bluuebunny/crossref_metadata_2025_split huggingface dataset:
Month-long Respiratory Support by a Wearable Pumping Artificial Lung in an Ovine Model
Authors: Orizondo Ryan A. , Omecinski Katelin S. , May Alexandra G. , Dhamotharan Vishaal , Frankowski Brian J. , Burgreen Greg W. , Ye Sang-Ho , Kocyildirim Ergin , Sanchez Pablo G. , D’Cunha Jonathan , Wagner William R. , Federspiel William J. 
Published: October 2020

Background.
A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way.

Methods.
The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2–2.5 L/min and 28–30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support.

Results.
Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment.

Conclusions.
These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.
DIAGNOSTIC ACCURACY OF A NOCTURIA SINGLE QUESTION SCALE AS A PREDICTOR OF SEVERITY OF LOWER URINARY TRACT SYMPTOMS IN MEN
Authors: Silva Caroline Santos , Bellucci Carlos Henrique Suzuki , de Paula Miranda Eduardo , Alvaia Mateus Andrade , Tiraboschi Ricardo Brianezi , Bastos Netto Jose Murillo , Gomes Cristiano Mendes , de Bessa Junior José 
Published: October 2020

ABSTRACTObjectivesTo evaluated the accuracy of a single question on nocturia to identify men with moderate and severe LUTS.MethodsWe evaluated men aged ≥40 years who presented for medical evaluation at two different urological clinics. They completed the IPSS and the Nocturia Single Question Scale (NSQS). NSQS consists of a single question assessing nocturia frequency ranging from 0 to 4. The severity of LUTS using NSQS (index test) versus IPSS (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.ResultsThe accuracy of the NSQS to discriminate patients with severe LUTS based on the ROC curve was 75% (CI 95% 73 – 82%; p<0.001).ConclusionPatients without nocturia or a single void/night (NSQS <2) have low probability, while NSQS ≥ 3 has a high probability of having moderate or severe LUTS. NSQS is an acceptable alternative to the IPSS, being a fast and simple tool to identify men according to LUTS’s severity.
Scalable, effective, and rapid decontamination of SARS-CoV-2 contaminated N95 respirators using germicidal ultra-violet C (UVC) irradiation device
Authors: Rathnasinghe Raveen , Karlicek Robert F. , Schotsaert Michael , Koffas Mattheos , Arduini Brigitte , Jangra Sonia , Wang Bowen , Davis Jason L. , Alnaggar Mohammed , Costa Anthony , Vincent Richard , Garcia-Sastre Adolfo , Vashishth Deepak , Balchandani Priti 
Published: October 2020

AbstractImportanceParticulate respirators such as N95 masks are an essential component of personal protective equipment (PPE) for front-line workers. This study describes a rapid and effective UVC irradiation system that would facilitate the safe re-use of N95 respirators and provides supporting information for deploying UVC for decontamination of SARS-CoV-2 during the COVID19 pandemic.ObjectiveTo assess the inactivation potential of the proposed UVC germicidal device as a function of time by using 3M® 8211 - N95 particulate respirators inoculated with SARS-CoV-2.DesignA germicidal UVC device to deliver tailored UVC dose was developed and snippets (2.5cm2) of the 3M-N95 respirator were inoculated with 106 plaque-forming units (PFU) of SARS-CoV-2 and were UV irradiated. Different exposure times were tested (0-164 seconds) by fixing the distance between the lamp (10 cm) and the mask while providing an exposure of at least 5.43 mWcm-2.SettingThe current work is broadly applicable for healthcare-settings, particularly during a pandemic such as COVID-19.ParticipantsNot applicable.Main Outcome(s) and Measure(s)Primary measure of outcome was titration of infectious virus recovered from virus-inoculated respirator pieces after UVC exposure. Other measures included the method validation of the irradiation protocol, using lentiviruses (biosafety level-2 agent) and establishment of the germicidal UVC exposure protocol.ResultsAn average of 4.38×103 PFUml-1(SD 772.68) was recovered from untreated masks while 4.44×102 PFUml-1(SD 203.67), 4.00×102 PFUml-1(SD 115.47), 1.56×102 PFUml-1(SD 76.98) and 4.44×101 PFUml-1(SD 76.98) was recovered in exposures 2s,6s,18s and 54 seconds per side respectively. The germicidal device output and positioning was monitored and a minimum output of 5.43 mWcm-2 was maintained. Infectious SARS-CoV-2 was not detected by plaque assays (minimal level of detection is 67 PFUml-1) on N95 respirator snippets when irradiated for 120s per side or longer suggesting 3.5 log reduction in 240 seconds of irradiation.Conclusions and RelevanceA scalable germicidal UVC device to deliver tailored UVC dose for rapid decontamination of SARS-CoV-2 was developed. UVC germicidal irradiation of N95 snippets inoculated with SARS-CoV-2 for 120s per side resulted in 100% (3.5 log in total) reduction of virus. These data support the reuse of N95 particle-filtrate apparatus upon irradiation with UVC and supports use of UVC-based decontamination of SARS-CoV-2 virus during the COVID19 pandemic.
Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19
Authors: Hernández Cordero Ana I. , Li Xuan , Milne Stephen , Yang Chen Xi , Bossé Yohan , Joubert Philippe , Timens Wim , van den Berge Maarten , Nickle David , Hao Ke , Sin Don D. 
Published: October 2020

AbstractSARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We therefore used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian randomization to combine gene expression quantitative trait loci (eQTLs) from the Lung eQTL (n=1,038) and eQTLGen (n=31,784) studies with published COVID-19 genome-wide association study (GWAS) data from the COVID-19 Host Genetics Initiative. Additionally, we used COLOC to integrate plasma protein quantitative trait loci (pQTL) from the INTERVAL study (n=3,301) with COVID-19-associated loci. Finally, we determined any causal associations between plasma proteins and COVID-19 using multi-variable two-sample Mendelian randomization (MR). We found that the expression of 20 genes in lung and 31 genes in blood was associated with COVID-19. Of these genes, only three (LZTFL1, SLC6A20andABO) had been previously linked with COVID-19 in GWAS. The novel loci included genes involved in interferon pathways (IL10RB, IFNAR2andOAS1). Plasma ABO protein, which is associated with blood type in humans, demonstrated a significant causal relationship with COVID-19 in MR analysis; increased plasma levels were associated with an increased risk of having COVID-19 and risk of severe COVID-19. In summary, our study identified genes associated with COVID-19 that may be prioritized for future investigation. Importantly, this is the first study to demonstrate a causal association between plasma ABO protein and COVID-19.
Modulating the Blood-Brain Barrier by Light Stimulation of Molecular-Targeted Nanoparticles
Authors: Li Xiaoqing , Vemireddy Vamsidhara , Cai Qi , Xiong Hejian , Kang Peiyuan , Li Xiuying , Giannotta Monica , Hayenga Heather , Pan Edward , Sirsi Shashank , Mateo Celine , Kleinfeld David , Greene Chris , Campbell Matthew , Dejana Elisabetta , Bachoo Robert , Qin Zhenpeng 
Published: October 2020

AbstractThe blood-brain barrier (BBB) tightly regulates the entry of molecules into the brain by tight junctions that seals the paracellular space and receptor-mediated transcytosis. It remains elusive to selectively modulate these mechanisms and to overcome BBB without significant neurotoxicity. Here we report that light stimulation of tight junction-targeted plasmonic nanoparticles selectively opens up the paracellular route to allow diffusion through the compromised tight junction and into the brain parenchyma. The BBB modulation does not impair vascular dynamics and associated neurovascular coupling, or cause significant neural injury. It further allows antibody and adeno-associated virus delivery into local brain regions. This novel method offers the first evidence of selectively modulating BBB tight junctions and opens new avenues for therapeutic interventions in the central nervous system.One Sentence SummaryGentle stimulation of molecular-targeted nanoparticles selectively opens up the paracellular pathway and allows macromolecules and gene therapy vectors into the brain.
Distinct algorithms for combining landmarks and path integration in medial entorhinal, visual and retrosplenial cortex
Authors: Campbell Malcolm G. , Attinger Alexander , Ocko Samuel A. , Ganguli Surya , Giocomo Lisa M. 
Published: October 2020

AbstractDuring navigation, animals estimate their position using path integration and landmarks, engaging many brain areas. Whether these areas follow specialized or universal cue integration principles remains unknown. Here, we combined electrophysiology with virtual reality to quantify cue integration across thousands of neurons in three areas that support navigation: primary visual (V1), retrosplenial (RSC) and medial entorhinal cortex (MEC). Path integration influenced position estimates in MEC more than in V1 and RSC. V1 coded position retrospectively, likely reflecting delays in sensory processing, whereas MEC coded position prospectively, and RSC was intermediate between the two. In combining path integration with landmarks, MEC showed signatures of Kalman filtering, and we report a distance-tuned neural population that could implement such filtering through attractor dynamics. Our results show that during navigation, MEC serves as a specialized cortical hub for reconciling path integration and landmarks to estimate position and suggest an algorithm for calculating these estimates.
Comparison of Efficacy of Dexamethasone and Methylprednisolone in Improving the Partial Pressure of Arterial Oxygen and Fraction of Inspired Oxygen Ratio among COVID-19 Patients
Authors: Rana Muhammad Asim , Hashmi Mubashar , Pervaiz Rizwan , Qayyum Ahad , Saleem Muhammad , Munir Muhammad Faisal , Saif Muneeb Ullah 
Published: October 2020

AbstractIntroductionThe severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), created a pandemic in late 2019. Acute respiratory distress syndrome can occur in patients with COVID-19 due to viral replication and an uncontrolled immune reaction. Therefore, antiviral and anti-inflammatory treatments are of particular interest to clinicians. We compared the efficacy of methylprednisolone and dexamethasone in reducing inflammation and improving the partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 or P/F) ratio in COVID-19 patients.MethodsWe selected 60 files for this retrospective quasi-experimental study using a convenient sampling technique and divided them into two groups of 30 patients each who had received either dexamethasone or methylprednisolone. The data were taken from the medical records of the treated patients. Group 1 patients were given dexamethasone 8 mg twice daily, and Group 2 patients were given methylprednisolone 40 mg twice daily for eight days during their stay in our high dependency unit and our Intensive Care Unit. The remaining treatment was the same for both groups using antibiotics and anticoagulation. We reviewed C-reactive protein (CRP), serum ferritin level, and P/F ratio before and after the administration of both drugs for eight days. We used a paired t-test to assess the effectiveness of both drugs on the P/F ratio of participants.ResultsThe initial mean CRP level of Group 1 was 110.34 mg/L, which decreased to 19.45 mg/L after administration of dexamethasone; similarly, the CRP of Group 2 was 108.65 mg/L, which decreased to 43.82 mg/L after administering methylprednisolone for eight days. Both dexamethasone and methylprednisolone significantly improved the P/F ratio (p<0.05), and dexamethasone was significantly more effective than methylprednisolone (p<0.05).ConclusionSteroids’ ability to reduce inflammation and suppress the immune response make them an effective tool in the treatment of COVID-19. Steroid therapy is effective in controlling inflammation markers, and, specifically, dexamethasone is effective in improving the P/F ratio in COVID-19 patients. Physicians should consider the use of dexamethasone use in appropriate patients with COVID-19.
System Dynamics Model of Possible Covid-19 Trajectories Under Various Non-Pharmaceutical Intervention Options in a Low Resource Setting
Authors: Lucy Kivuti-Bitok W , S.Abiodun Momodu , Joyce Cheptum Jebet , Fredrick Kimemia , Isaac Gichuki , Irene Ngune 
Published: October 2020

AbstractWe present a population-based System Dynamics Model (SDM) of possible Covid-19 trajectories under various intervention options in the uniqueness of Kenya. We developed a stock and flow based SDM. We parametrized the SDM using published data and where data was not available, expert opinion was sought. Following validation test, the model was simulated to determined possible outcomes of non-pharmaceutical interventions in management of Covid-19. We simulate the possible impact of; social distancing, quarantining, curfew and cross-county travel restriction, lockdown of selected cities in Kenya and quarantining. We varied interventions in terms of start dates, duration of implementation and effectiveness of the interventions. We estimated the outcomes in terms of number of possible infections, recoveries and deaths. With the current state of interventions, we estimated a peak of Covid-19 in September 2020 with an estimated 13.5 Million Covid-19 cases and 33.8 thousand deaths in Kenya. The largest possible reduction in infections and mortality was achievable through increase in the effectiveness of the interventions. The suggested interventions would delay the epidemic peak of Covid-19 to between late Nov 2020 and early December 2020 with an estimated13M cases a 500 thousand reduction in Covid-19 cases and 32.4 deaths (a reduction in 1400 deaths). We conclude that SDM enables understanding of the complexity and impact of different interventions scenarios of Covid-19 in Kenya.
Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3
Authors: Wang Hao-Yuan , Yang Haojun , Holm Mikael , Oltion Keely , Tom Harrison , Al-Khdhairawi Amjad Ayad Qatran , Weber Jean-Frédéric F. , Blanchard Scott C. , Ruggero Davide , Taunton Jack 
Published: October 2020

AbstractTernatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A). A potentially related cytotoxic natural product (“A3”) was isolated from Aspergillus, but only 4 of its 11 stereocenters could be assigned. Here, we synthesized SR-A3 and SS-A3 – two out of 128 possible A3 epimers – and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalyzed by eEF1A in vitro. Increased residence time – stereospecifically conferred by the unique β-hydroxyl in SR-A3 – was also observed in cells. Consistent with its prolonged duration of action, thrice-weekly dosing with SR-A3 led to dramatically increased survival in an aggressive Myc-driven mouse lymphoma model. Our results demonstrate the potential of SR-A3 as a cancer therapeutic and exemplify an evolutionary mechanism for enhancing cyclic peptide binding kinetics via stereospecific side-chain hydroxylation.
EMPress enables tree-guided, interactive, and exploratory analyses of multi-omic datasets
Authors: Cantrell Kalen , Fedarko Marcus W. , Rahman Gibraan , McDonald Daniel , Yang Yimeng , Zaw Thant , Gonzalez Antonio , Janssen Stefan , Estaki Mehrbod , Haiminen Niina , Beck Kristen L. , Zhu Qiyun , Sayyari Erfan , Morton Jamie , Tripathi Anupriya , Gauglitz Julia M. , Marotz Clarisse , Matteson Nathaniel L. , Martino Cameron , Sanders Jon G. , Carrieri Anna Paola , Song Se Jin , Swafford Austin D. , Dorrestein Pieter C. , Andersen Kristian G. , Parida Laxmi , Kim Ho-Cheol , Vázquez-Baeza Yoshiki , Knight Rob 
Published: October 2020

AbstractStandard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive tool for visualizing trees in the context of microbiome, metabolome, etc. community data scalable beyond modern large datasets like the Earth Microbiome Project. EMPress provides novel functionality—including ordination integration and animations—alongside many standard tree visualization features, and thus simplifies exploratory analyses of many forms of ‘omic data.
Antinociceptive, hypothermic, and appetitive effects of vaped and injected Δ9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex
Authors: Moore Catherine F. , Davis Catherine M. , Harvey Eric L. , Taffe Michael A. , Weerts Elise M. 
Published: October 2020

AbstractAdvances in drug vapor exposure systems utilizing e-cigarette technology have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Wistar and Sprague Dawley rats (N=22, 5-6/group) received THC via IP injection (1-20 mg/kg) and passive exposure to THC vapor (200 mg/ml; 5 conditions) in a within subject design. The effects of vaped and injected THC were determined using the tail-withdrawal assay for nociception, rectal measurements of body temperature, and progressive-ratio responding for food pellets. Plasma THC concentrations were assessed after 10 mg/kg IP THC or THC vapor. THC produced dose and exposure-dependent antinociception and hypothermia. THC vapor produced inverted U-shaped effects in motivation to obtain food, while IP THC reduced PR breakpoints. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL). THC vapor exposure produces reliable, dose-orderly effects on nociception, body temperature, and food-maintained behavior that is comparable to effects observed after IP THC. There are considerable differences between the time course of behavioral outcomes produced by these two different routes of administration.
Targeting the SHP2 phosphatase promotes vascular damage and inhibition of tumor growth
Authors: Wang Yuyi , Salvucci Ombretta , Ohnuki Hidetaka , Tran Andy D. , Ha Taekyu , Feng Jing-Xin , DiPrima Michael , Kwak Hyeongil , Wang Dunrui , Kruhlak Michael , Tosato Giovanna 
Published: October 2020

AbstractThe tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and SHP2 inhibition reduces tumor growth. Here, we report that SHP2 is an essential promoter of endothelial cell survival and growth in the remodeling tumor vasculature. Using genetic and chemical approaches to inhibit SHP2 activity in endothelial cells, we show that SHP2 inhibits pro-apoptotic STAT3 and stimulates proliferative ERK1/2 signaling. Systemic SHP2 inhibition in mice bearing tumors selected for SHP2-independent tumor-cell growth, promotes degeneration of the tumor vasculature and blood extravasation; reduces tumor vascularity and blood perfusion; and increases tumor hypoxia and necrosis. Reduction of tumor growth ensues, independent of SHP2 targeting in the tumor cells, blocking immune checkpoints or recruiting anti-tumor macrophages. We also show that inhibiting the Angiopoietin/TIE2/AKT cascade magnifies the vascular and anti-tumor effects of SHP2 inhibition by blocking tumor endothelial AKT signaling, not a target of SHP2. Since the SHP2 and Ang2/TIE2 pathways are active in vascular endothelial cells of human melanoma and colon carcinoma, SHP2 inhibitors alone or with Ang2/Tie2 inhibitors hold promise to effectively target the tumor endothelium.
Can crop phenology and plant height be channelized to improvise wheat productivity in diverse production environments?
Authors: Mohan D , Mamrutha H M , Khobra Rinki , Singh Gyanendra , Singh GP 
Published: October 2020

AbstractNon-grain parameters like height, flowering and maturity should also be tried to break yield plateau in wheat. This study explores such possibilities by analysing performance of released and pre-released varieties evaluated in ten diverse production environments of India during the period 2000-2020. Regression analysis supports relevance of such non-grain determinants in grain yield under every environment but magnitude of impact can vary. Collective contribution of non-grain parameters can be high in a production environment where growth condition is most favourable for wheat growth and every factor is important in such situations. They contribute less in the environments engrossed with abiotic stress and merely one or two factors can be earmarked for selection. Besides yield, this selection strategy can also enhance grain weight in certain environments. At a time when selection for grain attributes is not providing further push; it would be worth trying to explore these non-grain field indicators as selection strategy for further advancement in productivity and grain weight of bread wheat.
Otx2 stimulates adult retinal ganglion cell regeneration
Authors: Torero-Ibad Raoul , Quenech’du Nicole , Prochiantz Alain , Moya Kenneth L. 
Published: October 2020

AbstractRetinal ganglion cell axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain. Retinal ganglion cell axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision. OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that, in response to stress, exogenous OTX2 increases thein vitroandin vivosurvival of retinal ganglion cells. The present results show that, in addition to promoting adult retinal ganglion cell survival, OTX2 also stimulates the regeneration of their axonsin vitroandin vivo. This dual activity of OTX2 on retinal ganglion cell survival and regeneration is of potential interest for degenerative diseases affecting this cell type.