bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular phenotyping for personalized lifestyle treatments of chronic abdominal pain in Irritable Bowel Syndrome: A randomized pilot study
Authors: Davydov Dmitry M. , Shahabi Leila , Naliboff Bruce 
Published: August 2019

AbstractBackgroundDifferent physical exercise interventions for pain and other related symptoms largely follow non‐personalized guidelines and show a high degree of variability in outcome. These interventions are considered to have different pathways toward improvement in autonomic regulation of energy metabolism. The current pilot study was conducted to assess the predictive value of individual cardiovascular (CV) activity markers at rest to predict clinical outcomes for two popular exercise‐based interventions (walking and yoga) in patients with Irritable Bowel Syndrome (IBS).MethodsTwenty‐seven adult participants with IBS were randomly assigned to a 16‐biweekly Iyengar yoga or walking program. They completed pre‐ and post‐treatment assessments on IBS symptom severity, affective and somatic complaints, and various measures of resting autonomic function including blood pressure (BP), heart rate and its variability, baroreceptor sensitivity (BRS) to activations and inhibitions with gains of brady‐ and tachycardiac baro‐responses, and BP start points for these spontaneous baroreflexes.ResultsPretreatment BRS was differentially related to clinical response for the treatment groups. Specifically, a significant decrease in pain severity was found in response to yoga for those participants who had lower resting BRS to activations, but decreased pain severity was associated with higher resting BRS for those in the walking group. The effect was not related to affective symptom relief. Other CV measures showed similar associations with clinical outcomes for both groups.ConclusionsThe data suggest therefore that CV based phenotypes may be useful in personalizing clinical interventions for IBS. They may also point to autonomic mechanisms that are targets for such interventions.
THE FINAL (MISSIONS) FRONTIER: EXTRATERRESTRIALS, EVANGELISM, AND THE WIDE CIRCLE OF HUMAN EMPATHY
Authors: Curry Eugene A. 
Published: August 2019

AbstractThe possible existence of extraterrestrials has provoked more than five centuries of theological speculation on how these beings, if they exist, relate to God. A certain stream of thought present in these debates argues that the eventual discovery of aliens would obligate human Christians to evangelize them for the salvation of their souls. Current research into humanity's prehistory suggests that, if this ever actually happens, it will have been partially facilitated by humanity's remarkable capacity for interspecies empathy—an ability that seems to be genetic in nature and which stems from our species' ancient experience with dogs. In light of the above, recommendations are made concerning future potential exomissionary screening criteria and a concluding section touches on the role of animals in God's work.
“THE PEOPLE OF THIS COUNTRY HAVE HAD ENOUGH OF EXPERTS”: IN DEFENSE OF THE “ELITES” OF THE SCIENCE‐AND‐RELIGION DEBATE
Authors: Harris Mark 
Published: August 2019

AbstractThis article takes a critical stance on John H. Evans's 2018 book, Morals Not Knowledge: Recasting the Contemporary U.S. Conflict between Religion and Science. Highlighting the significance of the book for the science‐and‐religion debate, particularly the book's emphasis on moral questions over knowledge claims revealed in social‐scientific studies of the American public, I also suggest that the distinction between the “elites” of the academic science‐and‐religion field and the religious “public” is insufficiently drawn. I argue that various nuances should be taken into account concerning the portrayal of “elites,” nuances which potentially change the way that “conflict” between science and religion is envisaged, as well as the function of the field. Similarly, I examine the ways in which the book construes science and religion as distinct knowledge systems, and I suggest that, from a theological perspective—relevant for much academic activity in science and religion—there is value in seeing science and religion in terms of a single knowledge system. This perspective may not address the public's interest in moral questions directly—important as they are—but nevertheless it fulfils the academic function of advancing the frontiers of human knowledge and self‐understanding.
THE COLLECTIVE CHARACTERS OF RELIGIOUS CONGREGATIONS
Authors: Byerly T. Ryan , Byerly Meghan 
Published: August 2019

AbstractOur primary aim in this article is to advocate for the interdisciplinary study of the collective character traits of local religious congregations, taking as our focal example local Christian congregations. It should be clear that such study presently lies on the frontier of interdisciplinary religious studies. Yet, as we will attempt to show in the first section, the way has been paved for the study of such collective character traits through salient developments within several academic disciplines in recent decades. This frontier, in other words, is open for exploration, and there are available tools that can help us explore it. We will illustrate how such exploration may be undertaken fruitfully in the second section by focusing on two distinct kinds of virtuous collective character traits of Christian congregations: traits that enable a congregation to fulfill its distinctive role in the missio Dei, and traits that enable a congregation's members to flourish in their interpersonal relationships. In each case, we will identify a candidate collective virtue of the relevant type, discuss its nature from philosophical and theological perspectives, and, drawing on relevant empirical research, provide reason for thinking that applying empirical methods to it can yield additional insights about its value.
Temperature effect on biochar properties from slow pyrolysis of coconut flesh waste
Authors: Mohamed Noor Nurhidayah , Shariff Adilah , Abdullah Nurhayati , Mohamad Aziz Nur Syairah 
Published: August 2019

The aim of this study was to investigate the effect of pyrolysis temperature on the biochar yield and properties via slow pyrolysis of coconut flesh waste. The temperature used in the slow pyrolysis experiment was varied between 350°C to 600°C at a constant heating rate of 5°C/min. The results indicated that higher pyrolysis temperature could reduce the percentage of biochar yield. The increment of pyrolysis temperature from 350°C to 600°C would reduce the biochar yield from 23.54 wt.% to 13.97 wt.%. The effect of pyrolysis temperature was also significant on the composition and physical properties of biochar yield. The physicochemical properties of biochar were identified by proximate, elemental, heating value, SEM images and BET surface area analyses. The increment of pyrolysis temperature from 350°C to 600°C increased the ash content of biochar from 4.63 wt.% to 8.19 wt.%, the fixed carbon content from 45.20 wt.% to 79.09 wt.% and carbon content from 72.70 wt.% to 83.25 wt.%. Meanwhile the volatile matter and oxygen content of biochar were decreased from 50.17 wt.% to 12.71 wt.% and 13.86 wt.% to 10.99 wt.%, respectively as the pyrolysis temperature was increased from 350°C to 600°C. The increment of pyrolysis temperature from 350°C to 600°C increased the surface area of biochar by 8 fold from 0.3971 m2/g to 3.4486 m2/g. Meanwhile, the higher heating value of biochar was decreased from 33.95 MJ/kg to 27.49 MJ/kg as the pyrolysis temperature was increased from 350°C to 600°C.
Clostridioides difficile: diagnosis and treatments
Authors: Guery Benoit , Galperine Tatiana , Barbut Frédéric 
Published: August 2019

AbstractClostridioides difficile(formerlyClostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically,C difficileinfection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology ofC difficileinfection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis ofC difficileinfection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treatC difficileinfection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment ofC difficileinfection based on the most recent data available.
Academic neurosurgery in the UK: present and future directions
Authors: Waqar Mueez , Davies Benjamin M , Zakaria Rasheed , Barone Damiano G , Kolias Angelos G , Yu Kenny K , Ellenbogen Jonathan R , Brennan Paul M , Kotter Mark RN , Gray William P , King Andrew T , Turner Carole , Kitchen Neil , May Paul , Jenkinson Michael D , Hutchinson Peter J 
Published: August 2019

AbstractAcademic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK’s international standing is considered.
Spectra of Indu–Bala product of graphs and some new pairs of cospectral graphs
Authors: Patil Shreekant , Mathapati Mallikarjun 
Published: August 2019

Recently Indulal and Balakrishnan [Distance spectrum of Indu–Bala product of graphs, AKCE Int. J. Graph Comb. 13 (2016) 230–234] put forward a new graph operation, namely, the Indu–Bala product [Formula: see text] of graphs [Formula: see text] and [Formula: see text], and it is obtained from two disjoint copies of the join [Formula: see text] of [Formula: see text] and [Formula: see text] by joining the corresponding vertices in the two copies of [Formula: see text]. In this paper, we obtain the adjacency spectra, the Laplacian spectra and the signless Laplacian spectra of [Formula: see text] in terms of the corresponding spectra of [Formula: see text] and [Formula: see text]. As applications, these results enable us to construct infinitely many pairs of respective cospectral graphs. Further, the Laplacian spectra enable us to get the formulas of the number of spanning trees and Kirchhoff index of [Formula: see text] in terms of the Laplacian spectra of regular graphs [Formula: see text] and [Formula: see text].
Identification of Recurrent ActivatingHER2Mutations in Primary Canine Pulmonary Adenocarcinoma
Authors: Lorch Gwendolen , Sivaprakasam Karthigayini , Zismann Victoria , Perdigones Nieves , Contente-Cuomo Tania , Nazareno Alexandra , Facista Salvatore , Wong Shukmei , Drenner Kevin , Liang Winnie S. , Amann Joseph M. , Sinicropi-Yao Sara L. , Koenig Michael J. , La Perle Krista , Whitsett Timothy G. , Murtaza Muhammed , Trent Jeffrey M. , Carbone David P. , Hendricks William P.D. 
Published: August 2019

AbstractPurpose:Naturally occurring primary canine lung cancers share clinicopathologic features with human lung cancers in never-smokers, but the genetic underpinnings of canine lung cancer are unknown. We have charted the genomic landscape of canine lung cancer and performed functional characterization of novel, recurrent HER2 (ERBB2) mutations occurring in canine pulmonary adenocarcinoma (cPAC).Experimental Design:We performed multiplatform genomic sequencing of 88 primary canine lung tumors or cell lines. Additionally, in cPAC cell lines, we performed functional characterization of HER2 signaling and evaluated mutation-dependent HER2 inhibitor drug dose-response.Results:We discovered somatic, coding HER2 point mutations in 38% of cPACs (28/74), but none in adenosquamous (cPASC, 0/11) or squamous cell (cPSCC, 0/3) carcinomas. The majority (93%) of HER2 mutations were hotspot V659E transmembrane domain (TMD) mutations comparable to activating mutations at this same site in human cancer. Other HER2 mutations were located in the extracellular domain and TMD. HER2V659E was detected in the plasma of 33% (2/6) of dogs with localized HER2V659E tumors. HER2V659E cPAC cell lines displayed constitutive phosphorylation of AKT and significantly higher sensitivity to the HER2 inhibitors lapatinib and neratinib relative to HER2-wild-type cell lines (IC50 &lt; 200 nmol/L in HER2V659E vs. IC50 &gt; 2,500 nmol/L in HER2WT).Conclusions:This study creates a foundation for molecular understanding of and drug development for canine lung cancer. These data also establish molecular contexts for comparative studies in dogs and humans of low mutation burden, never-smoker lung cancer, and mutant HER2 function and inhibition.
Enhanced SLAMF7 Homotypic Interactions by Elotuzumab Improves NK Cell Killing of Multiple Myeloma
Authors: Pazina Tatiana , James Ashley M. , Colby Kimberly B. , Yang Yibin , Gale Andrew , Jhatakia Amy , Kearney Alper Y. , Graziano Robert F. , Bezman Natalie A. , Robbins Michael D. , Cohen Adam D. , Campbell Kerry S. 
Published: August 2019

Abstract
Elotuzumab (Elo) is an IgG1 monoclonal antibody targeting SLAMF7 (CS1, CRACC, and CD319), which is highly expressed on multiple myeloma (MM) cells, natural killer (NK) cells, and subsets of other leukocytes. By engaging with FcγRIIIA (CD16), Elo promotes potent NK cell–mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) toward SLAMF7+ MM tumor cells. Relapsed/refractory MM patients treated with the combination of Elo, lenalidomide, and dexamethasone have improved progression-free survival. We previously showed that Elo enhances NK cell activity via a costimulation mechanism, independent of CD16 binding. Here, we further studied the effect of Elo on cytotoxicity of CD16-negative NK-92 cells. Elo, but not other SLAMF7 antibodies, uniquely enhanced cytotoxicity mediated by CD16-negative NK-92 cells toward SLAMF7+ target cells. Furthermore, this CD16-independent enhancement of cytotoxicity required expression of SLAMF7 containing the full cytoplasmic domain in the NK cells, implicating costimulatory signaling. The CD16-independent costimulation by Elo was associated with increased expression of NKG2D, ICAM-1, and activated LFA-1 on NK cells, and enhanced cytotoxicity was partially reduced by NKG2D blocking antibodies. In addition, an Fc mutant form of Elo that cannot bind CD16 promoted cytotoxicity of SLAMF7+ target cells by NK cells from most healthy donors, especially if previously cultured in IL2. We conclude that in addition to promoting NK cell–mediated ADCC (CD16-dependent) responses, Elo promoted SLAMF7–SLAMF7 interactions in a CD16-independent manner to enhance NK cytotoxicity toward MM cells.
L’ennui chez Madame Bovary: justification ou condamnation?
Authors: Paixão Grace Alves da , Amorim Anaximandro Oliveira Santos 
Published: August 2019

Ce travail a pour but de montrer comment l’ennui chez le personnage Madame Bovary (du roman éponyme) fut le déclencheur du scandale et par conséquent du procès judiciaire de Gustave Flaubert, auteur du roman. Ainsi, on propose un article divisé en quatre parties : une où l’on parle de l’auteur ; une où l’on parle de l’ouvrage ; une où l’on parle du procès à proprement parler (et comment le langage y fut question d’importance) ; et une dernière où l’on analyse la question même de l’ennui grâce à des passages du roman. Pour cela, on adopte une méthodologie de révision bibliographique ayant comme base le livre Madame Bovary no tribunal do júri : do crime ao castigo ? (2011), de la professeure Telma Boudou.
Characterization of the CACNA1C-R518C Missense Mutation in the Pathobiology of Long-QT Syndrome Using Human Induced Pluripotent Stem Cell Cardiomyocytes Shows Action Potential Prolongation and L-Type Calcium Channel Perturbation
Authors: Estes Steven I. , Ye Dan , Zhou Wei , Dotzler Steven M. , Tester David J. , Bos J. Martijn , Kim C.S. John , Ackerman Michael J. 
Published: August 2019

Background:

The
CACNA1C
-encoded cardiac L-type calcium channel (Cav1.2) is essential for cardiocyte action potential duration (APD). We previously reported the CACNA1C-p.R518C variant associated with prolonged QT intervals, cardiomyopathy, and sudden cardiac death in several pedigrees.

Methods:
To characterize a patient-derived human induced pluripotent stem cell–derived cardiomyocyte (hiPSC-CM) CACNA1C-p.R518C model, CACNA1C-p.R518C hiPSC-CMs were generated from a 13-year-old man (QTc, >480 ms) with a family history of sudden cardiac death. An isogenic hiPSC-CM gene-corrected control was created using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9). APD and calcium handling were assessed by live cell imaging with Arclight voltage and Fluo-4 calcium indicators, respectively. The APD and L-type calcium channel biophysical properties were further assessed by whole-cell patch clamp technique.

Results:

The Bazett formula-corrected, Arclight-measured APD
90
of CACNA1C-p.R518C hiPSC-CMs was significantly longer (622±11 ms; n=92) than the isogenic control hiPSC-CMs (453±5 ms; n=62;
P
<0.0001). Patch clamp assessment of CACNA1C-p.R518C hiPSC-CMs paced at 1 Hz confirmed a prolonged APD
90
(689±29 ms; n=10) compared with the patient’s isogenic control hiPSC-CMs (434±30 ms; n=8;
P
<0.05). Fluo-4–measured calcium transient decay time suggested calcium mishandling in CACNA1C-p.R518C. Patch clamp analysis revealed increased L-type calcium channel window current, slow decay time at various voltages, and increased late calcium current for CACNA1C-p.R518C hiPSC-CMs when compared with isogenic control hiPSC-CMs.

Conclusions:

Using patient-specific hiPSC-CM mutant and isogenic control lines, we demonstrate that the CACNA1C-p.R518C variant is the self-sufficient, monogenetic substrate for the patient’s long-QT syndrome phenotype. These data further bolster the conclusion that
CACNA1C
is a bona fide, definite evidence long-QT syndrome susceptibility gene.
Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort
Authors: Liu Tiange , Zhang Mingyu , Guallar Eliseo , Wang Guoying , Hong Xiumei , Wang Xiaobin , Mueller Noel T. 
Published: August 2019

Background
Preeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort.

Methods and Results

A total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (
PR
s) and 95%
CI
s. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose–response trend for Mn (
P
for trend<0.001) and to some extent for Cd (
P
for trend=0.009) quintiles. After multivariable adjustment, a 1
SD
increment in Mn was associated with 32% lower risk of developing preeclampsia (
PR
=0.68; 95%
CI
, 0.54–0.86), whereas a 1
SD
increment in Cd was associated with 15% higher risk of preeclampsia (
PR
=1.15; 95%
CI
, 0.98–1.36). Null associations were observed for Se, Pb, and Hg.

Conclusions
Findings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.
Fluoxetine and Fractures After Stroke
Authors: Dennis Martin , Forbes John , Graham Catriona , Hackett Maree L. , Hankey Graeme J. , House Allan , Lewis Steff , Lundström Erik , Sandercock Peter , Mead Gillian ,   on behalf of the FOCUS Trial Collaboration
Published: August 2019

Background and Purpose—
The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk.

Methods—
A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures.

Results—

Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13–3.45;
P
=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29–3.51;
P
=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20–3.34;
P
=0.008) were independently associated with fractures.

Conclusions—
Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients’ function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN83290762.