bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Age, Distraction, and Simulated Central Vision Impairment on Hazard Detection in a Driving Simulator
Authors: Zhang Christine (Ting) , Bowers Alex R. , Savage Steven W. 
Published: April 2020

SIGNIFICANCE
Despite similar levels of visual acuity and contrast sensitivity reductions, simulated central vision impairment increased response times to a much greater extent in older than in younger participants.

PURPOSE
Driving is crucial for maintaining independence in older age, but age-related vision impairments and in-vehicle auditory distractions may impair driving safety. We investigated the effects of age, simulated central vision impairment, and auditory distraction on detection of pedestrian hazards.

METHODS
Thirty-two normally sighted participants (16 younger and 16 older) completed four highway drives in a simulator and pressed the horn whenever they saw a pedestrian. Pedestrians ran toward the road on a collision course with the approaching vehicle. Simulated central vision impairment was achieved by attaching diffusing filters to a pair of laboratory goggles, which reduced visual acuity to 20/80 and contrast sensitivity by 0.35 log units. For drives with distraction, subjects listened to an audiobook and repeated out loud target words.

RESULTS
Simulated central vision impairment had a greater effect on reaction times (660-millisecond increase) than age (350-millisecond increase) and distraction (160-millisecond increase) and had a greater effect on older than younger subjects (828- and 492-millisecond increase, respectively). Simulated central vision impairment decreased safe response rates from 94.7 to 78.3%. Distraction did not, however, affect safety because older subjects drove more slowly when distracted (but did not drive more slowly with vision impairment), suggesting that they might have perceived greater threat from the auditory distraction than the vision impairment.

CONCLUSIONS
Older participants drove more slowly in response to auditory distraction. However, neither older nor younger participants adapted their speed in response to simulated vision impairment, resulting in unsafe detections. These results underline the importance of evaluating safety of responses to hazards as well as reaction times in a paradigm that flexibly allows participants to modify their driving behaviors.
Prevalence, Pathophysiology, Diagnostic Modalities, and Treatment Options for Dysphagia in Critically Ill Patients
Authors: Brodsky Martin B. , Nollet Joeke L. , Spronk Peter E. , González-Fernández Marlís 
Published: April 2020

Abstract
Postextubation dysphagia may impose a substantial burden on intensive care unit patients and healthcare systems. Approximately 517,000 patients survive mechanical ventilation during critical care annually. Reports of postextubation dysphagia prevalence are highly variable ranging between 3% and 93%. Of great concern is aspiration leading to the development of aspiration pneumonia when patients resume oral feeding. Screening for aspiration with a water swallow test has been reported to be positive for 12% of patients in the intensive care unit after extubation. This review aims to increase awareness of postextubation dysphagia and provide an updated overview of the current knowledge regarding prevalence, pathophysiology, diagnostic modalities, and treatment options.
Does Type of Sponsorship of Randomized Controlled Trials Influence Treatment Effect Size Estimates in Rehabilitation
Authors: Fuentes Jorge , Armijo-Olivo Susan , da Costa Bruno R. , Ha Christine , Saltaji Humam , Arenti Chiara , Negrini Stefano , Cummings Greta G. 
Published: April 2020

Background
Sponsorship bias could affect research results to inform decision makers when using the results of these trials. The extent to which sponsorship bias affect results in the field of physical therapy has been unexplored in the literature. Therefore, the main aim of this study was to evaluate the influence of sponsorship bias on the treatment effects of randomized controlled trials in physical therapy area.

Methods
This was a meta-epidemiological study. A random sample of randomized controlled trials included in meta-analyses of physical therapy area were identified. Data extraction including assessments of appropriate influence of funders was conducted independently by two reviewers. To determine the association between biases related to sponsorship biases and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach.

Results
We analyzed 393 trials included in 43 meta-analyses. The most common sources of sponsorship for this sample of physical therapy trials were government (n = 205, 52%), followed by academic (n = 44, 11%) and industry (n = 39, 10%). The funding was not declared in a high percentage of the trials (n = 85, 22%). The influence of the trial sponsor was assessed as being appropriate in 246 trials (63%) and considered inappropriate/unclear in 147 (37%) of them. We have moderate evidence to say that trials with inappropriate/unclear influence of funders tended to have on average a larger effect size than those with appropriate influence of funding (effect size = 0.15; 95% confidence interval = −0.03 to 0.33).

Conclusions
Based on our sample of physical therapy trials, it seems that most of the trials are funded by either government and academia and a small percentage are funded by the industry. Treatment effect size estimates were on average 0.15 larger in trials with lack of appropriate influence of funders as compared with trials with appropriate influence of funding. Contrarily to other fields, industry funding was relatively small and their influence perhaps less marked. All these results could be explained by the relative youth of the field and/or the absence of clear industry interests. In front of the call for action by the World Health Organization to strengthen rehabilitation in health systems, these results raise the issue of the need of public funding in the field.
Feasibility of Short-Term PrEP Uptake for Men Who Have Sex With Men With Episodic Periods of Increased HIV Risk
Authors: Egan James E. , Ho Ken , Stall Ron , Drucker Moe T. , Tappin Ryan , Hendrix Craig W. , Marzinke Mark A. , Safren Steven A. , Mimiaga Matthew J. , Psaros Christina , Elsesser Steven , Mayer Kenneth H. 
Published: April 2020

Background:
Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate is efficacious in reducing HIV acquisition. For some gay, bisexual, and other men who have sex with men (MSM), daily ongoing PrEP may be unsuitable for use as a long-term prevention strategy because of episodic risk, cost issues, or concerns about the biological consequences of medication.

Setting:
This study evaluated the feasibility of short-term, fixed-interval episodic PrEP (Epi-PrEP) for use among vacationing MSM. We describe the feasibility of implementing a clinic-based Epi-PrEP pilot program for 48 MSM who reported occasional condomless sex and anticipated a defined high-risk time.

Methods:
This was a nonrandomized naturalistic study of an observational clinical intervention. The primary outcome assessed was adherence, as measured by self-report and plasma tenofovir levels.

Results:
Of 54 MSM who enrolled in the study, 48 completed the 3-month visit. The majority (93.7%) had tenofovir concentrations consistent with daily use on returning from vacation. Almost 3/4 reported condomless sex during vacation, and about 1/3 reported recreational drug use. During the 3-month follow-up, 1 participant had become HIV-infected because of a lapse in continued access to the PrEP after study. Although adverse events were common, none were serious. More than 70% of participants indicated an interest in daily ongoing PrEP use.

Conclusions:
Epi-PrEP was well tolerated by at risk MSM in this study, with high levels of medication adherence. Many participants felt the experience of initiating PrEP while on vacation could be a means for transition to long-term PrEP use.
Opioid analgesia: recent developments
Authors: Stein Christoph 
Published: April 2020

Purpose of review
Opioids are potent drugs for the treatment of severe pain, but they are burdened by detrimental side-effects, such as respiratory depression, addiction, sedation and constipation. Their clinical application is undisputed in acute (e.g. perioperative) and cancer pain, but their use in chronic nonmalignant pain has met increasing scrutiny and has contributed to the opioid crisis. Thus, novel analgesics with reduced side-effects are badly needed.

Recent findings
Current research topics include enkephalinase inhibitors, allosteric and multivalent ligands, biased opioid receptor signaling and selective activation of peripheral opioid receptors in injured tissues.

Summary
Opioids still appear to be most promising among current approaches in the development of analgesics. Basic knowledge about pathophysiology of clinical pain and novel insights in pharmacology suggest that the most interesting perspectives are augmenting endogenous opioid actions and selectively targeting peripheral opioid receptors. The latter approach is additionally supported by evidence from clinical studies. Some biased, multivalent and peripherally selective agonists have advanced to phase III trials, but novel drugs have not become available for clinical application. Future strategies in analgesic drug development might include public–private partnerships and nonprofit pharmaceutical companies, as exemplified by the AIDS crisis and proposals to combat antibiotic resistance.
Galectins in the brain: advances in neuroinflammation, neuroprotection and therapeutic opportunities
Authors: Barake Francisca , Soza Andrea , González Alfonso 
Published: April 2020

Purpose of review
Galectin interactions with glycoproteins and glycolipids modulate a variety of cellular responses that are now increasingly explored to better understand neuroinflammation processes and eventually find new therapeutic opportunities for neurological diseases.

Recent findings
Gal-1 confirmed its indirect neuroprotective roles through anti-inflammatory properties whereas Gal-3 remains elusive, showing anti-inflammatory or pro-inflammatory roles depending on damaging conditions and genetic background of mice models. Interestingly, microglial intracellular rather than extracellular overexpression of Gal-3 arose as contributing to the pathogenesis of Huntington disease, involving NLRP3 inflammasome activation and inhibition of autophagic removal of damaged endolysosomes. Decreasing Gal-3 expression had favorable effects upon disease symptoms. Gal-3 expanded its role in this endolysosomal surveillance system originally involving Gal-8 and Gal-9, which protect cells against neuropathogenic proteins and becomes impaired or even detrimental under neurodegenerative conditions. Also, Gal-1, Gal-3 and Gal-4, together with changes in glycan structures define the outcome of neuroinflammation and remyelination processes. Gal-8 emerged as a new neuroprotector factor, which added to its immunosuppressive role and presence in human cerebrospinal fluid (CSF) may generate a neuroprotective environment in the brain.

Summary
Galectins modulate neuroinflammation and neurodegenerative processes contributing to microglia polarization, immunosurveillance and neuroprotection through extracellular and intracellular interactions with particular and dynamic patterns of glycans, suggesting potential therapeutic targets.
Advances in physical rehabilitation of multiple sclerosis
Authors: Centonze Diego , Leocani Letizia , Feys Peter 
Published: April 2020

Purpose of review
Multiple sclerosis (MS) is a neurological disorder that heavily affects quality of life (QoL) and demands a multidisciplinary therapeutic approach. This includes multiple protocols and techniques of physical rehabilitation, ranging from conventional exercise paradigms to noninvasive brain stimulation (NIBS). Recently, studies showing the clinical efficacy of physical rehabilitation have remarkably increased, suggesting its disease-modifying potential.

Recent findings
Studies in animal models of MS have shown that physical exercise ameliorates the main disease pathological hallmarks, acting as a pro-myelinating and immunomodulatory therapy. NIBS techniques have been successfully applied to treat pain and urinary symptoms and lower limb function and spasticity, especially in combination with physical rehabilitation. Physical rehabilitation is reported to be well tolerated and effective in improving muscle function and fitness even in more disabled patients, and to enhance balance, walking and upper limb functional movements. Moreover, the dual motor--cognitive task performance can be improved by combined training protocols.

Summary
The literature here reviewed indicates the importance of clinical and preclinical research in addressing the impact of neurorehabilitation on MS disability, highlighting the need of further studies to reach a more comprehensive understanding of the mechanisms involved, the best combination of techniques and the proper timing of application.
Update on T cells in the virally infected brain: friends and foes
Authors: Ai Shenjian , Klein Robyn S. 
Published: April 2020

Purpose of review
The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated.

Recent findings
The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific.

Summary
T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.
“Leaky” and “Unstable” Neural Integrator Can Coexist—Paradox Observed in Multiple Sclerosis
Authors: Gupta Palak , Shaikh Aasef G. 
Published: April 2020

Abstract:
The mechanism for stable gaze-holding requires a neural integrator that converts pulse of neural discharge to steady firing rate. The integrator is feedback-dependent, impaired feedback manifests as either “unstable” integration when it is too much or “leaky” when it is too little. The “unstable” integrator is known to cause sinusoidal oscillations of the eyes called pendular nystagmus, whereas the “leaky” integrator causes jerky eye oscillations called gaze-evoked nystagmus. We hypothesized that integrator can be simultaneously leaky and unstable. Mechanistically, some parts of network are served by increased feedback gain (unstable network), while other part would be decreased feedback gain (leaky). Both leaky and unstable, the network converges on the ocular motor plant, leading to simultaneously present gaze-evoked jerk and sinusoidal nystagmus. We tested our hypothesis by measuring eye movements with search coil technique in 7 multiple sclerosis patients. Five of these patients had gaze-evoked nystagmus and superimposed pendular nystagmus. The gaze-evoked nystagmus depicted all the features of “leaky” integrator, that is, the drifts were always toward the null that was located at the central eye-in-orbit orientation, there were no drifts at null, and the drift velocity increased as the eyes moved farther away from the null. The pendular nystagmus had all the features of “unstable” integrator, that is, constant 4- to 6-Hz frequency, eye-in-orbit position dependence of the oscillation amplitude, and the voluntary saccade causing an oscillatory phase reset. These features were then simulated in a computational model conceptualizing our hypothesis of simultaneously leaky and unstable neural integrator.
Central Venous Obstruction–Induced Intracranial Hypertension in Hemodialysis Patients: An Underrecognized Cause of Elevated Intracranial Pressure
Authors: Mackay Devin D. , Takacs Sara M. 
Published: April 2020

Background:
Central venous obstruction (stenosis or occlusion) is common in patients with renal failure on hemodialysis and may be associated with intracranial hypertension (IH). Causes include vein injury from an endoluminal device, lumen obstruction from a device or thrombus, external vein compression, and high venous flow leading to vein intimal hyperplasia. A combination of high venous flow and central venous obstruction can lead to intracranial venous hypertension, impaired cerebrospinal fluid (CSF) resorption, and subsequent IH.

Evidence Acquisition:
We conducted a search of the English literature using the Ovid MEDLINE Database and PubMed, with a focus on reports involving IH and central venous obstruction in the setting of hemodialysis. We reviewed CSF flow dynamics, the risk factors and causes of central venous obstruction, and the evaluation, management, and outcomes of central venous obstruction-induced IH.

Results:
Twenty-four cases of IH related to central venous obstruction in hemodialysis patients were identified. Twenty patients had headaches (83.3%) and 9 had visual symptoms (37.5%). The brachiocephalic vein was the most common site of stenosis or occlusion (20/24, 83.3%). Twenty-one patients (87.5%) had resolution of IH with treatment. Two patients died from complications of IH (8.3%).

Conclusions:
Central venous obstruction–induced IH is likely underrecognized by clinicians and mimics idiopathic IH. Hemodialysis patients with IH should be screened with computed tomography venography of the chest. Optimal treatment is with vascular intervention or a CSF diversion procedure and can help prevent vision loss from papilledema or nervous system damage. Medical management may be appropriate in mild cases or as a bridge to definitive interventional treatment. Increased awareness among clinicians has potential to facilitate the timely diagnosis of this treatable condition with potential for good neurologic and visual outcomes.
Neurosarcoidosis Masquerading as Giant Cell Arteritis With Incidental Meningioma
Authors: Solyman Omar M. , Vizcaino Maria Adelita , Fu Roxana , Henderson Amanda D. 
Published: April 2020

Abstract:
We present a case of vision loss secondary to neurosarcoidosis, which initially presented with severe bilateral vision loss, temporal headaches, and elevated erythrocyte sedimentation rate, concerning for giant cell arteritis. However, temporal artery biopsy was negative. Initial neuroimaging features were misinterpreted to represent a meningioma that did not account for his clinical presentation. Clinical course, including atypically rapid enlargement of presumed meningioma, development of skin lesions, appearance of optic nerve enhancement on MRI, and steroid response, strongly increased suspicion for sarcoidosis. Biopsy of a skin lesion demonstrated noncaseating granulomatous inflammation, consistent with sarcoidosis.
Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome
Authors: Weiskopf Daniela , Schmitz Katharina S. , Raadsen Matthijs P. , Grifoni Alba , Okba Nisreen M.A. , Endeman Henrik , van den Akker Johannes P.C. , Molenkamp Richard , Koopmans Marion P.G. , van Gorp Eric C.M. , Haagmans Bart L. , de Swart Rik L. , Sette Alessandro , de Vries Rory D. 
Published: April 2020

AbstractCOVID-19 is associated with lymphopenia and ‘cytokine storm’, but no information is available on specific cellular immune responses to SARS-CoV-2. Here, we characterized SARS-CoV-2-specific CD4+ and CD8+ T-cells in patients with acute respiratory distress syndrome. The spike protein (S) proved a potent T-cell antigen and specific T-cells predominantly produced Th1 cytokines. These novel data are important in vaccine design and will facilitate evaluation of vaccine candidate immunogenicity.
International Electronic Health Record-Derived COVID-19 Clinical Course Profiles: The 4CE Consortium
Authors: Brat Gabriel A , Weber Griffin M , Gehlenborg Nils , Avillach Paul , Palmer Nathan P , Chiovato Luca , Cimino James , Waitman Lemuel R , Omenn Gilbert S , Malovini Alberto , Moore Jason H , Beaulieu-Jones Brett K , Tibollo Valentina , Murphy Shawn N , L’Yi Sehi , Keller Mark S , Bellazzi Riccardo , Hanauer David A , Serret-Larmande Arnaud , Gutierrez-Sacristan Alba , Holmes John J , Bell Douglas S , Mandl Kenneth D , Follett Robert W , Klann Jeffrey G , Murad Douglas A , Scudeller Luigia , Bucalo Mauro , Kirchoff Katie , Craig Jean , Obeid Jihad , Jouhet Vianney , Griffier Romain , Cossin Sebastien , Moal Bertrand , Patel Lav P , Bellasi Antonio , Prokosch Hans U , Kraska Detlef , Sliz Piotr , Tan Amelia LM , Ngiam Kee Yuan , Zambelli Alberto , Mowery Danielle L , Schiver Emily , Devkota Batsal , Bradford Robert L , Daniar Mohamad ,   APHP/Universities/INSERM COVID-19 research collaboration, Daniel Christel , Benoit Vincent , Bey Romain , Paris Nicolas , Serre Patricia , Orlova Nina , Dubiel Julien , Hilka Martin , Jannot Anne Sophie , Bréant Stéphane , Leblanc Judith , Griffon Nicolas , Burgun Anita , Bernaux Melodie , Sandrin Arnaud , Salamanca Elisa , Ganslandt Thomas , Gradinger Tobias , Champ Julien , Boeker Martin , Martel Patricia , Esteve Loic , Gramfort Alexandre , Grisel Olivier , Leprovost Damien , Moreau Thomas , Varoquaux Gael , Vie Jill-Jenn , Wassermann Demian , Mensch Arthur , Caucheteux Charlotte , Haverkamp Christian , Lemaitre Guillaume , Krantz Ian D. , Cormont Sylvie , South Andrew M ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Cai Tianxi , Kohane Isaac S 
Published: April 2020

ABSTRACTWe leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across 5 countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on comorbidities and temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.