bluuebunny/crossref_metadata_2025_split huggingface dataset:
A herbal premix containing Macrotyloma uniflorum, ginger, and whey curtails obesity in rats fed a high-fat diet by a novel mechanism
Authors: Panda Vandana S. , Shah Taasin , S Sudhamani 
Published: May 2019

The present study designed and evaluated a polyherbal premix comprising Macrotyloma uniflorum, whey protein, Zingiber officinale, and Mentha piperita. Animals were fed a high-fat diet (HFD) for 30 days and were daily administered the premix (1.5 g/kg) in milk (PM) and water (PW), aerobic exercise (AE), premix in milk and water along with AE (PMAE and PWAE), ferulic acid (100 mg/kg), and the reference drug fluoxetine (6 mg/kg). All treatments showed significant reduction in food intake, weight gain, abdominal circumference, and body mass index compared with their initial values. All treatments generated a faster peak of the satiety marker cholecystokinin compared with the HFD group and control groups; PMAE and PWAE exhibited sustained satiety. The HFD-elevated blood glucose levels were significantly attenuated on the 30th day by all treatments when compared with their 15th day and basal values; PMAE exhibited the best results. All treatments significantly attenuated the HFD-elevated serum insulin, homeostasis model assessment of insulin resistance, C-reactive protein, triglycerides, total cholesterol, very-low-density lipoprotein, and low-density lipoprotein levels and significantly restored the HFD-depleted high-density lipoprotein and adiponectin levels. HFD-elevated thiobarbituric acid reactive substances values were attenuated successfully and the HFD-depleted reduced glutathione, superoxide dismutase, and catalase levels were significantly restored by all treatments. The histological findings corroborated the biochemical results. Novelty The polyherbal premix brought about appetite regulation and induction of satiety to control obesity in HFD-fed rats through homeostasis of energy metabolism. The premix along with exercise is a complete way to combat obesity.
Exosomal Induction of Tumor Innervation
Authors: Vermeer Paola D. 
Published: May 2019

Abstract
The naïve view of tumors as isolated islands of rogue cells has given way to a deeper understanding of cancer as being closer to a foreign organ. This “organ” contains immunologic, vascular, and neural connections to its host that provide not only mechanisms for disease progression but also opportunities for therapeutic intervention. The presence of nerves within tumor tissues has long been appreciated. However, a mechanistic understanding of how tumors recruit nerves has been slower to emerge. Tumor release of neurotrophic factors and axonal guidance molecules likely directs axons toward the tumor bed. Newly emerging data support a contribution of tumor-released exosomes in the induction of axonogenesis toward the tumor. Exosomes, small membrane-bound vesicles that carry a complex cargo (DNA, RNA, miRNA, lipids, and proteins), protect their cargo from the low pH of the tumor microenvironment. They also represent an efficient means of local and distal communication between the tumor and potentially innervating nerves. Likely, a combination of neurotrophins, guidance molecules, and exosomes work in concert to promote tumor innervation. As such, defining the critical components driving tumor innervation will identify new targets for intervention. Moreover, with a deepening understanding, tumor innervation may emerge as a new hallmark of cancer.
Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer
Authors: Chera Bhishamjit S. , Kumar Sunil , Beaty Brian T. , Marron David , Jefferys Stuart , Green Rebecca , Goldman Emily C. , Amdur Robert , Sheets Nathan , Dagan Roi , Hayes D. Neil , Weiss Jared , Grilley-Olson Juneko E. , Zanation Adam , Hackman Trevor , Blumberg Jeffrey M. , Patel Samip , Weissler Mark , Tan Xianming M. , Parker Joel S. , Mendenhall William , Gupta Gaorav P. 
Published: May 2019

Abstract

Purpose:
To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Experimental Design:
A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non–HPV-associated malignancy was also analyzed.

Results:
Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (&gt;200 copies/mL) and &gt;95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or &gt;10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049).

Conclusions:
A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.
Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia
Authors: McMahon Christine M. , Ferng Timothy , Canaani Jonathan , Wang Eunice S. , Morrissette Jennifer J.D. , Eastburn Dennis J. , Pellegrino Maurizio , Durruthy-Durruthy Robert , Watt Christopher D. , Asthana Saurabh , Lasater Elisabeth A. , DeFilippis RosaAnna , Peretz Cheryl A.C. , McGary Lisa H.F. , Deihimi Safoora , Logan Aaron C. , Luger Selina M. , Shah Neil P. , Carroll Martin , Smith Catherine C. , Perl Alexander E. 
Published: May 2019

AbstractGilteritinib is a potent and selective FLT3 kinase inhibitor with single-agent clinical efficacy in relapsed/refractory FLT3-mutated acute myeloid leukemia (AML). In this context, however, gilteritinib is not curative, and response duration is limited by the development of secondary resistance. To evaluate resistance mechanisms, we analyzed baseline and progression samples from patients treated on clinical trials of gilteritinib. Targeted next-generation sequencing at the time of AML progression on gilteritinib identified treatment-emergent mutations that activate RAS/MAPK pathway signaling, most commonly in NRAS or KRAS. Less frequently, secondary FLT3-F691L gatekeeper mutations or BCR–ABL1 fusions were identified at progression. Single-cell targeted DNA sequencing revealed diverse patterns of clonal selection and evolution in response to FLT3 inhibition, including the emergence of RAS mutations in FLT3-mutated subclones, the expansion of alternative wild-type FLT3 subclones, or both patterns simultaneously. These data illustrate dynamic and complex changes in clonal architecture underlying response and resistance to mutation-selective tyrosine kinase inhibitor therapy in AML.Significance:Comprehensive serial genotyping of AML specimens from patients treated with the selective FLT3 inhibitor gilteritinib demonstrates that complex, heterogeneous patterns of clonal selection and evolution mediate clinical resistance to tyrosine kinase inhibition in FLT3-mutated AML. Our data support the development of combinatorial targeted therapeutic approaches for advanced AML.See related commentary by Wei and Roberts, p. 998.This article is highlighted in the In This Issue feature, p. 983
Effect of Air Tamponade on Tilt of the Intraocular Lens after Phacovitrectomy
Authors: Leisser Christoph , Hirnschall Nino , Findl Oliver 
Published: May 2019

<b><i>Purpose:</i></b> The aim of the study was to examine whether air tamponade has a significant effect on postoperative tilt of the intraocular lens (IOL) in combined phacoemulsification with implantation of an IOL and vitrectomy compared to balanced salt solution. <b><i>Procedures:</i></b> This randomized, controlled, monocentre study included patients scheduled for combined phacoemulsification with IOL implantation and pars plana vitrectomy. Patients were randomized for balanced salt solution or air tamponade. Postoperative tilt and decentration of the IOL were measured 2 months after surgery with a Purkinje meter. <b><i>Results:</i></b> Thirty-four patients were included into the analysis. Tilt of the IOL was on average 4.1 ± 1.9°, without significant differences between balanced salt solution and air tamponade (<i>p</i> = 0.462). Decentration of the IOL was on average 0.31 ± 0.14 mm, without significant differences between balanced salt solution and air tamponade (<i>p</i> = 0.42). <b><i>Conclusions:</i></b> Air tamponade does not induce significantly more tilt or decentration of the IOL in combined phacoemulsification and vitrectomy compared to balanced salt solution. Potentially, this may not hold true for cases with a capsulorhexis that does not overlap the IOL optic.
Characteristics and Clinical Outcomes of Patients With Spontaneous Coronary Artery Dissection
Authors: Clare Ryan , Duan Lewei , Phan Derek , Moore Naing , Jorgensen Michael , Ichiuji Anne , Shen Albert Y. , Lee Ming‐Sum 
Published: May 2019

Background

The goal of this study is to report the characteristics and long‐term clinical outcomes of patients with spontaneous coronary artery dissection (SCAD) and to identify factors associated with recurrent
SCAD
.

Methods and Results

This is a retrospective cohort study that included patients who underwent coronary angiography for evaluation of acute myocardial infarction between 2006 and 2016. Among 26 598 patients hospitalized with a principal diagnosis of acute myocardial infarction, 208 (0.78%) were diagnosed with
SCAD
. Patients with
SCAD
were younger (49.0±11.6 versus 65.6±12.2 years) and more likely to be women (88.9% versus 31.6%). Atherosclerotic risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes mellitus, were less prevalent. Median follow‐up was 4.7 years. Mortality was lower in patients with SCAD (1‐year mortality: 2.4% versus 8.8%;
P
<0.001). After using propensity score matching to control for differences in age, sex, and comorbidities, the difference in mortality was no longer present, suggesting that lower mortality in patients with SCAD is attributed primarily to their baseline characteristics. Recurrent
SCAD
occurred in 22 patients (10.6%). Multivariate Cox regression modeling showed concomitant fibromuscular dysplasia (hazard ratio, 5.1; 95%
CI
, 1.6–15.8;
P
=0.005) and migraine headaches (hazard ratio, 3.4; 95%
CI
, 1.4–8.4;
P
=0.008) to be associated with increased risk of recurrent
SCAD
.

Conclusions

Among patients with acute myocardial infarction, patients with
SCAD
have a lower risk of mortality, which is attributed primarily to their younger age, female sex, and low prevalence of atherosclerotic risk factors. Risk of recurrent
SCAD
persists years after the initial presentation. Patients with fibromuscular dysplasia and migraine are at higher risk for recurrent
SCAD
.
Epigenome-Wide Association Study Indicates Hypomethylation of
MTRNR2L8
in Large-Artery Atherosclerosis Stroke
Authors: Shen Yupei , Peng Chen , Bai Qingke , Ding Ying , Yi Xin , Du Huihui , He Lin , Zhou Daizhan , Chen Xu 
Published: May 2019

Background and Purpose—
Ischemic stroke, a complex and heterogeneous disease, is the second leading cause of death worldwide. Genetic factors and epigenetic modification contribute to the pathogenesis of this disease. However, the effects of epigenetic factors on this disease have not been systematically investigated. Our study was designed to identify methylation alterations in large-artery atherosclerotic stroke.

Methods—
We conducted an epigenome-wide association analysis of large-artery atherosclerotic stroke using an Infinium HumanMethylation450 array (cases:controls=12:12), and the differentially methylated loci were validated in 2 cohorts (cases:controls, 110:122 and 191:191, respectively) using a Sequenom EpiTYPER assay.

Results—

In the screening stage, 1012 differentially methylated CpG sites annotated in 672 genes were found to be significantly associated with large-artery atherosclerotic stroke (mean methylation difference >5%,
P
<0.01). Disease, Gene Ontology, and pathway analysis highlighted the enrichment of these differentially methylated genes in cardiovascular, metabolic, neurological and immune-related functional gene clusters (
P
<0.05). We identified a differentially methylated region in the promoter of a humanin gene (
MTRNR2L8
, mean methylation difference=−13.01%,
P
=8.86×10
–14
). We constructed a diagnostic prediction model that was based on the mean number of significantly changed CpG loci in
MTRNR2L8
and showed high diagnostic specificity and sensitivity (
P
<0.0001, area under the curve=0.774).

Conclusions—

Together, these findings demonstrate that DNA methylation plays an important role in large-artery atherosclerotic stroke and that methylation of
MTRNR2L8
is a potential therapeutic target and diagnostic biomarker for stroke.
Ethnic Differences in 90-Day Poststroke Medication Adherence
Authors: Lank Rebecca J. , Lisabeth Lynda D. , Levine Deborah A. , Zahuranec Darin B. , Kerber Kevin A. , Shafie-Khorassani Fatema , Case Erin , Zuniga Belinda G. , Cooper George M. , Brown Devin L. , Morgenstern Lewis B. 
Published: May 2019

Background and Purpose—
We assessed ethnic differences in medication adherence 3 months poststroke in a population-based study as an initial step in investigating the increased stroke recurrence risk in Mexican Americans compared with non-Hispanic whites.

Methods—

Ischemic stroke cases from 2008 to 2015 from the Brain Attack Surveillance in Corpus Christi project in Texas were followed prospectively for 3 months poststroke to assess medication adherence. Medications in 5 drug classes were analyzed: statins, antiplatelets, anticoagulants, antihypertensives, and antidepressants. For each drug class, patients were considered adherent if they reported never missing a dose in a typical week. The χ
2
tests or Kruskal-Wallis nonparametric tests were used for ethnic comparisons of demographics, risk factors, and medication adherence. A multivariable logistic regression model was constructed for the association of ethnicity and medication nonadherence.

Results—

Mexican Americans (n=692) were younger (median 65 years versus 68 years,
P
<0.001), had more diabetes mellitus (
P
<0.001) and hypertension (
P
<0.001) and less atrial fibrillation (
P
=0.003), smoking (
P
=0.003), and education (
P
<0.001) than non-Hispanic whites (n=422). Sex, insurance status, high cholesterol, previous stroke/transient ischemic attack history, excessive alcohol use, tPA (tissue-type plasminogen activator) treatment, National Institutes of Health Stroke Scale score, and comorbidity index did not significantly differ by ethnicity. There was no significant difference in medication adherence for any of the 5 drug classes between Mexican Americans and non-Hispanic whites.

Conclusions—
This study did not find ethnic differences in medication adherence, thus challenging this patient-level factor as an explanation for stroke recurrence disparities. Other reasons for the excessive stroke recurrence burden in Mexican Americans, including provider and health system factors, should be explored.
Non–Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Supranormal Renal Function
Authors: Lee So-Ryoung , Choi Eue-Keun , Han Kyung-Do , Jung Jin-Hyung , Cha Myung-Jin , Oh Seil , Lip Gregory Y.H. 
Published: May 2019

Background and Purpose—
In clinical trials, the reduced efficacy of non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention was reported for patients with nonvalvular atrial fibrillation with a creatinine clearance (CrCl) >95 mL/min compared with that of warfarin. We examined the effectiveness, safety, and net clinical benefit of NOACs compared with warfarin in Asian patients with atrial fibrillation and supranormal renal function.

Methods—
Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, we included patients with nonvalvular atrial fibrillation with CrCl >80 mL/min. Among these incident oral anticoagulant users with rivaroxaban (n=6297), dabigatran (n=4241), apixaban (n=3395), edoxaban (n=1187), and warfarin (n=9884) were analyzed. Propensity score weighting was used to balance covariates across study groups. Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome defined as ischemic stroke+intracranial hemorrhage+gastrointestinal bleeding+all-cause death were analyzed using Cox regression analysis with warfarin as the reference.

Results—

Baseline characteristics were well balanced among all groups (mean age, 66±11 years; 63% were men; mean CHA
2
DS
2
-VASc score, 3.0±1.8). Forty-five percent of the patients had CrCl >95 mL/min. Pooled NOACs yielded lower risks of ischemic stroke (hazard ratio, 0.51; 95% CI, 0.43–0.60) and the composite outcome (hazard ratio, 0.64; 95% CI, 0.58–0.70) than warfarin in patients with CrCl >80 mL/min. These benefits were consistent in those with CrCl >95 mL/min. All 4 NOACs reduced the risks of ischemic stroke and the composite outcome in both patients with CrCl >80 mL/min and >95 mL/min.

Conclusions—
The NOACs showed better effectiveness and safety than warfarin in the patients with atrial fibrillation and supranormal renal function; this was consistently observed for all 4 NOACs and in patients with CrCl >95 mL/min.
Chronic Cortical Cerebral Microinfarcts Slow Down Cognitive Recovery After Acute Ischemic Stroke
Authors: Sagnier Sharmila , Okubo Gosuke , Catheline Gwenaëlle , Munsch Fanny , Bigourdan Antoine , Debruxelles Sabrina , Poli Mathilde , Olindo Stéphane , Renou Pauline , Rouanet François , Dousset Vincent , Tourdias Thomas , Sibon Igor 
Published: May 2019

Background and Purpose—
Cortical cerebral microinfarcts (CMIs) have been associated with vascular dementia and Alzheimer disease. The aim of the present study was to evaluate the role of cortical CMI detected on 3T magnetic resonance imaging, on the evolution of cognition during the year following an acute ischemic stroke.

Methods—
We conducted a prospective and monocentric study, including patients diagnosed for a supratentorial ischemic stroke with a National Institutes of Health Stroke Scale score ≥1, without prestroke dementia or neurological disability. Cortical CMIs were assessed on a brain 3T magnetic resonance imaging realized at baseline, as well as markers of small vessel disease, stroke characteristics, and hippocampal atrophy. Cognitive assessment was performed at 3 time points (baseline, 3 months, and 1 year) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo’s cancellation task. Generalized linear mixed models were performed to evaluate the relationships between the number of cortical CMI and changes in cognitive scores over 1 year.

Results—

Among 199 patients (65±13 years old, 68% men), 88 (44%) had at least one cortical CMI. Hypertension was the main predictor of a higher cortical CMI load (B=0.58,
P
=0.005). The number of cortical CMI was associated with an increase time at the Zazzo’s cancellation task over 1 year (B=3.84,
P
=0.01), regardless of the other magnetic resonance imaging markers, stroke severity, and demographic factors.

Conclusions—
Cortical CMIs are additional magnetic resonance imaging markers of poorer processing speed after ischemic stroke. These results indicate that a high load of cortical CMI in patients with stroke can be considered as a cerebral frailty condition which counteracts to the recovery process, suggesting a reduced brain plasticity among these patients.
Church Action for Fair Trade as Public Theology: Learning from the Experience of the Mainstreaming of Fair Trade in the United Kingdom
Authors: Dawson Mark 
Published: May 2019

Abstract
Church action for Fair Trade in the United Kingdom serves as an example of an activity, inspired and guided by theology, which has grown to involve the active participation of large numbers of churchgoers. Public recognition of Fair Trade is high, embracing a wide, secular society. The expansion of Fair Trade has come at a price, however, with the increasing involvement of large commercial organisations threatening diminution of the original theological insight. In learning from the experience of the mainstreaming of Fair Trade in the United Kingdom, it could be argued that the theological reflection that gave rise to the Fair Trade movement was the beginning of a public theology. It needs to be acknowledged and now taken further, to respond to the changing context. A public theology involving congregations should be nurtured, so that the public theological insight can be disseminated and its guidance put into practice.
Ethical Dimensions of Arbitrator Resignations: General Duties, Specific Quandaries, and Sanctions for Suspect Withdrawals
Authors: Levine Judith 
Published: May 2019

Abstract
This article deals with the ethical implications of arbitrator resignations. When an arbitrator resigns it can severely disrupt proceedings. Arbitrators have a positive duty to complete the mandate for which they have been appointed, and a corollary duty not to resign without justification. This article considers steps that can be taken at the outset of proceedings to minimise the likelihood of resignation. It then discusses ethical dilemmas associated with five common circumstances that can arise during the course of arbitral proceedings which might justify resignation. The article then recalls rare but disturbing instances when a resignation itself may be ethically dubious and sets out measures available to discourage such conduct. Ethical issues connected with resignation have traditionally been given less prominence than discussion of conflicts and challenges, but should not be overlooked in any new endeavors aimed at developing a code of conduct for international arbitration.
Thermal Effects of the Surface Heat Flux on Cloud Systems over the Tibetan Plateau in Boreal Summer
Authors: Chen Jinghua , Wu Xiaoqing , Yin Yan , Lu Chunsong , Xiao Hui , Huang Qian , Deng Liping 
Published: May 2019

ABSTRACT
The influence of surface heat fluxes on the generation and development of cloud and precipitation and its relative importance to the large-scale circulation patterns are investigated via cloud-resolving model (CRM) simulations over the Tibetan Plateau (TP) during boreal summer. Over the lowland (e.g., along the middle and lower reaches of the Yangtze River), the dynamical and thermal properties of the atmosphere take more responsibility than the surface heat fluxes for the triggering of heavy rainfall events. However, the surface thermal driving force is a necessary criterion for the triggering of heavy rainfall in the eastern and western TP (ETP and WTP). Strong surface heat fluxes can trigger shallow convections in the TP. Furthermore, moisture that is mainly transported from the southern tropical ocean has a greater influence on the heavy rainfall events of the WTP than those of the ETP. Cloud microphysical processes are substantially less active and heavy rainfall cannot be produced when surface heat fluxes are weakened by half in magnitude over the TP. In addition, surface heating effects are largely responsible for the high occurrence frequency of convection during the afternoon, and the cloud tops of convective systems show a positive relationship with the intensity of surface heat fluxes.