bluuebunny/crossref_metadata_2025_split huggingface dataset:
A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR
Authors: Sievers Philipp , Sill Martin , Schrimpf Daniel , Stichel Damian , Reuss David E , Sturm Dominik , Hench Jürgen , Frank Stephan , Krskova Lenka , Vicha Ales , Zapotocky Michal , Bison Brigitte , Castel David , Grill Jacques , Debily Marie-Anne , Harter Patrick N , Snuderl Matija , Kramm Christof M , Reifenberger Guido , Korshunov Andrey , Jabado Nada , Wesseling Pieter , Wick Wolfgang , Solomon David A , Perry Arie , Jacques Thomas S , Jones Chris , Witt Olaf , Pfister Stefan M , von Deimling Andreas , Jones David T W , Sahm Felix 
Published: October 2020

Abstract

Background
Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.

Methods
Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.

Results
EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.

Conclusions
Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.
Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials
Authors: Ellingson Benjamin M , Brown Matthew S , Boxerman Jerrold L , Gerstner Elizabeth R , Kaufmann Timothy J , Cole Patricia E , Bacha Jeffrey A , Leung David , Barone Amy , Colman Howard , van den Bent Martin J , Wen Patrick Y , Alfred Yung W K , Cloughesy Timothy F , Goldin Jonathan G 
Published: October 2020

Abstract
Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation.
Antimicrobial Management of Respiratory Infections in Severe Acute Respiratory Syndrome Coronavirus 2 Patients: Clinical and Antimicrobial Stewardship Programs Conundrums
Authors: Goldstein Ellie J C , Tillotson Glenn , Redell Mark 
Published: October 2020

Abstract
The role of empirical and even directed antimicrobial management of patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is problematic; antibiotics are used frequently among these patients to treat confirmed or suspected coinfection or just the symptoms. In the rapidly changing clinical landscape of SARS-CoV-2, there is minimal guidance for selecting appropriate treatment versus non-antimicrobial treatment, and clinicians are pressed to make daily decisions under the stress of absence of data while watching patients deteriorate. We review current data and patterns of antimicrobial use and the potential approach for antimicrobial stewardship in the context of SARS-CoV-2.
Radial-velocity search and statistical studies for short-period planets in the Pleiades open cluster
Authors: Takarada Takuya , Sato Bun’ei , Omiya Masashi , Hori Yasunori , Fujii Michiko S 
Published: October 2020

Abstract
We report on a radial-velocity search for short-period planets in the Pleiades open cluster. We observed 30 Pleiades member stars at the Okayama Astrophysical Observatory with the High Dispersion Echelle Spectrograph. To evaluate and mitigate the effects of stellar activity on radial-velocity (RV) measurements, we computed four activity indicators (full width at half maximum, Vspan, Wspan, and SHα). Among our sample, no short-period planet candidates were detected. Stellar intrinsic RV jitter was estimated to be 52 m s−1, 128 m s−1, and 173 m s−1 for stars with $v$ sin i of 10 km s−1, 15 km s−1, and 20 km s−1, respectively. We determined the planet occurrence rate from our survey and set the upper limit to 11.4% for planets with masses 1–13 MJUP and period 1–10 d. To set a more stringent constraint on the planet occurrence rate, we combined the result of our survey with those of other surveys targeting open clusters with ages in the range 30–300 Myr. As a result, the planet occurrence rate in young open clusters was found to be less than 7.4%, 2.9%, and 1.9% for planets with an orbital period of 3 d and masses of 1–5, 5–13, and 13–80 MJUP, respectively.
How is Liquidity Priced in Global Markets?
Authors: Chaieb Ines , Errunza Vihang , Langlois Hugues 
Published: October 2020

Abstract
We develop a new global asset pricing model to study how illiquidity interacts with market segmentation and investability constraints in 42 markets. Noninvestable stocks that can only be held by foreign investors earn higher expected returns compared to freely investable stocks due to limited risk sharing and higher illiquidity. In addition to the world market premium, on average, developed and emerging market noninvestables earn an annual unspanned local market risk premium of $1.17\%$ and $9.04\%$, and a liquidity level premium of $1.06\%$ and $2.39\%$, respectively. These results obtained in a conditional setup are robust to the choice of liquidity measure.
Safety and efficacy of fostamatinib in rheumatoid arthritis patients with an inadequate response to methotrexate in phase II OSKIRA-ASIA-1 and OSKIRA-ASIA-1X study
Authors: Tanaka Yoshiya , Millson David , Iwata Shigeru , Nakayamada Shingo 
Published: October 2020

AbstractObjectiveThe primary objectives of two phase II studies of fostamatinib were to evaluate efficacy (OSKIRA-Asia-1: NCT01569074) and long-term safety/tolerability (OSKIRA-Asia-1X: NCT01640054) in patients from Asia with active RA despite MTX treatment.MethodsOSKIRA-Asia-1 was a 12-week, multicentre, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive one of four fostamatinib doses (groups A–D; n = 31, 33, 33, 33) or placebo (group E; n = 33). OSKIRA-Asia-1X was a long-term extension study (100 mg fostamatinib qd) of patients who completed OSKIRA-Asia-1. RA signs and symptoms were measured by ACR response criteria and DAS based on a 28-joint count. Physical function status was assessed with the HAQ–Disability Index. Safety findings were monitored.ResultsIn OSKIRA-Asia-1, fostamatinib revealed numerical improvements in ACR 20% response (ACR20) at week 12 in group A (100 mg bid) and group B (100 mg bid, then 150 mg qd) vs placebo. Statistically significant improvements in ACR20 and ACR50 at week 8 and in ACR70 at week 12, and statistically significant achievement in low disease activity (defined as DAS based on a 28-joint count ≤3.2 based on C-reactive protein) occurred in groups A and B. Improvement in physical function was numerically higher in group A. The most common adverse events were hypertension, diarrhoea and neutropenia. In OSKIRA-Asia-1X, the most common adverse events were nasopharyngitis, hypertension, RA and neutropenia.ConclusionFostamatinib achieved both statistically and clinically significant improvements in RA signs and symptoms. The safety and tolerability of fostamatinib (plus MTX) were consistent with previous studies.Trial registrationOSKIRA-Asia-1 trial registration: https://clinicaltrials.gov, NCT01569074; OSKIRA-Asia-1X trial registration: https://clinicaltrials.gov, NCT01640054.
Remote Ecological Momentary Testing of Learning and Memory in Adults With Serious Mental Illness
Authors: Parrish Emma M , Kamarsu Snigdha , Harvey Philip D , Pinkham Amy , Depp Colin A , Moore Raeanne C 
Published: October 2020

Abstract
Smartphone-based ecological mobile cognitive tests (EMCTs) can measure cognitive abilities in the real world, complementing traditional neuropsychological assessments. We evaluated the validity of an EMCT of recognition memory designed for use with people with serious mental illness, as well as relevant contextual influences on performance. Participants with schizophrenia (SZ), schizoaffective disorder, and bipolar disorder (BD) completed in-lab assessments of memory (Hopkins Verbal Learning Test, HVLT), other cognitive abilities, functional capacity, and symptoms, followed by 30 days of EMCTs during which they completed our Mobile Variable Difficulty List Memory Test (VLMT) once every other day (3 trials per session). List length on the VLMT altered between 6, 12, and 18 items. On average, participants completed 75.3% of EMCTs. Overall performance on VLMT 12 and 18 items was positively correlated with HVLT (ρ = 0.52, P &lt; .001). People with BD performed better on the VLMT than people with SZ. Intraindividual variability on the VLMT was more specifically associated with HVLT than nonmemory tests and not associated with symptoms. Performance during experienced distraction, low effort, and out of the home location was reduced yet still correlated with the in-lab HVLT. The VLMT converged with in-lab memory assessment, demonstrating variability within person and by different contexts. Ambulatory cognitive testing on participants’ personal mobile devices offers more a cost-effective and “ecologically valid” measurement of real-world cognitive performance.
Mycetoma – a history of the first contributions to the description of the disease and its pathogenesis
Authors: Hay R J 
Published: October 2020

Abstract
Tracking the history of the discovery of mycetoma is not simple because identifying the roots of medical knowledge depends on utilising sources that employ imprecise and sometimes confusing descriptions when compared with those based on modern medical terminology. Ancient sources of information include writings, such as poetry, archaeology and paleopathology, as well as legend and folklore. The earliest precise descriptions of mycetoma were recorded in the mid-19th century by medical officers working in southern India. But interest in the disease spread rapidly both among doctors in India and elsewhere, from Algeria to Mexico to Sudan. Although over time the names of organisms have changed, the clinical and pathological descriptions still stand as testament to those early detailed studies. Some of the conclusions of the early investigators, particularly the general lack of effective treatment and the difficulty in diagnosis, remain true today.
Action Research in Age Management: The Quality of Ageing at Work Model
Authors: Garavaglia Emma , Marcaletti Francesco , Iñiguez-Berrozpe Tatiana 
Published: October 2020

Abstract
This article discusses the introduction of age management practices within organizations and the possible resistance to their implementation, linked to the persistence of stereotypes and barriers associated with employee age and the presence of hostile organizational cultures. The article proposes to adopt an action research approach to facilitate the implementation of these practices, presenting for this purpose an action research model, the Quality of Ageing at Work, tested in 31 organizations in Italy and Spain. In light of a review of the literature on age management and action research, it describes the methodology of the Quality of Ageing at Work model and discusses it through the presentation of an organizational case. The Quality of Ageing at Work model consists of alternate phases of action and reflection through which researchers, in constant dialogue with field actors (in this case, managers, work councils, and workers), analyze organizational needs, by applying qualitative and quantitative tools, discuss them, and propose solutions. The main result of the intervention can be considered the increased awareness and autonomy of the organization in implementing an age management plan. This result confirms the effectiveness of interventions built on the dialogical and iterative principles of action research, generating, in a democratic way, new awareness and knowledge and producing organizational change.
EFSA under Revision: Transparency and Sustainability in the Food Chain
Authors: Leone Luca 
Published: October 2020

Abstract
In a time of structural challenges to the integrity, validity, and reliability of science, the new Regulation 2019/1381 aims to rethink the risk assessment phase for greater transparency and sustainability in the food chain. The novel set of provisions calls, inter alia, for Member States’ and civil society’s involvement in the management structure and scientific panels of the European Food Safety Authority (EFSA). Using the European process of ‘agencification’ as a theoretical background, this analysis addresses which problems the reformed legal framework aims to solve as regards EFSA’s governance and which new questions it simultaneously brings to the forefront.
Alcohol Consumption in Response to the COVID-19 Pandemic in the United States
Authors: Barbosa Carolina , Cowell Alexander J. , Dowd William N. 
Published: October 2020

Objectives:
Excessive alcohol use is a serious and growing public health problem. Alcoholic beverage sales in the United States increased greatly immediately after the stay-at-home orders and relaxing of alcohol restrictions associated with the COVID-19 pandemic. However, it is not known to what degree alcohol consumption changed. This study assesses differences in alcohol drinking patterns before and after the enactment of stay-at-home orders.

Methods:
In May 2020, a cross-sectional online survey of 993 individuals using a probability-based panel designed to be representative of the US population aged 21 and older was used to assess alcohol drinking patterns before (February, 2020) and after (April, 2020) the enactment of stay-at-home orders among those who consumed alcohol in February, 2020 (n = 555). Reported differences in alcohol consumption were computed, and associations between differences in consumption patterns and individual characteristics were examined.

Results:
Compared to February, respondents reported consuming more drinks per day in April (+29%, P < 0.001), and a greater proportion reported exceeding recommended drinking limits (+20%, P < 0.001) and binge drinking (+21%, P = 0.001) in April. These differences were found for all sociodemographic subgroups assessed. February to April differences in the proportion exceeding drinking limits were larger for women than men (P = 0.026) and for Black, non-Hispanic people than White, non-Hispanic people (P = 0.028).

Conclusions:
There is an association among the COVID-19 pandemic, the public health response to it, changes in alcohol policy, and alcohol consumption. Public health monitoring of alcohol consumption during the pandemic is warranted.
Can Upstream Patient Education Improve Fracture Care in a Digital World? Use of a Decision Aid for the Treatment of Displaced Diaphyseal Clavicle Fractures
Authors: Lai Cara H. , DeBaun Malcolm R. , Van Rysselberghe Noelle , Abrams Geoffrey D. , Kamal Robin N. , Bishop Julius A. , Gardner Michael J. 
Published: October 2020

Background:
The increasing proportion of telemedicine and virtual care in orthopaedic surgery presents an opportunity for upstream delivery of patient facing tools, such as decision aids. Displaced diaphyseal clavicle fractures (DDCFs) are ideal for a targeted intervention because there is no superior treatment, and decisions are often dependent on patient's preference. A decision aid provided before consultation may educate a patient and minimize decisional conflict similarly to inperson consultation with an orthopaedic traumatologist.

Methods:
Patients with DDCF were enrolled into 2 groups. The usual care group participated in a discussion with a trauma fellowship-trained orthopaedic surgeon. Patients in the intervention group were administered a DDCF decision aid designed with the International Patient Decision Aid Standards. Primary comparisons were made based on a decisional conflict score. Secondary outcomes included treatment choice, pain score, QuickDASH, and opinion toward cosmetic appearance.

Results:
A total of 41 patients were enrolled. Decisional conflict scores were similar and low between the 2 groups: 11.8 (usual care) and 11.4 (decision aid). There were no differences in secondary outcomes between usual care and the decision aid.

Discussion:
Our decision aid for the management of DDCF produces a similarly low decisional conflict score to consultation with an orthopaedic trauma surgeon. This decision aid could be a useful resource for surgeons who infrequently treat this injury or whose practices are shifting toward telemedicine visits. Providing a decision aid before consultation may help incorporate patient's values and preferences into the decision-making process between surgery and nonoperative management.

Level of Evidence:
Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Utility of Common Biomarkers for Diagnosing Infection in Nonunion
Authors: Brinker Mark R. , Macek Jenny , Laughlin Mitzi , Dunn Warren R. 
Published: October 2020

Objectives:
To evaluate the diagnostic utility of leukocyte count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) for distinguishing between septic and aseptic nonunions.

Design:
A single-gate (cohort) design was used, using 1 set of eligibility criteria applied to a consecutive sample of nonunions.

Setting:
Private quaternary referral center.

Patients/Participants:
Inclusion criteria were consecutive patients (≥18 years) with a nonunion requiring surgery that allowed for direct or medullary canal tissue sampling from the nonunion site. The cohort included 204 subjects with 211 nonunions.

Intervention:
Blood samples were drawn for laboratory analysis of WBC, ESR, and CRP before surgery.

Main Outcome Measurements:
The reference standard used to define infection was the fracture-related infection confirmatory criteria. Measures of diagnostic accuracy were calculated. To assess the additional diagnostic gain of each index lab test while simultaneously considering the others, logistic regression models were fit.

Results:
The prevalence of infection was 19% (40 of 211 nonunion sites). The positive likelihood ratios (95% confidence interval) for WBC, ESR, and CRP were 1.07 (0.38–3.02), 1.27 (0.88–1.82) and 1.57 (0.94–2.60), respectively. Multivariable modeling adjusted for the effect of preoperative antibiotics showed that WBC (P = 0.42), ESR (P = 0.48), and CRP (P = 0.23) were not significant predictors of infection.

Conclusions:
In this consecutive sample of 211 nonunions in whom standard clinical practice would be to obtain index lab tests, our findings showed that WBC, ESR, and CRP were not significant predictors of infection.

Level of Evidence:
Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Vascular Complications of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Regression Analysis
Authors: Jia Deng , Yang Isabelle Xiaorui , Ling Ryan Ruiyang , Syn Nicholas , Poon Wynne Hsing , Murughan Kavita , Tan Chuen Seng , Choong Andrew M. T. L. , MacLaren Graeme , Ramanathan Kollengode 
Published: October 2020

Objectives:
Perform a systematic review and meta-analysis of vascular complications associated with extracorporeal membrane oxygenation and identify prognostic and predictive factors.

Data Sources:
Systematic search for publications reporting vascular complications on extracorporeal membrane oxygenation, published from 1972 to January 31, 2020, was conducted via PubMed, Scopus, and Embase.

Study Selection:
Of 4,076 references screened, 47 studies with 6,583 patients were included in final analyses. Studies with fewer than 10 patients were excluded.

Data Extraction:
Relevant data, including demographics, comorbidities, extracorporeal membrane oxygenation and cannulation characteristics, occurrence rates of early and late vascular complications, patient outcomes, and use of distal perfusion cannula, were extracted from selected articles into an excel sheet specifically designed for this review.

Data Synthesis:
Random-effects meta-analyses and meta-regression analyses were undertaken. Overall pooled estimate of vascular complications in our meta-analysis was 29.5% (95% CI, 23.6–35.9%). Two-thousand three-hundred forty-seven vascular complications in 6,124 venoarterial extracorporeal membrane oxygenation patients compared with 95 in 459 venovenous extracorporeal membrane oxygenation patients (odds ratio, 2.35; 95% CI, 1.87–2.96; p < 0.0001) were analyzed. Successful weaning off extracorporeal membrane oxygenation occurred in 60.6% of pooled patients; 46.2% were eventually discharged. Pooled prevalences of vascular complications like significant bleeding, limb ischemia, and cannula site bleeding were 15.4% (95% CI, 8.6–23.7%), 12.6% (95% CI, 10.0–15.5%), and 12.6% (95% CI, 9.6–18.5%), respectively. Meta-analysis showed that the use of distal perfusion cannula was associated with lower odds of limb ischemia (odds ratio, 1.93; 95% CI, 1.17–2.47; p = 0.03) Meta-regression showed that male sex, smoking, advanced age, and comorbidities contributed to higher in-hospital mortality, while distal perfusion cannula was protective.

Conclusions:
Nearly a third of patients on extracorporeal membrane oxygenation develop vascular complications; elderly males with comorbidities appear vulnerable. The use of distal perfusion cannulas caused significant reduction in limb ischemia and mortality.