bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of HLA class II binding to the LAG‐3 T cell co‐inhibitory receptor
Authors: MacLachlan Bruce J. , Mason Georgina H. , Greenshields‐Watson Alexander , Triebel Frederic , Gallimore Awen , Cole David K. , Godkin Andrew 
Published: October 2020

AbstractImmune checkpoint inhibitors (antibodies that block the T cell co‐inhibitory receptors PD‐1/PD‐L1 or CTLA‐4) have revolutionized the treatment of some forms of cancer. Importantly, combination approaches using drugs that target both pathways have been shown to boost the efficacy of such treatments. Subsequently, several other T cell inhibitory receptors have been identified for the development of novel immune checkpoint inhibitors. Included in this list is the co‐inhibitory receptor lymphocyte activation gene‐3 (LAG‐3), which is upregulated on T cells extracted from tumor sites that have suppressive or exhausted phenotypes. However, the molecular rules that govern the function of LAG‐3 are still not understood. Using surface plasmon resonance combined with a novel bead‐based assay (AlphaScreenTM), we demonstrate that LAG‐3 can directly and specifically interact with intact human leukocyte antigen class II (HLA‐II) heterodimers. Unlike the homologue CD4, which has an immeasurably weak affinity using these biophysical approaches, LAG‐3 binds with low micromolar affinity. We further validated the interaction at the cell surface by staining LAG‐3+ cells with pHLA‐II‐multimers. These data provide new insights into the mechanism by which LAG‐3 initiates T cell inhibition.
Measures of central sensitization and their measurement properties in musculoskeletal trauma: A systematic review
Authors: Middlebrook Nicola , Rushton Alison B , Abichandani Deepa , Kuithan Pauline , Heneghan Nicola R. , Falla Deborah 
Published: October 2020

AbstractBackground and ObjectiveChronic pain following musculoskeletal trauma is common, which may partially be attributed to the early presence of central sensitization (CS). Multiple measures are suggested to assess clinical features of CS, yet no systematic review has evaluated the measurement properties of these measures in a musculoskeletal trauma population.Databases and Data TreatmentThis systematic review, which followed a published and PROSPERO registered protocol (CRD42018091531), aimed to establish the scope of CS measures used within a musculoskeletal trauma population and evaluate their measurement properties. Searches were conducted in two stages by two independent reviewers. The Consensus‐based Standards for the selection of Health Measurement Instruments (COSMIN) checklist was used to evaluate risk of bias and overall quality was assessed using the modified Grading of Recommendations Assessment, Development and Evaluation.ResultsFrom 86 studies, 30 different CS outcome measures were identified. Nine studies evaluated measurement properties of nine outcome measures; eight evaluated reliability and one evaluated construct validity. Measures included seven quantitative sensory testing methods (pressure, cold and electrical pain thresholds; warm, cold and vibration detection thresholds; vibration perception thresholds), pain drawings and a pinwheel. Risk of bias was assessed as doubtful/inadequate for all but one study, overall quality of evidence was low/very low for all measures. Reliability of measures ranged from poor to excellent.ConclusionsMany measures are used to evaluate CS but with limited established measurement properties in musculoskeletal trauma. High quality research to establish measurement properties of CS outcome measures is required.
Copper Doped Li3VO4 as Anode Material for Lithium‐ion Batteries
Authors: Mulaudzi Isaac , Zhang Yi , Ndlovu Gebhu F. , Wu Yuping , Legodi Malebogo A. , van Ree Teunis 
Published: October 2020

AbstractLi3VO4 has been considered as a promising anode material because of its high theoretical capacity (394mAh g−1) and zero strain during the charge and discharge processes. However, its electronic conductivity is low, which has led to an electrochemical performance unfavourable for practical application. In this work, copper‐doped Li3VO4 is prepared by a simple and inexpensive sol‐gel method. The doped Li3VO4 delivers high initial discharge and charge capacities of up to 63 mAh g−1 after 25 cycles for 5 % Cu‐doped material at a rate of 0.5 C. Conductive Cu is found to enable better Li+ ion storage due to the improved electronic conductivity, Li ion diffusion, and structural stability, improving cycling and rate performance. This work provides some hints for preparing Li3VO4 based anodes with high electrochemical performance.
The effect of gradient nonlinearities on fiber orientation estimates from spherical deconvolution of diffusion magnetic resonance imaging data
Authors: Guo Fenghua , de Luca Alberto , Parker Greg , Jones Derek K. , Viergever Max A. , Leemans Alexander , Tax Chantal M. W. 
Published: October 2020

AbstractGradient nonlinearities in magnetic resonance imaging (MRI) cause spatially varying mismatches between the imposed and the effective gradients and can cause significant biases in rotationally invariant diffusion MRI measures derived from, for example, diffusion tensor imaging. The estimation of the orientational organization of fibrous tissue, which is nowadays frequently performed with spherical deconvolution techniques ideally using higher diffusion weightings, can likewise be biased by gradient nonlinearities. We explore the sensitivity of two established spherical deconvolution approaches to gradient nonlinearities, namely constrained spherical deconvolution (CSD) and damped Richardson‐Lucy (dRL). Additionally, we propose an extension of dRL to take into account gradient imperfections, without the need of data interpolation. Simulations show that using the effective b‐matrix can improve dRL fiber orientation estimation and reduces angular deviations, while CSD can be more robust to gradient nonlinearity depending on the implementation. Angular errors depend on a complex interplay of many factors, including the direction and magnitude of gradient deviations, underlying microstructure, SNR, anisotropy of the effective response function, and diffusion weighting. Notably, angular deviations can also be observed at lower b‐values in contrast to the perhaps common assumption that only high b‐value data are affected. In in vivo Human Connectome Project data and acquisitions from an ultrastrong gradient (300 mT/m) scanner, angular differences are observed between applying and not applying the effective gradients in dRL estimation. As even small angular differences can lead to error propagation during tractography and as such impact connectivity analyses, incorporating gradient deviations into the estimation of fiber orientations should make such analyses more reliable.
The apoptosis‐inducing factor family: Moonlighting proteins in the crosstalk between mitochondria and nuclei
Authors: Novo Nerea , Ferreira Patricia , Medina Milagros 
Published: October 2020

AbstractIn Homo sapiens, the apoptosis‐inducing factor (AIF) family is represented by three different proteins, known as AIF, AMID and AIFL, that have in common the mitochondrial localisation in healthy cells, the presence of FAD‐ and NADH‐dependent domains involved in an ‐albeit yet not well understood‐ oxidoreductase function and their capability to induce programmed cell death. AIF is the best characterised family member, while the information about AMID and AIFL is much scarcer. Nonetheless, available data support different roles as well as mechanisms of action of their particular apoptogenic and redox domains regarding both pro‐apoptotic and anti‐apoptotic activities. Moreover, diverse cellular functions, to date far from fully clarified, are envisaged for the transcripts corresponding to these three proteins. Here, we review the so far available knowledge on the moonlighting human AIF family from their molecular properties to their relevance in health and disease, through the evaluation of their potential cell death and redox functions in their different subcellular locations. This picture emerging from the current knowledge of the AIF family envisages its contribution to regulate signalling and transcription machineries in the crosstalk among mitochondria, the cytoplasm and the nucleus.
Cellular effects of nicotine salt‐containing e‐liquids
Authors: Ghosh Arunava , Beyazcicek Ozge , Davis Eric S. , Onyenwoke Rob U. , Tarran Robert 
Published: October 2020

Abstract“Pod‐based” e‐cigarettes such as JUUL are currently the most prevalent electronic nicotine delivery systems (ENDS) in the United States. JUUL‐type ENDS utilize nicotine salts protonated with benzoic acid rather than freebase nicotine. However, limited information is available on the cellular effects of these products. Cytoplasmic Ca2+ is a universal second messenger that controls many cellular functions including cell growth and cell death. Of note, dysregulation of cell Ca2+ homeostasis has been linked with several disease processes including autoimmune disease and several types of cancer. We exposed HEK293T cells and THP‐1 macrophage‐like cells to different JUUL e‐liquids. We evaluated their effects on cellular viability and Ca2+ signaling by measuring fluorescence from calcein‐AM/propidium iodide and Fluo‐4, respectively. E‐liquid autofluorescence was used to look for e‐liquid permeation into cells. To identify the mechanisms behind the Ca2+ responses, different inhibitors of Ca2+ channels and phospholipase C signaling were used. JUUL e‐liquids caused significant cytotoxic effects, with “Mint” flavor being the most cytotoxic. The Mint flavored e‐liquid also caused a significant elevation in cytoplasmic Ca2+. Using autofluorescence, the permeation of JUUL e‐liquids into live cells was confirmed, indicating that intracellular organelles are directly exposed to e‐liquids. Further studies identified the endoplasmic reticulum as being the source of e‐liquid‐induced changes in cytoplasmic Ca2+. Nicotine salt‐based e‐liquids cause cytotoxicity and elevate cytoplasmic Ca2+, indicating that they can exert biological effects beyond what would be expected with nicotine alone. These effects are flavor‐dependent, and we propose that flavored e‐liquids be reassessed for potential lung toxicity.
Serum IL‐36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity, insulin resistance, and inflammation
Authors: Li Yan , Chen Sisi , Zhao Tingqi , Li Mingcai 
Published: October 2020

AbstractBackgroundThe interleukin (IL)‐36 cytokines include IL‐36α, IL‐36β, IL‐36γ, and IL‐36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM).MethodsThe study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high‐performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL‐36α, IL‐36γ, IL‐36Ra, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay.ResultsSerum IL‐36α, IL‐36γ, and IL‐17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL‐36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL‐36α was positively correlated with high sensitivity C‐reactive protein. Serum IL‐36α was negatively correlated with IL‐36Ra. Serum IL‐17 was negatively correlated with low‐density lipoprotein cholesterol.ConclusionsThis study demonstrated that T2DM patients displayed increased IL‐36α and IL‐36γ expression and decreased IL‐36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL‐36 cytokines may be a new target for the diagnosis or treatment of T2DM.
Weakened impact of autumn Arctic sea ice concentration change on the subsequent winter Siberian High variation around the late‐1990s
Authors: Chen Shangfeng , Wu Renguang , Chen Wen , Song Linye , Cheng Wei , Shi Wenjing 
Published: October 2020

AbstractPrevious studies suggested that autumn Arctic sea ice concentration (SIC) change around the Kara–Laptev seas has a marked impact on the following winter Siberian High (SH). This analysis reveals that the autumn Arctic SIC‐winter SH connection experienced a marked interdecadal weakening around the late‐1990s according to observational and reanalysis data. Before the late‐1990s, autumn Arctic SIC loss induces pronounced Arctic warming via modulating surface heat fluxes and reduces poleward meridional temperature gradient, which leads to weakening of westerly winds over mid‐latitude Eurasia and contributes to formation of a high‐pressure ridge around Ural mountain. The Ural high‐pressure ridge provides a favourable dynamical condition for the amplification of SH. Consequently, the autumn Arctic SIC‐winter SH connection is strong. In addition, the North Atlantic is dominated by a marked triple sea surface temperature anomaly pattern from autumn to winter, which also partly contributes to a strengthened SH via modulating the Ural high‐pressure ridge. After the late‐1990s, Arctic warming and atmospheric anomalies over Eurasia related to the autumn Arctic SIC loss are much weaker. Accordingly, the autumn Arctic SIC‐winter SH connection is very weak. Changes in the autumn Arctic SIC‐related Arctic warming and atmospheric anomalies are suggested to be related to differences in the autumn Arctic SIC anomalies, with a much weaker amplitude and northward retreat after than before the late‐1990s. Further analysis indicates that the weaker autumn Arctic SIC anomalies over Kara–Laptev seas after the late‐1990s is related to the northward retreat of the mean Arctic SIC.
Direct statistical downscaling of monthly streamflow from atmospheric variables in catchments with differing contributions from snowmelt
Authors: Huang Shaochun , Lawrence Deborah , Irene Brox Nilsen , Li Hong 
Published: October 2020

AbstractThe climate–hydrological modelling chain is the most widely used approach for assessing likely future changes in streamflow but is also associated with large uncertainties. We present an alternative approach for modelling monthly streamflow directly from large‐scale atmospheric variables using statistical downscaling to streamflow for 42 catchments with flow generation regimes ranging from largely snowmelt‐driven to entirely rainfall‐driven. It aims to find the most appropriate combination of predictors and methods, which can best include information pertaining to snow storage and provide robust streamflow simulations under changing climate conditions. The effects of selection of probable predictors (five groups of potential variables from reanalysis data, three moving windows, calibration periods of two different lengths) and methods (eight combinations of pre‐processing methods and statistical models) were considered. Results indicate that the following selection of probable predictors gave a good and robust model performance: a combination of 13 independent climate variables and their lagged information, a 3‐month moving window and a calibration period of 31 years. Three combinations of methods performed best: (a) principal component analysis (PCA) and the relevance vector machine (RVM) statistical model using gridded data, (b) PCA and RVM using interpolated data and (c) the Pearson correlation analysis and RVM using interpolated data. Monthly streamflow was well reproduced for most catchments, with a median NSE (Nash and Sutcliffe efficiency) of 0.82 and PBIAS (percentage bias) of 0 in the calibration period and a median NSE over 0.60 and PBIAS less than −6 in the validation period. The best performance of the methods was associated with snow‐dominated catchments in inland regions. We also established that lagged information on atmospheric variables gave better results than snow variables from reanalysis data. The poorest results were associated with rainfall‐dominated catchments, and this was strongly correlated with the inter‐ versus the intra‐annual variability in monthly streamflow.
Service Dogs for Veterans and Military Members With Posttraumatic Stress Disorder: Replication With the PTSD Checklist for DSM‐5
Authors: Jensen Clare L. , Rodriguez Kerri E. , O'Haire Marguerite E. 
Published: October 2020

AbstractPsychiatric service dogs are an emerging complementary intervention for veterans and military members with posttraumatic stress disorder (PTSD). Recent cross‐sectional studies have documented significant, clinically relevant effects regarding service dogs and PTSD symptom severity. However, these studies were conducted using the PTSD Checklist (PCL) for the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The present study aimed to replicate and advance these findings using the latest version of the PCL for the fifth edition of the DSM (PCL‐5). Participants included 186 military members and veterans who had received a PTSD service dog (n = 112) or who were on the waitlist to receive one in the future (n = 74). A cross‐sectional design was used to investigate the association between having a service dog and PCL‐5 total and symptom cluster scores. After controlling for demographic variables, there was a significant association between having a service dog and lower PTSD symptom severity both in total, B = ‐14.52, p < .001, d = ‐0.96, and with regard to each symptom cluster, ps < .001, ds = ‐0.78 to ‐0.94. The results replicated existing findings using the largest sample size to date and the most recent version of the PCL. These findings provide additional preliminary evidence for the efficacy of service dogs as a complementary intervention for military members and veterans with PTSD and add to a growing body of foundational research serving to rationalize investment in the further clinical evaluation of this emerging practice.
Competency‐Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus
Authors: Faucett Erynne A. , Wolter Nikolaus E. , Balakrishnan Karthik , Ishman Stacey L. , Mehta Deepak , Parikh Sanjay , Nguyen Lily H. P. , Preciado Diego , Rutter Michael J. , Prager Jeremy D. , Green Glenn E. , Pransky Seth M. , Elluru Ravi , Husein Murad , Roy Soham , Johnson Kaalan E. , Friedberg Jacob , Johnson Romaine F. , Bauman Nancy M. , Myer Charles M. , Deutsch Ellen S. , Gantwerker Eric A. , Willging J. Paul , Hart Catherine K. , Chun Robert H. , Lam Derek J. , Ida Jonathan B. , Manoukian John J. , White David R. , Sidell Douglas R. , Wootten Christopher T. , Inglis Andrew F. , Derkay Craig S. , Zalzal George , Molter David W. , Ludemann Jeffrey P. , Choi Sukgi , Schraff Scott , Myer Charles M. , Cotton Robin T. , Vijayasekaran Shyan , Zdanski Carlton J. , El‐Hakim Hamdy , Shah Udayan K. , Soma Marlene A. , Smith Marshall E. , Thompson Dana M. , Javia Luv Ram , Zur Karen B. , Sobol Steven E. , Hartnick Christopher J. , Rahbar Reza , Vaccani Jean‐Philippe , Hartley Benjamin , Daniel Sam J. , Jacobs Ian N. , Richter Gresham T. , de Alarcon Alessandro , Bromwich Matthew A. , Propst Evan J. 
Published: October 2020

Objectives/HypothesisCreate a competency‐based assessment tool for pediatric esophagoscopy with foreign body removal.Study DesignBlinded modified Delphi consensus process.SettingTertiary care center.MethodsA list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as “keep” or “remove” and comments were incorporated. In the second round, experts rated the importance of each item on a seven‐point Likert scale. Consensus was determined with a goal of 7 to 25 final items.ResultsThe response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to “keep” all items and 172 comments were incorporated. Twenty‐four task‐specific and 7 previously‐validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task‐specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus.ConclusionsIt is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated.Level of Evidence5. Laryngoscope, 131:1168–1174, 2021
Impact of intradetrusor botulinum toxin A injections on serum and urinary concentrations of nerve growth factor and brain‐derived neurotrophic factor in patients with multiple sclerosis and neurogenic detrusor overactivity
Authors: Philippova Ekaterina S. , Bazhenov Igor V. , Ziryanov Alexander V. , Bazarny Vladimir V. 
Published: October 2020

AbstractAimsTo evaluate the practical relevance of changes in serum and urinary neurotrophins levels in patients with multiple sclerosis (MS) and neurogenic lower urinary tract dysfunction (NLUTD) after intradetrusor injections of botulinum toxin A (BoNTA).MethodsThe study included 36 patients with MS and NLUTD and 20 controls. The patients with NLUTD received intradetrusor injection of BoNTA (200 U). The nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) levels were measured in serum and urine at baseline and then at 1, 3, and 6 months by enzyme‐linked immunosorbent assay. Urinary NGF and BDNF were normalized to creatinine (NGF/Cr, BDNF/Cr). Patients' assessment included urodynamic examination and Neurogenic Bladder Symptom Score (NBSS).ResultsAfter BoNTA injections, no significant changes were observed in the serum NGF and BDNF or the urinary BDNF/Cr. The urinary NGF/Cr was significantly higher in MS patients (1.23 ± 0.34) at baseline compared with controls (0.084 ± 0.02; p = .021). The urinary NGF/Cr decreased to 0.51 ± 0.12 (p = .001) and 0.53 ± 0.32 (p = .005) at 1 and 3 months, increasing to 1.12 ± 0.49 (p = .003) at 6 months. The urinary NGF/Cr level at baseline demonstrated a low diagnostic accuracy in predicting a better response to the BoNTA treatment (area under the curve = 0.661; p = .047) and no correlation with the urodynamic parameters.ConclusionsThe urinary NGF/Cr at baseline or its reduction at the first month following treatment does not serve as a predictor for the response to the BoNTA injections or for urodynamic changes.