bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ionizing Radiation Alters the Transition/Transversion Ratio in the Exome of Human Gingiva Fibroblasts
Authors: Nath Neetika , Hagenau Lisa , Weiss Stefan , Tzvetkova Ana , Jensen Lars R. , Kaderali Lars , Port Matthias , Scherthan Harry , Kuss Andreas W. 
Published: June 2020

Abstract
Little is known about the mutational impact of ionizing radiation (IR) exposure on a genome-wide level in mammalian tissues. Recent advancements in sequencing technology have provided powerful tools to perform exome-wide analyses of genetic variation. This also opened up new avenues for studying and characterizing global genomic IR-induced effects. However, genotypes generated by next generation sequencing (NGS) studies can contain errors, which may significantly impact the power to detect signals in common and rare variant analyses. These genotyping errors are not explicitly detected by the standard Genotype Analysis ToolKit (GATK) and Variant Quality Score Recalibration (VQSR) tool and thus remain a potential source of false-positive variants in whole exome sequencing (WES) datasets. In this context, the transition-transversion ratio (Ti/Tv) is commonly used as an additional quality check. In case of IR experiments, this is problematic when Ti/Tv itself might be influenced by IR treatment. It was the aim of this study to determine a suitable threshold for variant filters for NGS datasets from irradiated cells in order to achieve high data quality using Ti/Tv, while at the same time being able to investigate radiation-specific effects on the Ti/Tv ratio for different radiation doses. By testing a variety of filter settings and comparing the obtained results with publicly available datasets, we observe that a coverage filter setting of depth (DP) 3 and genotype quality (GQ) 20 is sufficient for high quality single nucleotide variants (SNVs) calling in an analysis combining GATK and VSQR and that Ti/Tv values are a consistent and useful indicator for data quality assessment for all tested NGS platforms. Furthermore, we report a reduction in Ti/Tv in IR-induced mutations in primary human gingiva fibroblasts (HGFs), which points to an elevated proportion of transversions among IR-induced SNVs and thus might imply that mismatch repair (MMR) plays a role in the cellular damage response to IR-induced DNA lesions.
Gene Expression and Cellular Markers of Occupational Radiation Exposure in Chernobyl Shelter Construction Workers
Authors: Bazyka Dimitry , Ilienko Iryna , Golyarnik Natalya , Belyaev Oleg , Lyaskivska Olena 
Published: June 2020

Abstract
Low-dose radiation effects were studied in Ukrainian personnel of the Chernobyl exclusion zone. The aim of this study was to determine the influence of borderline exposure to annual professional limits and age on expression of molecular markers. Study groups included 300 radiation workers performing construction work on the New Safe Confinement (Arch) upon the Chernobyl “Shelter” [external dose, 26.1 ± 18.1 mSv; age, 43.1 ± 10.3 y overall and 48.7 ± 5.9 y for 69 control persons]. Methods included gene expression using RT-PCR, flow cytometry of lymphocyte antigens, gamma-H2AX, Cyclin D1 expression, and relative telomere length using flow-FISH. A statistically significant upregulation of VEGFA BAX, DDB2, NFKB1 was shown at doses below 35 mSv. In workers aged under 40 y with doses higher than 35 mSv, an upregulation of 16 genes was revealed—VEGFA, TERF2, TERF1, BIRC5, BAX, TP53, DDB2, CDKN1B, CDKN2A, NFKB2, MAPK14, TGFBR1, MKNK2, CDKN1A, NFKB1, TP53I3; and four genes were downregulated—MADD, FASL, CSF2, and TERT. In workers older than 40 y, 8 genes were upregulated and 12 were downregulated. All groups showed an increased and dose-dependent gamma-H2AX expression. Downregulation of CCND1 genes in older groups was accompanied by lower numbers of Cyclin D1 protein expression and lower CD3+ and CD4+ cell counts. Upregulation of CSF2 in those over 40 y old positively correlated with B-cell and NK-cell counts. A non-linear type of gene expression response was demonstrated: in doses over 35 mSv for those over 40 y, the increased expression of gamma-H2AX is associated with upregulation of cell survival positive regulators—BIRC5, BRCA1, DDB2, CCND1, TERT genes, and longer telomeres; the younger age group was characterized by TERF1 and TERF2 upregulation and telomere shortening.
Traumatic Brain Injury-Related Emergency Department Visits Among American Indian and Alaska Native Persons—National Patient Information Reporting System, 2005-2014
Authors: Sarmiento Kelly , Kennedy Jordan , Daugherty Jill , Peterson Alexis B. , Evans Mary E. , Haberling Dana L. , Billie Holly 
Published: June 2020

Objective:
The American Indian/Alaska Native (AI/AN) population has a disproportionately high rate of traumatic brain injuries (TBIs). However, there is little known about incidence and common mechanisms of injury among AI/AN persons who seek care in an Indian Health Service (IHS) or tribally managed facility.

Methods:
Using the IHS National Patient Information Reporting System, we assessed the incidence of TBI-related emergency department visits among AI/AN children and adults seen in IHS or tribally managed facilities over a 10-year period (2005-2014).

Results:
There were 44 918 TBI-related emergency department visits during the study period. Males and persons aged 18 to 34 years and 75 years and older had the highest rates of TBI-related emergency department visits. Unintentional falls and assaults contributed to the highest number and proportion of TBI-related emergency department visits. The number and age-adjusted rate of emergency department visits for TBI were highest among persons living in the Southwest and Northern Plains when compared with other IHS regions.

Conclusion:
Thousands of AI/AN children and adults are seen each year in emergency departments for TBI and the numbers increased over the 10-year period examined. Evidence-based interventions to prevent TBI-related emergency department visits, such as programs to reduce the risk for older adult falls and assault, are warranted.
Assessing Negative Attributions After Brain Injury With the Ambiguous Intentions Hostility Questionnaire
Authors: Neumann Dawn , Sander Angelle M. , Perkins Susan M. , Bhamidipalli Surya Sruthi , Witwer Noelle , Combs Dennis , Hammond Flora M. 
Published: June 2020

Objectives:
(1) To explore the construct validity of the Ambiguous Intentions Hostility Questionnaire (AIHQ) in participants with traumatic brain injury (TBI) (ie, confirm negative attributions are associated with anger and aggression); and (2) use the AIHQ to examine negative attribution differences between participants with and without TBI.

Setting:
Two rehabilitation hospitals.

Participants:
Eighty-five adults with TBI and 86 healthy controls (HCs).

Design:
Cross-sectional survey.

Main Measures:
The AIHQ, a measure of negative attributions (intent, hostility, and blame), anger, and aggressive responses to hypothetical scenarios.

Results:
Attributions were significantly correlated with anticipated anger and aggressive responses to AIHQ scenarios. Compared with HCs, participants with TBI reported stronger negative attributions (P ≤ .001), anger (P = .021), and aggressive responses (P = .002) to the scenarios.

Conclusion:
Negative attributions were associated with anger and aggression responses, demonstrating construct validity of the AIHQ in the TBI population. Participants with TBI judged others' behaviors more severely than HCs, similar to prior research using a different attribution measure. The AIHQ has promise as a practical instrument for assessing negative attributions after TBI.
Visual outcomes and corneal biomechanics after V4c implantable collamer lens implantation in subclinical keratoconus
Authors: Li Kangjun , Wang Zheng , Zhang Dexiu , Wang Shanshan , Song Xiaocui , Li Yaxin , Wang Ming X. 
Published: June 2020

Purpose:
To quantitatively evaluate the safety, efficacy, stability, predictability, and corneal biomechanical parameters after V4c implantable collamer lens (ICL) implantation in subclinical keratoconus.

Setting:
Xi'an AIER Eye Hospital, Xi'an, China.

Design:
Retrospective case series.

Methods:
Patients undergoing V4c ICL/toric ICL implantation were examined. Scheimpflug tomography (Pentacam) was used to measure the Belin-Ambrosio enhanced ectasia total deviation index. Dynamic Scheimpflug biomechanical analysis (CorVis ST) was used to measure the corneal biomechanical parameters and Corvis Biomechanical Index. The Tomographic and Biomechanical Index was measured by combined Pentacam with CorVis ST. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, and adverse effects were also investigated.

Results:
A total of 60 eyes of 60 patients (mean age ± SD, 27.21 ± 7.24 years) were included. The mean preoperative UDVA and CDVA were 1.08 ± 0.25 and 0.12 ± 0.04 logarithm of the minimum angle of resolution (logMAR) (20/230 and 20/28 Snellen VA), respectively. After 2 years, the mean postoperative UDVA and CDVA were 0.01 ± 0.06 and −0.05 ± 0.03 logMAR (20/20 and 20/18 Snellen VA), respectively. The mean difference between the intended and achieved spherical equivalent (SE) was −0.08 ± 0.47 diopter (D), and the SE was within ±1.00 D of the intended correction in 57 eyes (95%), and 58 eyes (97%) had astigmatism less than 0.50 D. The refractive results were stable 2 years postoperatively, and the corneal biomechanical parameters returned to their preoperative levels at 3 months.

Conclusions:
The V4c ICL/toric ICL in subclinical keratoconus offered predictable correction of SE refractive error. Refractive results and corneal biomechanics were stable at the 2-year follow-up.
Clinicians Report Barriers and Facilitators to High-Quality Ambulatory Oncology Care
Authors: Lafferty Megan , Manojlovich Milisa , Griggs Jennifer J. , Wright Nathan , Harrod Molly , Friese Christopher R. 
Published: June 2020

Background
Ambulatory oncology practices treat thousands of Americans on a daily basis with high-risk and high-cost antineoplastic agents. However, we know relatively little about these diverse practices and the organizational structures influencing care delivery.

Objective
The aim of this study was to examine clinician-reported factors within ambulatory oncology practices that affect care delivery processes and outcomes for patients and clinicians.

Methods
Survey data were collected in 2017 from 298 clinicians (nurses, physicians, nurse practitioners, and physician assistants) across 29 ambulatory practices in Michigan. Clinicians provided written comments about favorable and unfavorable aspects of their work environments that affected their ability to deliver high-quality care. We conducted inductive content analysis and used the Systems Engineering Initiative for Patient Safety work system model to organize and explain our findings.

Results
Clinicians reported factors within all 5 work-system components of the Systems Engineering Initiative for Patient Safety model that affected care delivery and outcomes. Common themes surfaced, such as unfavorable aspects including staffing inadequacy and high patient volume, limited physical space, electronic health record usability issues, and order entry. Frequent favorable aspects focused on the skills of colleagues, collaboration, and teamwork. Some clinicians explicitly reported how work system factors were relational and influenced patient, clinician, and organizational outcomes.

Conclusions
These findings show how work-system components are interactive and relational reflecting the complex nature of care delivery.

Implications for Nursing Practice
Data obtained from frontline clinicians can support leaders in making organizational changes that are congruent with clinician observations of practices’ strengths and opportunities for improvement.
Cholinesterases and Anticholinergic Medications in Postoperative Pediatric Delirium
Authors: Meyburg Jochen , Ritsert Mona-Lisa , Traube Chani , Plaschke Konstanze , von Haken Rebecca 
Published: June 2020

Objectives:
To describe the relationships between anticholinergic drug exposure, cholinesterase enzyme activity, inflammation, and the development of postoperative delirium in children.

Design:
Single-center prospective cohort study.

Setting:
Twenty-two bed PICU in a tertiary-care academic medical center in Germany.

Patients:
A consecutive cohort of children admitted after major elective surgery.

Interventions:
Children were screened for delirium bid over 5 consecutive postoperative days. Acetylcholinesterase and butyrylcholinesterase plasma activity levels were measured prior to surgery and once daily during the 5 day study period. Number of anticholinergic drugs and Anticholinergic Drug Scale score were calculated for each patient.

Measurements and Main Results:
Ninety-three children (age range, 0–17 yr) were included. The number of anticholinergic drugs as well as the Anticholinergic Drug Scale score were significantly correlated with development of postoperative delirium, independently of disease severity. Baseline cholinesterase enzyme levels did not differ between patients who did and did not develop postoperative delirium. Butyrylcholinesterase levels, but not acetylcholinesterase levels, dropped by 33% postoperatively, independent of the presence of postoperative delirium. Postoperative butyrylcholinesterase levels were inversely related to number of anticholinergic drugs, Anticholinergic Drug Scale score, and C-reactive protein levels.

Conclusions:
Anticholinergic drug exposure was related to development of postoperative delirium in this cohort, with demonstration of a dose-response relationship. As there are alternative options available for many of these medications, it may be reasonable to avoid anticholinergic exposure in the PICU whenever possible.
Brief Resolved Unexplained Event
Authors: Gerber Nicole L. , Fawcett Kelsey J. , Weber Emily G. , Patel Roshni , Glick Alexander F. , Farkas Jonathan S. , Mojica Michael A. 
Published: June 2020

Objectives
This study aimed to evaluate patients who presented to the pediatric emergency department with an apparent life-threatening event (ALTE) to (1) determine if these patients would meet the criteria for brief resolved unexplained event (BRUE), a new term coined by the American Academy of Pediatrics in May, 2016; (2) risk stratify these patients to determine if they meet the BRUE low-risk criteria; and (3) evaluate outcomes of patients meeting the criteria for BRUE.

Methods
We conducted a retrospective chart review of patients who presented to a large urban academic center pediatric emergency department with an ALTE from January 2013 to May 2015 (before the publication of the BRUE guideline). Children ≤12 months of age were identified by the International Classification of Diseases, Ninth/Tenth Revision. Two physician reviews were performed to determine if patients met the ALTE diagnostic criteria. Data were then extracted from these charts to complete objectives.

Results
Seventy-eight patients met the diagnostic criteria for ALTE. Only 1 of those patients met the diagnostic criteria for BRUE, but not for low-risk BRUE. This patient underwent an extensive inpatient evaluation and was eventually discharged after monitoring with a benign diagnosis. Most patients did not meet the criteria for BRUE because the event was not unexplained.

Conclusions
Only 1 patient who presented to the ED with ALTE met the criteria for BRUE, and this patient did not meet the low-risk criteria. This study corroborates previous research on BRUE and continues to highlight the importance of conducting a thorough history and physical examination on all patients presenting to the ED with concerning events.
Interactions Between Acute Infarcts and Cerebrovascular Pathology Predict Poststroke Dementia
Authors: Yatawara Chathuri , Guevarra Anne , Ng Kok Pin , Chander Russell , Kandiah Nagaendran 
Published: June 2020

Background:Chronic cerebrovascular pathology accelerates the incidence of poststroke dementia (PSD). Whether the risk of PSD varies according to different types of chronic cerebrovascular pathology remains unclear.Objectives:We investigated whether PSD is associated with a unique pattern of interactions between chronic cerebrovascular pathologies and acute stroke lesions.Materials and Method:In this case-control study of acute mild stroke patients (n=185), cases included patients who developed PSD at a 6-month poststroke follow-up, and controls included patients who remained nondemented at 6 months, matched on prestroke cognitive status. Magnetic resonance imaging was performed at initial stroke presentation; neuropsychological assessments were performed 6 months after the stroke.Results:White matter hyperintensities (WMH), chronic lacunes, microbleeds, and acute infarcts were not associated with PSD after controlling for demographics, cardiovascular risk, and global cortical atrophy. The risk of PSD was largest for patients with acute large subcortical infarcts (>15 mm) and concomitant periventricular WMH compared with patients with large subcortical infarcts and punctate/absent periventricular WMH [odds ratio (OR)=5.85, 95% confidence interval (CI)=1.85-40.04]. A moderate risk of PSD was observed for patients with acute multiple small infarcts (3 to 15 mm) and concomitant lacunes (OR=2.48, 95% CI=0.94-6.51) or concomitant lobar microbleeds (OR=2.20, 95% CI=0.89-5.41), compared with patients with acute multiple small infarcts and absent lacunes or microbleeds. Single small infarcts did not interact with cerebrovascular pathology to affect PSD.Conclusions:The risk of PSD varies depending on the presence of chronic cerebrovascular pathologies and type of acute infarcts. Clinical implications support a precision medicine approach for stratifying those at highest risk of PSD.
Neck Circumference and Cerebral Gray Matter Volume
Authors: Shin Chol , Kim Regina E.Y. , Thomas Robert J. , Yun Chang-Ho , Lee Seung Ku , Abbott Robert D. 
Published: June 2020

Background:
While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease.

Methods:
Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study.

Results:
For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent.

Conclusions:
In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.
Vision reconstructs the cellular composition of binocular circuitry during the critical period
Authors: Tan Liming , Tring Elaine , Ringach Dario L. , Zipursky S. Lawrence , Trachtenberg Joshua T. 
Published: June 2020

AbstractHigh acuity binocularity is established in primary visual cortex during an early postnatal critical period. In contrast to current models for the developmental of binocular neurons, we find that the binocular network present at the onset of the critical period is dismantled and remade. Using longitudinal imaging of receptive field tuning (e.g. orientation selectivity) of thousands of layer 2/3 neurons through development, we show most binocular neurons present at critical-period onset are poorly tuned and rendered monocular. These are replenished by newly formed binocular neurons that are established by a vision-dependent recruitment of well-tuned ipsilateral inputs to contralateral monocular neurons with matched tuning properties. The binocular network in layer 4 is equally unstable but does not improve. Thus, vision instructs a new and more sharply tuned binocular network in layer 2/3 by exchanging one population of neurons for another and not by refining an extant network.One Sentence SummaryUnstable binocular circuitry is transformed by vision into a network of highly tuned complex feature detectors in the cortex.
Sensei: How many samples to tell evolution in single-cell studies?
Authors: Liang Shaoheng , Willis Jason , Dou Jinzhuang , Mohanty Vakul , Huang Yuefan , Vilar Eduardo , Chen Ken 
Published: June 2020

1AbstractCellular heterogeneity underlies cancer evolution and metastasis. Advances in single-cell technologies such as single-cell RNA sequencing and mass cytometry have enabled interrogation of cell type-specific expression profiles and abundance across heterogeneous cancer samples obtained from clinical trials and preclinical studies. However, challenges remain in determining sample sizes needed for ascertaining changes in cell type abundances in a controlled study. To address this statistical challenge, we have developed a new approach, named Sensei, to determine the number of samples and the number of cells that are required to ascertain such changes between two groups of samples in single-cell studies. Sensei expands the t-test and models the cell abundances using a beta-binomial distribution. We evaluate the mathematical accuracy of Sensei and provide practical guidelines on over 20 cell types in over 30 cancer types based on knowledge acquired from the cancer cell atlas (TCGA) and prior single-cell studies. We provide a web application to enable user-friendly study design via https://kchen-lab.github.io/sensei/table_beta.html.