treatment of COVID-19 patients following additional in vivo safety and efficacy studies.DisclosuresNone declared.
Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis
Authors: Hofemeier Arne D. , Limon Tamara , Muenker Till M. , Wallmeyer Bernhard , Jurado Alejandro , Afshar Mohammad E. , Ebrahimi Majid , Gilbert Penney M. , Betz Timo 
Published: June 2020

AbstractThe mechanical properties and tension of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue development a key requirement to advance our understanding of muscle function and development. Recently developed elasticin vitroculture chambers allow for raising 3D muscle tissue under controlled conditions and measurements of tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in the muscle tissue. High resolution 3D video microscopy of engineered muscle development, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.
Interplay of BAF and MLL4 promotes cell type-specific enhancer activation
Authors: Park Young-Kwon , Lee Ji-Eun , O’Haren Tommy , McKernan Kaitlin , Yan Zhijiang , Wang Weidong , Peng Weiqun , Ge Kai 
Published: June 2020

AbstractCell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identified BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we showed that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers.