bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training upregulates Nrf2 protein in the rostral ventrolateral medulla of mice with heart failure
Authors: Wafi Ahmed M. , Yu Li , Gao Lie , Zucker Irving H.
Published: September 2019

Chronic heart failure (CHF) is associated with global oxidative stress, which contributes to sympathoexcitation. Increased reactive oxygen species in the brain accumulate within neurons and lead to enhanced neuronal excitability. Exercise training (ExT) is associated with a reduction of oxidative stress by upregulation of antioxidant enzymes. The link between ExT and antioxidant enzyme expression in the brain of animals with CHF is not clear. We hypothesized that ExT enhances transcription and translation of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene, a master transcription factor that modulates antioxidant enzyme gene expression, in the rostral ventrolateral medulla (RVLM) of mice with CHF. Mice were divided into the following groups: Sham sedentary (Sham-Sed), Sham-ExT, CHF-Sed, and CHF-ExT. After 8 wk of ExT, we measured Nrf2 and NAD(P)H dehydrogenase [quinone] 1 (NQO-1) message and protein expression along with maximal exercise tolerance and urinary norepinephrine (NE) excretion. We found that Nrf2 and NQO-1 mRNA and protein expression in the RVLM were lower in CHF-Sed mice compared with Sham-Sed. ExT attenuated the CHF-induced reduction of Nrf2 and NQO-1 mRNA and protein expression in the RVLM. NE excretion was higher in CHF-Sed mice compared with Sham-Sed (666.8 ± 79.3 ng/24 h, n = 6 vs. 397.8 ± 43.7 ng/24 h, P = 0.04). CHF-ExT mice exhibited reduced urinary NE excretion compared with CHF-Sed (360.7 ± 41.7 ng, n = 4 vs. 666.8 ± 79.3 ng, n = 6; P = 0.03). We conclude that ExT-induced upregulation of Nrf2 in the RVLM contributes to the beneficial effects of ExT on sympathetic function in the heart failure state.

NEW & NOTEWORTHY This study provide evidence for an important role for exercise training in the modulation of antioxidant enzyme production in the rostral ventrolateral medulla (RVLM) in the heart failure state. We show here a correlation between exercise training and the expression of the antioxidant transcription factor Nrf2 in the RVLM. Exercise training reduced sympathetic function (norepinephrine excretion) and upregulated both Nrf2 and the antioxidant enzyme NQO-1. We conclude that Nrf2 in the RVLM may be an important target for controlling sympathetic outflow in heart failure.
Low-Cost Air Gap Metasurface Structure for High Absorption Efficiency Energy Harvesting
Authors: Hu Wei , Yang Zhao , Zhao Fading , Wen Guangjun , Li Jian , Huang Yongjun , Inserra Daniele , Chen Zhizhang (David)
Published: September 2019

This manuscript deals with the design of a metamaterial-based surface structure for high efficiency wireless power harvesting or collection. Differently from the previously presented structures which require the use of thicker and low-loss (and for this reason high cost) dielectric substrates, the presented work employs a dual-layer structure with a thin low-loss material and an air gap; they allow for the design of very high absorption efficiency metamaterial-based surfaces, with noticeably reduced costs. Furthermore, the air gap thickness can be used as a new degree-of-freedom (more easily adjustable than the thickness of a single-layer structure) for the optimization of other design requirements such as bandwidth or structure sizes. In comparison with other existing designs, the proposed metasurface shows a comparable absorption efficiency of 84.4% but with a larger power collection surface and lower costs.
Elastic-Plastic Behavior of Compacted Loess under Direct and Cyclic Tension
Authors: He Shixin , Bai Haibo
Published: September 2019

Tensile strain is one of the main variables that affect fracturing in soil. This paper focuses on an experimental investigation of the deformation characteristics of remolded loess in direct and cyclic tension tests. The material behavior was approximated as elastic-plastic by ignoring the effect of time. In direct tests, the results showed that the change in slope of the stress-strain curve depended on the water content. The plastic constitutive relation was described by two methods. In cyclic loading and unloading tests, the remolded loess exhibited hysteresis (a phase lag), which led to dissipation of the mechanical energy. And no compaction limit phenomenon was found. A simple mathematical model was proposed to predict the plastic cyclic characteristics, and it was validated by the new test data.
Factors Influencing the Efficacy of Anti-PD-1 Therapy in Chinese Patients with Advanced Melanoma
Authors: Zhao Lingdi , Yang Yonghao , Ma Baozhen , Li Wei , Li Tiepeng , Han Lu , Zhang Yong , Shang Yi-Man , Lin Hongwei , Gao Quanli
Published: September 2019

Purpose. Anti-PD-1 antibody improves the survival of patients with advanced melanoma. However, the efficacy and safety of anti-programmed death protein 1 (PD-1) antibody have not been fully elucidated in Chinese melanoma patients, who show high frequency of mucosal and acral melanoma subtypes; besides, the factors influencing the efficacy of anti-PD-1 antibody have not been evaluated broadly. Patients and Methods. Patients with advanced melanoma treated with regimens containing anti-PD-1 antibody from June 2016 to January 2019 were evaluated. Baseline characteristics and blood parameters were assessed, and outcome and adverse events were evaluated according to different regimens. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Results. A total of 51 patients with advanced melanoma were included in this study. The overall objective response rate (ORR) was 17.6%, the disease control rate was 58.5%, and the median time to progression was 5.2 months. The ORR of patients with PD-1 blockade-based combination therapy, without liver metastases and higher level of C-reactive protein (CRP) before PD-1 blockade, is higher than that of those not. Univariate analysis based on clinical features showed that ECOG scores, liver metastasis, elevated lactate dehydrogenase (LDH), and CRP levels were the factors affecting time to progression (TTP). Multivariate analysis showed that elevated CRP before PD-1 blockade was an independent predictive factor for ORR of PD-1 blockade therapy (P=0.009), while only Eastern Cooperative Oncology Group (ECOG) score was an independent predictor for TTP (P=0.032). The treatment was well tolerated in these cohort patients, and there was no treatment-related death. Conclusion. Anti-PD-1 antibody-containing regimen was safe and effective in Chinese patients with advanced melanoma, and elevated CRP and ECOG score were independent factors predicting the efficacy of anti-PD-1 therapy.
Hemoglobinopathies in the North of Morocco: Consanguinity Pilot Study
Authors: Laghmich Achraf , Alaoui Ismaili Fatima Zahra , Zian Zeineb , Barakat Amina , Ghailani Nourouti Naima , Bennani Mechita Mohcine
Published: September 2019

Consanguinity is a social behavior characterized by the arrangement of marriages between relatives. It coincides generally with the geographic distribution of recessive genetic diseases as it increases the likelihood of homozygosis and, consequently, the incidence of their pathologies in the population. In this pilot study, we assess the effect of inbreeding on the burden of hemoglobinopathies in Northern Morocco. From January 2016 to December 2018, 197 children born in the studied region to three ancestral generations and diagnosed with hemoglobinopathies were subject to investigation. The rate of consanguinity in the parents’ generation of children with hemoglobinopathies was 50.25%, with first cousin marriages accounting for 68.69% of consanguineous unions (FI = 0.02). The corresponding rates in the general population, based on a sample of N = 900, were 29.67% and 82.02%, respectively. The marriages between first cousins are the most common among the other types of consanguineous unions. Our study propounds that consanguinity substantially contributes to the hemoglobinopathy burden in the studied region and has changed little over time. Refraining from consanguineous marriages and detecting couples at risk could contribute to the reduction of the incidence of genetic diseases in our country.
Privacy Protection of Social Networks Based on Classified Attribute Encryption
Authors: Zhang Lin , Li Li , Medwedeff Eric , Huang Haiping , Fu Xiong , Wang Ruchuan
Published: September 2019

With the rapid development of social networks, privacy has also attracted attention. Based on this problem, a privacy protection scheme for social networks based on classified attribute encryption (PPSSN) is proposed for the data owner and attribute management server to manage user permissions; the approach reduces data owner overhead and also avoids use of a property management server to limit access user collusion attacks. To balance the privacy and security of data publication, this scheme classifies users and designs access control for different users and different privileges. In addition, this paper also introduces a good friend data cache mechanism to improve and optimize the original scheme to reduce the cost of decryption. The efficiency and system overhead of the proposed scheme are compared and analyzed based on experiments. The experiments show that the proposed scheme improves query efficiency, reduces system cost, and enhances privacy security.
A ceRNA Circuitry Involving the Long Noncoding RNA Klhl14-AS, Pax8, and Bcl2 Drives Thyroid Carcinogenesis
Authors: Credendino Sara C. , Bellone Maria L. , Lewin Nicole , Amendola Elena , Sanges Remo , Basu Swaraj , Sepe Romina , Decaussin-Petrucci Myriam , Tinto Nadia , Fusco Alfredo , De Felice Mario , De Vita Gabriella
Published: September 2019

Klhl14-AS is a long noncoding RNA expressed since early specification of thyroid bud and is the most enriched gene in the mouse thyroid primordium at E10.5. Here, we studied its involvement in thyroid carcinogenesis by analyzing its expression in cancer tissues and different models of neoplastic transformation. Compared with normal thyroid tissue and cells, Klhl14-AS was significantly downregulated in human thyroid carcinoma tissue specimens, particularly the anaplastic histotype, thyroid cancer cell lines, and rodent models of thyroid cancer. Downregulating the expression of Klhl14-AS in normal thyroid cells decreased the expression of thyroid differentiation markers and cell death and increased cell viability. These effects were mediated by the binding of Klhl14-AS to two miRNAs, Mir182-5p and Mir20a-5p, which silenced Pax8 and Bcl2, both essential players of thyroid differentiation. MIR182-5p and MIR20a-5p were upregulated in human thyroid cancer and thyroid cancer experimental models and their effects on Pax8 and Bcl2 were rescued by Klhl14-AS overexpression, confirming Klhl14-AS as a ceRNA for both Pax8 and Bcl2. This work connects deregulation of differentiation with increased proliferation and survival in thyroid neoplastic cells and highlights a novel ceRNA circuitry involving key regulators of thyroid physiology.

Significance:

This study describes a new ceRNA with potential tumor suppression activity and helps us better understand the regulatory mechanisms during thyroid differentiation and carcinogenesis.
Analysis of Biomarkers and Association With Clinical Outcomes in Patients With Differentiated Thyroid Cancer: Subanalysis of the Sorafenib Phase III DECISION Trial
Authors: Brose Marcia S. , Schlumbeger Martin , Jeffers Michael , Kappeler Christian , Meinhardt Gerold , Peña Carol E.A.
Published: September 2019

Purpose:

The phase III DECISION trial (NCT00984282; EudraCT:2009-012007-25) established sorafenib efficacy in locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) refractory to radioactive iodine. We conducted a retrospective, exploratory biomarker analysis of patients from DECISION.

Experimental Design:

Candidate biomarkers [15 baseline plasma proteins, baseline and during-treatment serum thyroglobulin, and relevant tumor mutations (BRAF, NRAS, HRAS, and KRAS)] were analyzed for correlation with clinical outcomes.

Results:

Plasma biomarker and thyroglobulin data were available for 395 of 417 (94.7%) and 403 of 417 (96.6%) patients, respectively. Elevated baseline VEGFA was independently associated with poor prognosis for progression-free survival [PFS; HR = 1.82; 95% confidence interval (CI), 1.38–2.44; P = 0.0007], overall survival (HR = 2.13; 95% CI, 1.37–3.36; P = 0.013), and disease-control rate (DCR; OR = 0.30; P = 0.009). Elevated baseline thyroglobulin was independently associated with poor PFS (HR = 2.03; 95% CI, 1.52–2.71; P < 0.0001) and DCR (OR = 0.32; P = 0.01). Combined VEGFA/thyroglobulin signatures correlated with poor PFS (HR = 2.12; 95% CI, 1.57–2.87; P < 0.00001). Thyroglobulin decrease ≥30% from baseline was achieved by 76% and 14% of patients receiving sorafenib and placebo, respectively (P < 0.001). Patients with ≥30% thyroglobulin reduction had longer PFS than those without ≥30% reduction [HR (95% CI): sorafenib = 0.61 (0.40–0.94), P = 0.022; placebo = 0.49 (0.29–0.85), P = 0.009]. BRAF mutations were associated with better PFS; RAS mutations were associated with worse PFS, although neither was independently prognostic in multivariate models. No examined biomarker predicted sorafenib benefit.

Conclusions:

We identified biomarkers associated with poor prognosis in DTC, including elevated baseline VEGFA and thyroglobulin and the presence of RAS mutations. Serum thyroglobulin may be a biomarker of tumor response and progression.
A First-in-Human Phase I Study of INVAC-1, an Optimized Human Telomerase DNA Vaccine in Patients with Advanced Solid Tumors
Authors: Teixeira Luis , Medioni Jacques , Garibal Julie , Adotevi Olivier , Doucet Ludovic , Durey Marie-Agnès Dragon , Ghrieb Zineb , Kiladjian Jean-Jacques , Brizard Mara , Laheurte Caroline , Wehbe Maria , Pliquet Elodie , Escande Marie , Defrance Rémy , Culine Stephane , Oudard Stephane , Wain-Hobson Simon , Doppler Valérie , Huet Thierry , Langlade-Demoyen Pierre
Published: September 2019

Purpose:

Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors.

Patients and Methods:

INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan–Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry.

Results:

Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed.

Conclusions:

INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond.

See related commentary by Slingluff Jr, p. 529
The first photographic record of the Red Panda Ailurus fulgens (Cuvier, 1825) from Lamjung District outside Annapurna Conservation Area, Nepal
Authors: Ghimire Ganesh , Pearch Malcolm , Baral Badri , Thapa Bishnu , Baral Rishi
Published: September 2019

In May and June, 2018, a series of field surveys was undertaken to determine the presence of the Red Panda Ailurus fulgens in Marsyangdi Rural Municipality in Lamjung District, western Nepal.  A single, adult, Red Panda was photographed and recorded on video at Nafada Khola while scratch marks and distinctive scats provided evidence of Red Panda activity at eleven further localities at elevations between 3,150 and 3,650 m.  Threats to the habitat of A. fulgens within the study area are discussed.
Ornithophony in the soundscape of Anaikatty Hills, Coimbatore, Tamil Nadu, India
Authors: Divyapriya Chandrasekaran , Pramod Padmanabhan
Published: September 2019

An attempt has been made to understand the extent of ornithophony (vocalization of birds) in the soundscape of Anaikatty Hills.  The study was limited to 13 hours of daylight from dawn to dusk (06.00–19.00 h) between January 2015 and October 2016.  Six replicates of 5-minute bird call recordings were collected from each hour window in 24 recording spots of the study area.  Each 5-minute recording was divided into 150 ‘2-sec’ observation units for the detailed analysis of the soundscape. A total of 78 recordings amounting to 390 minutes of acoustic data allowed a preliminary analysis of the ornithophony of the area.  A total of 62 bird species were heard vocalizing during the study period and contributed 8,629 units.  A total of 73.75% acoustic space was occupied by birds, among which the eight dominant species alone contributed to 63.65% of ornithophony.  The remaining 26% of acoustic space was occupied by other biophonies (12.60%), geophony (5.57%), indistinct sounds (7.66%), and anthropogenic noise (0.41%).  Passerines dominated the vocalizations with 7,269 (84.24%) and non-passerines with 1,360 (15.76%) units.  Birds vocalized in all 13 observation windows, with a peak in the first three hours of the day (06.00–09.00 h).  Vocalizations of non-passerines were prominent in the dusk hours (18.00–19.00 h).
Ethnobotanical survey of indigenous leafy vegetables consumed in rural areas of Terai-Dooars region of West Bengal, India
Authors: Mazumder Mallika , Sarkar Anup Kumar
Published: September 2019

There is always a need for novel, high quality, functional and inexpensive foods among consumers in the global markets.  Leafy vegetables can fulfill such needs.  Leafy vegetables are now used worldwide as food for their nutritional and medicinal values.   In the present work an ethnobotanical survey was carried out on the utilization of edible plants by local communities of the Terai-Dooars Region of West Bengal.  The information has been documented by interviewing traditional farmers, herbalists, various older men and women following different ethnobotanical methods.  A total of 103 plant species under 44 families with their short botanical description, use, range of demands and cultivation status have been documented.
Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile
Authors: Hoogendoorn Ayla , den Hoedt Sandra , Hartman Eline M.J. , Krabbendam-Peters Ilona , te Lintel Hekkert Maaike , van der Zee Leonie , van Gaalen Kim , Witberg Karen Th. , Dorst Kristien , Ligthart Jurgen M.R. , Drouet Ludovic , Van der Heiden Kim , van Lennep Jeanine Roeters , van der Steen Antonius F.W. , Duncker Dirk J. , Mulder Monique T. , Wentzel Jolanda J.
Published: September 2019

Objective:

In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined.

Approach and Results:

FH pigs (3 years old, homozygous
LDLR
R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%–34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%–77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3–1.9] versus 0.8 [0.6–0.9];
P
=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios.

Conclusions:

In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.
ADAMTS8 Promotes the Development of Pulmonary Arterial Hypertension and Right Ventricular Failure
Authors: Omura Junichi , Satoh Kimio , Kikuchi Nobuhiro , Satoh Taijyu , Kurosawa Ryo , Nogi Masamichi , Ohtsuki Tomohiro , Al-Mamun Md Elias , Siddique Mohammad Abdul Hai , Yaoita Nobuhiro , Sunamura Shinichiro , Miyata Satoshi , Hoshikawa Yasushi , Okada Yoshinori , Shimokawa Hiroaki
Published: September 2019

Rationale:

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with aberrant pulmonary artery smooth muscle cells (PASMCs) proliferation, endothelial dysfunction, and extracellular matrix remodeling.

Objective:

Right ventricular (RV) failure is an important prognostic factor in PAH. Thus, we need to elucidate a novel therapeutic target in both PAH and RV failure.

Methods and Results:

We performed microarray analysis in PASMCs from patients with PAH (PAH-PASMCs) and controls. We found a ADAMTS8 (disintegrin and metalloproteinase with thrombospondin motifs 8), a secreted protein specifically expressed in the lung and the heart, was upregulated in PAH-PASMCs and the lung in hypoxia-induced pulmonary hypertension (PH) in mice. To elucidate the role of ADAMTS8 in PH, we used vascular smooth muscle cell-specific ADAMTS8-knockout mice (ADAMTS
ΔSM22
). Hypoxia-induced PH was attenuated in ADAMTS
ΔSM22
mice compared with controls. ADAMTS8 overexpression increased PASMC proliferation with downregulation of AMPK (AMP-activated protein kinase). In contrast, deletion of ADAMTS8 reduced PASMC proliferation with AMPK upregulation. Moreover, deletion of ADAMTS8 reduced mitochondrial fragmentation under hypoxia in vivo and in vitro. Indeed, PASMCs harvested from ADAMTS
ΔSM22
mice demonstrated that phosphorylated DRP-1 (dynamin-related protein 1) at Ser637 was significantly upregulated with higher expression of profusion genes (Mfn1 and Mfn2) and improved mitochondrial function. Moreover, recombinant ADAMTS8 induced endothelial dysfunction and matrix metalloproteinase activation in an autocrine/paracrine manner. Next, to elucidate the role of ADAMTS8 in RV function, we developed a cardiomyocyte-specific ADAMTS8 knockout mice (ADAMTS8
ΔαMHC
). ADAMTS8
ΔαMHC
mice showed ameliorated RV failure in response to chronic hypoxia. In addition, ADAMTS8
ΔαMHC
mice showed enhanced angiogenesis and reduced RV ischemia and fibrosis. Finally, high-throughput screening revealed that mebendazole, which is used for treatment of parasite infections, reduced ADAMTS8 expression and cell proliferation in PAH-PASMCs and ameliorated PH and RV failure in PH rodent models.

Conclusions:

These results indicate that ADAMTS8 is a novel therapeutic target in PAH.
Genome-Wide Analysis of Left Ventricular Image-Derived Phenotypes Identifies Fourteen Loci Associated With Cardiac Morphogenesis and Heart Failure Development
Authors: Aung Nay , Vargas Jose D. , Yang Chaojie , Cabrera Claudia P. , Warren Helen R. , Fung Kenneth , Tzanis Evan , Barnes Michael R. , Rotter Jerome I. , Taylor Kent D. , Manichaikul Ani W. , Lima Joao A.C. , Bluemke David A. , Piechnik Stefan K. , Neubauer Stefan , Munroe Patricia B. , Petersen Steffen E.
Published: September 2019

Background:

The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear at present.

Methods:

The LV parameters were measured from the cardiovascular magnetic resonance studies of the UK Biobank. Genotyping was done using Affymetrix arrays, augmented by imputation. We performed genome-wide association studies of 6 LV traits—LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction, LV mass, and LV mass to end-diastolic volume ratio. The replication analysis was performed in the MESA study (Multi-Ethnic Study of Atherosclerosis). We identified the candidate genes at genome-wide significant loci based on the evidence from extensive bioinformatic analyses. Polygenic risk scores were constructed from the summary statistics of LV genome-wide association studies to predict the heart failure events.

Results:

The study comprised 16 923 European UK Biobank participants (mean age 62.5 years; 45.8% men) without prevalent myocardial infarction or heart failure. We discovered 14 genome-wide significant loci (3 loci each for LV end-diastolic volume, LV end-systolic volume, and LV mass to end-diastolic volume ratio; 4 loci for LV ejection fraction, and 1 locus for LV mass) at a stringent
P
<1×10
−8
. Three loci were replicated at Bonferroni significance and 7 loci at nominal significance (
P
<0.05 with concordant direction of effect) in the MESA study (n=4383). Follow-up bioinformatic analyses identified 28 candidate genes that were enriched in the cardiac developmental pathways and regulation of the LV contractile mechanism. Eight genes (
TTN, BAG3, GRK5, HSPB7, MTSS1, ALPK3, NMB
, and
MMP11
) supported by at least 2 independent lines of in silico evidence were implicated in the cardiac morphogenesis and heart failure development. The polygenic risk scores of LV phenotypes were predictive of heart failure in a holdout UK Biobank sample of 3106 cases and 224 134 controls (odds ratio 1.41, 95% CI 1.26 – 1.58, for the top quintile versus the bottom quintile of the LV end-systolic volume risk score).

Conclusions:

We report 14 genetic loci and indicate several candidate genes that not only enhance our understanding of the genetic architecture of prognostically important LV phenotypes but also shed light on potential novel therapeutic targets for LV remodeling.
Occurrence Rate of Delirium in Acute Stroke Settings
Authors: Shaw Robert C. , Walker Graham , Elliott Emma , Quinn Terence J.
Published: September 2019

Background and Purpose—

Delirium is associated with increased mortality, length of stay, and poor functional outcome following critical illness. The epidemiology of delirium in stroke is poorly described. We sought to collate evidence around occurrence (incidence or prevalence) of delirium in acute stroke.

Methods—

We searched multiple cross-disciplinary electronic databases using a prespecified search strategy, complemented by hand searching. Eligible studies described delirium in acute (first 6 weeks) stroke. We compared delirium occurrence using random-effects models to describe summary estimates. We assessed risk of bias using the Newcastle-Ottawa tool, incorporating this in sensitivity analyses. We performed subgroup analyses for delirium diagnostic method (confusion assessment method scoring, clinical diagnosis, other), duration and timing of delirium assessment (>1 or <1 week), and performed meta-regression based on the year of publication.

Results—

Of 8822 titles, we included 32 papers (6718 participants) in the quantitative analysis. Summary estimate for occurrence of delirium was 25% (95% CI, 20%–30%; moderate quality evidence). Limiting to studies at low risk of bias (22 studies, 4422 participants), the occurrence rate was 23% (95% CI, 17%–28%). Subgroup summary estimates suggest that delirium occurrence may vary with assessment method: confusion assessment method, 21% (95% CI, 16%–27%); clinical diagnosis, 27% (95% CI, 19%–38%); other, 32% (95% CI, 22%–43%) but not with duration and timing of assessment. Meta-regression suggested decline in occurrence of delirium comparing historical to more recent studies (slope, 0.03 [SE, 0.004];
P
<0.0001).

Conclusions—

Delirium is common, affecting 1 in 4 acute stroke patients. Reported rates of delirium may be dependent on assessment method. Our estimate of delirium occurrence could be used for audit, to plan intervention studies, and inform clinical practice.

Clinical Trial Registration—

URL:
http://www.crd.york.ac.uk/PROSPERO/
. Unique identifier: CRD42015029251.
Setting the Table Anew: Law and Spirit in a Nineteenth-Century Hasidic Code
Authors: Mayse Ariel Evan
Published: September 2019

This essay interrogates the legal discourse of Shulḥan ha-Tahor, a curious—and curiously understudied—work of Hasidic halakhah written by Rabbi Yitzḥak Ayzik Yehudah Yehiel Safrin of Komarno. The book is, at heart, a systematic reformulation of Jewish law in light of Kabbalah, Hasidism, and the quest for personal mystical experience. Shulḥan ha-Tahor offers a rare case study for the interface of mystical experience, Hasidic devotional values, and kabbalistic doctrine as they explicitly shape the codified forms—and norms—of halakhah. The essay reveals a different side of Jewish modernity through a close reading of an exceptional nineteenth-century legal code.
The efficacy of molecular markers associated with virulence in root-knot nematodes
Authors: Mistanoğlu İbrahim , Özalp Tevfik , Devran Zübeyir
Published: September 2019

Root-knot nematodes (Meloidogyne spp.) are major crop pests that cause heavy economic losses. The use of resistant cultivars is one of the most important management methods. The Mi-1 gene in tomato confers effective resistance against several species of Meloidogyne. However, Mi-1-virulent root-knot nematodes restrict the use of resistant cultivars. Molecular markers associated with virulence have been developed in previous studies but not validated in large number of Meloidogyne populations so far. In this study, molecular markers were screened in a total of 69 (a)virulent Meloidogyne incognita and M. javanica isolates. The results showed these markers did not separate virulent and avirulent populations from Turkey. In addition, polymerase chain reaction products obtained from primers HM1.F2/HM1.R2 were digested with 30 restriction enzymes but no differences among populations were found. To the best of our knowledge, this is the first report on screening large root-knot nematode populations with these markers.
The Dangers of the Obvious but Often Disregarded Details in the International Criminal Law Demarcation Debate: Norm-Integration and the Triple-Thesis ‘Argument’
Authors: Matwijkiw Anja
Published: September 2019

When responses to international crimes are managed in terms of post-conflict justice, this event may end ‘the demarcation debate’ before it has begun, thereby rendering it superfluous among legal scholars. This is to say that the transition from theory to reality arguably has the effect of cancelling any sharp distinction between international criminal law, international human rights law and international humanitarian law, as well as extending international criminal justice into the moral territory. Certainly, this is a premise for the dual-aspect defense of those rights that help to explain the non-separation. However, to the extent that the defense discords with traditional assumptions, relevant aspects of pro-separation reasoning must be considered. These are accommodated under the triple-thesis whereby the unequal status of different (rights-)categories limit norm-integration. The author’s account of the competing programs shows a series of flaws in the case of the triple-thesis doctrine, amounting to a vicious circle ‘argument’.
A new sponge species of the genus Antho (Demospongiae, Microcionidae) from the Tyrrhenian deep Sea
Authors: COSTA GABRIELE , PANSINI MAURIZIO , BERTOLINO MARCO
Published: September 2019

The use of ROVs has greatly enhanced the possibility of obtaining information on living deep sponge communities (Bertolino et al. 2015). The aim of this work is to describe a new Mediterranean species, Antho (Plocamia) sarasiri sp. nov. (Microcionidae Carter, 1875), characterized by dumbbell spicules making up the framework of the choanosomal skeleton (Van Soest et al. 2013). Samples were collected by ROV during an oceanographic survey in September 2012 on board of the R/V ‘Astrea’ (ISPRA) in “Secca P.ta Fetovaia” (42°43’29.54”N 10° 9’31.64”E) (Elba Island, Tyrrhenian Sea) at 70 m depth. We compared our sample with additional material collected by Sarà & Siribelli (1960, 1962).
Phylogenetic differentiation and taxonomic consequences in the Saurodactylus brosseti species complex (Squamata: Sphaerodactylidae), with description of four new species
Authors: JAVANMARDI SOHEILA , VOGLER SVEN , JOGER ULRICH
Published: September 2019

We divide Saurodactylus brosseti into five species, based on molecular and morphological characteristics. Phylogenetic analysis of two mitochondrial markers (ND4 and 12S rRNA) reveals five separately evolving lineages (clades) in the S. brosseti species complex. Each can be assigned to a particular geographical range within the distribution area in Morocco: North, South, Anti-Atlas, East and Southeast. A dichotomous key for all species within the genus Saurodactylus is presented. Despite the high level of color pattern variation among and within the northern, southern, Anti-Atlas and eastern clades, the southeastern lineage shows a unique coloration which is not found in other clades. The ecological traits of the southeastern clade seem to differ from those of the other four lineages since it is basically associated with Acacia species. Like the relictual ecosystem characterized by these trees, it appears to be highly threatened by extinction.
A new species of Capnia (Plecoptera: Capniidae) from Lesser Khingan Range (Amur River Basin, Far East of Russia)
Authors: TESLENKO VALENTINA A.
Published: September 2019

Capnia khingana sp. n. (Plecoptera: Capniidae) is described as a new brachypterous species from the Lesser Khingan Range south of the Far East of Russia. Detailed descriptions and illustrations are provided for both sexes. According to the diagnostic characters of the male epiproct, C. khingana sp. n. may be tentatively assigned to the C. atra species group.
A new species of the genus Achalinus from southwestern Guangdong Province, China (Squamata: Xenodermatidae)
Authors: WANG JIAN , LI YAO , ZENG ZHAO-CHI , LYU ZHI-TONG , SUNG YIK-HEI , LI YOU-YU , LIN CHAO-YU , WANG YING-YONG
Published: September 2019

A new species of xenodermatid snake, Achalinus yunkaiensis J. Wang, Y. Li & Y.Y. Wang, sp. nov. was described based on a series of specimens collected from Dawuling Forestry Station located in the Yunkai Mountains of western Guangdong Province. It can be distinguished from known congeners by a significant genetic divergence at the mitochondrial CO1 gene fragment examined (p-distance ≥ 12.0%) and the following combination of characters: (1) dorsal scales strongly keeled, in 23 rows throughout the body, the most outer row on each side smooth and significantly enlarged; (2) tail relatively shorter, TaL/TL ratio 18.5–20.0%; (3) maxillary teeth 20–22; (4) length of suture between internasals subequal to that between the prefrontals; (5) nasal divided into two sections by nasal cleft, posterior one half as long as anterior; (6) loreal elongated, nearly twice as wide as high; (7) supralabials six; (8) infralabials six; (9) temporals 2+2+3 (rarely 2+2+4), the two anterior temporals in contact with eye; (10) ventrals 151–162, subcaudals 49–56 arranged in single row, not paired; (11) cloacal entire; (12) uniform brown (in adults) or black (in juveniles) above, tinged weakly iridescent, with a longitudinal dark-colored vertebral line; (13) light brown (in adults) or greyish white (in juveniles) beneath; and (14) dorsum with a longitudinal dark brown vertebral stripe from posterior margin of parietals to tail tip. Currently, 13 species are known in the genus Achalinus, with seven from mainland China.
Topographic Effects on the Luzon Diurnal Cycle during the BSISO
Authors: Riley Dellaripa Emily M. , Maloney Eric D. , Toms Benjamin A. , Saleeby Stephen M. , van den Heever Susan C.
Published: September 2019

Cloud-resolving simulations are used to evaluate the importance of topography to the diurnal cycle (DC) of precipitation (DCP) over Luzon, Philippines, and surrounding ocean during the July–August 2016 boreal summer intraseasonal oscillation (BSISO) event. Composites of surface precipitation for each 30-min time increment during the day are made to determine the mean DCP. The mean DCP is computed separately for suppressed and active BSISO conditions and compared across three simulations with varying topography—flat, true, and doubled topographic height. The magnitude of the topographic height helps to dictate the timing, intensity, and location of diurnal precipitation over and near Luzon. For example, the mean DCP in the true topography run peaks 1.5 h later, is broader by 1 h, and has a 9% larger amplitude during active conditions relative to suppressed conditions. By contrast, the flat run mean DCP is earlier and narrower by 0.5 h with a 5% smaller amplitude during active conditions versus suppressed conditions. Within the suppressed or active BSISO conditions, the mean DCP peak and amplitude increase as the topographic height increases. The presence of elevated topography focuses precipitation over the coastal mountains during suppressed conditions, while dictating which side of the domain (i.e., east Luzon and the Philippine Sea vs west Luzon and the South China Sea) more precipitation occurs in during active conditions. These topographic-induced changes are discussed in terms of mechanical and thermodynamic forcing differences between the two large-scale BSISO regimes for the three runs.
Warming and cooling device using thermoelectric Peltier elements tested on male mice
Authors: Madrahimov Nodir , Natanov Ruslan , Khalikov Abdurasul , Boyle Erin C , Jonigk Danny , Knoefel Ann-Katrin , Siemeni Thierry , Haverich Axel
Published: September 2019

Hypothermia is a treatment strategy for different clinical conditions and an essential part of cardiopulmonary bypass in complex cardiac procedures. Clinically, cooling patients is achieved via a mattress and heat exchanger integrated into a membrane oxygenator connected to a waterbed using a refrigerator system based on volatile and toxic liquids. Peltier elements are known as environmentally friendly thermoelectric generators that enable rapid warming and cooling. In this paper, we describe the construction of a novel device for rapid and precise control of mouse warming and cooling using thermoelectric Peltier elements. Six male BALB/c mice were subjected to deep hypothermia and were rewarmed under full physiological monitoring. After rewarming, all animals were observed for two hours, and pathology was evaluated in several organs. All animals tolerated the rapid cooling process well and remained active after rewarming. Temperature-relevant changes were seen via electrocardiography, with heart-rate patterns showing a strong linear correlation to body temperature. No myocardial ischaemia was seen. However, two animals experienced bradycardic atrial fibrillation which spontaneously converted to normal sinus rhythm during rewarming. No histological damage was seen in the heart, liver, kidney or lungs. Our device can effectively be used for heat shock and hypothermia studies in mice, and we foresee no obstacles for its application to other small rodents such as hamsters and young rats. In comparison to known experimental and clinical methods of hypothermia, our device is environmentally friendly, cost-effective and easy to handle, allowing precise control and maintenance of body temperatures ranging from 18℃ to 42℃.
Fuzzy-approximation-based prescribed performance control of air-breathing hypersonic vehicles with input constraints
Authors: Li Xingge , Li Gang , Zhao Yan , Kang Xuchao
Published: September 2019

In this article, aiming at the longitudinal dynamics model of air-breathing hypersonic vehicles, a fuzzy-approximation-based prescribed performance control scheme with input constraints is proposed. First, this article presents a novel prescribed performance function, which does not depend on the sign of initial tracking error. And combining prescribed performance control method with backstepping control, the control scheme can ensure that system can converge at a prescribed rate of convergence, overshoot, and steady-state error. In order to solve the problem that backstepping control method needs to be differentiated multiple times, fuzzy approximators are used to estimate the unknown functions, and norm estimation approach is used to simplify the computation of fuzzy approximator. Aiming at the problem of input saturation of actuator in subsystem of air-breathing hypersonic vehicle, the new auxiliary system is designed to ensure the stability and robustness of air-breathing hypersonic vehicle system under input constraints. Finally, the effectiveness of the proposed control strategy is verified by simulation analysis.
Neither precarious nor entrepreneur: The subjective experience of hybrid self-employed workers
Authors: Murgia Annalisa , Pulignano Valeria
Published: September 2019

This article focuses on the ‘hybridity’ of solo self-employment by shedding light on the lived experiences and meanings of the subjects within their institutional and socio-economic contexts. It offers an original perspective to the study of the hybridization of work by linking the subjective and objective conditions underpinning solo self-employed workers. The study found that solo self-employed workers exercise agency over their working lives while facing high levels of insecurity, and that their contextualized experiences are related to the dominant narratives about self-employment. At the same time, however, findings also show that solo self-employed are engaged in (re)-constructing their alternative and dissonant narratives as well.
Neuroprotective Effect of Huperzine A on d-Galactose-Induced Hearing Dysfunction
Authors: Li Cong , Shi Song
Published: September 2019

Background:

Administration of d-galactose (d-gal) has been used to create animal models of neurodegenerative diseases, and huperzine A has been used to treat the neurodegenerative diseases such as Alzheimer disease.

Methods:

An animal model of hearing dysfunction was established by administration of d-gal in the rats, and the effect of huperzine A on d-gal-induced abnormal hearing function and cochlear damage was investigated. Senescence of the cochlear tissues was examined by β-galactase staining, and messenger RNA expression of inflammatory cytokines was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR).

Results:

It was found that d-gal significantly increased auditory brainstem response (ABR) threshold and cellular senescence and decreased neurofilament in the cochlear tissues. Huperzine A could significantly attenuate d-gal-induced increase of ABR threshold and cellular senescence as well as reduction of neurofilament. Moreover, huperzine A could inhibit d-gal-induced activation of nuclear factor kappa-B (NF-κB) in Schwann cells and significantly blocked d-gal-stimulated gene expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α.

Conclusion:

These findings suggested that d-gal causes hearing dysfunction by inflammatory injury of cochlear neurons and that huperzine A could prevent hearing loss by protecting d-gal-induced physical damage of cochlear tissues.
Teacher and Video Modeling: A Survey of Use and Perspectives
Authors: Wynkoop Kaylee S. , Cardon Teresa A. , Kruis Nathan E. , Hawkins Paul M.
Published: September 2019

The current study investigated special education teacher use of and perspectives on video modeling (VM) interventions to improve skills of students with disabilities using survey methodology. To date, no studies were found that explicitly examine teachers’ use of and perspectives on VM. The primary purpose of this study was to estimate the number of teachers using VM and to begin to identify where, with whom, and with what types of skills have been targeted via VM. Further, we identified possible barriers that hinder or prevent teachers from implementing VM. Results showed that only 26.1% of participants reported using VM with a student and the most commonly reported barriers included lack of training, access to necessary resources, and time to create videos. Findings may be used to guide future research on ways to make VM implementation easier and more manageable for teachers.
Frequency and severity of hypersensitivity reactions in patients after VenaSeal™ cyanoacrylate treatment of superficial venous insufficiency
Authors: Gibson Kathleen , Minjarez Renee , Rinehardt Elena , Ferris Brian
Published: September 2019

Objective

Hypersensitivity reaction presenting as a distinctive erythematous rash has been reported following VenaSeal™ cyanoacrylate adhesive closure. We report the frequency of hypersensitivity reactions, time to onset, duration, and severity of symptoms in patients treated with cyanoacrylate adhesive closure at a single institution. Patient and procedural factors associated with hypersensitivity reactions were evaluated.

Methods

A combined retrospective/prospective review of cyanoacrylate adhesive closure-treated patients was conducted over five years. Data collected from electronic medical records were reviewed for the presence of hypersensitivity reactions along with the time of onset, duration of symptoms, and severity of reaction. Severity was classified as mild if no treatment or over the counter medication was provided, moderate if steroids were required, and severe if the reaction lasted >30 days or required vein excision.

Results

Three hundred and seventy-nine limbs were treated in 286 patients (313 treatment days). Hypersensitivity reactions occurred in 18 patients (5.8% treatments, 6.3% patients). Thirteen were mild (4.2%), four were moderate (1.3%), and one was severe (0.3%). No patient or procedural predictive factors for hypersensitivity reaction were identified other than a trend towards decreased hypersensitivity reactions in patients with Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) clinical class C4–C6 (p = .06). Second limb treatment on a subsequent day was performed in 27 patients, and no hypersensitivity reactions occurred. Symptom onset time ranged from 1 to 23 days, with a mean of 13 days (confidence interval (CI) ±3.5 days). Duration of symptoms ranged from 3 to 28 days (mean 10.8 CI ±4.9 days).

Conclusions

Hypersensitivity reactions occurred in 6.0% of patients treated with cyanoacrylate adhesive closure, but most were mild and self-limited. Severe reactions were uncommon. No predictive patient or procedural factors were found to be associated with hypersensitivity reactions other than a trend towards decreased risk in patients with advanced CEAP clinical class. Previous cyanoacrylate adhesive closure treatment was not a predictive factor for hypersensitivity reaction in patients undergoing treatment at a later date.