bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea
Authors: Osman Amal M , Tong Benjamin K , Landry Shane A , Edwards Bradley A , Joosten Simon A , Hamilton Garun S , Cori Jennifer M , Jordan Amy S , Stevens David , Grunstein Ronald R , McEvoy R Doug , Catcheside Peter G , Eckert Danny J 
Published: April 2020

Abstract

Study Objectives
Quantification of upper airway collapsibility in obstructive sleep apnea (OSA) could help inform targeted therapy decisions. However, current techniques are clinically impractical. The primary aim of this study was to assess if a simple, novel technique could be implemented as part of a continuous positive airway pressure (CPAP) titration study to assess pharyngeal collapsibility.

Methods
A total of 35 participants (15 female) with OSA (mean ± SD apnea–hypopnea index = 35 ± 19 events/h) were studied. Participants first completed a simple clinical intervention during a routine CPAP titration, where CPAP was transiently turned off from the therapeutic pressure for ≤5 breaths/efforts on ≥5 occasions during stable non-rapid eye movement (non-REM) sleep for quantitative assessment of airflow responses (%peak inspiratory flow [PIF] from preceding 5 breaths). Participants then underwent an overnight physiology study to determine the pharyngeal critical closing pressure (Pcrit) and repeat transient drops to zero CPAP to assess airflow response reproducibility.

Results
Mean PIF of breaths 3–5 during zero CPAP on the simple clinical intervention versus the physiology night were similar (34 ± 29% vs. 28 ± 30% on therapeutic CPAP, p = 0.2; range 0%–90% vs. 0%–95%). Pcrit was −1.0 ± 2.5 cmH2O (range −6 to 5 cmH2O). Mean PIF during zero CPAP on the simple clinical intervention and the physiology night correlated with Pcrit (r = −0.7 and −0.9, respectively, p &lt; 0.0001). Receiver operating characteristic curve analysis indicated significant diagnostic utility for the simple intervention to predict Pcrit &lt; −2 and &lt; 0 cmH2O (AUC = 0.81 and 0.92), respectively.

Conclusions
A simple CPAP intervention can successfully discriminate between patients with and without mild to moderately collapsible pharyngeal airways. This scalable approach may help select individuals most likely to respond to non-CPAP therapies.
Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers
Authors: Khodabukus Alastair , Kaza Amulya , Wang Jason , Prabhu Neel , Goldstein Richard , Vaidya Vishal S , Bursac Nenad 
Published: April 2020

Abstract
Traditional serum biomarkers used to assess skeletal muscle damage, such as activity of creatine kinase (CK), lack tissue specificity and sensitivity, hindering early detection of drug-induced myopathies. Recently, a novel four-factor skeletal muscle injury panel (MIP) of biomarkers consisting of skeletal troponin I (sTnI), CK mass (CKm), fatty-acid-binding protein 3 (Fabp3), and myosin light chain 3, has been shown to have increased tissue specificity and sensitivity in rodent models of skeletal muscle injury. Here, we evaluated if a previously established model of tissue-engineered functional human skeletal muscle (myobundle) can allow detection of the MIP biomarkers after injury or drug-induced myotoxicity in vitro. We found that concentrations of three MIP biomarkers (sTnI, CKm, and Fabp3) in myobundle culture media significantly increased in response to injury by a known snake venom (notexin). Cerivastatin, a known myotoxic statin, but not pravastatin, induced significant loss of myobundle contractile function, myotube atrophy, and increased release of both traditional and novel biomarkers. In contrast, dexamethasone induced significant loss of myobundle contractile function and myotube atrophy, but decreased the release of both traditional and novel biomarkers. Dexamethasone also increased levels of matrix metalloproteinase-2 and -3 in the culture media which correlated with increased remodeling of myobundle extracellular matrix. In conclusion, this proof-of-concept study demonstrates that tissue-engineered human myobundles can provide an in vitro platform to probe patient-specific drug-induced myotoxicity and performance assessment of novel injury biomarkers to guide preclinical and clinical drug development studies.
Physician Deaths from Corona Virus Disease (COVID-19)
Authors: Ing Edsel B. , Xu Alis (Qinyuan) , Salimi Ali , Torun Nurhan 
Published: April 2020

ABSTRACTOBJECTIVEThe COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events.METHODOn April 5, 2020, Google internet search was performed using the keywords “doctor” “physician” “death” “COVID” “COVID-19” and “coronavirus” in English and Farsi, and in Chinese using the Baidu search engine.RESULTSWe found 198 physician deaths from COVID-19, but complete details were missing for 49 individuals. The average age of the physicians that died was 63.4 years (range 28 to 90 years) and the median age was 66 years of age. Ninety percent of the deceased physicians were male (175/194). General practitioners and emergency room doctors (78/192), respirologists (5/192), internal medicine specialists (11/192) and anesthesiologists (6/192) comprised 52% of those dying. Two percent of the deceased were epidemiologists (4/192), 2% were infectious disease specialists (4/192), 5% were dentists (9/192), 4% were ENT (8/192), and 4% were ophthalmologists (7/192). The countries with the most reported physician deaths were Italy (79/198), Iran (43/198), China (16/198), Philippines (14/198), United States (9/192) and Indonesia (7/192).CONCLUSIONPhysicians from all specialties may die from COVID, and these deaths will likely increase as the pandemic progresses. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.
Fabrication and Modeling of Recessed Traces for Silicon-Based Neural Microelectrodes
Authors: Nolta Nicholas F , Ghelich Pejman , Han Martin 
Published: April 2020

AbstractChronically-implanted neural microelectrodes are powerful tools for neuroscience research and emerging clinical applications, but their usefulness is limited by their tendency to fail after monthsin vivo. One failure mode is the degradation of insulation materials that protect the conductive traces from the saline environment. Studies have shown that material degradation is accelerated by mechanical stresses, which tend to concentrate on raised topographies such as conducting traces. Therefore, to avoid raised topographies, we developed a fabrication technique that recesses (buries) the traces in dry-etched, self-aligned trenches. The depth of the trenches and the thickness of the traces are matched so that overlying insulation materials are flat, which, according to finite-element modeling, reduces stress concentrations in the insulation material. Here, we provide details on process optimization, modeling of intrinsic stress, and characterization using SEM, focused ion-beam cross sections, profilometry, and electrochemical impedance testing. The technique requires no extra masks, is easy to integrate with existing processes, and produces flatness within about 10 nm.
Pulsed Electromagnetic Fields Alleviates Hepatic Oxidative Stress and Lipids Accumulation in db/db mice
Authors: Liu Ying , Zhai Mingming 
Published: April 2020

PurposeNonalcoholic fatty liver disease (NAFLD), affected more than 70 % of patients with type 2 diabetes (T2DM), has become a common metabolic liver disease worldwide. However, the specifically treatments targeting NAFLD have not been found until now. Pulsed electromagnetic fields have positive effects on multiple diseases. However, the effects of PEMF on NAFLD in T2DM require further investigation. The present study assessed the effects of pulsed electromagnetic fields on the liver oxidative stress and lipid accumulation of db/db mice.Patients and methodsAnimals were exposed to 2 h of pulsed electromagnetic fields (15.38 Hz, 2 mT) or sham stimulated, and thereafter sacrificed at 8 weeks later. The biomarkers of oxidative stress, such as MDA, GSSG and GSH levels, were analysed with commercial kits. The activity of liver antioxidant enzymes as CAT, SOD and GSH-Px was detected. Hepatic expressions of CAT, GR, GSH-Px, SOD1, SOD2 and SREBP-1c at protein levels were determined with Western blotting. Hepatic weight was measured and triglyceride accumulation were visualized by Oil Red O staining.ResultsPEMF exposure could protect the liver from oxidative stress injury by decreasing MDA and GSSG level, promoting reduced GSH level, and increasing GSH-Px activity and expression in comparison with sham group. But CAT and SOD activity have no statistic difference as same as CAT, GR, SOD1 and SOD2 expression. Furthermore, PEMF exposure reduced liver weight and triglyceride content. Meanwhile, PEMF exposure ameliorated hepatic steatosis through reducing the expression of SREBP-1c to regulate the lipid synthesis.ConclusionThe present study provides evidence that PEMF could increase antioxidant enzymes activity and alleviate lipid accumulation in fatty liver. This implies that PEMF exposure has beneficial effects for the treatment of NAFLD in accompany with T2DM.
Subthreshold repertoire and threshold dynamics of midbrain dopamine neuron firingin vivo
Authors: Otomo Kanako , Perkins Jessica , Kulkarni Anand , Stojanovic Strahinja , Roeper Jochen , Paladini Carlos A. 
Published: April 2020

AbstractThe firing pattern of ventral midbrain dopamine neurons is controlled by afferent and intrinsic activity to generate prediction error signals that are essential for reward-based learning. Given the absence of intracellularin vivorecordings in the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. By establishing stablein vivowhole-cell recordings of >100 spontaneously active midbrain dopamine neurons in anaesthetized mice, we identified the repertoire of subthreshold membrane potential signatures associated with distinctin vivofiring patterns. We demonstrate that dopamine neuronin vivoactivity deviates from a single spike pacemaker pattern by eliciting transient increases in firing rate generated by at least two diametrically opposing biophysical mechanisms: a transient depolarization resulting in high frequency plateau bursts associated with a reactive, depolarizing shift in action potential threshold; and a prolonged hyperpolarization preceding slower rebound bursts characterized by a predictive, hyperpolarizing shift in action potential threshold. Our findings therefore illustrate a framework for the biophysical implementation of prediction error and sensory cue coding in dopamine neurons by tuning action potential threshold dynamics.
Exploration of endo-xylanase from novel strain ofBacillus velezensisAG20 isolated from the cave of Meghalaya
Authors: Ghosh Arabinda , Mahanta Shravanika , Banerjee Subhro , Baishya Debabrat 
Published: April 2020

ABSTRACTCave sets the example of extreme ecological niche and habitat for diversified microorganisms. Present study involved in the isolation of endoxylanase producing novel strainBacillus velezensisAG20 from the Krem Phyllut cave, Meghalaya, India. Culture dependent studies, molecular phylogentics, RNA secondary folding pattern based on 16S rDNA substantiated the identity of this novel strain.Bacillus velezensisAG20 revealed the superbug quality having resistance against various class of broad-spectrum antibiotics.Bacillus velezensisAG20 revealed biofilm formation over the cell surface in FESEM. Highest cell biomass and xylanase production supported in TB medium, further purified partially to 5.3 fold with 21% yield. Molecular weight of the purified xylanase found to be 45 kDa. Enzyme kinetics and pattern of hydrolysis revealed the evidence for the selection of linear birchwood xylan with Vmax= 21.0 ± 3.0 U/ml, Km = 1.25 mg/ml, Kcat= 1.75/s at optimum pH 7 and temperature 50°C also found significant statistically in Taguchi’s orthogonal design. Conversely, ruled out any exoacting activity against synthetic pNP-xylopyranoside substrate. Endo-xylanase isolated fromBacillus velezensisAG20 was moderately thermostable over temperatures 50 and 60°C. Time dependent hydrolysis of agro-waste sugar cane bagasse depicted the production of xylooligosaccharides (XOS) predominantly xylobiose, xylotriose and xylotetrose. Purified mixed XOS hold their prebiotic potential by promoting the growth of probioticsBifidobacteriumandLactobacillusas well as high stability (~90%) against systemic fluids. Mixed XOS (300 μg/ml) displayed anti-proliferation activities by reducing the growth of HT-29 and Caco-2 cells significantly 90% and 75%, respectively, after 48 h.IMPORTANCEExtremophiles dwelling inside the caves have laden with the extraordinary capabilities of bioconversion by nature. The pristine ecological niche inside the cave, absence of proper light and air, supports the livelihood of novel microorganisms. In India, Meghalaya is hoisting longest caves in the East Khasi Hills, providing conducive environment for novel bacterial strains. With the prime objective of isolating novel bacterial strains that produce extracellular xylanase our studies have been carried out. Considering the present industrial demand for nutraceutical, prebiotics, anti-proliferating agents and biofuels by the conversion of lignocellulosic biomass (LCB), novel enzymes are required. Xylanases from bacterial origin play a significant role in conversion of LCB into oligosaccharides. Therefore, exploration and characterization of xylanase producing novel isolate from cave may pave the new arena for the production of prebiotic and anti-inflammatory oligosaccharides from agro-waste.
Greater Effect of Polygenic Risk Score for Alzheimer’s Disease Among Younger Cases who are Apolipoprotein E-ε4 Carriers
Authors: Fulton-Howard Brian , Goate Alison M. , Adelson Robert P. , Koppel Jeremy , Gordon Marc L. ,   Alzheimer’s Disease Genetics Consortium, Barzilai Nir , Atzmon Gil , Davies Peter , Freudenberg-Hua Yun 
Published: April 2020

AbstractTo evaluate how age and Apolipoprotein E-ε4 (APOE4) status interact with APOE- independent polygenic risk score (PRSnon-APOE), we estimated PRSnon-APOE in superagers (age ≥ 90 years, N=346), 89- controls (age 60-89, N=2,930) and Alzheimer’s Disease (AD) cases (N=1,760). Employing superagers, we see a nearly five times greater odds ratio (OR) for AD comparing the top PRSnon-APOE decile to the lowest decile (OR=4.82, P=2.5×10-6), which is twice the OR as using 89- controls (OR=2.38, P=4.6×10-9). Thus PRSnon-APOE is correlated with age, which in turn is associated with APOE. Further exploring these relationships, we find that PRSnon-APOE modifies age-at-onset among APOE4 carriers, but not among non-carriers. More specifically, PRSnon-APOE in the top decile predicts an age-at-onset five years earlier compared to the lowest decile (70.1 vs 75.0 years; t-test P=2.4×10-5) among APOE4 carriers. This disproportionally large PRSnon-APOE among younger APOE4-positive cases is reflected in a significant statistical interaction between APOE4 status and age-at-onset (β=-0.02, P=4.8×10-3) as a predictor of PRSnon-APOE. Thus, the known AD risk variants are particularly detrimental in young APOE4 carriers.Disclosure StatementAMG has consulted for Eisai, Biogen, Pfizer, AbbVie, Cognition Therapeutics and GSK. She also served on the SAB at Denali Therapeutics from 2015-2018. YFH co-owns stock and stock options of Regeneron Pharmaceuticals. All other authors have no interests to declare.
Defining high-value information for COVID-19 decision-making
Authors:   COVID-19 Statistics, Policy modeling and Epidemiology Collective (C-SPEC), Bilinski Alyssa , Birger Ruthie , Burn Samantha , Chitwood Melanie , Clarke-Deelder Emma , Copple Tyler , Eaton Jeffrey , Ehrlich Hanna , Erlendsdottir Margret , Eshghi Soheil , Farid Monica , Fitzpatrick Meagan , Giardina John , Gonsalves Gregg , Hsieh Yuli Lily , Iloglu Suzan , Kao Yu-Han , MacKay Evan , Menzies Nick , Mulaney Bianca , Paltiel David , Perniciaro Stephanie , Phillips Maile , Rich Katherine , Salomon Joshua A , Sherak Raphael , Shioda Kayoko , Swartwood Nicole , Testa Christian , Thornhill Thomas , White Elizabeth , Williamson Anne , York Anna , Zhu Jinyi , Zhu Lin 
Published: April 2020

AbstractInitial projections from the first generation of COVID-19 models focused public attention on worst-case scenarios in the absence of decisive policy action. These underscored the imperative for strong and immediate measures to slow the spread of infection. In the coming weeks, however, as policymakers continue enlisting models to inform decisions on COVID-19, answers to the most difficult and pressing policy questions will be much more sensitive to underlying uncertainties. In this study, we demonstrate a model-based approach to assessing the potential value of reducing critical uncertainties most salient to COVID-19 decision-making and discuss priorities for acquiring new data to reduce these uncertainties. We demonstrate how information about the impact of non-pharmaceutical interventions could narrow prediction intervals around hospitalizations over the next few weeks, while information about the prevalence of undetected cases could narrow prediction intervals around the timing and height of the peak of the epidemic.
The Aryl Hydrocarbon Receptor Promotes Differentiation During Mouse Preimplantational Embryo Development
Authors: Nacarino-Palma Ana , Merino Jaime M. , Fernández-Salguero Pedro M. 
Published: April 2020

ABSTRACTMammalian embryogenesis is a complex process controlled by transcription factors that dynamically regulate the balance between pluripotency and differentiation. Transcription factor AhR is known to regulateOct4/Pou5f1andNanog, both essential genes in pluripotency, stemness and early embryo development. Yet, the molecular mechanisms controllingOct4/Pou5f1andNanogduring embryo development remain largely unidentified. Here, we show that AhR is required for proper embryo differentiation by regulating pluripotency factors and by maintaining adequate metabolic activity. AhR lacking embryos (AhR-/-) showed a more pluripotent phenotype characterized by a delayed expression of differentiation markers of the first and second cell divisions. Accordingly, central pluripotency factors OCT4/POU5F1, NANOG, and SOX2 were overexpressed inAhR-/- embryos at initial developmental stages. An altered intracellular localization of these factors was observed in absence of AhR and, importantly, OCT4 had an opposite expression pattern with respect to AhR from the 2-cell stage to blastocyst, suggesting a negative regulatory mechanism of OCT4/POU5F by AhR. Hippo signalling, rather than being repressed, was upregulated in very earlyAhR-/- embryos, possibly contributing to their undifferentiation at later stages. Consistently, AhR-null blastocysts overexpressed the early marker of inner cell mass (ICM) differentiation Sox17 whereas downregulated extraembryonic differentiation-driving genesCdx2andGata3. Moreover, the persistent pluripotent phenotype ofAhR-/- embryos was supported by an enhanced glycolytic metabolism and a reduction in mitochondrial activity. We propose that AhR is a regulator of pluripotency and differentiation in early mouse embryogenesis and that its deficiency may underline the reduced viability and increased resorptions of AhR-null mice.
Generating functional protein variants with variational autoencoders
Authors: Hawkins-Hooker Alex , Depardieu Florence , Baur Sebastien , Couairon Guillaume , Chen Arthur , Bikard David 
Published: April 2020

AbstractThe design of novel proteins with specified function and controllable biochemical properties is a longstanding goal in bio-engineering with potential applications across medicine and nanotechnology. The vast expansion of protein sequence databases over the last decades provides an opportunity for new approaches which seek to learn the sequence-function relationship directly from natural sequence variation. Advances in deep generative models have led to the successful modelling of diverse kinds of high-dimensional data, from images to molecules, allowing the generation of novel, realistic samples. While deep models trained on protein sequence data have been shown to learn biologically meaningful representations helpful for a variety of downstream tasks, their potential for direct use in protein engineering remains largely unexplored. Here we show that variational autoencoders trained on a dataset of almost 70000 luciferase-like oxidoreductases can be used to generate novel, functional variants of theluxAbacterial luciferase. We propose separate VAE models to work with aligned sequence input (MSA VAE) and raw sequence input (AR-VAE), and offer evidence that while both are able to reproduce patterns of amino acid usage characteristic of the family, the MSA VAE is better able to capture long-distance dependencies reflecting the influence of 3D structure. To validate the practical utility of the models, we used them to generate variants ofluxAwhose function was tested experimentally. As further evidence of the practicality of these methods for design, we showed that conditional variants of both models could be used to increase the solubility ofluxAwithout disrupting function. Altogether 18/24 of the variants generated using the AR-VAE and 21/23 variants generated using the MSA VAE retained some luminescence activity, despite containing as many as 35 differences relative to any training set sequence. These results demonstrate the feasibility of using deep generative models to explore the space of possible protein sequences and generate useful variants, providing a method complementary to rational design and directed evolution approaches.
The role of auxiliary parameters in evaluating voxel-wise encoding models for 3T and 7T BOLD fMRI data
Authors: Boos Moritz , Guntupalli J. Swaroop , Rieger Jochem W. , Hanke Michael 
Published: April 2020

AbstractIn neuroimaging, voxel-wise encoding models are a popular tool to predict brain activity elicited by a stimulus. To evaluate the accuracy of these predictions across multiple voxels, one can choose between multiple quality metrics. However, each quality metric requires specifying auxiliary parameters such as the number and selection criteria of voxels, whose influence on model validation is unknown. In this study, we systematically vary these parameters and observe their effects on three common quality metrics of voxel-wise encoding models in two open datasets of 3- and 7-Tesla BOLD fMRI activity elicited by musical stimuli. We show that such auxiliary parameters not only exert substantial influence on model validation, but also differ in how they affect each quality metric. Finally, we give several recommendations for validating voxel-wise encoding models that may limit variability due to different numbers of voxels, voxel selection criteria, and magnetic field strengths.