bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold water immersion attenuates anabolic signaling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training
Authors: Fyfe Jackson J. , Broatch James R. , Trewin Adam J. , Hanson Erik D. , Argus Christos K. , Garnham Andrew P. , Halson Shona L. , Polman Remco C. , Bishop David J. , Petersen Aaron C. 
Published: September 2019

We determined the effects of cold water immersion (CWI) on long-term adaptations and post-exercise molecular responses in skeletal muscle before and after resistance training. Sixteen men (22.9 ± 4.6 y; 85.1 ± 17.9 kg; mean ± SD) performed resistance training (3 day/wk) for 7 wk, with each session followed by either CWI [15 min at 10°C, CWI (COLD) group, n = 8] or passive recovery (15 min at 23°C, control group, n = 8). Exercise performance [one-repetition maximum (1-RM) leg press and bench press, countermovement jump, squat jump, and ballistic push-up], body composition (dual X-ray absorptiometry), and post-exercise (i.e., +1 and +48 h) molecular responses were assessed before and after training. Improvements in 1-RM leg press were similar between groups [130 ± 69 kg, pooled effect size (ES): 1.53 ± 90% confidence interval (CI) 0.49], whereas increases in type II muscle fiber cross-sectional area were attenuated with CWI (−1,959 ± 1,675 µM2 ; ES: −1.37 ± 0.99). Post-exercise mechanistic target of rapamycin complex 1 signaling (rps6 phosphorylation) was blunted for COLD at post-training (POST) +1 h (−0.4-fold, ES: −0.69 ± 0.86) and POST +48 h (−0.2-fold, ES: −1.33 ± 0.82), whereas basal protein degradation markers (FOX-O1 protein content) were increased (1.3-fold, ES: 2.17 ± 2.22). Training-induced increases in heat shock protein (HSP) 27 protein content were attenuated for COLD (−0.8-fold, ES: −0.94 ± 0.82), which also reduced total HSP72 protein content (−0.7-fold, ES: −0.79 ± 0.57). CWI blunted resistance training-induced muscle fiber hypertrophy, but not maximal strength, potentially via reduced skeletal muscle protein anabolism and increased catabolism. Post-exercise CWI should therefore be avoided if muscle hypertrophy is desired. NEW & NOTEWORTHY This study adds to existing evidence that post-exercise cold water immersion attenuates muscle fiber growth with resistance training, which is potentially mediated by attenuated post-exercise increases in markers of skeletal muscle anabolism coupled with increased catabolism and suggests that blunted muscle fiber growth with cold water immersion does not necessarily translate to impaired strength development.
Improving Response to FLT3 Inhibitors–BCL2 the Rescue?
Authors: Perl Alexander E. 
Published: September 2019

Abstract
As single agents, FLT3 inhibitors are active in FLT3-mutated acute myeloid leukemia (AML) therapy but not curative. The BCL2 inhibitor, venetoclax, enhances responses to low intensity AML chemotherapy but its activity is limited by MCL1 upregulation. FLT3 inhibitors downregulate MCL1 and synergize with venetoclax in preclinical AML models.
See related article by Ma et al., p. 6815
Mirc11Disrupts Inflammatory but Not Cytotoxic Responses of NK Cells
Authors: Nanbakhsh Arash , Srinivasamani Anupallavi , Holzhauer Sandra , Riese Matthew J. , Zheng Yongwei , Wang Demin , Burns Robert , Reimer Michael H. , Rao Sridhar , Lemke Angela , Tsaih Shirng-Wern , Flister Michael J. , Lao Shunhua , Dahl Richard , Thakar Monica S. , Malarkannan Subramaniam 
Published: September 2019

AbstractNatural killer (NK) cells generate proinflammatory cytokines that are required to contain infections and tumor growth. However, the posttranscriptional mechanisms that regulate NK cell functions are not fully understood. Here, we define the role of the microRNA cluster known as Mirc11 (which includes miRNA-23a, miRNA-24a, and miRNA-27a) in NK cell–mediated proinflammatory responses. Absence of Mirc11 did not alter the development or the antitumor cytotoxicity of NK cells. However, loss of Mirc11 reduced generation of proinflammatory factors in vitro and interferon-γ–dependent clearance of Listeria monocytogenes or B16F10 melanoma in vivo by NK cells. These functional changes resulted from Mirc11 silencing ubiquitin modifiers A20, Cbl-b, and Itch, allowing TRAF6-dependent activation of NF-κB and AP-1. Lack of Mirc11 caused increased translation of A20, Cbl-b, and Itch proteins, resulting in deubiquitylation of scaffolding K63 and addition of degradative K48 moieties on TRAF6. Collectively, our results describe a function of Mirc11 that regulates generation of proinflammatory cytokines from effector lymphocytes.
Construção do pensamento e das práticas científicas
Authors: Monteiro Canale Ricardo Angelo 
Published: September 2019

Este artigo tem por pretensão analisar a construção e o processo do pensamento e do conhecimento científico e suas práticas na era industrial e pós-industrial. Além disso, o artigo demonstra a relação entre os diferentes grupos científicos e suas práticas (e.g. teórica, experimental ou instrumental) para: i) a troca de objetos de conhecimento e divulgação científica; ii) a formação crítica dos sujeitos; iii) o desenvolvimento de Estado; e iv) a dominação social.

Palavras-chave: Ciência. Pensamento científico. Difusão e divulgação do conhecimento científico. Zonas de troca. Estado e sociedade.
Conhecimento científico
Authors: Rosetto Marcia 
Published: September 2019

O papel da informação e do conhecimento para as pessoas e as organizações pode ser analisada pelo menos em duas dimensões – filosófica e tecnológica –, e faz parte das transformações sociais e desempenhando um papel central na sociedade. Para a ciência, tanto a informação como o conhecimento, devem ter suas origens documentadas sendo que o fluxo da informação científica é determinado pelos padrões adotados e na forma de sua mediação e comunicação. Na área de História da Ciência (HC) o documento é um dos principais recursos para o desenvolvimento de pesquisas, incluindo os processos que permitem o acesso ao documento nas coleções/repositórios, assim como as classificações, terminologias e as formas de comunicação e divulgação desses conteúdos. Os estudos historiográficos na área da Ciência da Informação (CI) sobre “documento e informação” remetem aos projetos promovidos por Paul Otlet e Henry La Fontaine, que consolidaram bibliografias, repertórios e teorias e processos para a organização e acesso à massa documental, e são considerados como uma das raízes da CI. Para a área da HC, os estudos e projetos organizados por George Sarton o identificam como um dos principais articuladores para a institucionalização da área e sendo responsável pela criação da revista Isis e a Bibliographie Analytique des Publications Relatives à l’Histoire de la Science, entre outros tipos de documentos. Durante a realização da pesquisa no âmbito do Programa de Pós-Graduandos em História da Ciência da PUC/SP, com o uso de múltiplas fontes, foram identificados fatores das possíveis inter-relações entre essas duas áreas que tem características interdisciplinares.
ALDH2 (Aldehyde Dehydrogenase 2) Protects Against Hypoxia-Induced Pulmonary Hypertension
Authors: Zhao Yu , Wang Bailu , Zhang Jian , He Dayu , Zhang Qun , Pan Chang , Yuan Qiuhuan , Shi Yinan , Tang Haiyang , Xu Feng , Wei Shujian , Chen Yuguo 
Published: September 2019

Objective:
Hypoxia-induced pulmonary hypertension (HPH) increases lipid peroxidation with generation of toxic aldehydes that are metabolized by detoxifying enzymes, including ALDH2 (aldehyde dehydrogenase 2). However, the role of lipid peroxidation and ALDH2 in HPH pathogenesis remain undefined.

Approach and Results:

To determine the role of lipid peroxidation and ALDH2 in HPH, C57BL/6 mice, ALDH2 transgenic mice, and ALDH2 knockout (ALDH2
−/−
) mice were exposed to chronic hypoxia, and recombinant tissue-specific ALDH2 overexpression adeno-associated viruses were introduced into pulmonary arteries via tail vein injection for ALDH2 overexpression. Human pulmonary artery smooth muscle cells were used to elucidate underlying mechanisms in vitro. Chronic hypoxia promoted lipid peroxidation due to the excessive production of reactive oxygen species and increased expression of lipoxygenases in lung tissues. 4-hydroxynonenal but not malondialdehyde level was increased in hypoxic lung tissues which might reflect differences in detoxifying enzymes. ALDH2 overexpression attenuated the development of HPH, whereas ALDH2 knockout aggravated it. Specific overexpression of ALDH2 using AAV1 (adeno-associated virus)-ICAM (intercellular adhesion molecule) 2p-ALDH2 and AAV2-SM22αp (smooth muscle 22 alpha)-ALDH2 viral vectors in pulmonary artery smooth muscle cells, but not endothelial cells, prevented the development of HPH. Hypoxia or 4-hydroxynonenal increased stabilization of HIF (hypoxia-inducible factor)-1α, phosphorylation of Drp1 (dynamin-related protein 1) at serine 616, mitochondrial fission, and pulmonary artery smooth muscle cells proliferation, whereas ALDH2 activation suppressed the latter 3.

Conclusions:
Increased 4-hydroxynonenal level plays a critical role in the development of HPH. ALDH2 attenuates the development of HPH by regulating mitochondrial fission and smooth muscle cell proliferation suggesting ALDH2 as a potential new therapeutic target for pulmonary hypertension.
Arterial Stiffness Modulates the Association of Resting Heart Rate With Rapid Renal Function Decline in Individuals With Type 2 Diabetes Mellitus
Authors: Liu Jian-Jun , Liu Sylvia , Gurung Resham L , Ang Keven , Ee Tang Wern , Sum Chee Fang , Tavintharan Subramaniam , Hadjadj Samy , Lim Su Chi 
Published: September 2019

Objective:
Resting heart rate (RHR) has been associated with cardiovascular risk, but data on renal outcomes are still scarce. We aimed to study the association of RHR with rapid renal function decline (RRFD) and to explore whether the association of RHR with RRFD is modulated by arterial stiffness in individuals with type 2 diabetes mellitus.

Approach and Results:

One thousand one hundred forty-two Asian people with type 2 diabetes mellitus were followed for 3.9±0.9 years in a regional hospital and a primary care facility. RRFD was defined as eGFR decline of 5 mL/min per 1.73 m2 or greater per year. Arterial stiffness was assessed by carotid-femoral pulse wave velocity. One hundred sixty-eight participants (15%) were classified as having RRFD. Participants with elevated RHR were younger, had higher levels of HbA1c, albuminuria, C-reactive protein, and pulse wave velocity. Compared with the lowest quartile, participants in quartile 4 had a higher risk for RRFD after adjustment for known risk factors (adjusted odds ratio 1.91 [1.11–3.28]). RHR improved discrimination and net reclassification for prediction of RRFD above traditional risk factors. Remarkably, arterial stiffness modulated the association of RHR with RRFD (
P
for interaction =0.03). RHR was significantly associated with risk of RRFD only in those with increased arterial stiffness (pulse wave velocity above age-reference value 7.7 m/s).

Conclusions:
RHR independently predicts RRFD, and the association is modulated by arterial stiffness. An elevated heart rate may be one factor in the spectrum of cardiovascular risk factors associated with renal functional impairment, especially in those with type 2 diabetes mellitus and an increased arterial stiffness.
Dynamic Changes in the Molecular Signature of Adverse Left Ventricular Remodeling in Patients With Compensated and Decompensated Chronic Primary Mitral Regurgitation
Authors: McCutcheon Keir , Dickens Caroline , van Pelt Jos , Dix-Peek Therese , Grinter Sacha , McCutcheon Lindsay , Patel Atulkumar , Hale Martin , Tsabedze Nqoba , Vachiat Ahmed , Zachariah Don , Duarte Raquel , Janssens Stefan , Manga Pravin 
Published: September 2019

Background:
There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies.

Methods and Results:

We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased
NPPA
expression levels (21.6-fold,
P
=0.004), decreased transcripts of genes important in cell survival, and enrichment of extracellular matrix genes. Decompensated CPMR was associated with downregulation of SERCA2 (0.77-fold,
P
=0.009) and mitochondrial gene expression levels and upregulation of genes related to inflammation, the extracellular matrix, and apoptosis, which were refractory to carvedilol therapy.

Conclusions:
Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.
Experimental Evaluation of a Novel Percutaneous Transseptal Catheter-Based Mitral Valve Replacement Technology
Authors: Vahl Torsten P. , Grogan Aaron , Cheng Yanping , Yi Genghua , von Oepen Randolf , Khalique Omar K. , Wallace Daniel T. , Modine Thomas , Granada Juan F. 
Published: September 2019

Background:
Transcatheter mitral valve replacement is a novel therapeutic approach aiming to treat patients with severe mitral regurgitation. This study aimed to evaluate the biological and technical performance of a novel transseptal transcatheter mitral valve replacement system (Cephea Valve Technologies, Santa Cruz, CA) in a preclinical model.

Methods:
Biological performance and healing response were evaluated following open-heart surgical implantation procedures in 10 sheep utilizing an antegrade transatrial access. Valve performance was assessed with fluoroscopy, echocardiography, and histology at 30 (n=2), 60 (n=3), and 90 days (n=5). Feasibility of transseptal valve delivery and performance was tested acutely in 10 pigs.

Results:
In the chronic studies, all animals survived without problems until completion of the study. The hemodynamics of the study valves were excellent with low rates of paravalvular leak. There was no left ventricular outflow tract obstruction. Pathological evaluation showed excellent position and condition of the mitral implants without evidence for thrombosis, endocarditis, or excessive calcification. Subsequently, mitral valves were implanted in 10 pigs using a dedicated transseptal delivery system. The implants remained in stable position with excellent hemodynamic profile. Correct valve position and function was confirmed by echocardiography and autopsy.

Conclusions:
The transseptal delivery of the Cephea transcatheter mitral valve replacement system in an experimental model was feasible and safe. The chronic studies demonstrated a favorable healing response. Further human studies are needed to evaluate the performance of this novel valve system in patients with severe mitral regurgitation.
Body Mass Index Drives Changes in DNA Methylation
Authors: Sun Dianjianyi , Zhang Tao , Su Shaoyong , Hao Guang , Chen Tao , Li Quan-Zhen , Bazzano Lydia , He Jiang , Wang Xiaoling , Li Shengxu , Chen Wei 
Published: September 2019

Rationale:
Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking.

Objective:
To identify 5′—cytosine—phosphate—guanine—3′ in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort.

Methods and Results:

Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (P
FDR
<0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (
P
<0.001 both in blacks and in whites).

Conclusions:
The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.
Association of Aortic Aneurysms and Dissections With Subarachnoid Hemorrhage
Authors: Al‐Kawaz Mais , Kamel Hooman , Murthy Santosh B. , Merkler Alexander E. 
Published: September 2019

Background

It is uncertain whether aortic diseases, such as aneurysm and dissection, are associated with intracranial aneurysm formation and aneurysmal subarachnoid hemorrhage (
SAH
).

Methods and Results

We used data on claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. Our exposure variable was hospitalization with an unruptured or ruptured aortic aneurysm or aortic dissection. The outcome was nontraumatic
SAH
. Variables were ascertained by
International Classification of Diseases, Ninth Revision, Clinical Modification
(

ICD
‐9‐
CM

), diagnosis codes. Survival statistics were used to calculate incidence rates. Cox proportional hazards analysis was used to examine the association between aortic aneurysm/dissection and
SAH
while adjusting for demographics, vascular risk factors, and Charlson comorbidities. Among 1 781 917 beneficiaries, 32 551 (1.8%) had a documented aortic aneurysm or dissection. During 4.6±2.2 years of follow‐up, 2538 patients (0.14%) developed a nontraumatic
SAH
. The incidence of
SAH
was 9 (95%
CI
, 7–11) per 10 000 patients per year in those with aortic aneurysm/dissection compared with 3 (95%
CI
, 3–3) per 10 000 patients per year in those without aortic aneurysm/dissection. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, patients with aortic aneurysm/dissection faced an increased risk of
SAH
(hazard ratio, 1.4; 95%
CI
, 1.02–1.9;
P
=0.04).

Conclusions

In a nationally representative sample of Medicare beneficiaries, aortic aneurysm/dissection was associated with an increased risk of nontraumatic
SAH
.
Outcomes of Surgery for Brainstem Cavernous Malformations
Authors: Kearns Kathryn N. , Chen Ching-Jen , Tvrdik Petr , Park Min S. , Kalani M. Yashar S. 
Published: September 2019

Background and Purpose—
The goal of this study was to systematically review the outcomes and complications after surgical resection of brain stem cavernous malformations (BCMs).

Methods—
A systematic literature review was performed using the PubMed database for studies published between 1986 and 2018. All studies comprising ≥2 patients with surgically resected BCMs and available follow-up data were included. Data extracted from studies included patient demographics, BCM location, and surgical outcomes.

Results—
Eighty-six studies comprising 2493 patients (adult and pediatric) were included for final analysis. Complete resection was achieved in 92.3% (fixed-effects pooled estimate [FE], 92.9% [91.7%–94.0%]; random-effects pooled estimate [RE], 89.4% [86.5%–92.0%]) of patients, and rehemorrhage of residual BCMs occurred in 58.6% (FE, 58.8% [49.7%–67.6%]; RE, 57.2% [43.5%–70.2%]). Postoperative morbidity occurred in 34.8% (FE, 30.9% [29.0%–32.8%]; RE, 31.1% [25.8%–36.6%]) of patients. Postoperative morbidities included motor deficit in 11.0% (FE, 9.9% [8.1%–11.7%]; RE, 11.1% [7.0%–16.0%]), sensory deficit in 6.7% (FE, 6.3% [4.8%–7.9%]; RE, 7.6% [4.5%–11.5%]), tracheostomy/gastrostomy in 6.0% (FE, 5.2% [4.3%–6.1%]; RE, 3.8% [2.6%–5.3%]), and other cranial nerve deficits in 29.4% (FE, 27.6% [25.3%–29.9%]; RE, 33.9% [25.7%–42.6%]) of patients. At final follow-up, 57.9% (FE, 57.6% [55.6%–59.6%]; RE, 57.2% [52.1%–62.3%]) and 25.9% (FE, 24.1% [22.4%–25.9%]; RE, 18.5% [14.6%–22.8%]) of patients had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.6% (FE, 1.9% [1.4%–2.5%]; RE, 1.8% [1.4%–2.5%]).

Conclusions—
High cure rates and low rates of postoperative morbidity can be achieved with surgery in patients with BCMs. Most patients had improved preoperative symptoms at final follow-up. To avoid rehemorrhage, complete resection should be the goal of surgery.
The Unity of LXX Genesis and Exodus
Authors: van der Louw Theo A. W. 
Published: September 2019

Abstract
Attempts to advocate multiple authorship for the Greek Pentateuch depend principally on statistics and are tenuous methodologically. Research methods from Translation Studies, applied to Genesis and Exodus, bring out their continuity. A sounding of the translational approach in Gen 2-3, Gen 27-28, Gen 48/50 and Exod 1-2 suggests that the Gen translator’s approach is shifting and flows seamlessly into that of the initial Exod chapters. Lexical and syntactic examples, too, illustrate that Exod continues or builds on or further develops the renderings found in the latter part of Gen. A natural explanation for this state of affairs is that the translator of Gen, whose approach had become increasingly idiomatic, completed Gen 50 and continued with Exod in the same vein. Our findings call for a verification of the multiple authorship hypothesis for the rest of the Pentateuch. They imply a less monolithic evaluation of LXX text-critical evidence.
Inter-religious Relations as a New Foundation for Comparative Religion
Authors: Reeh Niels 
Published: September 2019

Abstract
This article argues that the problems that comparative religion encountered in the 1980s and onward did not arise from the comparative project as such, but rather from the fact that comparative religion was founded on an analytical strategy that relied on defining religion. In order to overcome these problems and critique of Jonathan Z. Smith, Talal Asad and others, it is proposed that the comparative study of religion could be re-established on the basis of a different analytical strategy and more specifically on the basis of a relational perspective, in which the crucial point of departure is the finding that religions in many periods and cultural settings seem to constitute themselves in relation to at least one significant other religion. In periods and cultural settings, where religions relate to each other, we do in fact have a commonality between all religions, namely the inter-religious relation. This relation can ensure that we are not comparing things that have nothing in common. If the inter-religious relation is the point of departure, the comparative study of religion can be transformed in such a way that it is not overturned by the social constructionism or post-modernism of J. Z. Smith, Talal Asad and others.