bluuebunny/crossref_metadata_2025_split huggingface dataset:
Video analysis of high-magnitude head impacts in men’s collegiate lacrosse
Authors: Kindschi Kari , Higgins Michael , Hillman Andrea , Penczek Gregory , Lincoln Andrew 
Published: June 2017

Background/aimLacrosse is one of the fastest growing sports in the USA. Efforts to minimise head injuries focus on promoting safe play through player and coach education, rules enforcement and use of effective protective equipment. The study aims to determine event characteristics of high-magnitude head impacts in men’s collegiate lacrosse competitions through video analysis.MethodsSeventeen Division I men’s collegiate lacrosse players wore instrumented helmets that collected biomechanical measures of head impacts. During 15 competitions, the magnitude of linear acceleration, rotational velocity and helmet impact location were recorded. Impacts with linear accelerations above a 70gthreshold were correlated with video to confirm impact location and to determine event characteristics—source of impact and player activity at the time of impact.ResultsA total of 122 high-magnitude impacts were reviewed on video. Player-to-player contact (n=94, 77.0%) was the most common impact mechanism, followed by stick-to-player contact (n=11, 9.0%). Impacts occurred most often when the athlete was delivering a body check (n=39, 32.0%), fighting for loose ball possession (n=35, 28.7%) or attacking the goal (n=35, 28.7%). The most frequent impact locations were the front of the helmet (n=46, 37.8%) and the left side of the helmet (n=26, 21.3%).ConclusionsIn men’s collegiate lacrosse games, the majority of high-magnitude head impacts resulted from player-to-player contact when the sensored athlete did not have possession of the ball. Video analysis provides the game context for head impact mechanisms, which is critical to developing sport-specific injury prevention strategies.
Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice
Authors: Ha Jung-Heun , Doguer Caglar , Collins James F. 
Published: June 2017

High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed AIN-93G-based diets containing high (HFe) (~8,800 ppm) or adequate (AdFe) (~80 ppm) iron in combination with low (~0.9 ppm), adequate (~9 ppm), or high (~180 ppm) copper for several weeks. Iron and copper homeostasis was subsequently assessed. Mice consuming the HFe diets grew slower, were anemic, and had lower hepatic copper levels and serum ceruloplasmin activity. These physiological perturbations were all prevented by higher dietary copper, demonstrating that copper depletion was the underlying cause. Furthermore, homeostatic regulation of copper absorption was noted in the mice consuming the AdFe diets, with absorption increasing as dietary copper decreased. HFe-fed mice did not have impaired copper absorption (disproving our hypothesis), but homeostatic control of absorption was disrupted. There were also noted perturbations in the tissue distribution of copper in the HFe-fed mice, suggesting that altered storage and thus bioavailability contributed to the noted copper deficiency. Dietary iron loading thus antagonizes copper homeostasis leading to pathological symptoms of severe copper depletion. NEW & NOTEWORTHY High-iron feeding is a common experimental method to model human iron-overload disorders in rodents. Here, we show that dietary iron loading causes severe copper deficiency due to perturbations in the homeostatic regulation of intestinal copper absorption and tissue distribution, which may decrease the bioavailability of copper for use in cuproenzyme synthesis. Whether high-dose iron supplementation in humans antagonizes copper homeostasis is worthy of consideration.
An assessment of the autonomic nervous system in the electrohypersensitive population: a heart rate variability and skin conductance study
Authors: Andrianome Soafara , Gobert Jonathan , Hugueville Laurent , Stéphan-Blanchard Erwan , Telliez Frederic , Selmaoui Brahim 
Published: June 2017

The aim of the study was twofold: first, to compare the activity of the autonomic nervous system (ANS) between the population self-declared as electrohypersensitive (EHS) and their matched control individuals without intended exposure to electromagnetic fields (EMF). The second objective was to determine whether acute exposure to different radiofrequency signals modifies ANS activity in EHS. For that purpose, two different experiments were undertaken, in which ANS activity was assessed through heart rate variability (HRV) and skin conductance (SC). In the first experiment, a comparison between the EHS group ( n = 30) and the control group ( n = 25) showed that the EHS has an increased number of responses to auditory stimuli as measured by skin conductance activity, and that none of the short-term heart rate variability parameters differ between the two matched study groups. The second experiment, performed in a shielded chamber, involved 10 EHS from the first experiment. The volunteers participated in two different sessions (sham and exposure). The participants were consecutively exposed to four EMF signals (GSM 900, GSM 1800, DECT, and Wi-Fi) at environmental level (1 V/m). The experiment was double blinded and counterbalanced. The HRV variables studied did not differ between the two sessions. Concerning electrodermal activity, the data issued from skin conductance and tonic activity did not differ between the sessions, but showed a time variability. In conclusion, the HRV and SC profiles did not significantly differ between the EHS and control populations under no exposure. Exposure did not have an effect on the ANS parameters we have explored. NEW & NOTEWORTHY This study provided analysis on the skin conductance parameters using a newly developed method (peak/min, extraction of skin conductance responses) that had not been performed previously. Additionally, the skin conductance signal was decomposed, considering tonic and phasic activities to be a distinct compound. Moreover, this is the first time a study has been designed into two steps to understand whether the autonomic nervous system is disturbed in the EHS population.
Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions
Authors: Kar Siddhartha P. , Berchuck Andrew , Gayther Simon A. , Goode Ellen L. , Moysich Kirsten B. , Pearce Celeste Leigh , Ramus Susan J. , Schildkraut Joellen M. , Sellers Thomas A. , Pharoah Paul D.P. 
Published: June 2017

Abstract
In this review, we summarize current progress in the genetic epidemiology of epithelial ovarian cancer (EOC), focusing exclusively on elucidating the role of common germline genetic variation in conferring susceptibility to EOC. We provide an overview of the more than 30 EOC risk loci identified to date by genome-wide association studies (GWAS) and describe the contribution of large-scale, cross-cancer type, custom genotyping projects, such as the OncoArray and the Collaborative Oncological Gene-Environment Study, to locus discovery and replication. We discuss the histotype-specific nature of these EOC risk loci, pleiotropy, or overlapping genetic effects between EOC and other hormone-related cancer types, and the application of findings to polygenic risk prediction for EOC. The second part of the article offers a concise review of primarily laboratory-based studies that have led to the identification of several putative EOC susceptibility genes using common variants at the known EOC risk loci as starting points. More global biological insights emerging from network- and pathway-based analyses of GWAS for EOC susceptibility are also highlighted. Finally, we delve into potential future directions, including the need to identify EOC risk loci in non-European populations and the next generation of GWAS functional studies that are likely to involve genome editing to establish the cell type–specific carcinogenic effects of EOC risk variants Cancer Epidemiol Biomarkers Prev; 27(4); 395–404. ©2018 AACR.
See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Von Hippel–Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood
Authors: Rednam Surya P. , Erez Ayelet , Druker Harriet , Janeway Katherine A. , Kamihara Junne , Kohlmann Wendy K. , Nathanson Katherine L. , States Lisa J. , Tomlinson Gail E. , Villani Anita , Voss Stephan D. , Schiffman Joshua D. , Wasserman Jonathan D. 
Published: June 2017

Abstract
Von Hippel–Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the SHDx genes (SDHA, SDHB, SDHC, SDHD, SDHA, and SDHAF2), although other genes also have been described (MAX and TMEM127). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors. Clin Cancer Res; 23(12); e68–e75. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
Cancer and Central Nervous System Tumor Surveillance in Pediatric Neurofibromatosis 2 and Related Disorders
Authors: Evans D. Gareth R. , Salvador Hector , Chang Vivian Y. , Erez Ayelet , Voss Stephan D. , Druker Harriet , Scott Hamish S. , Tabori Uri 
Published: June 2017

Abstract
The neurofibromatoses consist of at least three autosomal-dominant inherited disorders: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. For over 80 years, these conditions were inextricably tied together under generalized neurofibromatosis. In 1987, the localization of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q led to a consensus conference at Bethesda, Maryland. The two main neurofibromatoses, NF1 and NF2, were formally separated. More recently, the SMARCB1 and LZTR1 genes on 22q have been confirmed as causing a subset of schwannomatosis. The last 26 years have seen a great improvement in understanding of the clinical and molecular features of these conditions as well as insights into management. Childhood presentation of NF2 (often with meningioma) in particular predicts a severe multitumor disease course. Malignancy is rare in NF2, particularly in childhood; however, there are substantial risks from benign and low-grade central nervous system (CNS) tumors necessitating MRI surveillance to optimize management. At least annual brain MRI, including high-resolution images through the auditory meatus, and a clinical examination and auditory assessment are required from diagnosis or from around 10 to 12 years of age if asymptomatic. Spinal imaging at baseline and every 2 to 3 years is advised with more frequent imaging if warranted on the basis of sites of tumor involvement. The malignancy risk in schwannomatosis is not well defined but may include an increased risk of malignant peripheral nerve sheath tumor in SMARCB1. Imaging protocols are also proposed for SMARCB1 and LZTR1 schwannomatosis and SMARCE1-related meningioma predisposition. Clin Cancer Res; 23(12); e54–e61. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas
Authors: Islam Shariful , Qi Wenqing , Morales Carla , Cooke Laurence , Spier Catherine , Weterings Eric , Mahadevan Daruka 
Published: June 2017

Abstract
Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2, which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of &gt;90%. Kaplan–Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083–93. ©2017 AACR.
Antitumor Effects of Epidrug/IFNα Combination Driven by Modulated Gene Signatures in Both Colorectal Cancer and Dendritic Cells
Authors: Fragale Alessandra , Romagnoli Giulia , Licursi Valerio , Buoncervello Maria , Del Vecchio Giorgia , Giuliani Caterina , Parlato Stefania , Leone Celeste , De Angelis Marta , Canini Irene , Toschi Elena , Belardelli Filippo , Negri Rodolfo , Capone Imerio , Presutti Carlo , Gabriele Lucia 
Published: June 2017

Abstract
Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRF) to access regulatory sequences in IFN-stimulated genes (ISG) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNα2 (ARI) hampers the aggressiveness of both colorectal cancer metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function. Here, we investigated the molecular signals induced by ARI treatment and found that this drug combination increased the accessibility to regulatory sequences of ISGs and IRFs that were epigenetically silenced in both colorectal cancer cells and DCs. Likewise, specific ARI-induced histone methylation and acetylation changes marked epigenetically affected ISG promoters in both metastatic cancer cells and DCs. Analysis by ChIP-seq confirmed such ARI-induced epigenetically regulated IFN signature. The activation of this signal endowed DCs with a marked migratory capability. Our results establish a direct correlation between reexpression of silenced ISGs by epigenetic control and ARI anticancer activity and provide new knowledge for the development of innovative combined therapeutic strategies for colorectal cancer. Cancer Immunol Res; 5(7); 604–16. ©2017 AACR.
Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy
Authors: Ross Samantha Barratt , Bagnall Richard D. , Ingles Jodie , Van Tintelen J. Peter , Semsarian Christopher 
Published: June 2017

Background—
Hypertrophic cardiomyopathy is a genetically heterogeneous myocardial disease with >1000 causal variants identified. Nonunique variants account for disease in many families. We sought to characterize nonunique variants in Australian families and determine whether they arise from common ancestral mutations or recurrent mutation events.

Methods and Results—

Genetic test results of 467 index patients from apparently unrelated families with hypertrophic cardiomyopathy were evaluated. Causal variants were found in 185 of 467 (40%) families. Nonunique variants accounted for 122 of 185 (66%) families. The most common single genetic cause of hypertrophic cardiomyopathy is the recurrent
MYBPC3
(myosin-binding protein-C) variant c.1504C>T, p.Arg502Trp, which was found in 13 of 185 (7%) families with a causal variant identified. Thirteen variants in
MYBPC3
and
MYH7
(myosin heavy chain 7) were each identified >3 times and accounted for 78 of 185 (42%) hypertrophic cardiomyopathy families with a causal variant. Haplotype analysis of these 13 variants was performed on 126 individuals from 70 Australian families, and 11 variants arose through recurrent mutation events. Two variants,
MYBPC3
c.1928-2A>G and
MYH7
c.2681A>G, p.Glu894Gly, were found on 1 haplotype in 6 families each, supportive of a single mutation event inherited from a common ancestor.

Conclusions—
The majority of families with a causal variant identified have a nonunique variant. Discovery of the genetic origins of human disease forms a fundamental basis for improved understanding of disease pathogenesis and phenotype development.
Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction
Authors: Vedin Ola , Lam Carolyn S.P. , Koh Angela S. , Benson Lina , Teng Tiew Hwa Katherine , Tay Wan Ting , Braun Oscar Ö. , Savarese Gianluigi , Dahlström Ulf , Lund Lars H. 
Published: June 2017

Background—
The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%–50%) and preserved EF (HFpEF; EF ≥50%) has been much less explored.

Methods and Results—
We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89–0.93] versus HFmrEF and risk ratio, 0.90 [0.88–0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84–0.95] versus HFmrEF and hazard ratio, 0.84 [0.80–0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time.

Conclusions—
HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.
Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices: Observations From the ROCKET AF Trial
Authors: Leef George C. , Hellkamp Anne S. , Patel Manesh R. , Becker Richard C. , Berkowitz Scott D. , Breithardt Günter , Halperin Jonathan L. , Hankey Graeme J. , Hacke Werner , Nessel Christopher C. , Singer Daniel E. , Fox Keith A.A. , Mahaffey Kenneth W. , Piccini Jonathan P. 
Published: June 2017

Background

Although implantation of cardiac implantable electronic devices (
CIED
s) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting.

Methods and Results

Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo
CIED
implantation or revision. In this post‐hoc, postrandomization, on‐treatment analysis, only the first intervention per patient was analyzed. During a median follow‐up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo
CIED
implantation (64.2%) or revision procedures (35.8%). Patients who received
CIED
s were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive
CIED
s. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30‐day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing.

Conclusions

Bleeding and thromboembolic events were low in both rivaroxaban‐ and warfarin‐treated patients. Periprocedural use of oral factor Xa inhibitors in
CIED
implantation requires further study in prospective, randomized trials.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00403767.