bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between the frequency of football practice during skeletal growth and the presence of a cam deformity in adult elite football players
Authors: Tak Igor , Weir Adam , Langhout Rob , Waarsing Jan Hendrik , Stubbe Janine , Kerkhoffs Gino , Agricola Rintje 
Published: January 2015

Background/aimCam deformity (CD) is likely a bony adaptation in response to high-impact sports practice during skeletal growth. We ascertained whether a dose–response relationship exists between the frequency of football practice during skeletal growth and the presence of a CD in adulthood, and if the age at which a football player starts playing football is associated with the presence of a CD in adulthood.MethodsPrevalence of a CD (α angle>60°) and a pathological CD (α angle>78°) was studied using standardised anteroposterior (AP) and frog-leg lateral (FLL) radiographs that were obtained during seasonal screening. The age of starting to play football with a low frequency (LF; ≤3 times/week) and high frequency (HF; ≥4 times/week) was retrospectively assessed. The differences in prevalence of a CD per hip, in either view, between groups were calculated by logistic regression with generalised estimating equations.Results63 players (mean(±SD) age 23.1(±4.2) years) participated, yielding 126 hips for analysis. The prevalence of a CD in the FLL was 40% (n=82) in players who started playing HF football from the age of 12 years or above, and 64% (n=44) in those playing HF football before the age of 12 years (p=0.042). This was also true for a pathological CD (12% vs 30%, p=0.038). The AP views revealed no difference.ConclusionsOur results indicate a probable dose–response relationship between the frequency of football practice during skeletal growth and the development of a CD, which should be confirmed in future prospective studies.
Does teaching children to swim increase exposure to water or risk-taking when in the water? Emerging evidence from Bangladesh
Authors: Mecrow Tom Stefan , Linnan Michael , Rahman Aminur , Scarr Justin , Mashreky Saidur Rahman , Talab Abu , Rahman A K M Fazlur 
Published: January 2015

BackgroundSwimSafe, a basic swimming and safe rescue curriculum, has been taught to large numbers of children in Bangladesh. Teaching swimming potentially increases risk if it increases water exposure or high-risk practices in water. This study compares water exposure and risk practices for SwimSafe graduates (SS) with children who learned swimming naturally.MethodsInterviewers obtained detailed water exposure histories for the preceding 48 h from 3936 SS aged 6–14 and 3952 age-matched and sex-matched children who had learned swimming naturally. Frequencies of water exposure and water entries for swimming or playing were compared.ResultsThere were 9741 entries into water among the 7046 participants in the 48 h prior to interview. About one-third (31.2%) had no water entries, one-tenth (10.5%) entered once, half (49.2%) entered twice and a tenth (9.1%) entered three or more times. Proportions of children in each group were similar. About 99.5% of both groups only entered the water for bathing. For those entering to swim or play, the mean number of entries was similar (SS 1.63, natural swimmer (NS) 1.36, p=0.40). Swimming or playing alone in the water was rare (1 SS, 0 NS).ConclusionsMost water exposure for children is for bathing. Less than 1% swam or played in the water during the 48 h recall period (0.6% SS, 0.4% NS). Learning swimming in SwimSafe did not increase water exposure nor did it increase water entry for playing or swimming compared with children who learned to swim naturally.
Critical assessment of the morbidity associated with ruptured cerebral arteriovenous malformations
Authors: Majumdar Monica , Tan Lee A , Chen Michael 
Published: January 2015

BackgroundAn accurate understanding of the morbidity and mortality associated with brain arteriovenous malformation (AVM) hemorrhage is important in determining the management of unruptured AVMs. Recent studies suggest this morbidity to be lower than assumed. We sought to perform a detailed critical assessment of the morbidity associated with ruptured brain AVMs.MethodsA retrospective chart review from a single-center tertiary care medical center was performed. Inclusion criteria were patients admitted with intracranial hemorrhage caused by a previously untreated AVM. Forty variables were analyzed including patient demographics, imaging findings, clinical course, and clinical examinations.ResultsFrom 2008 to 2013, of the 51 patients who fit our inclusion criteria, we found admission National Institutes of Health Stroke Scale (NIHSS) scores of 0, 1–9, and ≥10 in 22%, 24%, and 55%, respectively. Hematoma location was parenchymal in 33%, intraventricular in 10%, subarachnoid in 4%, and combined in 53%. Deep venous drainage was present in 35% of cases and associated aneurysms were present in 37%. 43% underwent emergency hematoma evacuation while four patients died during their admission. Of those who survived, 74% had neurologic deficits upon discharge (NIHSS ≥1), with 25.5% of patients having a severe deficit (NIHSS ≥10). On follow-up, 55% were independent in their daily activities of living.ConclusionsOur assessment of morbidity associated with brain AVM rupture is higher than previously assumed and reported. These results should be further validated in a larger, more representative sample. An accurate understanding of the morbidity associated with AVM rupture is important as more patients with unruptured brain AVMs seek consultation.
Broad, Hybrid Capture–Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches
Authors: Drilon Alexander , Wang Lu , Arcila Maria E. , Balasubramanian Sohail , Greenbowe Joel R. , Ross Jeffrey S. , Stephens Phil , Lipson Doron , Miller Vincent A. , Kris Mark G. , Ladanyi Marc , Rizvi Naiyer A. 
Published: January 2015

Abstract
Purpose: Broad, hybrid capture–based next-generation sequencing (NGS), as a clinical test, uses less tissue to identify more clinically relevant genomic alterations compared with profiling with multiple non-NGS tests. We set out to determine the frequency of such genomic alterations via this approach in tumors in which previous extensive non-NGS testing had not yielded a targetable driver alteration.
Experimental Design: We enrolled patients with lung adenocarcinoma with a ≤15 pack-year smoking history whose tumors previously tested “negative” for alterations in 11 genes (mutations in EGFR, ERBB2, KRAS, NRAS, BRAF, MAP2K1, PIK3CA, and AKT1 and fusions involving ALK, ROS1, and RET) via multiple non-NGS methods. We performed hybridization capture of the coding exons of 287 cancer-related genes and 47 introns of 19 frequently rearranged genes and sequenced these to deep, uniform coverage.
Results: Actionable genomic alterations with a targeted agent based on NCCN guidelines were identified in 26% [8 of 31: EGFR G719A, BRAF V600E, SOCS5-ALK, HIP1-ALK, CD74-ROS1, KIF5B-RET (n = 2), CCDC6-RET]. Seven of these patients either received or are candidates for targeted therapy. Comprehensive genomic profiling using this method also identified a genomic alteration with a targeted agent available on a clinical trial in an additional 39% (12 of 31).
Conclusions: Broad, hybrid capture–based NGS identified actionable genomic alterations in 65% [95% confidence interval (CI), 48%–82%] of tumors from never or light smokers with lung cancers deemed without targetable genomic alterations by earlier extensive non-NGS testing. These findings support first-line profiling of lung adenocarcinomas using this approach as a more comprehensive and efficient strategy compared with non-NGS testing. Clin Cancer Res; 21(16); 3631–9. ©2015 AACR.
See related commentary by McCutcheon and Giaccone, p. 3584
CD44 Regulates Pancreatic Cancer Invasion through MT1-MMP
Authors: Jiang Wei , Zhang Yaqing , Kane Kevin T. , Collins Meredith A. , Simeone Diane M. , di Magliano Marina Pasca , Nguyen Kevin Tri 
Published: January 2015

Abstract
Pancreatic cancer is one of the deadliest human malignancies due to its early metastatic spread and resistance to therapy. The mechanisms regulating pancreatic cancer metastasis are so far poorly understood. Here, using both in vitro and in vivo approaches, it is demonstrated that CD44, a transmembrane glycoprotein expressed on a subset of pancreatic cancer cells, is required for the induction of epithelial–mesenchymal transition (EMT) and the activation of an invasive program in pancreatic cancer. Mechanistically, the transcription factor Snail1 (SNAI1), a regulator of the EMT program, is a downstream target of CD44 in primary pancreatic cancer cells and regulates membrane bound metalloproteinase (MMP14/MT1-MMP) expression. In turn, MT1-MMP expression is required for pancreatic cancer invasion. Thus, these data establish the CD44–Snail–MMP axis as a key regulator of the EMT program and of invasion in pancreatic cancer.
Implications: This study sets the stage for CD44 and MT1-MMP as therapeutic targets in pancreatic cancer, for which small molecule or biologic inhibitors are available.
Visual Overview: http://mcr.aacrjournals.org/content/early/2014/09/10/1541-7786.MCR-14-0076/F1.large.jpg.
Mol Cancer Res; 13(1); 9–15. ©2014 AACR.
The Ras–Membrane Interface: Isoform-Specific Differences in the Catalytic Domain
Authors: Parker Jillian A. , Mattos Carla 
Published: January 2015

Abstract
The small GTPase Ras is mutated in about 20% of human cancers, primarily at active site amino acid residues G12, G13, and Q61. Thus, structural biology research has focused on the active site, impairment of GTP hydrolysis by oncogenic mutants, and characterization of protein–protein interactions in the effector lobe half of the protein. The C-terminal hypervariable region has increasingly gained attention due to its importance in H-Ras, N-Ras, and K-Ras differences in membrane association. A high-resolution molecular view of the Ras–membrane interaction involving the allosteric lobe of the catalytic domain has lagged behind, although evidence suggests that it contributes to isoform specificity. The allosteric lobe has recently gained interest for harboring potential sites for more selective targeting of this elusive “undruggable” protein. The present review reveals critical insight that isoform-specific differences appear prominently at these potentially targetable sites and integrates these differences with knowledge of Ras plasma membrane localization, with the intent to better understand the structure–function relationships needed to design isoform-specific Ras inhibitors. Mol Cancer Res; 13(4); 595–603. ©2015 AACR.
Tumors: Wounds That Do Not Heal—Redux
Authors: Dvorak Harold F. 
Published: January 2015

AbstractSimilarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/VEGF, I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound-healing response to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel that serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by “granulation tissue” (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called “scar tissue” in wounds and “desmoplasia” in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity. Cancer Immunol Res; 3(1); 1–11. ©2015 AACR.
Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis
Authors: Marbury Thomas , Matsushima Nobuko , Chen Shuquan , Wickremasingha Prachi K. , He Ling , Dishy Victor , Brown Karen S. , Parasrampuria Dolly A. 
Published: January 2015

SummaryEdoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke prevention in patients with atrial fibrillation and for the treatment and secondary prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism. Among elderly patients who require anticoagulation therapies, some may have end-stage renal disease (ESRD). This open-label, phase 1, randomised, two-way crossover study was conducted to evaluate the pharmacokinetics of edoxaban in 10 subjects on haemodialysis. Eligible subjects with ESRD on chronic haemodialysis received a single, oraldose of edoxaban 15 mg 2 hours (h) prior to (on-dialysis) or in between (off-dialysis) haemodialysis sessions. Haemodialysis resulted in a minor decrease in mean total exposure (AUC0-∞; 676.2 ng⋅h/ml) as compared with that observed in subjects off-dialysis (691.7 ng⋅h/ml). Mean maximum observed plasma concentration (Cmax) values were comparable between on-dialysis and off-dialysis treatments (53.3 vs 56.3 ng/ml, respectively). Mean apparent total body clearance (CL/F) values were 24.1 and 22.5 l/h during the on-dialysis and off-dialysis treatment periods, respectively. Dialyser clearance was 5.7 l/h and haemodialysis clearance was 6.1 l/h. Haemodialysis clearance was only 6.1 l/h, suggesting that it only accounts for one-fourth of the total clearance in these subjects. A single, oral dose of 15 mg of edoxaban was well tolerated by subjects with ESRD. In conclusion, based on these single-dose PK data, a supplementary dose of edoxaban may not be required following a haemodialysis session. Importantly, haemodialysis is not an effective mechanism for removal of edoxaban from the blood.
Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab
Authors: Honickel Markus , Treutler Stefanie , Ryn Joanne van , Tillmann Sabine , Rossaint Rolf , Grottke Oliver 
Published: January 2015

SummaryUrgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both threeand four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.Note: This study was performed at the RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Screening for Rheumatic Heart Disease
Authors: Mirabel Mariana , Bacquelin Raoul , Tafflet Muriel , Robillard Corinne , Huon Bertrand , Corsenac Philippe , de Frémicourt Isabelle , Narayanan Kumar , Meunier Jean-Michel , Noël Baptiste , Hagège Albert Alain , Rouchon Bernard , Jouven Xavier , Marijon Eloi 
Published: January 2015

Background—
Rheumatic heart disease (RHD) remains a major public health problem worldwide. Although early diagnosis by echocardiography may potentially play a key role in developing active surveillance, systematic evaluation of simple approaches in resource poor settings are needed.

Methods and Results—
We prospectively compared focused cardiac ultrasound (FCU) to a reference approach for RHD screening in a school children population. FCU included (1) the use of a pocket-sized echocardiography machine, (2) nonexpert staff (2 nurses with specific training), and (3) a simplified set of echocardiographic criteria. The reference approach used standardized echocardiographic examination, reviewed by an expert cardiologist, according to 2012 World Heart Federation criteria. Among the 6 different echocardiographic criteria, first tested in a preliminary phase, mitral regurgitation jet length ≥2 cm or any aortic regurgitation was considered best suited to be FCU criteria. Of the 1217 subjects enrolled (mean, 9.6±1 years; 49.6% male), 49 (4%) were diagnosed with RHD by the reference approach. The sensitivity of FCU for the detection of RHD was 83.7% (95% confidence interval, 73.3–94.0) for nurse A and 77.6% (95% confidence interval, 65.9–89.2) for nurse B. FCU yielded a specificity of 90.9% (95% confidence interval, 89.3–92.6) and 92.0% (95% confidence interval, 90.4–93.5) according to users. Percentage of agreement among nurses was 91.4%.

Conclusions—
FCU by nonexperts using pocket devices seems feasible and yields acceptable sensitivity and specificity for RHD detection when compared with the state-of-the-art approach, thereby opening new perspectives for mass screening for RHD in low-resource settings.
Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia
Authors: Teraa Martin , Sprengers Ralf W. , Schutgens Roger E.G. , Slaper-Cortenbach Ineke C.M. , van der Graaf Yolanda , Algra Ale , van der Tweel Ingeborg , Doevendans Pieter A. , Mali Willem P.Th.M. , Moll Frans L. , Verhaar Marianne C. 
Published: January 2015

Background—
Patients with severe limb ischemia may not be eligible for conventional therapeutic interventions. Pioneering clinical trials suggest that bone marrow–derived cell therapy enhances neovascularization, improves tissue perfusion, and prevents amputation. The objective of this trial was to determine whether repetitive intra-arterial infusion of bone marrow mononuclear cells (BMMNCs) in patients with severe, nonrevascularizable limb ischemia can prevent major amputation.

Methods and Results—
The Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial is a randomized, double-blind, placebo-controlled clinical trial in 160 patients with severe, nonrevascularizable limb ischemia. Patients were randomly assigned to repetitive (3 times; 3-week interval) intra-arterial infusion of BMMNC or placebo. No significant differences were observed for the primary outcome, ie, major amputation at 6 months, with major amputation rates of 19% in the BMMNC versus 13% in the placebo group (relative risk, 1.46; 95% confidence interval, 0.62–3.42). The safety outcome (all-cause mortality, occurrence of malignancy, or hospitalization due to infection) was not significantly different between the groups (relative risk, 1.46; 95% confidence interval, 0.63–3.38), neither was all-cause mortality at 6 months with 5% versus 6% (relative risk, 0.78; 95% confidence interval, 0.22–2.80). Secondary outcomes quality of life, rest pain, ankle-brachial index, and transcutaneous oxygen pressure improved during follow-up, but there were no significant differences between the groups.

Conclusions—
Repetitive intra-arterial infusion of autologous BMMNCs into the common femoral artery did not reduce major amputation rates in patients with severe, nonrevascularizable limb ischemia in comparison with placebo. The general improvement in secondary outcomes during follow-up in both the BMMNC and the placebo group, as well, underlines the essential role for placebo-controlled design of future trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00371371.
Effect of a Moderate Fat Diet With and Without Avocados on Lipoprotein Particle Number, Size and Subclasses in Overweight and Obese Adults: A Randomized, Controlled Trial
Authors: Wang Li , Bordi Peter L. , Fleming Jennifer A. , Hill Alison M. , Kris‐Etherton Penny M. 
Published: January 2015

Background

Avocados are a nutrient‐dense source of monounsaturated fatty acids (
MUFA
) that can be used to replace saturated fatty acids (
SFA
) in a diet to lower low density lipoprotein cholesterol (
LDL
‐C). Well‐controlled studies are lacking on the effect of avocado consumption on cardiovascular disease (
CVD
) risk factors.

Methods and Results

A randomized, crossover, controlled feeding trial was conducted with 45 overweight or obese participants with baseline LDL‐C in the 25th to 90th percentile. Three cholesterol‐lowering diets (6% to 7% SFA) were fed (5 weeks each): a lower‐fat diet (LF: 24% fat); 2 moderate‐fat diets (34% fat) provided similar foods and were matched for macronutrients and fatty acids: the avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the moderate‐fat diet (MF) mainly used high oleic acid oils to match the fatty acid content of one avocado. Compared with baseline, the reduction in LDL‐C and non‐high‐density lipoprotein (HDL) cholesterol on the AV diet (−13.5 mg/
dL
, −14.6 mg/
dL
) was greater (
P
<0.05) than the MF (−8.3 mg/
dL
, −8.7 mg/
dL
) and LF (−7.4 mg/
dL
, −4.8 mg/
dL
) diets. Furthermore, only the AV diet significantly decreased LDL particle number (LDL‐P, −80.1 nmol/L,
P
=0.0001), small dense LDL cholesterol (LDL
3+4
, −4.1 mg/
dL
,
P
=0.04), and the ratio of LDL/HDL (−6.6%,
P
<0.0001) from baseline.

Conclusions

Inclusion of one avocado per day as part of a moderate‐fat, cholesterol‐lowering diet has additional
LDL
‐C,
LDL
‐P, and non‐
HDL
‐C lowering effects, especially for small, dense
LDL
. Our results demonstrate that avocados have beneficial effects on cardio‐metabolic risk factors that extend beyond their heart‐healthy fatty acid profile.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01235832.