bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling purinergic regulation in the epididymis: activation of V‐ATPase‐dependent acidification by luminal ATP and adenosine
Authors: Battistone Maria A. , Merkulova Maria , Park Yoo‐Jin , Peralta Maria A. , Gombar Flavia , Brown Dennis , Breton Sylvie 
Published: February 2019

Key points
In the epididymis, elaborate communication networks between epithelial cells are important with respect to establishing an optimal acidic luminal environment for the maturation and storage of spermatozoa, which is essential for male fertility.
Proton secretion by epididymal clear cells is achieved via the proton pumping V‐ATPase located in their apical membrane.
In the present study, we dissect the molecular mechanisms by which clear cells respond to luminal ATP and adenosine to modulate their acidifying activity via the adenosine receptor ADORA2B and the pH‐sensitive ATP receptor P2X4.
We demonstrate that the hydrolysis of ATP to produce adenosine by ectonucleotidases plays a key role in V‐ATPase‐dependent proton secretion, and is part of a feedback loop that ensures acidification of the luminal compartment
These results help us better understand how professional proton‐secreting cells respond to extracellular cues to modulate their functions, and how they communicate with neighbouring cells.
AbstractCell–cell cross‐talk is crucial for the dynamic function of epithelia, although how epithelial cells detect and respond to variations in extracellular stimuli to modulate their environment remains incompletely understood. In the present study, we used the epididymis as a model system to investigate epithelial cell regulation by luminal factors. In the epididymis, elaborate communication networks between the different epithelial cell types are important for establishing an optimal acidic luminal environment for the maturation and storage of spermatozoa. In particular, clear cells (CCs) secrete protons into the lumen via the proton pumping V‐ATPase located in their apical membrane, a process that is activated by luminal alkalinization. However, how CCs detect luminal pH variations to modulate their function remains uncharacterized. Purinergic regulation of epithelial transport is modulated by extracellular pH in other tissues. In the present study, functional analysis of the mouse cauda epididymis perfused in vivo showed that luminal ATP and adenosine modulate the acidifying activity of CCs via the purinergic ADORA2B and P2X4 receptors, and that luminal adenosine content is itself regulated by luminal pH. Altogether, our observations illustrate mechanisms by which CCs are activated by pH sensitive P2X4 receptor and ectonucleotidases, providing a feedback mechanism for the maintenance of luminal pH. These novel mechanisms by which professional proton‐secreting cells respond to extracellular cues to modulate their functions, as well as how they communicate with neighbouring cells, might be translatable to other acidifying epithelia.
Pre-post Evaluation of the “Supporting Student-Athlete Mental Wellness” Module for College Coaches
Authors: Kroshus Emily , Wagner Jessica , Wyrick David L. , Hainline Brian 
Published: February 2019

This study sought to determine whether completion of the National Collegiate Athletic Association’s “Supporting Student-Athlete Mental Wellness” online module for coaches increased mental health literacy, reduced stigma, and increased intentions to: 1) communicate proactively with team members about the importance of mental health care seeking, and 2) respond appropriately to support an athlete believed to be struggling with a mental health issue. College head coaches completed pre-test surveys (n = 969) and immediate post-test surveys (n = 347, completion rate = 36%). Module completion was associated with increased mental health literacy, decreased stigma about help seeking and increased intentions to engage in culture setting communication. These findings suggest that the online module is a good start for coach education about mental health; however, additional modifications may be warranted to the extent coach referral to sports medicine staff or provision of emotional support to student-athletes struggling with mental health concerns are considered desired behaviors.
Identification of Recessive Lethal Alleles in the Diploid Genome of a Candida albicans Laboratory Strain Unveils a Potential Role of Repetitive Sequences in Buffering Their Deleterious Impact
Authors: Marton Timea , Feri Adeline , Commere Pierre-Henri , Maufrais Corinne , d’Enfert Christophe , Legrand Melanie 
Published: February 2019

Candida albicans
is a major fungal pathogen, whose mode of reproduction is mainly clonal. Its genome is highly tolerant to rearrangements, in particular loss of heterozygosity events, known to unmask recessive lethal and deleterious alleles in heterozygous diploid organisms such as
C. albicans
. By combining a site-specific DSB-inducing system and mining genome sequencing data of 182
C. albicans
isolates, we were able to ascribe the chromosome 7 homozygosis bias of the
C. albicans
laboratory strain SC5314 to an heterozygous SNP introducing a premature STOP codon in the
MTR4
gene. We have also proposed genome-wide candidates for new recessive lethal alleles. We additionally observed that the major repeat sequences (MRS) on chromosome 7 acted as hot spots for interhomolog recombination. Maintaining MRS in
C. albicans
could favor haplotype exchange, of vital importance to LOH events, leading to homozygosis of recessive lethal or deleterious alleles that inevitably accumulate upon clonality.
Risk factors associated with myopia in schoolchildren in Ireland
Authors: Harrington Siofra Christine , Stack Jim , O'Dwyer Veronica 
Published: February 2019

AimTo examine the demographic and social factors associated with myopia in schoolchildren in Ireland.MethodsThirty-seven schools participated, representing a mix of urban and rural schools and schools in socioeconomically disadvantaged and non-disadvantaged areas in Ireland. Examination included cyclopleged autorefraction (1% cyclopentolate hydrochloride). Height and weight of participants were measured. Parents filled in a participant’s lifestyle questionnaire, including questions on daily screen time use and daylight exposure. Myopia was defined as spherical equivalent ≤−0.50 D.ResultsData from 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), were examined. Myopia prevalence was significantly higher in children aged 12–13 years old (OR=7.7, 95%CI 5.1 to 11.6, p<0.001) and significantly associated with non-white ethnicity (OR=3.7, 95% CI 2.5 to 5.3, p<0.001). Controlling for age group and ethnicity, myopia prevalence was also significantly linked with height (p<0.001) and higher in participants in the following groups: using screens >3 hours per day (OR=3.7, 95% CI 2.1 to 6.3, p<0.001), obesity (OR=2.7, 95% CI 1.9 to 3.9, p<0.001), sedentary lifestyle (OR=2.9, 95% CI 1.9 to 4.4, p<0.001), frequently reading/writing (OR=2.2, 95% CI 1.4 to 3.5, p=0.001), less daylight exposure during summer time (OR=5.00, 95% CI 2.4 to 10.3, p<0.001), spring season births (OR=1.9, 95% CI 1.1 to 3.3, p=0.02), paternal history of myopia (OR=2.4, 95% CI 1.8 to 3.3, p<0.001) and bottle fed for the first three months of life (OR=1.7, 95% CI 1.3 to 2.5, p=0.02).ConclusionsThe associations found between myopia prevalence in schoolchildren in Ireland and demographic and lifestyle factors suggest that longitudinal research investigating the associations between myopia prevalence and these factors may be beneficial in advising preventative public health programmes.
Iris colour and astigmatism among Chinese teenagers
Authors: Pan Chen-Wei , Ke Chaofu , Hu Dan-Ning , Li Jun , Zhong Hua 
Published: February 2019

Background/aimsIris colour might contribute to refractive development, but it is uncertain whether it is related to astigmatism. We aim to examine the association of iris colour with the presence of astigmatism in a school-based sample of Chinese students.Methods2346 grade 7 students from 10 middle schools aged 13 to 14 years in Southwestern China participated in the study. We obtained standardised slit-lamp photographs and developed a grading system assessing iris colour (higher grade denoting darker). Astigmatism was defined as a cylinder power of more than 0.50, 0.75 or 1.00 dioptre (D). Logistic regression models with generalised estimating equation were fitted to assess the relationship between iris colour and astigmatism, accounting for the correlation between both eyes. ORs and 95% CIs were presented.ResultsThe overall prevalence of astigmatism for three different definitions was 30.4% (95% CI 28.6% to 32.2%) (<−0.5 D), 12.7 % (95% CI 11.3% to 14.0%) (<−0.75 D) and 5.3% (95% CI 4.4% to 6.2%) (<−1.0 D), respectively. In multivariate analysis adjusting for the effect of gender and height, darker iris colour was associated with an increasing trend of astigmatism (p for trend <0.05). Compared with individuals with iris colour of grade 4 or 5 (the darkest), those with grade 1 or 2 (the lightest) were significantly less likely to be affected by astigmatism (<−0.75 D) in gender-adjusted model (OR 0.67) and multivariate-adjusted model (OR 0.72).ConclusionDarker iris colour might be a risk factor for astigmatism in Chinese adolescents.
Characteristics and toxicant emissions of JUUL electronic cigarettes
Authors: Talih Soha , Salman Rola , El-Hage Rachel , Karam Ebrahim , Karaoghlanian Nareg , El-Hellani Ahmad , Saliba Najat , Shihadeh Alan 
Published: February 2019

IntroductionJUUL is an electronic cigarette (ECIG) with a compact form factor. It is prefilled with a liquid that is advertised to contain a high concentration of nicotine salt. JUUL commands 50% of the US ECIG market share, and its wide popularity with underage users has triggered unprecedented actions by the US FDA. Apart from its nicotine salt-containing liquid and compact form, a salient advertised design feature is a control circuit that limits the heating coil temperature, presumably reducing unwanted toxicants. In this study, several tobacco-flavoured JUUL devices were reverse engineered, and their aerosol emissions were studied.MethodsTotal nicotine and its partitioning (freebase and protonated), propylene glycol/vegetable glycerin (PG/VG) ratio, and carbonyls were quantified by gas chromatography (GC) and high performance liquid chromatography (HPLC). The temperature control functionality of JUUL was investigated using a temperature-controlled bath in which the coil was submerged.ResultsThe liquid nicotine concentration was found to be 69 mg/mL, and the liquid and aerosol PG/VG ratio was found to be 30/70. In 15 puffs, JUUL emitted 2.05 (0.08) mg of nicotine, overwhelmingly in the protonated form. Carbonyl yields were significantly lower than those reported for combustible cigarettes, but similar to other closed-system ECIG devices. The heating coil resistance was 1.6 (0.66) Ohm, while the maximum power delivered by the JUUL device was 8.1 W. The control circuit limited the peak operating temperature to approximately 215C.ConclusionsJUUL emits a high-nicotine concentration aerosol predominantly in the protonated form. JUUL’s nicotine-normalised formaldehyde and total aldehyde yields are lower than other previously studied ECIGs and combustible cigarettes.
Energy–momentum distributions of Ruban universe in general relativity and teleparallel gravity
Authors: Aktaş C. 
Published: February 2019

In this study, we obtain Einstein, Bergmann–Thomson (BT), Landau–Lifshitz (LL), Møller, Papapetrou (PP) and Tolman energy–momentum (EM) distributions for Ruban universe model in general relativity (GR) and teleparallel gravity (TG). We obtain same results for Einstein, Bergmann–Thomson and Landau–Lifshitz energy–momentum distributions in GR and TG. Also, we get same results for Einstein and Tolman energy–momentum distributions in GR. The Møller energy–momentum results are different in GR and TG. Also, using Ruban universe model, we obtain LRS Bianchi type I solutions and we get zero energy–momentum results for this universe model in GR and TG. These results of LRS Bianchi type I universe model agree with Aygün et al., Taşer et al., Doğru et al., Banerjee–Sen, Tryon and Xulu in different gravitation theories.
Sm3+-doped bismuthate glasses and proton-implanted near-infrared waveguides
Authors: Chen Jing-Yi , Pan He , Zhang Liao-Lin , Guo Hai-Tao , Liu Chun-Xiao 
Published: February 2019

Sm[Formula: see text]-doped bismuthate glass has been synthesized by means of the classic melt-quenching technique. Its optical properties were characterized, which included refractive index, absorption and fluorescence spectra. The measured data suggest that the Sm[Formula: see text]-doped bismuthate glass is suitable for optoelectronic applications. A Sm[Formula: see text]-doped bismuthate glass waveguide operating at 1.539 [Formula: see text]m has been manufactured by using the proton implantation with a 0.4 MeV energy and a 8.0 × 10[Formula: see text] ions⋅cm[Formula: see text] fluence for the first time to our knowledge. The effective refractive indices of the propagation modes for the glass waveguide were obtained by the m-line technique. The energy loss caused by the collision of the irradiated protons and the nuclei of the target Sm[Formula: see text]-doped bismuthate glass was calculated by the SRIM 2013. The refractive index profile and the near-field guided mode distribution for the waveguide structure were fitted through the reflectivity calculation method (RCM) and the FD-BPM method, respectively. The proton-implanted Sm[Formula: see text]-doped bismuthate glass waveguide is an alternative for an integrated device in the telecommunication band.
Electronic, transport, and magnetic properties of (Ca, Ba)0.9La0.1Fe1.9Pt0.1As2 compounds
Authors: Guler A. , Boyraz C. , Avci S. , Arda L. , Özdemir M. , Oner Y. 
Published: February 2019

Superconductivity and magnetic properties were studied for La and Pt substituted (Ca, Ba)[Formula: see text]La[Formula: see text]Fe[Formula: see text]Pt[Formula: see text]As2 samples using structural, resistivity and magnetic measurement techniques. All bulk samples were synthesized by solid-state reaction method and annealed under a specific annealing technique with a time-dependent annealing process in vacuumed quartz tubes. ThCr2Si2-type crystal structure was concluded for both samples varying with in- and out-of-plane lattice parameters. The superconducting critical temperatures were determined by resistivity and under H = 20 Oe magnetization measurements, which were performed between the temperature ranges of 0–200 K. The upper and lower critical fields were determined and possible Meissner effects were roughly figured out to understand the level of shielding from M–H measurements. The maximum critical temperature was obtained from Ca[Formula: see text]La[Formula: see text]Fe[Formula: see text]Pt[Formula: see text]As2.
T-Type Cav3.1 Channels Mediate Progression and Chemotherapeutic Resistance in Glioblastoma
Authors: Visa Anna , Sallán Marta C. , Maiques Oscar , Alza Lía , Talavera Elisabet , López-Ortega Ricard , Santacana Maria , Herreros Judit , Cantí Carles 
Published: February 2019

Abstract

T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacologic blockers have limited selectivity for TTCC and are unable to distinguish between TTCC isoforms. Here we analyzed the expression of TTCC transcripts in human GBM cells and show a prevalence of Cacna1g/Cav3.1 mRNAs. Infection of GBM cells with lentiviral particles carrying short hairpin RNA against Cav3.1 resulted in GBM cell death by apoptosis. We generated a murine GBM xenograft via subcutaneous injection of U87-MG GBM cells and found that tumor size was reduced when Cav3.1 expression was silenced. Furthermore, we developed an in vitro model of temozolomide-resistant GBM that showed increased expression of Cav3.1 accompanied by the activation of macroautophagy. We confirmed a positive correlation between Cav3.1 and autophagic markers in both GBM cultures and biopsies. Of note, Cav3.1 knockdown resulted in transcriptional downregulation of p62/SQSTM1 and deficient autophagy. Together, these data identify Cav3.1 channels as potential targets for slowing GBM progression and recurrence based on their role in regulating autophagy.

Significance:
These findings identify Cav3.1 calcium channels as a molecular target to regulate autophagy and prevent progression and chemotherapeutic resistance in glioblastoma.
Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck
Authors: Lee Jong Woo , Parameswaran Janaki , Sandoval-Schaefer Teresa , Eoh Kyung Jin , Yang Dong-hua , Zhu Fang , Mehra Ranee , Sharma Roshan , Gaffney Stephen G. , Perry Elizabeth B. , Townsend Jeffrey P. , Serebriiskii Ilya G. , Golemis Erica A. , Issaeva Natalia , Yarbrough Wendell G. , Koo Ja Seok , Burtness Barbara 
Published: February 2019

Abstract

Purpose:
Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting in treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed and an oncogenic driver, its inhibition has only modest clinical effects in HPV-negative HNSCC. We explored a novel combination of AURKA and WEE1 inhibition to overcome intrinsic resistance to AURKA inhibition.
Experimental Design: AURKA protein expression was determined by fluorescence-based automated quantitative analysis of patient specimens and correlated with survival. We evaluated treatment with the AURKA inhibitor alisertib (MLN8237) and the WEE1 inhibitor adavosertib (AZD1775), alone or in combination, using in vitro and in vivo HNSCC models.

Results:
Elevated nuclear AURKA correlated with worse survival among patients with p16(−) HNSCC. Alisertib caused spindle defects, G2–M arrest and inhibitory CDK1 phosphorylation, and cytostasis in TP53 mutant HNSCC FaDu and UNC7 cells. Addition of adavosertib to alisertib instead triggered mitotic entry and mitotic catastrophe. Moreover, in FaDu and Detroit 562 xenografts, this combination demonstrated synergistic effects on tumor growth and extended overall survival compared with either vehicle or single-agent treatment.

Conclusions:
Combinatorial treatment with adavosertib and alisertib leads to synergistic antitumor effects in in vitro and in vivo HNSCC models. These findings suggest a novel rational combination, providing a promising therapeutic avenue for TP53-mutated cancers.
Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities
Authors: Robinson Timothy J. , Freedman Jennifer A. , Al Abo Muthana , Deveaux April E. , LaCroix Bonnie , Patierno Brendon M. , George Daniel J. , Patierno Steven R. 
Published: February 2019

Abstract
Studies of alternative RNA splicing (ARS) have the potential to provide an abundance of novel targets for development of new biomarkers and therapeutics in oncology, which will be necessary to improve outcomes for patients with cancer and mitigate cancer disparities. ARS, a key step in gene expression enabling individual genes to encode multiple proteins, is emerging as a major driver of abnormal phenotypic heterogeneity. Recent studies have begun to identify RNA splicing–related genetic and genomic variation in tumors, oncogenes dysregulated by ARS, RNA splice variants driving race–related cancer aggressiveness and drug response, spliceosome-dependent transformation, and RNA splicing–related immunogenic epitopes in cancer. In addition, recent studies have begun to identify and test, preclinically and clinically, approaches to modulate and exploit ARS for therapeutic application, including splice-switching oligonucleotides, small molecules targeting RNA splicing or RNA splice variants, and combination regimens with immunotherapies. Although ARS data hold such promise for precision oncology, inclusion of studies of ARS in translational and clinical cancer research remains limited. Technologic developments in sequencing and bioinformatics are being routinely incorporated into clinical oncology that permit investigation of clinically relevant ARS events, yet ARS remains largely overlooked either because of a lack of awareness within the clinical oncology community or perceived barriers to the technical complexity of analyzing ARS. This perspective aims to increase such awareness, propose immediate opportunities to improve identification and analysis of ARS, and call for bioinformaticians and cancer researchers to work together to address the urgent need to incorporate ARS into cancer biology and precision oncology.
Association Between Heart Transplantation and Subsequent Risk of Stroke Among Patients With Heart Failure
Authors: Merkler Alexander E. , Chen Monica L. , Parikh Neal S. , Murthy Santosh B. , Yaghi Shadi , Goyal Parag , Okin Peter M. , Karas Maria G. , Navi Babak B. , Iadecola Costantino , Kamel Hooman 
Published: February 2019

Background and Purpose—
It is uncertain whether heart transplantation decreases the risk of stroke. The objective of our study was to determine whether heart transplantation is associated with a decreased risk of subsequent stroke among patients with heart failure awaiting transplantation.

Methods—

We performed a retrospective cohort study using administrative data from New York, California, and Florida between 2005 and 2015. Individuals with heart failure awaiting heart transplantation were identified using previously validated
International Classification of Diseases, Ninth Revision, Clinical Modification
diagnosis codes for heart failure in combination with code V49.83 for awaiting organ transplant status. Individuals with prior stroke were excluded. Our primary exposure variable was heart transplantation, modeled as a time-varying covariate and defined by procedure code 37.51. The primary outcome was stroke, defined as the composite of ischemic and hemorrhagic stroke. Survival statistics were used to calculate stroke incidence, and Cox proportional hazards analysis was used to determine the association between heart transplantation and stroke while adjusting for demographics, stroke risk factors, Elixhauser comorbidities, and implantation of a left ventricular assist device.

Results—
We identified 7848 patients with heart failure awaiting heart transplantation, of whom 1068 (13.6%) underwent heart transplantation. During a mean follow-up of 2.7 years, we identified 428 strokes. The annual incidence of stroke was 0.7% (95% CI, 0.5%–1.0%) after heart transplantation versus 2.4% (95% CI, 2.2%–2.6%) among those awaiting heart transplantation. After adjustment for potential confounders, heart transplantation was associated with a lower risk of stroke (hazard ratio, 0.4; 95% CI, 0.2–0.6).

Conclusions—
Heart transplantation is associated with a decreased risk of stroke among patients with heart failure awaiting transplantation.