bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF
Authors: Ruggeri Elena , Lira-Albarrán Saúl , Grow Edward J , Liu Xiaowei , Harner Royce , Maltepe Emin , Ramalho-Santos Miguel , Donjacour Annemarie , Rinaudo Paolo 
Published: September 2020

Abstract
The preimplantation stage of development is exquisitely sensitive to environmental stresses, and changes occurring during this developmental phase may have long-term health effects. Animal studies indicate that IVF offspring display metabolic alterations, including hypertension, glucose intolerance and cardiac hypertrophy, often in a sexual dimorphic fashion. The detailed nature of epigenetic changes following in-vitro culture is, however, unknown. This study was performed to evaluate the epigenetic (using whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq)) and transcriptomic changes (using RNA-seq) occurring in the inner cell mass (ICM) of male or female mouse embryos generated in vivo or by IVF. We found that the ICM of IVF embryos, compared to the in-vivo ICM, differed in 3% of differentially methylated regions (DMRs), of which 0.1% were located on CpG islands. ATAC-seq revealed that 293 regions were more accessible and 101 were less accessible in IVF embryos, while RNA-seq revealed that 21 genes were differentially regulated in IVF embryos. Functional enrichment analysis revealed that stress signalling (STAT and NF-kB signalling), developmental processes and cardiac hypertrophy signalling showed consistent changes in WGBS and ATAC-seq platforms. In contrast, male and female embryos showed minimal changes. Male ICM had an increased number of significantly hyper-methylated DMRs, while only 27 regions showed different chromatin accessibility and only one gene was differentially expressed. In summary, this study provides the first comprehensive analysis of DNA methylation, chromatin accessibility and RNA expression changes induced by IVF in male and female ICMs. This dataset can be of value to all researchers interested in the developmental origin of health and disease (DOHaD) hypothesis and might lead to a better understanding of how early embryonic manipulation may affect adult health.
SilencerDB: a comprehensive database of silencers
Authors: Zeng Wanwen , Chen Shengquan , Cui Xuejian , Chen Xiaoyang , Gao Zijing , Jiang Rui 
Published: September 2020

AbstractGene regulatory elements, including promoters, enhancers, silencers, etc., control transcriptional programs in a spatiotemporal manner. Though these elements are known to be able to induce either positive or negative transcriptional control, the community has been mostly studying enhancers which amplify transcription initiation, with less emphasis given to silencers which repress gene expression. To facilitate the study of silencers and the investigation of their potential roles in transcriptional control, we developed SilencerDB (http://health.tsinghua.edu.cn/silencerdb/), a comprehensive database of silencers by manually curating silencers from 2300 published articles. The current version, SilencerDB 1.0, contains (1) 33 060 validated silencers from experimental methods, and (ii) 5 045 547 predicted silencers from state-of-the-art machine learning methods. The functionality of SilencerDB includes (a) standardized categorization of silencers in a tree-structured class hierarchy based on species, organ, tissue and cell line and (b) comprehensive annotations of silencers with the nearest gene and potential regulatory genes. SilencerDB, to the best of our knowledge, is the first comprehensive database at this scale dedicated to silencers, with reliable annotations and user-friendly interactive database features. We believe this database has the potential to enable advanced understanding of silencers in regulatory mechanisms and to empower researchers to devise diverse applications of silencers in disease development.
Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial
Authors: Hua Xinyang , Gray Alastair , Wolstenholme Jane , Clarke Philip , Molyneux Andrew J , Kerr Richard S C , Clarke Alison , Sneade Mary , Rivero-Arias Oliver 
Published: September 2020

Abstract

BACKGROUND
Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling.

OBJECTIVE
To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT.

METHODS
Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information.

RESULTS
Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences.

CONCLUSION
HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.
A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes
Authors: Hanson Derek , Hoffman Lindsey M , Nagabushan Sumanth , Goumnerova Liliana C , Rathmann Allison , Vogel Timothy , Ziegler David S , Chi Susan 
Published: September 2020

Abstract

Background
Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed. The Dana-Farber Cancer Institute–modified IRS-III protocol incorporates preclinically active agents, such as doxorubicin and actinomycin D, into the treatment regimen for ETMR and may improve patient outcomes.

Methods
The authors present a case series of 5 children with ETMR treated with an IRS-III-based chemotherapy backbone.

Results
All 5 patients received a gross-total tumor resection. Patients received between 12 and 51 weeks of IRS-III therapy at the discretion of their treating physician. Four patients received focal radiation therapy, with the fifth patient instead receiving a cycle of high-dose chemotherapy with autologous stem cell rescue. Four patients have progression-free survival of more than 18 months. Chemotherapy treatment was reasonably tolerated by all 5 patients with one case of mild sinusoidal obstructive syndrome and one case of Grade 3 peripheral neuropathy.

Conclusions
The patient outcomes in this small cohort are far better than would be expected based on the historical survival for this tumor. Given the tremendous need for effective therapy for ETMR, further investigation of this approach is warranted. An international consensus protocol based on the IRS-III regimen has been developed and will be available through a multicenter clinical trial and a global treatment registry.
Adjusting for protein quality by food source may affect nutrient density metrics
Authors: Drewnowski Adam 
Published: September 2020

AbstractMethods to assess nutrient density of foods, commonly known as nutrient profiling (NP), typically include protein as a component. In this study, the goal was to apply a correction for protein quality by food source to selected NP algorithms. Analyses of 378 component foods of the Fred Hutch food frequency questionnaire showed that animal-source foods (ie, meat, eggs, and dairy) along with some soy products and nuts were the only foods that provided &gt; 20% of the daily value (DV) of protein per 100 g or per 100 kcal. Most beans, pulses, legumes, grains, and vegetables provided &lt;10% DV of protein per 100 g or per 100 kcal. Adjusting for protein quality using a simplified Protein Digestibility Corrected Amino Acid Score (PDCAAS) had consequences for point-based NP models (namely, Nutri-Score) and for continuous nutrient density scores (namely, Nutrient Rich Foods). Quantitative methods that use protein content to capture nutrient density may require a protein-quality adjustment, especially when adapted for use in low- and middle-income countries where protein quality is an issue of public health concern.
Financial, Food, and Housing Insecurity Due to Coronavirus Disease 2019 Among At-Risk People With Human Immunodeficiency Virus in a Nonurban Ryan White HIV/AIDS Program Clinic
Authors: Sherbuk Jacqueline E , Williams Brooke , McManus Kathleen A , Dillingham Rebecca 
Published: September 2020

Abstract
Coronavirus disease 2019 negatively impacts social determinants of health that contribute to disparities for people with human immunodeficiency virus (HIV). Insecurity of food, housing, and employment increased significantly in April 2020 among patients with lower incomes at a Ryan White HIV/AIDS program clinic in the Southern United States.
Science rules! A qualitative study of scientists’ approaches to grant lottery
Authors: Philipps Axel 
Published: September 2020

AbstractUsing peer review to assess the validity of research proposals has always had its fair share of critics, including a more-than-fair-share of scholars. The debate about this method of assessing these proposals now seems trivial when compared with assessing the validity for granting funding by lottery. Some of the same scholars have suggested that the way grant lottery was being assessed has made random allocation seem even-handed, less biased and more supportive of innovative research. But we know little of what researchers actually think about grant lottery and even less about the thoughts of those scientists who rely on funding. This paper examines scientists’ perspectives on selecting grants by ‘lots’ and how they justify their support or opposition. How do they approach something scientifically that is, in itself, not scientific? These approaches were investigated with problem-centered interviews conducted with natural scientists in Germany. The qualitative interviews for this paper reveal that scientists in dominated and dominating field positions are, more or less, open to the idea of giving a selection process by lots a try. Nonetheless, they are against pure randomization because from their point of view it is incompatible with scientific principles. They rather favor a combination of grant lottery and peer review processes, assuming that only under these conditions could randomly allocated funding be an integral and legitimate part of science.
Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial
Authors: Xu Chang , Selhub Jacob , Jacques Paul , Paynter Nina P , MacFadyen Jean G , Glynn Robert J , Ridker Paul M , Solomon Daniel H 
Published: September 2020

Abstract

Objectives
Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) 1–5, correlate with AEs.

Method
We examined data from the LD-MTX arm of the randomized double-blind Cardiovascular Inflammation Reduction Trial (CIRT). All AEs were blindly adjudicated and monitoring laboratories were tested centrally. The MTX-PGs 1–5 were assessed in one reference laboratory using liquid chromatography–tandem mass spectrometry. Based on prior literature, MTX-PGs 3–5 were chosen as the exposure of interest and quartiles of MTX-PGs 3–5 were assessed for their relationship with all AEs and each pre-specified category of AE using adjusted Cox proportional hazards regression.

Results
Of the 2391 subjects randomized to LD-MTX, MTX-PG levels were available for 1319 subjects (median dosage 16.1 mg/week) from the 8 month visit. We followed these subjects for a median of 2.2 years [interquartile range (IQR) 1.5–2.9]. Higher MTX-PG3–5 levels were related to an increased risk of anaemia [compared with quartile 1 (Q1); hazard ratio (HR) for Q4 1.27 (95% CI 0.98, 1.65), P for trend = 0.05] and a decreased risk of thrombocytopenia [HR for Q4 0.52 (95% CI 0.32, 0.84), P for trend = 0.05]. MTX-PG3–5 levels &gt;134 nmol/l were associated with an increased risk of liver abnormalities [HR 1.36 (95% CI 1.08, 1.72)].

Conclusions
Higher MTX- PG3–5 levels were modestly associated with LD-MTX AEs, including anaemia and liver function abnormalities, but a reduced risk of thrombocytopenia and haemorrhage.

Clinical trial registration
NCT 01594333.
Identification of White Matter Networks Engaged in Object (Face) Recognition Showing Differential Responses to Modulated Stimulus Strength
Authors: Li Muwei , Ding Zhaohua , Gore John C 
Published: September 2020

Abstract
Blood-oxygenation-level-dependent (BOLD) signals in magnetic resonance imaging indirectly reflect neural activity in cortex, but they are also detectable in white matter (WM). BOLD signals in WM exhibit strong correlations with those in gray matter (GM) in a resting state, but their interpretation and relationship to GM activity in a task are unclear. We performed a parametric visual object recognition task designed to modulate the BOLD signal response in GM regions engaged in higher order visual processing, and measured corresponding changes in specific WM tracts. Human faces embedded in different levels of random noise have previously been shown to produce graded changes in BOLD activation in for example, the fusiform gyrus, as well as in electrophysiological (N170) evoked potentials. The magnitudes of BOLD responses in both GM regions and selected WM tracts varied monotonically with the stimulus strength (noise level). In addition, the magnitudes and temporal profiles of signals in GM and WM regions involved in the task coupled strongly across different task parameters. These findings reveal the network of WM tracts engaged in object (face) recognition and confirm that WM BOLD signals may be directly affected by neural activity in GM regions to which they connect.
Determinants of dengue virus dispersal in the Americas
Authors: Allicock Orchid M , Sahadeo Nikita , Lemey Philippe , Auguste Albert J , Suchard Marc A , Rambaut Andrew , Carrington Christine V F 
Published: September 2020

AbstractDengue viruses (DENVs) are classified into four serotypes, each of which contains multiple genotypes. DENV genotypes introduced into the Americas over the past five decades have exhibited different rates and patterns of spatial dispersal. In order to understand factors underlying these patterns, we utilized a statistical framework that allows for the integration of ecological, socioeconomic, and air transport mobility data as predictors of viral diffusion while inferring the phylogeographic history. Predictors describing spatial diffusion based on several covariates were compared using a generalized linear model approach, where the support for each scenario and its contribution is estimated simultaneously from the data set. Although different predictors were identified for different serotypes, our analysis suggests that overall diffusion of DENV-1, -2, and -3 in the Americas was associated with airline traffic. The other significant predictors included human population size, the geographical distance between countries and between urban centers and the density of people living in urban environments.
Evaluating the effectiveness of the PA Foundation's Mental Health Outreach fellowship
Authors: Forbes Jennifer , Pierce Caroline , Sappe-Watkins Lynette 
Published: September 2020

ABSTRACT

Objectives:
Mental Health First Aid (MHFA) is designed to help the general public acquire the knowledge and skills needed to respond to a person in a mental health emergency and offer support to someone in emotional distress. Through the PA Foundation's Mental Health Outreach Fellowship, 16 physician assistants (PAs) were selected to become MHFA instructors and teach the course to members of their local communities over 1 year.

Methods:
MHFA course evaluations, completed by course participants, were reviewed to determine the effectiveness of the PA fellows as instructors.

Results:
The fellows' mean evaluation instructor presentation score was 4.82 and the mean course content score was 4.75. The national mean for instructor presentation was 4.72 for presentation and 4.66 for course content. The maximum possible score in each category was a 5.

Conclusions:
The PAs selected for the Mental Health Outreach Fellowship were effective MHFA instructors. Benefits to having a PA serve as the instructor include positively affecting communities by increasing the public's mental health literacy, reducing the stigma associated with mental illness, increasing visibility and promotion of the PA profession, and enhancement of a PA's individual career through education and service.
Impact of Skin Suture Pattern on Incision Perfusion Using Intraoperative Laser Angiography: A Randomized Clinical Trial of Patients With Ankle Fractures
Authors: Shorten Peter , Haimes Mark , Nesbit Robert , Bartlett Craig , Schottel Patrick 
Published: September 2020

Objectives:
To assess which skin suture pattern—simple, vertical mattress, horizontal mattress, Allgöwer–Donati (AD), or running subcuticular—enables the greatest degree of perfusion as measured by indocyanine green laser angiography after ankle fracture surgery.

Design:
Prospective, randomized.

Setting:
Level 1 Academic Trauma Center.

Patients/Participants:
Seventy-five patients undergoing ankle fracture surgery were prospectively randomized to 1 of 5 skin suture patterns (n = 15 per cohort). Patient demographics and operative parameters were similar between groups.

Main Outcome Measurements:
Skin perfusion was assessed intraoperatively after skin closure using indocyanine green laser angiography and quantified in fluorescence units. Two perfusion values were collected: (1) mean incision perfusion was the mean of 10 points along the incision and (2) mean perfusion impairment was the perfusion difference between the incision and the skin adjacent to it. We also collected a postoperative patient scar assessment score.

Results:
Running subcuticular closure had significantly better mean incision perfusion than all other closure patterns. Mean perfusion impairment also favored running subcuticular closure, which was significantly lower than all other suture patterns except AD. We found no patient perceived cosmetic differences between the 5 suture pattern types.

Conclusions:
Running subcuticular suture pattern resulted in the greatest incision perfusion than simple, horizontal mattress, vertical mattress, and AD techniques after ankle fracture fixation.

Level of Evidence:
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Fate of the Uninsured Ankle Fracture: Significant Delays in Treatment Result in an Increased Risk of Surgical Site Infection
Authors: Zelle Boris A. , Johnson Taylor R. , Ryan James C. , Martin Case W. , Cabot John H. , Griffin Leah P. , Bullock Travis S. , Ahmad Farhan , Brady Christina I. , Shah Kush 
Published: September 2020

Objective:
To examine the impact of insurance status on access to orthopaedic care and incidence of surgical site complications in patients with closed unstable ankle fractures.

Design:
Retrospective chart review.

Setting:
Certified Level-1 urban trauma center and county facility.

Participants:
Four hundred eighty-nine patients with closed unstable ankle fractures undergoing open reduction and internal fixation between 2014 and 2016.

Intervention:
Open reduction and internal fixation of unstable ankle fracture.

Main Outcome Measures:
Time from injury to presentation, time from injury to surgery, rate of surgical site infections, and loss to follow-up.

Results:
A total of 489 patients (70.5% uninsured vs. 29.5% insured) were enrolled. Uninsured patients were more likely to be present to an outside hospital first (P = 0.004). Time from injury to presentation at our hospital was significantly longer in uninsured patients (4.5 ± 7.6 days vs. 2.3 ± 5.5 days, P < 0.001). Time from injury to surgery was significantly longer in uninsured patient (9.4 ± 8.5 days vs. 7.3 ± 9.1 days, P < 0.001). Uninsured patients were more likely to be lost to postoperative follow-up care (P = 0.002). A logistic regression analysis demonstrated that delayed surgical timing was directly associated with an increased risk of postoperative surgical site infection (P = 0.002).

Conclusions:
Uninsured patients with ankle fractures requiring surgery experience significant barriers regarding access to health care. Delay of surgical management significantly increases the risk of surgical site infections in closed unstable ankle fractures.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.