bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Study: The Effect of Nutritional Intervention on Body Composition and Physical Performance of a Female Squash Player
Authors: Rosimus Christopher 
Published: November 2017

The body composition of a squash player may affect athletic performance as carrying excessive body fat may increase injury risk and impair agility and speed. This case study outlines the effect of a nutritional intervention on body composition, vitamin D status, and physical performance of a female squash player. A structured, 6-week, moderate energy–restricted diet (70–78% of estimated energy requirement of 2,300 kcal) was implemented with weekly support. A daily supplement of vitamin D, omega-3 fatty acids, and a multivitamin and whey protein was used. Full blood count, vitamin D status, body composition, and physical performance assessments were carried out at baseline and Week 6 of intervention. Body composition changes were measured using the BOD POD™ and skinfold calipers. Body fat was 23% at baseline and 22% at Week 6. Mean sum of eight skinfolds was 127.4 ± 2.2 mm at baseline and 107.3 ± 0.4 mm at Week 6. Lean body mass-to-fat mass ratio improved from 3.4 at baseline to 3.7 at Week 6. The greatest increments compared with baseline in serum markers were 25-hydroxyvitamin D3 (68%), ferritin (31%), eosinophils (20%), and triglycerides (16%). All physical performance measures improved, with reactive strength index (4.8%), and on-court repeated speed (6.0%) showing the greatest improvements from baseline. This intervention demonstrates that structured energy restriction alongside appropriately structured strength and conditioning training is an effective way to gradually reduce the body fat and improve the body composition of a female athlete.
Case Study: Dose Response of Caffeine on 20-km Handcycling Time Trial Performance in a Paratriathlete
Authors: Graham-Paulson Terri , Perret Claudio , Goosey-Tolfrey Victoria 
Published: November 2017

Caffeine’s (CAF) ability to influence upper-body exercise endurance performance may be related to an individual’s training status. This case study therefore aimed to investigate the ergogenic effects of CAF dose on 20-km time trial (TT) performance of an elite male paratriathlete (wheelchair user; age = 46 years, body mass = 76.9 kg, body fat = 25.4%, and handcycling ). The athlete completed four 20-km handcycling TTs on a Cyclus II ergometer under controlled laboratory conditions following the ingestion of 2, 4, and 6 mg/kg CAF or placebo (PLA). Blood lactate concentration, power output, arousal, and ratings of perceived exertion were recorded. Ingestion of 2, 4, and 6 mg/kg CAF resulted in a 2%, 1.5%, and 2.7% faster TT compared with PLA (37:40 min:s). The participant’s blood lactate concentration increased throughout all trials and was greater during CAF compared with PLA. There were no obvious differences in ratings of perceived exertion between trials despite different performance times. Baseline arousal scores differed between PLA and 4 mg/kg CAF (1 = low), and 2 and 6 mg/kg CAF (3 = moderate). Arousal increased at each time point following the ingestion of 4 and 6 mg/kg CAF. The largest CAF dose resulted in a positive pacing strategy, which, when combined with an end spurt, resulted in the fastest TT. CAF improved 20-km TT performance of an elite male paratriathlete, which may be related to greater arousal and an increased power output for a given rating of perceived exertion.
Effect of 4-Week Ingestion of Tomato-Based Carotenoids on Exercise-Induced Inflammation, Muscle Damage, and Oxidative Stress in Endurance Runners
Authors: Nieman David C. , Capps Courtney L. , Capps Christopher R. , Shue Zack L. , McBride Jennifer E. 
Published: November 2017

This double-blind, randomized, placebo-controlled crossover trial determined if ingestion of a supplement containing a tomato complex with lycopene, phytoene, and phytofluene (T-LPP) and other compounds for 4 weeks would attenuate inflammation, muscle damage, and oxidative stress postexercise and during recovery from a 2-hr running bout that included 30 min of −10% downhill running. Study participants ingested the T-LPP supplement or placebo with the evening meal for 4 weeks prior to running 2 hr at high intensity. Blood samples and delayed onset muscle soreness ratings were taken pre- and post-4-week supplementation, and immediately following the 2-hr run, and then 1-hr, 24-hr, and 48-hr postrun. After a 2-week washout period, participants crossed over to the opposite treatment and repeated all procedures. Plasma lycopene, phytoene, and phytofluene increased significantly in T-LPP compared with placebo (p < .001 for each). Significant time effects were shown for serum creatine kinase, delayed onset muscle soreness, C-reactive protein, myoglobin, 9- and 13-hydroxyoctadecadienoic acids, ferric reducing ability of plasma, and six plasma cytokines (p < .001 for each). The pattern of increase for serum myoglobin differed between T-LPP and placebo (interaction effect, p = .016, with lower levels in T-LPP), but not for creatine kinase, delayed onset muscle soreness, C-reactive protein, the six cytokines, 9- and 13-hydroxyoctadecadienoic acids, and ferric reducing ability of plasma. No significant time or interaction effects were measured for plasma-oxidized low-density lipoprotein or serum 8-hydroxy-2′-deoxyguanosine. In summary, supplementation with T-LPP over a 4-week period increased plasma carotenoid levels 73% and attenuated postexercise increases in the muscle damage biomarker myoglobin, but not inflammation and oxidative stress.
Structure and Membrane Topography of the Vibrio-Type Secretin Complex from the Type 2 Secretion System of Enteropathogenic Escherichia coli
Authors: Hay Iain D. , Belousoff Matthew J. , Dunstan Rhys A. , Bamert Rebecca S. , Lithgow Trevor 
Published: October 2017

ABSTRACT

The β-barrel assembly machinery (BAM) complex is the core machinery for the assembly of β-barrel membrane proteins, and inhibition of BAM complex activity is lethal to bacteria. Discovery of integral membrane proteins that are key to pathogenesis and yet do not require assistance from the BAM complex raises the question of how these proteins assemble into bacterial outer membranes. Here, we address this question through a structural analysis of the type 2 secretion system (T2SS) secretin from enteropathogenic
Escherichia coli
O127:H6 strain E2348/69. Long β-strands assemble into a barrel extending 17 Å through and beyond the outer membrane, adding insight to how these extensive β-strands are assembled into the
E. coli
outer membrane. The substrate docking chamber of this secretin is shown to be sufficient to accommodate the substrate mucinase SteC.

IMPORTANCE
In order to cause disease, bacterial pathogens inhibit immune responses and induce pathology that will favor their replication and dissemination. In Gram-negative bacteria, these key attributes of pathogenesis depend on structures assembled into or onto the outer membrane. One of these is the T2SS. The
Vibrio
-type T2SS mediates cholera toxin secretion in
Vibrio cholerae
, and in
Escherichia coli
O127:H6 strain E2348/69, the same machinery mediates secretion of the mucinases that enable the pathogen to penetrate intestinal mucus and thereby establish deadly infections.
OrfX, a Nucleomodulin Required for
Listeria monocytogenes
Virulence
Authors: Prokop Andrzej , Gouin Edith , Villiers Véronique , Nahori Marie-Anne , Vincentelli Renaud , Duval Mélodie , Cossart Pascale , Dussurget Olivier 
Published: November 2017

ABSTRACT

Listeria monocytogenes
is a bacterial pathogen causing severe foodborne infections in humans and animals.
Listeria
can enter into host cells and survive and multiply therein, due to an arsenal of virulence determinants encoded in different loci on the chromosome. Several key
Listeria
virulence genes are clustered in
Listeria
pathogenicity island 1. This important locus also contains
orfX
(
lmo0206
), a gene of unknown function. Here, we found that OrfX is a small, secreted protein whose expression is positively regulated by PrfA, the major transcriptional activator of
Listeria
virulence genes. We provide evidence that OrfX is a virulence factor that dampens the oxidative response of infected macrophages, which contributes to intracellular survival of bacteria. OrfX is targeted to the nucleus and interacts with the regulatory protein RybP. We show that in macrophages, the expression of OrfX decreases the level of RybP, which controls cellular infection. Collectively, these data reveal that
Listeria
targets RybP and evades macrophage oxidative stress for efficient infection. Altogether, OrfX is after LntA, the second virulence factor acting directly in the nucleus.

IMPORTANCE
Listeria monocytogenes
is a model bacterium that has been successfully used over the last 30 years to refine our understanding of the molecular, cellular, and tissular mechanisms of microbial pathogenesis. The major virulence factors of pathogenic
Listeria
species are located on a single chromosomal locus. Here, we report that the last gene of this locus encodes a small secreted nucleomodulin, OrfX, that is required for bacterial survival within macrophages and in the infected host. This work demonstrates that the production of OrfX contributes to limiting the host innate immune response by dampening the oxidative response of macrophages. We also identify a target of OrfX, RybP, which is an essential pleiotropic regulatory protein of the cell, and uncover its role in host defense. Our data reinforce the view that the secretion of nucleomodulins is an important strategy used by microbial pathogens to promote infection.
Software for the Integration of Multiomics Experiments in Bioconductor
Authors: Ramos Marcel , Schiffer Lucas , Re Angela , Azhar Rimsha , Basunia Azfar , Rodriguez Carmen , Chan Tiffany , Chapman Phil , Davis Sean R. , Gomez-Cabrero David , Culhane Aedin C. , Haibe-Kains Benjamin , Hansen Kasper D. , Kodali Hanish , Louis Marie S. , Mer Arvind S. , Riester Markus , Morgan Martin , Carey Vince , Waldron Levi 
Published: November 2017

Abstract
Multiomics experiments are increasingly commonplace in biomedical research and add layers of complexity to experimental design, data integration, and analysis. R and Bioconductor provide a generic framework for statistical analysis and visualization, as well as specialized data classes for a variety of high-throughput data types, but methods are lacking for integrative analysis of multiomics experiments. The MultiAssayExperiment software package, implemented in R and leveraging Bioconductor software and design principles, provides for the coordinated representation of, storage of, and operation on multiple diverse genomics data. We provide the unrestricted multiple ‘omics data for each cancer tissue in The Cancer Genome Atlas as ready-to-analyze MultiAssayExperiment objects and demonstrate in these and other datasets how the software simplifies data representation, statistical analysis, and visualization. The MultiAssayExperiment Bioconductor package reduces major obstacles to efficient, scalable, and reproducible statistical analysis of multiomics data and enhances data science applications of multiple omics datasets. Cancer Res; 77(21); e39–42. ©2017 AACR.
Hypoxia-Inducible PIM Kinase Expression Promotes Resistance to Antiangiogenic Agents
Authors: Casillas Andrea L. , Toth Rachel K. , Sainz Alva G. , Singh Neha , Desai Ankit A. , Kraft Andrew S. , Warfel Noel A. 
Published: October 2017

Abstract
Purpose: Patients develop resistance to antiangiogenic drugs, secondary to changes in the tumor microenvironment, including hypoxia. PIM kinases are prosurvival kinases and their expression increases in hypoxia. The goal of this study was to determine whether targeting hypoxia-induced PIM kinase expression is effective in combination with VEGF-targeting agents. The rationale for this therapeutic approach is based on the fact that antiangiogenic drugs can make tumors hypoxic, and thus more sensitive to PIM inhibitors.
Experimental Design: Xenograft and orthotopic models of prostate and colon cancer were used to assess the effect of PIM activation on the efficacy of VEGF-targeting agents. IHC and in vivo imaging were used to analyze angiogenesis, apoptosis, proliferation, and metastasis. Biochemical studies were performed to characterize the novel signaling pathway linking PIM and HIF1.
Results: PIM was upregulated following treatment with anti-VEGF therapies, and PIM1 overexpression reduced the ability of these drugs to disrupt vasculature and block tumor growth. PIM inhibitors reduced HIF1 activity, opposing the shift to a pro-angiogenic gene signature associated with hypoxia. Combined inhibition of PIM and VEGF produced a synergistic antitumor response characterized by decreased proliferation, reduced tumor vasculature, and decreased metastasis.
Conclusions: This study describes PIM kinase expression as a novel mechanism of resistance to antiangiogenic agents. Our data provide justification for combining PIM and VEGF inhibitors to treat solid tumors. The unique ability of PIM inhibitors to concomitantly target HIF1 and selectively kill hypoxic tumor cells addresses two major components of tumor progression and therapeutic resistance. Clin Cancer Res; 24(1); 169–80. ©2017 AACR.
Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer
Authors: Labidi-Galy S. Intidhar , Olivier Timothée , Rodrigues Manuel , Ferraioli Domenico , Derbel Olfa , Bodmer Alexandre , Petignat Patrick , Rak Beata , Chopin Nicolas , Tredan Olivier , Heudel Pierre-Etienne , Stuckelberger Sarah , Meeus Pierre , Meraldi Patrick , Viassolo Valeria , Ayme Aurélie , Chappuis Pierre O. , Stern Marc-Henri , Houdayer Claude , Stoppa-Lyonnet Dominique , Buisson Adrien , Golmard Lisa , Bonadona Valérie , Ray-Coquard Isabelle 
Published: October 2017

Abstract
Purpose: BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of BRCA2 gene affects the clinical outcome of ovarian cancer patients.
Experimental Design: A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for BRCA1 and BRCA2 genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer (n = 316) was used as a validation cohort.
Results: In the study cohort, 78 patients were carriers of germline mutations of BRCA2. After adjustment for FIGO stage and macroscopic residual disease, BRCA2 carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20–0.64; P = 0.001] and prolonged PFI (29.7 vs. 15.5 months, P = 0.011), compared with noncarriers. BRCA2 carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42–1.07; P = 0.094) or PFI (19 vs. 15.5 months, P = 0.146). In the TCGA cohort, only BRCA2 carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13–0.68; P = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02–0.38; P = 0.001).
Conclusions: Among ovarian cancer patients, BRCA2 carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. Clin Cancer Res; 24(2); 326–33. ©2017 AACR.
Primary Immunoprevention of Epithelial Ovarian Carcinoma by Vaccination against the Extracellular Domain of Anti-Müllerian Hormone Receptor II
Authors: Mazumder Suparna , Johnson Justin M. , Swank Valerie , Dvorina Nina , Martelli Elizabeth , Ko Jennifer , Tuohy Vincent K. 
Published: November 2017

Abstract
Epithelial ovarian carcinoma (EOC) is the most prevalent form of ovarian cancer in the United States, representing approximately 85% of all cases and causing more deaths than any other gynecologic malignancy. We propose that optimized control of EOC requires the incorporation of a vaccine capable of inducing safe and effective preemptive immunity in cancer-free women. In addition, we hypothesize that ovarian-specific self-proteins that are “retired” from autoimmune-inducing expression levels as ovaries age but are expressed at high levels in emerging EOC may serve as vaccine targets for mediating safe and effective primary immunoprevention. Here, we show that expression of the extracellular domain of anti-Müllerian hormone receptor II (AMHR2-ED) in normal tissues is confined exclusively to the human ovary, drops to nonautoimmune inducing levels in postmenopausal ovaries, and is at high levels in approximately 90% of human EOC. We found that AMHR2-ED vaccination significantly inhibits growth of murine EOC and enhances overall survival without inducing oophoritis in aged female mice. The observed inhibition of EOC growth was mediated substantially by induction of AMHR2-ED–specific IgG antibodies that agonize receptor signaling of a Bax/caspase-3–dependent proapoptotic cascade. Our results indicate that AMHR2-ED vaccination may be particularly useful in providing safe and effective preemptive immunity against EOC in women at high genetic or familial risk who have the greatest need for a preventive vaccine and ultimately in cancer-free postmenopausal women who account for 75% of all EOC cases. Cancer Prev Res; 10(11); 612–24. ©2017 AACR.
See related editorial by Shoemaker et al., p. 607
Metaesquema, metaforma, metaobra
Authors: Conduru Roberto 
Published: October 2017

O texto analisa o Metaesquema de Hélio Oiticica, pertencente ao acervo da Pinacoteca do Estado de São Paulo. Partindo de indicações do artista sobre a série e lidando com as noções de esquema e forma, observa-se como a obra é um experimento que, ao mesmo tempo, segue e critica princípios do concretismo, apresentando características que seriam desdobradas no neoconcretismo. Em seguida, explorando a condição metafórica da obra de arte, o trabalho é relacionado à cidade, ao corpo e à dança, conectando-o, como metonímia, a outras séries do artista. Ao final, em diálogo com a bibliografia recente sobre os Metaesquemas, o texto destaca a ambiguidade própria ao trabalho em foco, tanto o Metaesquema quanto a obra de Oiticica.
Atrial Fibrillation Burden in Young Patients With Congenital Heart Disease
Authors: Mandalenakis Zacharias , Rosengren Annika , Lappas Georg , Eriksson Peter , Gilljam Thomas , Hansson Per-Olof , Skoglund Kristofer , Fedchenko Maria , Dellborg Mikael 
Published: November 2017

Background:
Patients with congenital heart disease (CHD) are assumed to be vulnerable to atrial fibrillation (AF) as a result of residual shunts, anomalous vessel anatomy, progressive valvulopathy, hypertension, and atrial scars from previous heart surgery. However, the risk of developing AF and the complications associated with AF in children and young adults with CHD have not been compared with those in control subjects.

Methods:
Data from the Swedish Patient and Cause of Death registers were used to identify all patients with a diagnosis of CHD who were born from 1970 to 1993. Each patient with CHD was matched by birth year, sex, and county with 10 control subjects from the Total Population Register in Sweden. Follow-up data were collected until 2011.

Results:
Among 21 982 patients (51.6% men) with CHD and 219 816 matched control subjects, 654 and 328 developed AF, respectively. The mean follow-up was 27 years. The risk of developing AF was 21.99 times higher (95% confidence interval, 19.26–25.12) in patients with CHD than control subjects. According to a hierarchical CHD classification, patients with conotruncal defects had the highest risk (hazard ratio, 84.27; 95% confidence interval, 56.86–124.89). At the age of 42 years, 8.3% of all patients with CHD had a recorded diagnosis of AF. Heart failure was the quantitatively most important complication in patients with CHD and AF, with a 10.7% (70 of 654) recorded diagnosis of heart failure.

Conclusions:
The risk of AF in children and young adults with CHD was 22 times higher than that in matched control subjects. Up to the age of 42 years, 1 of 12 patients with CHD had developed AF, and 1 of 10 patients with CHD with AF had developed heart failure. The patient groups with the most complex congenital defects carried the greatest risk of AF and could be considered for targeted monitoring.
How I treat heavy menstrual bleeding associated with anticoagulants
Authors: Boonyawat Kochawan , O’Brien Sarah H. , Bates Shannon M. 
Published: November 2017

Abstract
Anticoagulant-associated heavy menstrual bleeding (HMB) is an underrecognized but not uncommon problem in clinical practice. Premenopausal women should be advised of the potential effect of anticoagulant therapy on menstrual bleeding at the time of treatment initiation. Consequences of HMB should be assessed and treated on an ongoing basis. In the acute setting, the decision to withhold anticoagulants is based on an individual patient’s risk of thrombosis and the severity of the bleeding. For women who require long-term anticoagulation, a levonorgestrel intrauterine system, tranexamic acid (during menstrual flow), high-dose progestin-only therapy, or combined hormonal contraceptives are effective for controlling HMB. The risk of thrombosis during anticoagulant therapy with these treatments is not well studied but is likely to be low. Selection of type of hormonal therapy is based on patient preference, other indications for and contraindications to therapy, adverse effect profile, and ongoing thrombotic risk factors. Women who do not respond to medical treatment or who do not wish to retain their fertility should be considered for surgical management.
Management of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah’s Witness experience
Authors: George James N. , Sandler Steven A. , Stankiewicz Joanna 
Published: October 2017

Key Points
TTP in Jehovah’s Witness patients has been managed successfully without PEX. This experience, plus new TTP treatments, may make it possible for patients who are not Jehovah’s Witnesses to avoid PEX in the future.
Long term post PrePex male circumcision outcomes in an urban population in Uganda: a cohort study
Authors: Galukande M. , Nakaggwa F. , Busisa E. , Sekavuga Bbaale D. , Nagaddya T. , Coutinho A. 
Published: October 2017

Abstract
Objective
The objective of this study was to determine the long term adverse events profile at least a year after safe male circumcision.

Results
A cohort study, investigating patients who had undergone a non surgical circumcision procedure called Prepex. The study variables included scar appearance and sexual experiences. Clients were contacted for a phone interview and data were collected using a questionnaire, for some, a physical examination was done. We obtained ethical committee approval. Data from 304 out of a possible 625 men were analyzed, the rest was lost to follow up. The follow up period was 12–24 months. The mean age was 28 years. Up to 97% were satisfied with the penile scar appearance and the absence of pain. There was no keloids formation, though one developed a hypertrophic scar. Participants reported improved sexual intercourse enjoyment (post circumcision). Up to 17% resumed sexual intercourse before the 6-week long mandatory abstinence period. The average self-reported healing time was 4.7 weeks. There was a high level of scar appearance satisfaction, there was no keloids formation. There was a perceived improvement of sexual enjoyment after circumcision.
Trial registration ClinicalTrials. Gov Identifier: NCT02245126 (Date of registration: September 19, 2014)