bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWAS Data Hub: a resource of DNA methylation array data and metadata
Authors: Xiong Zhuang , Li Mengwei , Yang Fei , Ma Yingke , Sang Jian , Li Rujiao , Li Zhaohua , Zhang Zhang , Bao Yiming 
Published: October 2019

Abstract
Epigenome-Wide Association Study (EWAS) has become an effective strategy to explore epigenetic basis of complex traits. Over the past decade, a large amount of epigenetic data, especially those sourced from DNA methylation array, has been accumulated as the result of numerous EWAS projects. We present EWAS Data Hub (https://bigd.big.ac.cn/ewas/datahub), a resource for collecting and normalizing DNA methylation array data as well as archiving associated metadata. The current release of EWAS Data Hub integrates a comprehensive collection of DNA methylation array data from 75 344 samples and employs an effective normalization method to remove batch effects among different datasets. Accordingly, taking advantages of both massive high-quality DNA methylation data and standardized metadata, EWAS Data Hub provides reference DNA methylation profiles under different contexts, involving 81 tissues/cell types (that contain 25 brain parts and 25 blood cell types), six ancestry categories, and 67 diseases (including 39 cancers). In summary, EWAS Data Hub bears great promise to aid the retrieval and discovery of methylation-based biomarkers for phenotype characterization, clinical treatment and health care.
Recognition and processing of branched DNA substrates by Slx1–Slx4 nuclease
Authors: Gaur Vineet , Ziajko Weronika , Nirwal Shivlee , Szlachcic Aleksandra , Gapińska Marta , Nowotny Marcin 
Published: October 2019

Abstract
Structure-selective endonucleases cleave branched DNA substrates. Slx1 is unique among structure-selective nucleases because it can cleave all branched DNA structures at multiple sites near the branch point. The mechanism behind this broad range of activity is unknown. The present study structurally and biochemically investigated fungal Slx1 to define a new protein interface that binds the non-cleaved arm of branched DNAs. The DNA arm bound at this new site was positioned at a sharp angle relative to the arm that was modeled to interact with the active site, implying that Slx1 uses DNA bending to localize the branch point as a flexible discontinuity in DNA. DNA binding at the new interface promoted a disorder-order transition in a region of the protein that was located in the vicinity of the active site, potentially participating in its formation. This appears to be a safety mechanism that ensures that DNA cleavage occurs only when the new interface is occupied by the non-cleaved DNA arm. Models of Slx1 that interacted with various branched DNA substrates were prepared. These models explain the way in which Slx1 cuts DNA toward the 3′ end away from the branch point and elucidate the unique ability of Slx1 to cleave various DNA structures.
MIBiG 2.0: a repository for biosynthetic gene clusters of known function
Authors: Kautsar Satria A , Blin Kai , Shaw Simon , Navarro-Muñoz Jorge C , Terlouw Barbara R , van der Hooft Justin J J , van Santen Jeffrey A , Tracanna Vittorio , Suarez Duran Hernando G , Pascal Andreu Victòria , Selem-Mojica Nelly , Alanjary Mohammad , Robinson Serina L , Lund George , Epstein Samuel C , Sisto Ashley C , Charkoudian Louise K , Collemare Jérôme , Linington Roger G , Weber Tilmann , Medema Marnix H 
Published: October 2019

Abstract
Fueled by the explosion of (meta)genomic data, genome mining of specialized metabolites has become a major technology for drug discovery and studying microbiome ecology. In these efforts, computational tools like antiSMASH have played a central role through the analysis of Biosynthetic Gene Clusters (BGCs). Thousands of candidate BGCs from microbial genomes have been identified and stored in public databases. Interpreting the function and novelty of these predicted BGCs requires comparison with a well-documented set of BGCs of known function. The MIBiG (Minimum Information about a Biosynthetic Gene Cluster) Data Standard and Repository was established in 2015 to enable curation and storage of known BGCs. Here, we present MIBiG 2.0, which encompasses major updates to the schema, the data, and the online repository itself. Over the past five years, 851 new BGCs have been added. Additionally, we performed extensive manual data curation of all entries to improve the annotation quality of our repository. We also redesigned the data schema to ensure the compliance of future annotations. Finally, we improved the user experience by adding new features such as query searches and a statistics page, and enabled direct link-outs to chemical structure databases. The repository is accessible online at https://mibig.secondarymetabolites.org/.
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages
Authors: de Groot John , Penas-Prado Marta , Alfaro-Munoz Kristin , Hunter Kathy , Pei Be Lian , O’Brien Barbara , Weathers Shiao-Pei , Loghin Monica , Kamiya Matsouka Carlos , Yung W K Alfred , Mandel Jacob , Wu Jimin , Yuan Ying , Zhou Shouhao , Fuller Gregory N , Huse Jason , Rao Ganesh , Weinberg Jeffrey S , Prabhu Sujit S , McCutcheon Ian E , Lang Frederick F , Ferguson Sherise D , Sawaya Raymond , Colen Rivka , Yadav Shalini S , Blando Jorge , Vence Luis , Allison James , Sharma Padmanee , Heimberger Amy B 
Published: October 2019

Abstract

Background
We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.

Methods
In an open-label, single-center, single-arm phase II “window-of-opportunity” trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.

Results
No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients’ recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.

Conclusions
Immune analyses indicated that pembrolizumab anti–programmed cell death 1 (PD-1) monotherapy alone can’t induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing
Authors: Yoon Jihoon G , Hahn Hyung Min , Choi Sungkyoung , Kim Soo Jung , Aum Sowon , Yu Jung Woo , Park Eun Kyung , Shim Kyu Won , Lee Min Goo , Kim Yong Oock 
Published: October 2019

Abstract

BACKGROUND
Genetic factors play an important role in the pathogenesis of craniosynostosis (CRS). However, the molecular diagnosis of CRS in clinical practice is limited because of its heterogeneous etiology.

OBJECTIVE
To investigate the genomic landscape of CRS in a Korean cohort and also to establish a practical diagnostic workflow by applying targeted panel sequencing.

METHODS
We designed a customized panel covering 34 CRS-related genes using in-solution hybrid capture method. We enrolled 110 unrelated Korean patients with CRS, including 40 syndromic and 70 nonsyndromic cases. A diagnostic pipeline was established by combining in-depth clinical reviews and multiple bioinformatics tools for analyzing single-nucleotide variants (SNV)s and copy number variants (CNV)s.

RESULTS
The diagnostic yield of the targeted panel was 30.0% (33/110). Twenty-five patients (22.7%) had causal genetic variations resulting from SNVs or indels in 9 target genes (TWIST1, FGFR3, TCF12, ERF, FGFR2, ALPL, EFNB1, FBN1, and SKI, in order of frequency). CNV analysis identified 8 (7.3%) additional patients with chromosomal abnormalities involving 1p32.3p31.3, 7p21.1, 10q26, 15q21.3, 16p11.2, and 17p13.3 regions; these cases mostly presented with syndromic clinical features.

CONCLUSION
The present study shows the wide genomic landscape of CRS, revealing various genetic factors for CRS pathogenesis. In addition, the results demonstrate that an efficient diagnostic workup using target panel sequencing provides great clinical utility in the molecular diagnosis of CRS.
Interval between planning and frameless stereotactic radiosurgery for brain metastases: are our margins still accurate?
Authors: Bronnimann Charlotte , Huchet Aymeri , Benech-Faure Julie , Dutriaux Caroline , Saut Olivier , Blais Eivind , Mollier Olivier , Trouette Renaud , Vendrely Veronique 
Published: October 2019

Abstract

Background
Advances in intracranial stereotactic radiosurgery (SRS) have led to dramatically reduced planning target volume (PTV) margins. However, tumor growth between planning and treatment may lead to treatment failure. Our purpose was to assess the kinetics of tumor growth before SRS for brain metastases.

Methods
This retrospective, monocentric study included all consecutive patients (pts) treated for brain metastases secondary to melanoma (ML) and non-small cell lung cancer (NSCLC) between June 2015 and May 2016. All pts underwent diagnostic brain imaging and a radiosurgery planning MRI, during which gross tumor volume (GTV) was delineated. Linear and exponential models were used to extrapolate a theoretical GTV at first day of treatment, and theoretical time to outgrow the PTV margins.

Results
Twenty-three ML and 31 NSCLC brain metastases (42 pts, 84 brain imaging scans) were analyzed. Comparison of GTV at diagnosis and planning showed increased tumor volume for 20 ML pts (96%) and 22 NSCLC pts (71%). The shortest time to outgrow a 1 mm margin was 6 days and 3 days for ML and 14 and 8 days for NSCLC with linear and exponential models, respectively.

Conclusions
Physicians should bear in mind the interval between SRS planning and treatment. A mathematical model could screen rapidly progressing tumors.
Influenza vaccine uptake and attitudes of healthcare workers in Ireland
Authors: Hogan V , Lenehan M , Hogan M , Natin D P 
Published: October 2019

Abstract

Background
Influenza vaccination uptake by Irish healthcare workers remains sub-optimal despite local initiatives to increase it.

Aims
To investigate hospital workers' attitudes to influenza vaccination and how this influenced their decisions about vaccination.

Methods
A questionnaire survey of Irish hospital workers, measuring uptake of and attitudes to influenza vaccination.

Results
There were 747 responders, of whom 361 (48%) reported having received influenza vaccination. Attitudes predicting vaccination uptake included a belief that vaccination would protect family members (P < 0.0005, CI 1.191–1.739), a perception of susceptibility to ’flu (P < 0.0005, CI 1.182–1.685), a belief that all healthcare workers should be vaccinated (P < 0.005, CI 1.153–1.783), perceived ease of getting ’flu vaccination at work (P < 0.0005, CI 1.851–2.842) and encouragement by line managers (P < 0.05, CI 1.018–1.400). Attitudes negatively associated with vaccination uptake included fear of needles (P < 0.05, CI 0.663–0.985) and a belief that vaccination would cause illness (P < 0.0005, CI 0.436–0.647). Medical staff were significantly more likely to be vaccinated. Healthcare students were least likely to be vaccinated (P < 0.0005).

Conclusion
Addressing specific barriers to influenza vaccination in healthcare workers may improve uptake.
Sustained Response and Rationale of Programmed Cell Death-1-Targeting for Progressive Multifocal Leukoencephalopathy
Authors: Audemard-Verger Alexandra , Gasnault Jacques , Faisant Maxime , Besse Marie-Catherine , Martin-Silva Nicolas , Berra Mado , Fournier Luc , Boutemy Jonathan , Maigne Gwenola , De Boysson Hubert , Ruet Alexis , Vabret Astrid , Chapon Françoise , Martin-Blondel Guillaume , Aouba Achille 
Published: October 2019

Abstract
In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1+ macrophages could be the T-cells partnership in immune exhaustion and virus escape.
Loss of perlecan heparan sulfate glycosaminoglycans lowers body weight and decreases islet amyloid deposition in human islet amyloid polypeptide transgenic mice
Authors: Templin Andrew T , Mellati Mahnaz , Soininen Raija , Hogan Meghan F , Esser Nathalie , Castillo J Josh , Zraika Sakeneh , Kahn Steven E , Hull Rebecca L 
Published: October 2019

AbstractIslet amyloid is a pathologic feature of type 2 diabetes (T2D) that is associated with β-cell loss and dysfunction. These amyloid deposits form via aggregation of the β-cell secretory product islet amyloid polypeptide (IAPP) and contain other molecules including the heparan sulfate proteoglycan perlecan. Perlecan has been shown to bind amyloidogenic human IAPP (hIAPP) via its heparan sulfate glycosaminoglycan (HS GAG) chains and to enhance hIAPP aggregation in vitro. We postulated that reducing the HS GAG content of perlecan would also decrease islet amyloid deposition in vivo. hIAPP transgenic mice were crossed with Hspg2Δ3/Δ3 mice harboring a perlecan mutation that prevents HS GAG attachment (hIAPP;Hspg2Δ3/Δ3), and male offspring from this cross were fed a high fat diet for 12 months to induce islet amyloid deposition. At the end of the study body weight, islet amyloid area, β-cell area, glucose tolerance and insulin secretion were analyzed. hIAPP;Hspg2Δ3/Δ3 mice exhibited significantly less islet amyloid deposition and greater β-cell area compared to hIAPP mice expressing wild type perlecan. hIAPP;Hspg2Δ3/Δ3 mice also gained significantly less weight than other genotypes. When adjusted for differences in body weight using multiple linear regression modeling, we found no differences in islet amyloid deposition or β-cell area between hIAPP transgenic and hIAPP;Hspg2Δ3/Δ3 mice. We conclude that loss of perlecan exon 3 reduces islet amyloid deposition in vivo through indirect effects on body weight and possibly also through direct effects on hIAPP aggregation. Both of these mechanisms may promote maintenance of glucose homeostasis in the setting of T2D.
Creating and Validating a Shortened Version of the Community Balance and Mobility Scale for Application in People Who Are 61 to 70 Years of Age
Authors: Gordt Katharina , Mikolaizak A Stefanie , Taraldsen Kristin , Bergquist Ronny , Van Ancum Jeanine M , Nerz Corinna , Pijnappels Mirjam , Maier Andrea B , Helbostad Jorunn L , Vereijken Beatrix , Becker Clemens , Schwenk Michael 
Published: October 2019

Abstract

Background
The Community Balance and Mobility Scale (CBM) has been shown to be reliable and valid for detecting subtle balance and mobility deficits in people who are 61 to 70 years of age. However, item redundancy and assessment time call for a shortened version.

Objective
The objective was to create and validate a shortened version of the CBM (s-CBM) without detectable loss of psychometric properties.

Design
This was a cross-sectional study.

Methods
Exploratory factor analysis with data from 189 young seniors (aged 61-70 years; mean [SD] age = 66.3 [2.5] years) was used to create the s-CBM. Sixty-one young seniors (aged 61–70 years; mean [SD] age = 66.5 [2.6] years) were recruited to assess construct validity (Pearson correlation coefficient) by comparing the CBM versions with Fullerton Advance Balance Scale, Timed Up-and-Go, habitual and fast gait speed, 8 Level Balance Scale, 3-m tandem walk, and 30-second chair stand test. Internal consistency (Cronbach α), ceiling effects, and discriminant validity (area under the curve [AUC]) between fallers and nonfallers, and self-reported high and low function (Late-Life Function and Disability Index) and balance confidence (Activities-Specific Balance Confidence Scale), respectively, were calculated.

Results
The s-CBM, consisting of 4 items, correlated excellently with the CBM (r = 0.97). Correlations between s-CBM and other assessments (r = 0.07-0.72), and CBM and other assessments (r = 0.06-0.80) were statistically comparable in 90% of the correlations. Cronbach α was .84 for the s-CBM, and .87 for the CBM. No CBM-version showed ceiling effects. Discriminative ability of the s-CBM was statistically comparable with the CBM (AUC = 0.66-0.75 vs AUC = 0.65-0.79).

Limitations
Longitudinal studies with larger samples should confirm the results and assess the responsiveness for detecting changes over time.

Conclusions
The psychometric properties of the s-CBM were similar to those of the CBM. The s-CBM can be recommended as a valid and quick balance and mobility assessment in young seniors.
A Technology-Enabled Concussion Care Pathway Reduces Costs and Enhances Care
Authors: Alberts Jay L , Modic Michael T , Udeh Belinda L , Zimmerman Nicole , Cherian Kay , Lu Xiaoyang , Gray Robert , Figler Richard , Russman Andrew , Linder Susan M 
Published: October 2019

AbstractBackgroundThe standardization of care along disease lines is recommended to improve outcomes and reduce health care costs. The multiple disciplines involved in concussion management often result in fragmented and disparate care. A fundamental gap exists in the effective utilization of rehabilitation services for individuals with concussion.PurposeThe purpose of this project was to (1) characterize changes in health care utilization following implementation of a concussion carepath, and (2) present an economic evaluation of patient charges following carepath implementation.DesignThis was a retrospective cohort study.MethodsA review of electronic medical and financial records was conducted of individuals (N = 3937), ages 18 to 45 years, with primary diagnosis of concussion who sought care in the outpatient or emergency department settings over a 7-year period (2010–2016). Outcomes including encounter length, resource utilization, and charges were compared for each year to determine changes from pre- to post-carepath implementation.ResultsConcussion volumes increased by 385% from 2010 to 2015. Utilization of physical therapy increased from 9% to 20% while time to referral decreased from 72 to 23 days post-injury. Utilization of emergency medicine and imaging were significantly reduced. Efficient resource utilization led to a 20.7% decrease in median charges (estimated ratio of means [CI] 7.72 [0.53, 0.96]) associated with concussion care.LimitationsEncounter lengths served as a proxy for recovery time.ConclusionsThe implementation of the concussion carepath was successful in optimizing clinical practice with respect to facilitating continuity of care, appropriate resource utilization, and effective handoffs to physical therapy. The utilization of enabling technology to facilitate the collection of common outcomes across providers was vital to the success of standardizing clinical care without compromising patient outcomes.
Musculoskeletal consultations from childhood to adulthood: a longitudinal study
Authors: Prathivadi Bhayankaram N , Lacey R J , Barnett L A , Jordan K P , Dunn K M 
Published: October 2019

Abstract

Background
The Global Burden of Disease reports indicate that musculoskeletal conditions are important causes of disability worldwide. Such conditions may originate in childhood, but studies investigating changes longitudinally and from childhood to adulthood are infrequent.

Methods
Nine birth cohorts of children (starting at ages 7–15 years) were followed. Participants were identified from Consultations in Primary Care Archive, an electronic health record database of 11 English general practices. Musculoskeletal consultation prevalence figures were calculated, and reasons for consultation evaluated.

Results
Annual musculoskeletal consultation prevalence was similar across cohorts for each age. Prevalence increased from 6 to 16% between ages 7 and 22 and was higher in males until age 15, after which prevalence was higher in females. Pain was the most common reason for consultation. Back pain consultations increased from 1 consultation/1000 7 year olds to 84 consultations/1000 22 year olds. Lower limb pain consultations increased from 21 consultations/1000 7 year olds to 56 consultations/1000 22 year olds.

Conclusions
This study shows that from childhood, individuals are more likely to seek healthcare for musculoskeletal consultations as they age, but rates are not increasing over time. Changes in consultation rates by age, gender and pain region may inform studies on the development of chronic musculoskeletal pain over the life-course.
Association of SHI coverage and level of healthcare utilization and costs in the Philippines: a 10-year pooled analysis
Authors: Haw Nel Jason L , Uy Jhanna , Ho Beverly Lorraine 
Published: October 2019

AbstractBackgroundThe Philippine Health Insurance Corporation (PhilHealth), which manages the Philippine national health insurance program, is a critical actor in the country’s strategy for universal health coverage. Over the past decade, PhilHealth has passed significant coverage, benefits and payment reforms to contain costs and improve the affordability care for high-cost diseases, inpatient care and select outpatient services.MethodsWe studied the association of PhilHealth with health care utilization and health care costs using three rounds of the Philippine Demographic and Health Survey with data on individual outpatient and inpatient visits from 2008 to 2017.ResultsPhilHealth membership was associated with 42% greater odds of outpatient utilization and 47–100% greater odds inpatient utilization depending on survey year. Depending on facility type, use of PhilHealth to pay for care was associated with higher average health care costs of 244–865% for outpatient care and 135–206% for inpatient care.ConclusionsPhilHealth has likely decreased barriers to health care utilization but may have inadvertently driven up health care costs in the country. Results align with past studies that suggest that reforms in the prior decade have done little to contain health care costs for Filipinos.
Chemical Weapons and public health: assessing impact and responses
Authors: Ekzayez Abdulkarim , Flecknoe M Daniel , Lillywhite Louis , Patel Preeti , Papamichail Andreas , Elbahtimy Hassan 
Published: October 2019

ABSTRACT

Background
The recent use of Chemical Weapons (CWs) in armed conflicts and terror attacks highlights the importance of understanding their full impact in order to inform an effective response. This article argues that while the consequences of CWs on individual health have dominated our understanding of the impact of these weapons, far less attention has been directed to their impact on public health.

Methods
A review of the literature on the health impact of CWs was conducted, and two case studies of their use in urban settings were explored - Halabja in northern Iraq in 1988 and throughout Syria’s ongoing conflict.

Results
The importance of considering the long-term health consequences of CW use and their impact on healthcare and health systems was demonstrated.

Conclusions
This article highlights the importance of supporting future research on the topic and proposes a framework for assessing the public health impact of CW use.