bluuebunny/crossref_metadata_2025_split huggingface dataset:
The regulation of skeletal muscle fatigability and mitochondrial function by chronically elevated interleukin‐6
Authors: VanderVeen Brandon N. , Fix Dennis K. , Montalvo Ryan N. , Counts Brittany R. , Smuder Ashley J. , Murphy E. Angela , Koh Ho‐jin , Carson James A. 
Published: December 2018

New Findings
What is the central question of this study?
Interleukin‐6 has been associated with muscle mass and metabolism in both physiological and pathological conditions. A causal role for interleukin‐6 in the induction of fatigue and disruption of mitochondrial function has not been determined.

What is the main finding and its importance?
We demonstrate that chronically elevated interleukin‐6 increased skeletal muscle fatigability and disrupted mitochondrial content and function independent of changes in fibre type and mass.

AbstractInterleukin‐6 (IL‐6) can initiate intracellular signalling in skeletal muscle by binding to the IL‐6‐receptor and interacting with the transmembrane gp130 protein. Circulating IL‐6 has established effects on skeletal muscle mass and metabolism in both physiological and pathological conditions. However, the effects of circulating IL‐6 on skeletal muscle function are not well understood. The purpose of this study was to determine whether chronically elevated systemic IL‐6 was sufficient to disrupt skeletal muscle force, fatigue and mitochondrial function. Additionally, we examined the role of muscle gp130 signalling during overexpression of IL‐6. Systemic IL‐6 overexpression for 2 weeks was achieved by electroporation of an IL‐6 overexpression plasmid or empty vector into the quadriceps of either C57BL/6 (WT) or skeletal muscle gp130 knockout (KO) male mice. Tibialis anterior muscle in situ functional properties and mitochondrial respiration were determined. Interleukin‐6 accelerated in situ skeletal muscle fatigue in the WT, with a 18.5% reduction in force within 90 s of repeated submaximal contractions and a 7% reduction in maximal tetanic force after 5 min. There was no difference between fatigue in the KO and KO+IL‐6. Interleukin‐6 reduced WT muscle mitochondrial respiratory control ratio by 36% and cytochrome c oxidase activity by 42%. Interleukin‐6 had no effect on either KO respiratory control ratio or cytochrome c oxidase activity. Interleukin‐6 also had no effect on body weight, muscle mass or tetanic force in either genotype. These results provide evidence that 2 weeks of elevated systemic IL‐6 is sufficient to increase skeletal muscle fatigability and decrease muscle mitochondrial content and function, and these effects require muscle gp130 signalling.
Retrospective study in 608 cases on the rate of surgical site infections after orbital surgery without prophylactic systemic antibiotics
Authors: de Keizer Ronald Olaf Björn , Kozdras Genesis , Wubbels René , Van den Bosch Willem A , Paridaens Dion 
Published: December 2018

ObjectiveTo determine postoperative surgical site infection (SSI) rates in three separate patient groups who underwent orbital surgery without prophylactic systemic antibiotics.Study designSingle-centre retrospective descriptive case series.Study populationWe studied the notes of 639 consecutive patients who had undergone orbital surgery in our hospital from 2009 through 2013. All patients belonged to either of three groups: (1) clean orbital surgery (n=226); (2) clean orbital surgery with implant (n=290); (3) clean-contaminated surgery (n=92). Thirty-one patients were excluded.ResultsOf the total of 608 patients, without systemic antibiotic prophylaxis, only five were diagnosed with SSI 5/608 (0.82%): 1/226 in the ‘clean’ group, 3/290 in the ‘clean-with-implant’ group and 1/92 in the ‘clean-contaminated’ group. All five patients with SSI were effectively treated with antibiotics.ConclusionIn this study ‘clean’, ‘clean-with-implant’ and ‘clean-contaminated’ orbital surgery was safely performed without prophylactic antibiotics. Where postoperative infection did occur, the patients were effectively treated with systemic antibiotics. We suggest to restrict the administration of systemic antibiotic prophylaxis in orbital surgery.
Reasons for low utilisation of public facilities among households with hypertension: analysis of a population-based survey in India
Authors: Kujawski Stephanie A , Leslie Hannah H , Prabhakaran Dorairaj , Singh Kavita , Kruk Margaret E 
Published: December 2018

IntroductionIn India, for most patients, primary healthcare remains the intended entry point for the management of non-communicable disease risk factors. The extent and determinants of non-utilisation of public primary care among households with hypertension are not well examined. We explored health facility utilisation patterns and reasons for non-utilisation of public facilities in 21 states and union territories in India, with a focus on hypertension.MethodsWe used data from the 2012–2013 District Level Household and Facility Survey. We examined the self-reported usual source of care for all households, households with hypertension and─to understand multimorbidity for those with hypertension─households with hypertension and diabetes. Hypertension was defined by self-reported diagnosis or measurement of systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Diabetes was defined by self-reported diagnosis or fasting blood glucose level ≥ 7.0 mmol/L or non-fasting blood glucose level ≥ 11.1 mmol/L. We assessed facility utilisation choice and reasons for non-utilisation of public facilities by household with the presence of hypertension alone and hypertension with diabetes.ResultsIn 336 305 households, 37.6% (N=126 597) had at least one household member with hypertension, while 15.9% (N=53 385) had members with hypertension and diabetes. 20.0% of households sought care at public primary clinics, 29.9% at public hospitals and 48.3% at private facilities. Choice of private facilities increased with the burden of disease. Households with hypertension only and hypertension and diabetes cited quality reasons for non-utilisation of public facilities more than households without hypertension.ConclusionHouseholds, particularly those with hypertension, chose private over public primary facilities for usual care. Quality of care was an important determinant of facility choice in households with hypertension and diabetes. With the increase in hypertension and cardiovascular disease in India, quality of public primary healthcare must be addressed for current policy to become reality.
Effects of precipitation change on fine root morphology and dynamics at a global scale: a meta-analysis
Authors: Zhang Xin , Xing Yajuan , Yan Guoyong , Han Shijie , Wang Qinggui 
Published: December 2018

We compiled data from 495 observations and 103 papers and carried out a meta-analysis of the responses of fine root biomass, production, decomposition, and morphology to precipitation increases and decreases. In addition, we evaluated the effects of plant life form, soil depth, and experiment duration on the responses of fine roots to precipitation changes. Our results confirmed that decreased precipitation limited fine root diameter and accelerated turnover. Increased precipitation stimulated fine root elongation and enhanced the fine root accumulation. The responses of fine roots to precipitation changes varied among plants of different life forms. Tree fine root production and decomposition and non-tree fine root diameter varied most strongly under decreased precipitation. Specific root length of non-tree fine roots was much higher than that of tree fine roots under increased precipitation. Decreased precipitation limited the growth of fine roots in 20–40 cm deep soil, whereas increased precipitation promoted the growth of fine roots in both shallow and deep soil layers. The responses of fine roots to decreased precipitation were affected by experiment duration. Results filled the gap of evaluation data on the effect of precipitation change on fine root morphology and dynamics, which are useful for better predicting the C cycle under precipitation change.
Cardioprotection via the skin: nociceptor-induced conditioning against cardiac MI in the NIC of time
Authors: Ren Xiaoping , Roessler Anne E. , Lynch Thomas L. , Haar Lauren , Mallick Faryal , Lui Yong , Tranter Michael , Ren Michelle Huan , Xie Wen Rui , Fan Guo-Chang , Zhang Jun-Ming , Kranias Evangelia G. , Anjak Ahmad , Koch Sheryl , Jiang Min , Miao Qing , Wang Yang , Cohen Albert , Rubinstein Jack , Weintraub Neal L. , Jones W. Keith 
Published: December 2018

Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9−T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.
Postconditioning-like effect of exercis: new paradigm in experimental menopause
Authors: Szabó Renáta , Börzsei Denise , Karácsonyi Zoltán , Gesztelyi Rudolf , Nemes Kolos , Berkó Anikó Magyariné , Veszelka Médea , Török Szilvia , Kupai Krisztina , Varga Csaba , Juhász Béla , Pósa Anikó 
Published: December 2018

The progression of coronary artery diseases in premenopausal women is lower than in age-matched men; however, its probability increases rapidly after menopause. The aim of our study was to investigate the postconditioning-like effects of voluntary physical exercise on postmenopausal cardiovascular outcomes after myocardial infarction. We used fertile Wistar females [control (CTRL)] and pharmacologically induced estrogen-deficient (POVX; 750 µg/kg triptorelin im, every 4th week) rats. CTRL and POVX animals were randomly assigned to receive an injection of 0.1 mg isoproterenol (ISO)/kg. At the 20th hour after ISO injection, serum markers of myocardial injury, such as lactate dehydrogenase (LDH) and myoglobin, were measured. After a 3-wk resting period, ISO-treated and untreated animals were further divided into subgroups on the basis of 6 wk of physical exercise. At the end of the experiment, cardiac activity and content of the antioxidative heme oxygenase (HO) enzyme, levels of GSH and GSH + GSSG, activity of myeloperoxidase, as well as the concentration of TNF-α were determined. At the end of the experimental period, we observed a significant decrease in the activity and content of HO enzymes in POVX and POVX/ISO rats, whereas physical exercise significantly improved HO and GSH values in both CTRL and POVX rats. Furthermore, our training protocol significantly reduced the pathological levels of myeloperoxidase and TNF-α. Our findings clearly demonstrate that modulation of the HO system by voluntary physical exercise is a key process to decrease inflammatory parameters and ameliorate the antioxidative status in estrogen-deficient conditions postmyocardial injury. NEW & NOTEWORTHY We used a noninvasive rat model of estrogen deficiency and myocardial infarction. The long-term effects of isoproterenol treatment revealed reduced heme oxygenase enzyme activity and expression and decreased glutathione levels. Isoproterenol treatment enhanced the myeloperoxidase enzyme activity. Voluntary physical exercise ameliorated the antioxidative status by increasing of the heme oxygenase enzyme system. Voluntary physical exercise is a potential therapeutic tool to improve cardiac antioxidant status in menopausal women postmyocardial injury.
Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA
Authors: Dudley Jonathan C. , Schroers-Martin Joseph , Lazzareschi Daniel V. , Shi William Y. , Chen Simon B. , Esfahani Mohammad S. , Trivedi Dharati , Chabon Jacob J. , Chaudhuri Aadel A. , Stehr Henning , Liu Chih Long , Lim Harumi , Costa Helio A. , Nabet Barzin Y. , Sin Mandy L.Y. , Liao Joseph C. , Alizadeh Ash A. , Diehn Maximilian 
Published: December 2018

Abstract

Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation–informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined (P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer.

Significance:
This study shows that utDNA can be detected using HTS with high sensitivity and specificity in patients with early-stage bladder cancer and during post-treatment surveillance, significantly outperforming standard diagnostic modalities and facilitating noninvasive detection, genotyping, and monitoring.
This article is highlighted in the In This Issue feature, p. 453
The Biology of m6A RNA Methylation in Normal and Malignant Hematopoiesis
Authors: Vu Ly P. , Cheng Yuanming , Kharas Michael G. 
Published: December 2018

Abstract

Hematopoietic development and differentiation are highly regulated processes, and recent studies focusing on m6A mRNA methylation have uncovered how this mark controls cell fate in both normal and malignant hematopoietic states. In this review, we focus on how writers, readers, and erasers of RNA methylation can mediate distinct phenotypes on mRNAs and on cells. Targeting the RNA methylation program has emerged as a potential novel therapeutic strategy, and we explore the role for these regulators in both normal and dysregulated cell contexts.

Significance:
RNA methylation is required for cancer cell survival in solid tumors and in acute myeloid leukemia, and targeting this pathway has been proposed as a new therapeutic strategy in cancer. However, understanding the role for RNA methylation in both normal and malignant states is essential for understanding the potential consequences for therapeutic intervention.
O segredo na clínica da ambiguidade genital: um estudo de caso
Authors: Acácio Karolline Hélcias Pacheco , Zanotti Susane Vasconcelos , Monlleó Isabella Lopes 
Published: December 2018

O artigo apresenta o estatuto do segredo familiar como forma de enfrentamento ao diagnóstico de ambiguidade genital de uma criança. O estudo de caso, realizado a partir da escuta clínica de base psicanalítica, evidenciou a experiência destes pais frente a condição da ambiguidade genital, de forma particular e única. Destaca-se o modo como cada um tenta assimilar o real desta condição genética a partir de um segredo familiar estabelecido entre os pais e o irmão mais velho do paciente.
Perioperative Cerebral Microbleeds After Adult Cardiac Surgery
Authors: Patel Nikil , Banahan Caroline , Janus Justyna , Horsfield Mark A. , Cox Anthony , Li Xingfeng , Cappellugola Laurie , Colman Jordan , Egan Vincent , Garrard Peter , Chung Emma M.L. 
Published: December 2018

Background and Purpose—
Cerebral microbleeds (CMBs) have been observed using magnetic resonance imaging in patients with cardiovascular risk factors, cognitive deterioration, small vessel disease, and dementia. They are a well-known consequence of cerebral amyloid angiopathy, chronic hypertension, and diffuse axonal injury, among other causes. However, the frequency and location of new CMBs postadult cardiac surgery, in association with cognition and perioperative risk factors, have yet to be studied.

Methods—
Pre- and postsurgery magnetic resonance susceptibility-weighted images and neuropsychological tests were analyzed from a total of 75 patients undergoing cardiac surgery (70 men; mean age, 63±10 years). CMBs were identified by a neuroradiologist blinded to clinical details who independently assessed the presence and location of CMBs using standardized criteria.

Results—

New CMBs were identified in 76% of patients after cardiac surgery. The majority of new CMBs were located in the frontal lobe (46%) followed by the parietal lobe (15%), cerebellum (13%), occipital lobe (12%), and temporal lobe (8%). Patients with new CMBs typically began with a higher prevalence of preexisting CMBs (
P
=0.02). New CMBs were associated with longer cardiopulmonary bypass times (
P
=0.003), and there was a borderline association with lower percentage hematocrit (
P
=0.04). Logistic regression analysis suggested a ≈2% increase in the odds of acquiring new CMBs during cardiac surgery for every minute of bypass time (odds ratio, 1.02; 95% CI, 1.00–1.05;
P
=0.04). Postoperative neuropsychological decline was observed in 44% of patients and seemed to be unrelated to new CMBs.

Conclusions—
New CMBs identified using susceptibility-weighted images were found in 76% of patients who underwent cardiac surgery. CMBs were globally distributed with the highest numbers in the frontal and parietal lobes. Our regression analysis indicated that length of cardiopulmonary bypass time and lowered hematocrit may be significant predictors for new CMBs after cardiac surgery.

Clinical Trial Registration—

URL:
http://www.isrctn.com
. Unique identifier: 66022965.
An Empirical Model of Dyadic Link Formation in a Network with Unobserved Heterogeneity
Authors: Dzemski Andreas 
Published: December 2018

Abstract
I study a dyadic linking model in which agents form directed links that exhibit homophily and reciprocity. A fixed-effect approach accounts for unobserved sources of degree heterogeneity. I consider specification testing and inference with respect to the homophily and reciprocity parameters. The specification test compares observed transitivity to predicted transitivity. All test statistics account for the presence of an incidental parameter by using formulas based on an asymptotic approximation. In an application to favor networks in Indian villages, the specification test detects that the dyadic linking model underestimates the true transitivity of the network.
Inside Baseball: Coverage, quality, and culture in the Global WordNet
Authors: Benjamin Martin 
Published: December 2018

Inside Baseball: Coverage, quality, and culture in the Global WordNetThe Global WordNet is succeeding in producing relatively open linguistic data that is coordinated to a degree among numerous languages. The project has grown organically, with no overall plan or direction. The result is a certain amount of incoherence in determining what items should be treated in wordnets, and how the various wordnets should aspire to consistent quality. Using the example of terms related to baseball, which constitute a non-trivial portion of the Princeton WordNet, this paper discusses problems of coverage selection both for English and for other languages, as well as methods to improve quality and depth through public review of current content, and contribution of missing terms and definitions. It is proposed that proper names be removed entirely from WordNet and treated as a separate project, and that individual languages produce annexes of indigenous concepts that can be readily considered within sister projects as a supplement to the Anglo-American weighting of the current endeavor. To produce a consistent product that transmits inter-intelligible understanding at a high level across languages, it is proposed that an open committee of interested stakeholders convene to consider the project's goals and develop a roadmap for how to achieve them. Baseball dla zaawansowanych: pokrycie leksykalne, jakość i kultura w Global WordNetGlobal WordNet z powodzeniem tworzy stosunkowo otwarte dane językowe, do pewnego stopnia powiązane pomiędzy wieloma językami. Projekt żyje własnym życiem, bez żadnego ogólnego planu ani kierunku. Rezultatem jest pewna niespójność w określaniu, które elementy powinny znaleźć się w wordnetach oraz w jaki sposób różne wordnety powinny dążyć do utrzymania tej samej jakości. Na przykładzie terminów związanych z baseballem, które zajmują niemałą część Princeton WordNet, niniejszy artykuł omawia problemy wyboru pokrycia leksykalnego zarówno dla języka angielskiego, jak i innych języków, a także metody poprawy jakości poprzez publiczny przegląd aktualnych treści oraz dodanie brakujących terminów i definicji. Proponuje się, aby nazwy własne zostały całkowicie usunięte z WordNetu i potraktowane jako odrębny projekt, a w ramach poszczególnych języków utworzone zostały aneksy rodzimych pojęć, które można wziąć pod uwagę w ramach siostrzanych projektów jako uzupełnienie obecnego anglo-amerykańskiego przedsięwzięcia. W celu stworzenia spójnego produktu, który będzie charakteryzował się wzajemną zrozumiałością na wysokim poziomie w różnych językach, proponuje się zwołanie otwartego komitetu zainteresowanych podmiotów, aby rozważyć cele projektu i opracować plan działania, w jaki sposób cele te osiągnąć.
New Bulgarian, Polish, and Ukrainian phraseology and language corpora
Authors: Sosnowski Wojciech Paweł , Blagoeva Diana , Tymoshuk Roman 
Published: December 2018

New Bulgarian, Polish, and Ukrainian phraseology and language corporaThis article examines phraseological innovations in the Bulgarian, Polish and Ukrainian languages. Particular attention is paid to trends in the development of phraseology and to the sources of the enrichment of the phraseology of the three studied languages. The role of corpus technologies in research on language dynamics is described. Nowa bułgarska, polska i ukraińska frazeologia a korpusy językoweW artykule zostały przeanalizowane innowacje frazeologiczne w językach bułgarskim, polskim i ukraińskim. Szczególną uwagę autorzy zwracają na tendencje rozwojowe frazeologii oraz źródła wzbogacania zasobu frazeologicznego w trzech analizowanych językach. W artykule została przedstawiona rola technologii korpusowych w dziedzinie badania dynamiki rozwoju języka.