bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Caffeine on Repeat-High-Intensity-Effort Performance in Rugby League Players
Authors: Wellington Brandon M. , Leveritt Michael D. , Kelly Vincent G. 
Published: May 2016

Context:Repeat-high-intensity efforts (RHIEs) have recently been shown to occur at critical periods of rugby league matches.Purpose:To examine the effect that caffeine has on RHIE performance in rugby league players.Methods:Using a double-blind, placebo-controlled, crossover design, 11 semiprofessional rugby league players (age 19.0 ± 0.5 y, body mass 87.4 ± 12.9 kg, height 178.9 ± 2.6 cm) completed 2 experimental trials that involved completing an RHIE test after either caffeine (300 mg caffeine) or placebo (vitamin H) ingestion. Each trial consisted of 3 sets of 20-m sprints interspersed with bouts of tackling. During the RHIE test, 20-m-sprint time, heart rate (HR), rating of perceived exertion (RPE), and blood lactate were measured.Results:Total time to complete the nine 20-m sprints during the caffeine condition was 1.0% faster (28.46 ± 1.4 s) than during the placebo condition (28.77 ± 1.7 s) (ES = 0.18, 90%CI –0.7 to 0.1 s). This resulted in a very likely chance of caffeine being of benefit to RHIE performance (99% likely to be beneficial). These improvements were more pronounced in the early stages of the test, with a 1.3%, 1.0%, and 0.9% improvement in sprint performance during sets 1, 2, and 3 respectively. There was no significant difference in RPE across the 3 sets (P = .47, 0.48, 1.00) or mean HR (P = .36), maximal HR (P = .74), or blood lactate (P = .50) between treatment conditions.Conclusions:Preexercise ingestion of 300 mg caffeine produced practically meaningful improvements in RHIE performance in rugby league players.
Cumulative Training Dose’s Effects on Interrelationships Between Common Training-Load Models During Basketball Activity
Authors: Scanlan Aaron T. , Fox Jordan L. , Borges Nattai R. , Dascombe Ben J. , Dalbo Vincent J. 
Published: May 2016

Purpose:The influence of various factors on training-load (TL) responses in basketball has received limited attention. This study aimed to examine the temporal changes and influence of cumulative training dose on TL responses and interrelationships during basketball activity.Methods:Ten state-level Australian male junior basketball players completed 4 × 10-min standardized bouts of simulated basketball activity using a circuit-based protocol. Internal TL was quantified using the session rating of perceived exertion (sRPE), summated heart-rate zones (SHRZ), Banister training impulse (TRIMP), and Lucia TRIMP models. External TL was assessed via measurement of mean sprint and circuit speeds. Temporal TL comparisons were performed between 10-min bouts, while Pearson correlation analyses were conducted across cumulative training doses (0–10, 0–20, 0–30, and 0–40 min).Results:sRPE TL increased (P < .05) after the first 10-min bout of basketball activity. sRPE TL was only significantly related to Lucia TRIMP (r = .66–.69; P < .05) across 0–10 and 0–20 min. Similarly, mean sprint and circuit speed were significantly correlated across 0–20 min (r = .67; P < .05). In contrast, SHRZ and Banister TRIMP were significantly related across all training doses (r = .84–.89; P < .05).Conclusions:Limited convergence exists between common TL approaches across basketball training doses lasting beyond 20 min. Thus, the interchangeability of commonly used internal and external TL approaches appears dose-dependent during basketball activity, with various psychophysiological mediators likely underpinning temporal changes.
The Influence of Pole Length on Performance, O2 Cost, and Kinematics in Double Poling
Authors: Losnegard Thomas , Myklebust Håvard , Skattebo Øyvind , Stadheim Hans Kristian , Sandbakk Øyvind , Hallén Jostein 
Published: May 2016

Purpose:In the double-poling (DP) cross-country-skiing technique, propulsive forces are transferred solely through the poles. The aim of the current study was to investigate how pole length influences DP performance, O2 cost, and kinematics during treadmill roller skiing.Methods:Nine male competitive cross-country skiers (24 ± 3 y, 180 ± 5 cm, 72 ± 5 kg, VO2max running 76 ± 6 mL · kg–1 · min–1) completed 2 identical test protocols using self-selected (84% ± 1% of body height) and long poles (self-selected + 7.5 cm; 88% ± 1% of body height) in a counterbalanced fashion. Each test protocol included a 5-min warm-up (2.5 m/s; 2.5°) and three 5-min submaximal sessions (3.0, 3.5, and 4.0 m/s; 2.5°) for assessment of O2 cost, followed by a selfpaced 1000-m time trial (~3 min, >5.0 m/s; 2.5°). Temporal patterns and kinematics were assessed using accelerometers and 2D video.Results:Long poles reduced 1000-m time (mean ± 90% confidence interval; –1.0% ± 0.7%, P = .054) and submaximal O2 cost (–2.7% ± 1.0%, P = .002) compared with self-selected poles. The center-of-mass (CoM) vertical range of displacement tended to be smaller for long than for self-selected poles (23.3 ± 3.0 vs 24.3 ± 3.0 cm, P = .07). Cycle and reposition time did not differ between pole lengths at any speeds tested, whereas poling time tended to be shorter for self-selected than for long poles at the lower speeds (≤3.5 m/s, P ≤ .10) but not at the higher speeds (≥4.0 m/s, P ≥ .23).Conclusions:DP 1000-m time, submaximal O2 cost, and CoM vertical range of displacement were reduced in competitive cross-country skiers using poles 7.5 cm longer than self-selected ones.
Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice
Authors: Park Soyeong , Park Jung Wook , Pitot Henry C. , Lambert Paul F. 
Published: May 2016

ABSTRACT

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of
Bi-L E7
transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative.

IMPORTANCE
Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients.
One More Disguise in the Stealth Behavior of Streptococcus pyogenes
Authors: Fischetti Vincent A. , Dale James B. 
Published: May 2016

ABSTRACT

The ability to hide in the animal kingdom is essential for survival; the same is true for bacteria.
Streptococcus pyogenes
is considered one of the more successful stealth bacteria in its production of a hyaluronic acid capsule that is chemically identical to the hyaluronic acid lining human joints. It has also acquired the capacity to enter eukaryotic cells to avoid the onslaught of the host’s immune defenses, as well as drugs. From this intracellular vantage point, it may remain dormant from days to weeks, only to cause disease again at a later time, perhaps causing a relapse in a drug-treated patient. We now learn that it is able to enter macrophages as well, enabling the
Streptococcus
to use this “Trojan horse” approach to be transported to distant sites in the body.
Ebola Virus Disease: Therapeutic and Potential Preventative Opportunities
Authors: Fisher Robert , Borio Luciana 
Published: May 2016

ABSTRACT
The 2014 Ebola virus disease (EVD) epidemic in West Africa was unprecedented in its geographical distribution, scale, and toll on public health infrastructure. Standard public health measures were rapidly overwhelmed, and many projections on outbreak progression through the region were dire. At the beginning of the outbreak there were no treatments or vaccines that had been shown to be safe and effective for treating or preventing EVD, limiting health care providers to offer supportive care under extremely challenging circumstances and at great risk to themselves. Over time, however, drugs and vaccines in the development pipeline were prioritized based on all available research data and were moved forward for evaluation in clinical trials to demonstrate safety and efficacy. The armamentarium against EVD eventually included biologics such as monoclonal antibodies, convalescent plasma, and vaccines as well as small molecule therapeutics such as small interfering RNAs and nucleoside analogs. This article provides a high-level overview of the interventions and prophylactics considered for use in the outbreak and discusses the challenges faced when attempting to deploy investigational countermeasures in the midst of an evolving epidemic.
Bacterial Metabolism Shapes the Host–Pathogen Interface
Authors: Passalacqua Karla D. , Charbonneau Marie-Eve , O’Riordan Mary X.D. 
Published: May 2016

ABSTRACT
Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit successful colonization are surprisingly varied and highlight remarkable metabolic flexibility. The constraints and immune pressures of distinct niches within the human body set the stage for understanding the mechanisms by which bacteria acquire critical nutrients. In this article we discuss how different bacterial pathogens carry out carbon and energy metabolism in the host and how they obtain or use key nutrients for replication and immune evasion.
Study on the safety and efficacy of miltefosine for the treatment of children and adolescents with post-kala-azar dermal leishmaniasis in Bangladesh, and an association of serum vitamin E and exposure to arsenic with post-kala-azar dermal leishmaniasis: an open clinical trial and case–control study protocol
Authors: Mondal D , Hasnain M G , Hossain M S , Ghosh D , Ghosh P , Hossain H , Baker J , Nath R , Haque R , Matlashewski G , Hamano S 
Published: May 2016

IntroductionPost-kala-azar dermal leishmaniasis (PKDL) is a dermatological complication that occurs primarily among treated visceral leishmaniasis (VL) patients, and sporadically in a few without a history of VL. It mostly affects children and adolescents but is also common in adults. The conventional treatment with 120 intramuscular injections of sodium stibogluconate (SSG) is phasing out. Miltefosine (MF) is the only eventual alternative to SSG; however, its efficacy and safety profiles for treatment of children and adolescents with PKDL are lacking. In addition, risk factors for PKDL are poorly investigated. Host genetic, nutritional and environmental factors could be potential risk factors. As such, here we propose to evaluate the efficacy and safety of MF for 12 weeks at an allometric dose for children and adolescents with PKDL, and also to explore potential risk factors for PKDL.Methods and analysisA cross-sectional survey will look for suspected participants with PKDL among treated VL children and adolescents, a subsequent open clinical trial with MF at allometric dose, with a follow-up at 12 months. A case–control study will be carried out for PKDL risk factors. Assuming 95% cure rate, 95% CI and α=0.05, a sample size of 73 children with PKDL is needed. Considering an attrition rate of 10%, the final sample size is 80 children in each group. Descriptive and analytical analyses will be performed. Primary outcome is safety and cure rate of 12 weeks of treatment with MF.Ethics and disseminationInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Ethical Review Committee (ERC) approved the protocol (PR#013045). Written informed consent will be taken from all participants and their guardians (in case of minor). A Data and Safety Monitoring Board (DSMB) of ICDDR,B ERC will monitor all study activities to ensure the safety of the participants.Trial registration numberNCT02193022; Pre-results.
Does n-3 LCPUFA supplementation during pregnancy increase the IQ of children at school age? Follow-up of a randomised controlled trial
Authors: Gould Jacqueline F , Treyvaud Karli , Yelland Lisa N , Anderson Peter J , Smithers Lisa G , Gibson Robert A , McPhee Andrew J , Makrides Maria 
Published: May 2016

IntroductionDespite recommendations that pregnant women increase their docosahexaenoic acid (DHA) intake to support fetal brain development, a recent systematic review found a lack of high-quality data to support the long-term effects of DHA supplementation on children's neurodevelopment.Methods and analysisWe will assess child neurodevelopment at 7 years of age in follow-up of a multicentre double-blind randomised controlled trial of DHA supplementation in pregnancy. In 2010–2012, n=2399 Australian women with a singleton pregnancy <21 weeks’ gestation were randomised to receive 3 capsules daily containing a total dose of 800 mg DHA/day or a vegetable oil placebo until birth. N=726 children from Adelaide (all n=97 born preterm, random sample of n=630 born at term) were selected for neurodevelopmental follow-up and n=638 (preterm n=85) are still enrolled at 7 years of age. At the 7-year follow-up, a psychologist will assess the primary outcome, IQ, with the Wechsler Abbreviated Scale of Intelligence, Second Edition. Specific measures of executive functioning (Fruit Stroop and the Rey Complex Figure), attention (Test of Everyday Attention for Children), memory and learning (Rey Auditory Verbal Learning Test), language (Clinical Evaluation of Language Fundamentals, Fourth Edition) and basic educational skills (Wide Range Achievement Test, Fourth Edition) will also be administered. Caregivers will be asked to complete questionnaires measuring behaviour and executive functioning. Families, clinicians and research personnel are blinded to group assignment with the exception of families who requested unblinding prior to the follow-up. All analyses will be conducted according to the intention-to-treat principal.Ethics and disseminationAll procedures will be approved by the relevant institutional ethics committees prior to start of the study. The results of this study will be disseminated in peer-reviewed journal publications and academic presentations.Trial registration numbersACTRN12605000569606 and ACTRN12614000770662.
Paramedics' experiences of end-of-life care decision making with regard to nursing home residents: an exploration of influential issues and factors
Authors: Murphy-Jones Georgina , Timmons Stephen 
Published: May 2016

IntroductionFor a patient nearing the end of his or her life, transfer from a nursing home to the ED can be inappropriate, with potentially negative consequences, but transfer in these circumstances is, regrettably, all too common. There is a lack of published literature exploring how paramedics make decisions in end-of-life care situations. This study aims to explore how paramedics make decisions when asked to transport nursing home residents nearing the end of their lives.MethodsPhenomenological influenced design with a pragmatic approach. Semi-structured face-to-face interviews were conducted with six paramedics in an English NHS Ambulance Trust and subsequent data collected by text message. Audio-recorded interviews were transcribed verbatim and analysed using a thematic approach.ResultsThree themes emerged in relation to the decision to transport patients from nursing homes to EDs in end-of-life care situations. Paramedics identified difficulties in understanding nursing home residents' wishes. When a patient no longer had the capacity for decision making, paramedics' reasoning processes were aligned to best interest decision making, weighing the risks and benefits of hospitalisation. Paramedics found it challenging to balance patients' best interests with pressure from others: nursing staff, patients' relatives and colleagues.ConclusionsA range of factors influence paramedics' decisions to transport nursing home residents to EDs in end-of-life care situations. Decision making became a process of negotiation when the patient's perceived best interests conflicted with that of others, resulting in contrasting approaches by paramedics. This paper considers how paramedics might be better trained and supported in dealing with these situations, with the aim of providing dignified and appropriate care to patients as they reach the end of their lives.
Helicobacter pylori vacAtranscription is genetically-determined and stratifies the level of human gastric inflammation and atrophy
Authors: Sinnett Charlotte G , Letley Darren P , Narayanan Geetha L , Patel Sapna R , Hussein Nawfal R , Zaitoun Abed M , Robinson Karen , Atherton John C 
Published: May 2016

AimsHelicobacter pyloriinfection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxinvacA.Previously, we have described allelic variation invacAwhich determines toxin activity and disease risk. Here we aimed to quantifyvacAmRNA expression in the human stomach, define its genetic determinants and assess how well it predicts gastric pathology.MethodsGastric biopsies were donated by 39 patients withH. pyloriinfection attending for endoscopy at Queen's Medical Centre, Nottingham, UK. Total RNA was extracted, andvacAmRNA quantified by reverse transcriptase quantitative PCR. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system.H. pyloristrains were isolated from further biopsies, and the nucleotide sequence upstream ofvacAdetermined.ResultsvacAmRNA levels in human stomachs varied by two orders of magnitude independently ofvacAallelic type. AmongvacAi1-type (toxic) strains, increasedvacAexpression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005) and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem-loop structure within the 5′ untranslated region was significantly associated withvacAtranscript level and inflammation.ConclusionsIncreased gastricvacAexpression duringH. pyloriinfection is associated with inflammation and premalignant pathology. The +28 nucleotide within thevacA5′ stem-loop stratifies disease risk among toxicvacAi1-type strains.
Systematic Analysis of AU-Rich Element Expression in Cancer Reveals Common Functional Clusters Regulated by Key RNA-Binding Proteins
Authors: Hitti Edward , Bakheet Tala , Al-Souhibani Norah , Moghrabi Walid , Al-Yahya Suhad , Al-Ghamdi Maha , Al-Saif Maher , Shoukri Mohamed M. , Lánczky András , Grépin Renaud , Győrffy Balázs , Pagès Gilles , Khabar Khalid S.A. 
Published: May 2016

Abstract
Defects in AU-rich elements (ARE)-mediated posttranscriptional control can lead to several abnormal processes that underlie carcinogenesis. Here, we performed a systematic analysis of ARE-mRNA expression across multiple cancer types. First, the ARE database (ARED) was intersected with The Cancer Genome Atlas databases and others. A large set of ARE-mRNAs was over-represented in cancer and, unlike non-ARE-mRNAs, correlated with the reversed balance in the expression of the RNA-binding proteins tristetraprolin (TTP, ZFP36) and HuR (ELAVL1). Serial statistical and functional enrichment clustering identified a cluster of 11 overexpressed ARE-mRNAs (CDC6, KIF11, PRC1, NEK2, NCAPG, CENPA, NUF2, KIF18A, CENPE, PBK, TOP2A) that negatively correlated with TTP/HuR mRNA ratios and was involved in the mitotic cell cycle. This cluster was upregulated in a number of solid cancers. Experimentally, we demonstrated that the ARE-mRNA cluster is upregulated in a number of tumor breast cell lines when compared with noninvasive and normal-like breast cancer cells. RNA-IP demonstrated the association of the ARE-mRNAs with TTP and HuR. Experimental modulation of TTP or HuR expression led to changes in the mitosis ARE-mRNAs. Posttranscriptional reporter assays confirmed the functionality of AREs. Moreover, TTP augmented mitotic cell-cycle arrest as demonstrated by flow cytometry and histone H3 phosphorylation. We found that poor breast cancer patient survival was significantly associated with low TTP/HuR mRNA ratios and correlated with high levels of the mitotic ARE-mRNA signature. These results significantly broaden the role of AREs and their binding proteins in cancer, and demonstrate that TTP induces an antimitotic pathway that is diminished in cancer. Cancer Res; 76(14); 4068–80. ©2016 AACR.