bluuebunny/crossref_metadata_2025_split huggingface dataset:
The loss of slow skeletal muscle isoform of troponin T in spindle intrafusal fibres explains the pathophysiology of Amish nemaline myopathy
Authors: Oki Kentaro , Wei Bin , Feng Han‐Zhong , Jin Jian‐Ping 
Published: May 2019

Key points
The pathogenic mechanism and the neuromuscular reflex‐related phenotype (e.g. tremors accompanied by clonus) of Amish nemaline myopathy, as well as of other recessively inherited TNNT1 myopathies, remain to be clarified.
The truncated slow skeletal muscle isoform of troponin T (ssTnT) encoded by the mutant TNNT1 gene is unable to incorporate into myofilaments and is degraded in muscle cells.
By contrast to extrafusal muscle fibres, spindle intrafusal fibres of normal mice contain a significant level of cardiac TnT and a low molecular weight splice form of ssTnT. Intrafusal fibres of ssTnT‐knockout mice have significantly increased cardiac TnT.
Rotarod and balance beam tests have revealed abnormal neuromuscular co‐ordination in ssTnT‐knockout mice and a blunted response to a spindle sensitizer, succinylcholine.
The loss of ssTnT and a compensatory increase of cardiac TnT in intrafusal nuclear bag fibres may increase myofilament Ca2+‐sensitivity and tension, impairing spindle function, thus identifying a novel mechanism for the development of targeted treatment.
AbstractA nonsense mutation at codon Glu180 of TNNT1 gene causes Amish nemaline myopathy (ANM), a recessively inherited disease with infantile lethality. TNNT1 encodes the slow skeletal muscle isoform of troponin T (ssTnT). The truncated ssTnT is unable to incorporate into myofilament and is degraded in muscle cells. The symptoms of ANM include muscle weakness, atrophy, contracture and tremors accompanied by clonus. An ssTnT‐knockout (KO) mouse model recapitulates key features of ANM such as atrophy of extrafusal slow muscle fibres and increased fatigability. However, the neuromuscular reflex‐related symptoms of ANM have not been explained. By isolating muscle spindles from ssTnT‐KO and control mice aiming to examine the composition of myofilament proteins, we found that, in contrast to extrafusal fibres, intrafusal fibres contain a significant level of cardiac TnT and the low molecular weight splice form of ssTnT. Intrafusal fibres from ssTnT‐KO mice have significantly increased cardiac TnT. Rotarod and balance beam tests revealed impaired neuromuscular co‐ordination in ssTnT‐KO mice, indicating abnormality in spindle functions. Unlike the wild‐type control, the beam running ability of ssTnT‐KO mice had a blunted response to a spindle sensitizer, succinylcholine. Immunohistochemistry detected ssTnT and cardiac TnT in nuclear bag fibres, whereas fast skeletal muscle TnT was detected in nuclear chain fibres, and cardiac α‐myosin was present in one of the two nuclear bag fibres. The loss of ssTnT and a compensatory increase of cardiac TnT in nuclear bag fibres would increase myofilament Ca2+‐sensitivity and tension, thus affecting spindle activities. This mechanism provides an explanation for the pathophysiology of ANM, as well as a novel target for treatment.
Characterization of Spinal Needle Buckling Behavior
Authors: Hulburt Tessa , Booth Jessica , Pan Peter , Brown Philip 
Published: May 2019

Abstract
The use of large gauge (G) spinal anesthesia needles can increase complications due to buckling. The purpose of this study was to quantify the behavior of spinal needles in buckling using a repeatable laboratory model. A spinal anesthesia procedure and buckling complication was reproduced in vitro using a custom test fixture designed to match the boundary conditions of needle insertion as performed by an anesthesiologist and a uniaxial servohydraulic material testing machine (MTS, Eden Prairie, MN). Buckling tests were performed with 22 G Whitacre (Medline Industries, Inc., Northfield IL), SPROTTE® (Pajunk, Norcross, GA), and Gertie Marx (International Medical Development, Huntsville, UT) needles (n = 30) in a ballistics gelatin tissue surrogate (Clear Ballistics, Fort Smith, AR). In analyzing axial force results, critical buckling load results were 27.65 ± 0.92 N, signifying that needle fragility is not why buckling is challenging to detect. Force feedback during needle insertion increased linearly due to frictional forces from the tissue surrogate on the needle. The differential between the resultant insertion force and the critical buckling force is more important to the detection of needle buckling than the critical buckling force alone. A very small difference in these two forces could feel like expected resistance increase as the needle is further inserted into the multiple tissue layers. Comparison of the differential between the resultant insertion force and the critical buckling force should be considered when choosing a needle to best detect and prevent a buckling complication.
The Moderating Role of Recovery Durations in High-Intensity Interval-Training Protocols
Authors: Schoenmakers Patrick P.J.M. , Hettinga Florentina J. , Reed Kate E. 
Published: May 2019

Purpose: Over recent years, multiple studies have tried to optimize the exercise intensity and duration of work intervals in high-intensity-interval training (HIIT) protocols. Although an optimal work interval is of major importance to facilitate training adaptations, an optimal HIIT protocol can only be achieved with an adequate recovery interval separating work bouts. Surprisingly, little research has focused on the acute responses and long-term impact of manipulating recovery intervals in HIIT sessions. This invited commentary therefore aimed to review and discuss the current literature and increase the understanding of the moderating role of recovery durations in HIIT protocols. Conclusion: The acute responses to manipulations in recovery durations in repeated-sprint training (RST), sprint interval training (SIT), and aerobic interval training (AIT) protocols have recently begun to receive scientific interest. However, limited studies have manipulated only the recovery duration in RST, SIT, or AIT protocols to analyze the role of recovery durations on long-term training adaptations. In RST and SIT, longer recovery intervals (≥80 s) facilitate higher workloads in subsequent work intervals (compared with short recovery intervals), while potentially lowering the aerobic stimulus of the training session. In AIT, the total physiological strain endured per training protocol appears not to be moderated by the recovery intervals, unless the recovery duration is too short. This invited commentary highlights that further empirical evidence on a variety of RST, SIT, and AIT protocols and in exercise modalities other than cycling is needed.
Exposure to incivility hinders clinical performance in a simulated operative crisis
Authors: Katz Daniel , Blasius Kimberly , Isaak Robert , Lipps Jonathan , Kushelev Michael , Goldberg Andrew , Fastman Jarrett , Marsh Benjamin , DeMaria Samuel 
Published: May 2019

BackgroundEffective communication is critical for patient safety. One potential threat to communication in the operating room is incivility. Although examined in other industries, little has been done to examine how incivility impacts the ability to deliver safe care in a crisis. We therefore sought to determine how incivility influenced anaesthesiology resident performance during a standardised simulation scenario of occult haemorrhage.MethodsThis is a multicentre, prospective, randomised control trial from three academic centres. Anaesthesiology residents were randomly assigned to either a normal or ‘rude’ environment and subjected to a validated simulated operating room crisis. Technical and non-technical performance domains including vigilance, diagnosis, communication and patient management were graded on survey with Likert scales by blinded raters and compared between groups.Results76 participants underwent randomisation with 67 encounters included for analysis (34 control, 33 intervention). Those exposed to incivility scored lower on every performance metric, including a binary measurement of overall performance with 91.2% (control) versus 63.6% (rude) obtaining a passing score (p=0.009). Binary logistic regression to predict this outcome was performed to assess impact of confounders. Only the presence of incivility reached statistical significance (OR 0.110, 95% CI 0.022 to 0.544, p=0.007). 65% of the rude group believed the surgical environment negatively impacted performance; however, self-reported performance assessment on a Likert scale was similar between groups (p=0.112).ConclusionAlthough self-assessment scores were similar, incivility had a negative impact on performance. Multiple areas were impacted including vigilance, diagnosis, communication and patient management even though participants were not aware of these effects. It is imperative that these behaviours be eliminated from operating room culture and that interpersonal communication in high-stress environments be incorporated into medical training.
Not a dry eye in the house: treating rescue dogs with off‐licence cyclosporine
Authors: Williams David 
Published: May 2019

This series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, 'Not a dry eye in the house: treating rescue dogs with off‐licence cyclosporine', was submitted and is discussed by David Williams. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.The series is being coordinated by Steven McCulloch, senior lecturer in human animal studies at the Centre for Animal Welfare, University of Winchester. It aims to provide a framework that will help practising veterinarians find solutions when facing similar dilemmas.
European Stroke Organisation (ESO)- European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke
Authors: Turc Guillaume , Bhogal Pervinder , Fischer Urs , Khatri Pooja , Lobotesis Kyriakos , Mazighi Mikaël , Schellinger Peter D , Toni Danilo , de Vries Joost , White Philip , Fiehler Jens 
Published: May 2019

BackgroundMechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT.MethodsThese guidelines were developed based on the standard operating procedure of the European Stroke Organisation, and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.ResultsWe found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6–24 hour time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.ConclusionsMT is the standard of care in patients with LVO related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.
Preparation of xLi[Li1/3Mn2/3]O2⋅(1−x) Li[Ni1/3Mn1/3Co1/3]O2 by coprecipitation method
Authors: Shao Zhongcai , Yu Lina , Li Axiang , Cui Yonghui 
Published: May 2019

The xLi[Li[Formula: see text]Mn[Formula: see text]]O[Formula: see text](1−x)Li[Ni[Formula: see text]Mn[Formula: see text]Co[Formula: see text]]O2 was prepared by coprecipitation method in this paper. Co(NO3)2, NiCO[Formula: see text]Ni(OH)[Formula: see text]H2O, LiOH⋅H2O and MnSO[Formula: see text]H2O were used as the sources of cobalt, nickel, lithium and manganese. In the process of calcining and sintering, the temperature and time of the material were studied. The optimum conditions for the coprecipitation method synthesis were determined: precursor was pre-sintered at 500[Formula: see text]C for 5 h, then the precursor was successively sintered at 850[Formula: see text]C for 9 h to get the final product. The results of XRD and SEM showed that the composite particles and crystal structure of the particles exhibited basic integrity and high degree of crystallinity with [Formula: see text]-NaFeO2-type structure. The first charging and discharging capacities were 183.14 mA[Formula: see text]⋅[Formula: see text]h[Formula: see text]⋅[Formula: see text]g[Formula: see text] and 171.11 mA[Formula: see text]⋅[Formula: see text]h[Formula: see text]⋅[Formula: see text]g[Formula: see text] at 0.1 C with a discharge efficiency of 93%. The capacity retention rate was 95% over 20 cycles. It had a good electrochemical cycling performance.
Energy-efficient FPGA Spiking Neural Accelerators with Supervised and Unsupervised Spike-timing-dependent-Plasticity
Authors: Liu Yu , Yenamachintala Sai Sourabh , Li Peng 
Published: May 2019

The liquid state machine (LSM) is a model of recurrent spiking neural networks (SNNs) and provides an appealing brain-inspired computing paradigm for machine-learning applications. Moreover, operated by processing information directly on spiking events, the LSM is amenable to efficient event-driven hardware implementation. However, training SNNs is, in general, a difficult task as synaptic weights shall be updated based on neural firing activities while achieving a learning objective. In this article, we explore bio-plausible spike-timing-dependent-plasticity (STDP) mechanisms to train liquid state machine models with and without supervision. First, we employ a supervised STDP rule to train the output layer of the LSM while delivering good classification performance. Furthermore, a hardware-friendly unsupervised STDP rule is leveraged to train the recurrent reservoir to further boost the performance. We pursue efficient hardware implementation of FPGA LSM accelerators by performing algorithm-level optimization of the two proposed training rules and exploiting the self-organizing behaviors naturally induced by STDP.
Several recurrent spiking neural accelerators are built on a Xilinx Zync ZC-706 platform and trained for speech recognition with the TI46 speech corpus as the benchmark. Adopting the two proposed unsupervised and supervised STDP rules outperforms the recognition accuracy of a competitive non-STDP baseline training algorithm by up to 3.47%.
Transcutaneous electrical nerve stimulation attenuates cardiac sympathetic drive in heart failure: a 123MIBG myocardial scintigraphy randomized controlled trial
Authors: Campos Monique O. , Nóbrega Antonio C. L. , Miranda Sandra M. , Ribeiro Mario L. , Guerra Thais R. B. , Braghirolli Ana M. S. , Mesquita Claudio T. , Fernandes Igor A. 
Published: May 2019

Cardiac sympathetic overdrive provides inotropic support to the failing heart. However, as myocardial insult evolves, this compensatory response impairs contractile function and constitutes an independent mortality predictor and a primary target in the treatment of heart failure (HF). In this prospective, randomized, double-blind, controlled crossover trial, we proposed cervicothoracic transcutaneous electrical nerve stimulation (CTENS) as a nonpharmacological therapy on cardiac sympathetic activity in patients with HF. Seventeen patients with HF were randomly assigned to an in-home CTENS (30 min twice daily, 80-Hz frequency, and 150-μs pulse duration) or a control intervention (Sham) for 14 consecutive days. Following a 60-day washout phase, patients were crossed over to the opposite intervention. The heart-to-mediastinum ratio (HMR) and washout rate (WR) (indexes of sympathetic innervation density and activity from planar 123iodo-metaiodobenzylguanidine myocardial scintigraphy images, respectively), as well as blood pressure (BP) and heart rate (HR), were quantified before and after each intervention. HMR, BP, and HR did not change throughout the study. Nonetheless, CTENS reduced WR (CTENS −4 ± 10 vs. Sham +5 ± 15%, P = 0.03) when compared with Sham. When allocated in two independent groups, preserved (PCSI, HMR > 1.6, n = 10) and impaired cardiac sympathetic innervation (ICSI, HRM ≤1.6, n = 7), PCSI patients showed an important attenuation of WR (−11 ± 9 vs. Sham +8 ± 19%, P = 0.007) after CTENS. Nonetheless, neither Sham nor CTENS evoked changes in WR of the ICSI patients ( P > 0.05). These findings indicate that CTENS attenuates the cardiac sympathetic overdrive in patients with HF and a preserved innervation constitutes an essential factor for this beneficial neuromodulatory impact. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT03354689. NEW & NOTEWORTHY We found that short-term cervicothoracic transcutaneous electrical nerve stimulation (CTENS) attenuates cardiac sympathetic overdrive in patients with heart failure and a preserved autonomic innervation may constitute an essential factor to maximize this beneficial neuromodulatory effect. CTENS then emerges as an alternative noninvasive and nonpharmacological strategy to attenuate exaggerated cardiac sympathetic drive in patients with heart failure.
Gamma-Glutamyltransferase 1 Promotes Clear Cell Renal Cell Carcinoma Initiation and Progression
Authors: Bansal Ankita , Sanchez Danielle J. , Nimgaonkar Vivek , Sanchez David , Riscal Romain , Skuli Nicolas , Simon M. Celeste 
Published: May 2019

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. While the localized form of this disease can be treated surgically, advanced and metastatic stages are resistant to chemotherapies. Although more innovative treatments, such as targeted or immune-based therapies, exist, the need for new therapeutic options remains. ccRCC presents unique metabolic signatures and multiple studies have reported a significant increase in levels of reduced glutathione (GSH) and its precursors in ccRCC tumor samples compared with normal kidney tissues. These observations led us to investigate the effects of blocking the GSH pathway, particularly the gamma-glutamyltransferase 1 (GGT1) enzyme, in multiple ccRCC cell lines. In this study, we provide in vitro and in vivo evidence that GGT1/GSH pathway inhibition impacts ccRCC cell growth, through increased cell-cycle arrest. Of note, GGT1 inhibition also impairs ccRCC cell migration. Finally, pharmacologic GSH pathway inhibition decreases ccRCC cell proliferation and increases sensitivity to standard chemotherapy. Our results suggest that GGT1/GSH pathway inhibition represents a new strategy to overcome ccRCC chemoresistance.

Implications:
GGT1/GSH pathway inhibition represents a promising therapeutic strategy to overcome chemoresistance and inhibit progression of ccRCC tumors.
Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations
Authors: Kalluri Aditya S. , Vellarikkal Shamsudheen K. , Edelman Elazer R. , Nguyen Lan , Subramanian Ayshwarya , Ellinor Patrick T. , Regev Aviv , Kathiresan Sekar , Gupta Rajat M. 
Published: May 2019

Background:
The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations.

Methods:
We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells.

Results:

Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for
Vcam1
and
Cd36
demonstrates regional heterogeneity in EC populations throughout the aorta.

Conclusions:
We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease–relevant functions.
Climate Model Evaluation in the Presence of Observational Uncertainty: Precipitation Indices over the Contiguous United States
Authors: Gibson Peter B. , Waliser Duane E. , Lee Huikyo , Tian Baijun , Massoud Elias 
Published: May 2019

Abstract
Climate model evaluation is complicated by the presence of observational uncertainty. In this study we analyze daily precipitation indices and compare multiple gridded observational and reanalysis products with regional climate models (RCMs) from the North American component of the Coordinated Regional Climate Downscaling Experiment (NA-CORDEX) multimodel ensemble. In the context of model evaluation, observational product differences across the contiguous United States (CONUS) are also deemed nontrivial for some indices, especially for annual counts of consecutive wet days and for heavy precipitation indices. Multidimensional scaling (MDS) is used to directly include this observational spread into the model evaluation procedure, enabling visualization and interpretation of model differences relative to a “cloud” of observational uncertainty. Applying MDS to the evaluation of NA-CORDEX RCMs reveals situations of added value from dynamical downscaling, situations of degraded performance from dynamical downscaling, and the sensitivity of model performance to model resolution. On precipitation days, higher-resolution RCMs typically simulate higher mean and extreme precipitation rates than their lower-resolution pairs, sometimes improving model fidelity with observations. These results document the model spread and biases in daily precipitation extremes across the full NA-CORDEX model ensemble. The often-large divergence between in situ observations, satellite data, and reanalysis, shown here for CONUS, is especially relevant for data-sparse regions of the globe where satellite and reanalysis products are extensively relied upon. This highlights the need to carefully consider multiple observational products when evaluating climate models.