bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrically tunable single- and few-layer MoS
2
nanoelectromechanical systems with broad dynamic range
Authors: Lee Jaesung , Wang Zenghui , He Keliang , Yang Rui , Shan Jie , Feng Philip X.-L.
Published: April 2018

Atomically thin semiconductor resonators vibrating at radio frequencies with exceptional tunability and broad dynamic range.
Poro-elasto-capillary wicking of cellulose sponges
Authors: Ha Jonghyun , Kim Jungchul , Jung Yeonsu , Yun Giseok , Kim Do-Nyun , Kim Ho-Young
Published: April 2018

Capillary rise of water in porous cellulose sponges is investigated considering hygroscopic shape evolutions of micropores.
Room temperature solid-state quantum emitters in the telecom range
Authors: Zhou Yu , Wang Ziyu , Rasmita Abdullah , Kim Sejeong , Berhane Amanuel , Bodrog Zoltán , Adamo Giorgio , Gali Adam , Aharonovich Igor , Gao Wei-bo
Published: April 2018

An optically stable, room temperature single-photon emitter operating in telecom wavelength range is discovered in GaN.
Highly efficient electrochemical reforming of CH
4
/CO
2
in a solid oxide electrolyser
Authors: Lu Jinhai , Zhu Changli , Pan Changchang , Lin Wenlie , Lemmon John P. , Chen Fanglin , Li Chunsen , Xie Kui
Published: April 2018

Electrochemical reforming of CH
4
/CO
2
is demonstrated in a solid oxide electrolyser.
Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors
Authors: Morrison Sandra G. , Giebel Amanda M. , Toh Evelyn C. , Spencer Horace J. , Nelson David E. , Morrison Richard P.
Published: April 2018

Some members of the genus
Chlamydia
, including the human pathogen
Chlamydia trachomatis
, infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the
Chlamydia muridarum
plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to
C. muridarum
GI tropism. Infectivity and shedding of wild-type (WT)
C. muridarum
and three mutants containing nonsense mutations in different cytotoxin genes,
tc0437
,
tc0438
, and
tc0439
, were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in
tc0439
, was highly attenuated for GI infection and had a GI 50% infectious dose (ID
50
) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the
tc0439
mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in
tc0600
. The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.
Hepatitis B Virus Core Protein Dephosphorylation Occurs during Pregenomic RNA Encapsidation
Authors: Zhao Qiong , Hu Zhanying , Cheng Junjun , Wu Shuo , Luo Yue , Chang Jinhong , Hu Jianming , Guo Ju-Tao
Published: April 2018

Hepatitis B virus (HBV) core protein consists of an N-terminal assembly domain and a C-terminal domain (CTD) with seven conserved serines or threonines that are dynamically phosphorylated/dephosphorylated during the viral replication cycle. Sulfamoylbenzamide derivatives are small molecular core protein allosteric modulators (CpAMs) that bind to the heteroaryldihydropyrimidine (HAP) pocket between the core protein dimer-dimer interfaces. CpAM binding alters the kinetics and pathway of capsid assembly and can result in the formation of morphologically “normal” capsids devoid of viral pregenomic RNA (pgRNA) and DNA polymerase. In order to investigate the mechanism underlying CpAM inhibition of pgRNA encapsidation, we developed an immunoblotting assay that can resolve core protein based on its phosphorylation status and demonstrated, for the first time, that core protein is hyperphosphorylated in free dimers and empty capsids from both mock-treated and CpAM-treated cells but is hypophosphorylated in pgRNA- and DNA-containing nucleocapsids. Interestingly, inhibition of pgRNA encapsidation by a heat shock protein 90 (HSP90) inhibitor prevented core protein dephosphorylation. Moreover, core proteins with point mutations at the wall of the HAP pocket, V124A and V124W, assembled empty capsids and nucleocapsids with altered phosphorylation status. The results thus suggest that core protein dephosphorylation occurs in the assembly of pgRNA and that interference with the interaction between core protein subunits at dimer-dimer interfaces during nucleocapsid assembly alters not only capsid structure, but also core protein dephosphorylation. Hence, inhibition of pgRNA encapsidation by CpAMs might be due to disruption of core protein dephosphorylation during nucleocapsid assembly.

IMPORTANCE
Dynamic phosphorylation of HBV core protein regulates multiple steps of viral replication. However, the regulatory function was mainly investigated by phosphomimetic mutagenesis, which disrupts the natural dynamics of core protein phosphorylation/dephosphorylation. Development of an immunoblotting assay capable of resolving hyper- and hypophosphorylated core proteins allowed us to track the phosphorylation status of core proteins existing as free dimers and the variety of intracellular capsids and to investigate the role of core protein phosphorylation/dephosphorylation in viral replication. Here, we found that disruption of core protein interaction at dimer-dimer interfaces during nucleocapsid assembly (by CpAMs or mutagenesis) inhibited core protein dephosphorylation and pgRNA packaging. Our work has thus revealed a novel function of core protein dephosphorylation in HBV replication and the mechanism by which CpAMs, a class of compounds that are currently in clinical trials for treatment of chronic hepatitis B, induce the assembly of empty capsids.
Natural History of
Plasmodium odocoilei
Malaria Infection in Farmed White-Tailed Deer
Authors: Guggisberg Ann M. , Sayler Katherine A. , Wisely Samantha M. , Odom John Audrey R.
Published: April 2018

Malaria parasites of the genus
Plasmodium
are known to infect a variety of vertebrate hosts, including ungulates (hoofed mammals). A recent study found that up to a quarter of white-tailed deer (
Odocoileus virginianus
) in North America are infected with the parasite Plasmodium odocoilei. In addition to occupying an important ecological niche, white-tailed deer are popular game animals and deer farming represents a rapidly growing industry. However, the effect of P. odocoilei infection in this ecologically and economically important ungulate species is unknown. Our work is significant because (i) we identified a high prevalence of P. odocoilei in farmed deer and (ii) we found evidence for both cleared and persistent infection, as well as an association with decreased survival of young fawns.
Evolutionary Plasticity of AmrZ Regulation in
Pseudomonas
Authors: Baltrus David A. , Dougherty Kevin , Diaz Beatriz , Murillo Rachel
Published: April 2018

Microbes often display finely tuned patterns of gene regulation across different environments, with major regulatory changes controlled by a small group of “master” regulators within each cell. AmrZ is a master regulator of gene expression across pseudomonads and can be either a positive or negative regulator for a variety of pathways depending on the strain and genomic context. Here, we demonstrate that the phenotypic outcomes of regulation of swimming motility by AmrZ have switched at least twice independently in pseudomonads, so that AmrZ promotes increased swimming motility in
P. stutzeri
and
P. syringae
but represses this phenotype in
Pseudomonas fluorescens
and
Pseudomonas aeruginosa
. Since examples of switches in regulatory mode are relatively rare, further investigation into the mechanisms underlying shifts in regulator function for AmrZ could provide unique insights into the evolution of bacterial regulatory proteins.
The Heteroaryldihydropyrimidine Bay 38-7690 Induces Hepatitis B Virus Core Protein Aggregates Associated with Promyelocytic Leukemia Nuclear Bodies in Infected Cells
Authors: Huber Andrew D. , Wolf Jennifer J. , Liu Dandan , Gres Anna T. , Tang Jing , Boschert Kelsey N. , Puray-Chavez Maritza N. , Pineda Dallas L. , Laughlin Thomas G. , Coonrod Emily M. , Yang Qiongying , Ji Juan , Kirby Karen A. , Wang Zhengqiang , Sarafianos Stefan G.
Published: April 2018

Despite the availability of effective vaccines and treatments, HBV remains a significant global health concern, with more than 240 million individuals chronically infected. Current treatments are highly effective at controlling viral replication and disease progression but rarely cure infections. Therefore, much emphasis is being placed on finding therapeutics with new drug targets, such as viral gene expression, covalently closed circular DNA formation and stability, capsid formation, and host immune modulators, with the ultimate goal of an HBV cure. Understanding the mechanisms by which novel antiviral agents act will be imperative for the development of curative HBV therapies.
Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis
Authors: Delara Mahin , Chauhan Bhupendrasinh F , Le Mê-Linh , Abou-Setta Ahmed M , Zarychanski Ryan , ’tJong Geert W
Published: April 2018

Background

Systemic corticosteroids as the frontline treatment of respiratory distress syndrome (RDS) in preterm infants are associated with adverse effects on growth and neurodevelopmental outcome, but the pulmonary administration of steroids may help prevent the development of bronchopulmonary dysplasia (BPD) without these side effects.

Objectives

To evaluate the efficacy and safety of pulmonary application of corticosteroids in preterm infants with RDS.

Methods

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the WHO’s International Clinical Trials Registry and grey literature were searched with no restriction on date and language of publication from inception to May 2016. Using a random-effect model, we pooled data from randomised controlled trials (RCTs) comparing inhaled or endotracheal corticosteroids with the standard of care, placebo or no other intervention in preterm infants with RDS.

Results

We identified 873 potential citations and included 12 unique RCTs. Pulmonary corticosteroid therapy was associated with a significant reduction in the composite outcome of BPD or death (relative risk (RR) 0.85, 95% CI 0.76 to 0.96). Pulmonary application of corticosteroids significantly reduced the incidence of patent ductus arteriosus (PDA) (RR 0.82, 95% CI 0.74 to 0.92) and pneumonia (RR 0.57, 95% CI 0.35 to 0.92). There was no evidence of a significant difference regarding the risk of neurodevelopmental impairment or other side effects.

Conclusions

Pulmonary administration of corticosteroids reduces the incidence of BPD or death, pneumonia, PDA without causing any major side effects in preterm infants with RDS.
Patient safety climate in general public hospitals in China: differences associated with department and job type based on a cross-sectional survey
Authors: Zhou Ping , Bai Fei , Tang Hui-qin , Bai Jie , Li Min-qi , Xue Di
Published: April 2018

Objective

This study analysed differences in the perceived patient safety climate among different working departments and job types in public general hospitals in China.

Design

Cross-sectional survey.

Setting

Eighteen tertiary hospitals and 36 secondary hospitals from 10 areas in Shanghai, Hubei Province and Gansu Province, China.

Participants

Overall, 4753 staff, including physicians, nurses, medical technicians and managers, were recruited from March to June 2015.

Main outcome measure

The Patient Safety Climate in Healthcare Organisations (PSCHO) tool and the percentages of ‘problematic responses’ (PPRs) were used as outcome measures. Multivariable two-level random intercept models were applied in the analysis.

Results

A total of 4121 valid questionnaires were collected. Perceptions regarding the patient safety climate varied among departments and job types. Physicians responded with relatively more negative evaluations of ‘organisational resources for safety’, ‘unit recognition and support for safety efforts’, ‘psychological safety’, ‘problem responsiveness’ and overall safety climate. Paediatrics departments, intensive care units, emergency departments and clinical auxiliary departments require more attention. The PPRs for ‘fear of blame and punishment’ were universally significantly high, and the PPRs for ‘fear of shame’ and ‘provision of safe care’ were remarkably high, especially in some departments. Departmental differences across all dimensions and the overall safety climate primarily depended on job type.

Conclusions

The differences suggest that strategies and measures for improving the patient safety climate should be tailored by working department and job type.
Medical overuse in the Iranian healthcare system: a systematic review protocol
Authors: Arab-Zozani Morteza , Pezeshki Mohammad Zakaria , Khodayari-Zarnaq Rahim , Janati Ali
Published: April 2018

Introduction

Lack of resources is one of the main problems of all healthcare systems. Recent studies have shown that reducing the overuse of medical services plays an important role in reducing healthcare system costs. Overuse of medical services is a major problem in the healthcare system, and it threatens the quality of the services, can harm patients and create excess costs for patients. So far, few studies have been conducted in this regard in Iran. The main objective of this systematic review is to perform an inclusive search for studies that report overuse of medical services in the Iranian healthcare system.

Method and analysis

An extensive search of the literature will be conducted in six databases including PubMed, Embase, Scopus, Web of Science, Cochrane and Scientific Information Database using a comprehensive search strategy to identify studies on overuse of medical care. The search will be done without time limit until the end of 2017, completed by reference tracking, author tracking and expert consultation. The search will be conducted on 1 February 2018. Any study that reports an overuse in a service based on a specific standard will be included in the study. Two reviewers will screen the articles based on the title, abstract and full text, and extract data about type of service, clinical area and overuse rate. Quality appraisal will be assessed using the Joanna Briggs Institute checklist. Potential discrepancies will be resolved by consulting a third author.

Ethics and dissemination

Recommendations will be made to the Iranian MOHME (Ministry of Health and Medical Education) in order to make better evidence-based decisions about medical services in the future.

PROSPERO registration number

CRD42017075481
Study protocol for the SARON trial: a multicentre, randomised controlled phase III trial comparing the addition of stereotactic ablative radiotherapy and radical radiotherapy with standard chemotherapy alone for oligometastatic non-small cell lung cancer
Authors: Conibear John , Chia Brendan , Ngai Yenting , Bates Andrew Tom , Counsell Nicholas , Patel Rushil , Eaton David , Faivre-Finn Corinne , Fenwick John , Forster Martin , Hanna Gerard G , Harden Susan , Mayles Philip , Moinuddin Syed , Landau David
Published: April 2018

Introduction

Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS.

Methods and analysis

SARON is a large, randomised controlled, multicentre, phase III trial for patients with oligometastatic EGFR, ALK and ROS1 mutation negative NSCLC (1–3 sites of synchronous metastatic disease, one of which must be extracranial). 340 patients will be recruited over 3 years from approximately 30 UK sites and randomised to receive either standard platinum-doublet chemotherapy only (control arm) or standard chemotherapy followed by RRT/SABR to their primary tumour and then SABR/SRS to all other metastatic sites (investigational arm). The primary endpoint is OS; the study is powered to detect an improvement in median survival from 9.9 months in the control arm to 14.3 months in the investigational arm with 85% power and two-sided 5% significance level. The secondary endpoints are LC, progression-free survival, new distant metastasis-free survival, toxicity and quality of life. An early feasibility review will take place after 50 randomised patients. Patients requiring both conventional thoracic RT to the primary and SABR to a thoracic metastasis will be included in a thoracic SABR safety substudy to assess toxicity and planning issues in this subgroup of patients more thoroughly.

Ethics and dissemination

All participants are given a SARON patient information sheet and required to give written informed consent. Results will be submitted for presentation at local and international conferences and expected to be published in a peer-reviewed journal.

Trial registration number

NCT02417662.

Sponsor reference

UCL/13/0594.
Systematic review and meta-analysis of diabetes mellitus, cardiovascular and respiratory condition epidemiology in sexual minority women
Authors: Meads Catherine , Martin Adam , Grierson Jeffrey , Varney Justin
Published: April 2018

Objective

Sexual minority women (SMW) experience higher chronic disease risk factors than heterosexual counterparts. However, it was unclear if these risks translate into higher physical condition rates. This systematic review evaluates cardiovascular disease (CVD), hypertension, respiratory disease and diabetes mellitus in SMW.

Methods

A protocol was registered with the Prospero database (CRD42016050299). Included were studies reporting mortality, incidence or prevalence of the above-listed conditions in SMW compared with heterosexual women. Databases (platforms) searched from 2010 to December 2016 were Medline (Ovid), Embase (Elsevier), Cumulative Index to Nursing and Allied Health Literature (Elsevier), PsycINFO (Ovid), Social Policy and Practice (Ovid), Cochrane CENTRAL (Cochrane Library), Science Citation Index (Web of Science), and CAB Abstracts (Ovid). Search terms included Medical Subject Heading (MeSH) terms and text words. Extensive additional searches were conducted in specialist academic journals and websites. Two reviewers checked study eligibility. One independently extracted data and assessed quality, checked by a second reviewer, with disagreements resolved through discussion. The Critical Appraisal Skills Programme cohort checklist was used to assess risk of bias. Meta-analysis was conducted where more than four studies reported the same outcomes, with Comprehensive Meta-Analysis software, using adjusted ORs (AORs) and random-effects models. Heterogeneity was assessed using I2test.

Results

Identified were 23 103 citations, 692 full texts screened and 16 studies included (in 18 papers). One reported mortality (from Denmark), none incidence and 15 prevalence (14 USA, 1 Australia). Same-sex cohabiting women had higher mortality rates compared with opposite-sex cohabiting women in CVD (HR=1.37 (95% CI 1.22 to 1.54)) and respiratory disease (HR=2.10 (95% CI 1.74 to 2.53)). AOR meta-analyses of seven studies showed higher asthma rates in lesbians (OR=1.44 (95% CI 1.27 to 1.64), I2=0%) and bisexual women (OR=1.64 (95% CI 1.41 to 1.89), I2=0%) but no differences for CVD (5 studies), hypertension (5 studies) or diabetes mellitus (7 studies).

Conclusions

These new health estimates require further confirmatory epidemiological studies, and investigation into potential environmental, hormonal, physiological, psychological or genetic causes. This would be supported by routine collection of sexual identity measures in population-level epidemiological surveys.
Gain a child, lose a tooth? Using natural experiments to distinguish between fact and fiction
Authors: Gabel Frank , Jürges Hendrik , Kruk Kai E , Listl Stefan
Published: April 2018

Background

Dental diseases are among the most frequent diseases globally and tooth loss imposes a substantial burden on peoples' quality of life. Non-experimental evidence suggests that individuals with more children have more missing teeth than individuals with fewer children, but until now there is no causal evidence for or against this.

Methods

Using a Two-Stage Least Squares (2SLS) instrumental variables approach and large-scale cross-sectional data from the Survey of Health, Ageing, and Retirement in Europe (study sample: 34 843 non-institutionalised individuals aged 50+ from 14 European countries and Israel; data were collected in 2013), we investigated the causal relationship between the number of biological children and their parents’ number of missing natural teeth. Thereby, we exploited random natural variation in family size resulting from (i) the birth of multiples vs singletons, and (ii) the sex composition of the two first-born children (increased likelihood of a third child if the two first-born children have the same sex).

Results

2SLS regressions detected a strong causal relationship between the number of children and teeth for women but not for men when an additional birth occurred after the first two children had the same sex. Women then had an average of 4.27 (95% CI: 1.08 to 7.46) fewer teeth than women without an additional birth whose first two children had different sexes.

Conclusions

This study provides novel evidence for causal links between the number of children and the number of missing teeth. An additional birth might be detrimental to the mother’s but not the father’s oral health.
Genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B infection and hepatocellular carcinoma
Authors: Wang Xiaochen , He Qifeng , Shen Haiyuan , Lu Xiao-Jie , Sun Beicheng
Published: April 2018

Background

Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC).

Methods

In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously. Clustering analysis of genes was performed using the T cell exhaustion gene modules (modules 1–4) proposed by Speiseret al.

Results

CD8+ T cells from liver tissues of both CHB and HCC showed high levels of exhaustion markers, DOI: programmed cell death-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3), decreased proliferation (Ki67) and cell activity (CD69), and reduced production of effector cytokines (interferon-γ, interleukin-2 and tumour necrosis factor-α). Compared with CD8+ T cells from CHB tissues, those from HCC tissue showed higher expression levels of exhaustion markers, lower levels of proliferation, cell activity and the production of effector cytokines. Cluster analysis showed that exhaustion associated genes in CHB and HCC are inclined to distribute into modules 3 while those isolated from HCC into modules 1 and 2.

Conclusions

CD8+ T cell exhaustion existed both in CHB and HCC, but the phenotypes, functional states and underlying mechanisms are somewhat different between the two.
Does magnesium sulfate have a role in the management of severe traumatic brain injury in civilian and military populations? A systematic review and meta-analysis
Authors: Lyons Marc W H , Blackshaw W J
Published: April 2018

Introduction

Traumatic brain injury (TBI) is a significant cause of combat morbidity. Currently, the medical management of TBI is limited to supportive critical care. Magnesium sulfate has been studied as a potentially beneficial therapeutic agent.

Methods

A systematic review and meta-analysis was undertaken, examining the role of magnesium in the management of severe TBI in adults. The primary outcome of the study was all-cause mortality, with secondary outcomes of Glasgow Outcome Score (GOS) and GCS. EMBASE, MEDLINE, CINAHL, WHO Trial Registry and the Cochrane Library database were systematically searched, with data included until 1 February 2017. Inclusion criteria were: human study; aged >13 years; randomised controlled trial; severe TBI. Exclusion criteria were: data collected prior to 1 January 2002; magnesium commenced >24 hours postinjury; magnesium therapy for <24 hours. Statistical analysis was conducted using Stata (V.13.1).

Results

The pooled results of six studies found all-cause mortality not to be significantly different in the treatment group (RR 0.84, 95% CI 0.54 to 1.33; P=0.46) with an I2value of >70%. With regard to the secondary outcomes, no significant difference in GOS scores between treatment and control was demonstrated. GCS showed a significant improvement in the treatment group.

Conclusions

The meta-analysis found a lack of evidence for magnesium pharmacotherapy in severe TBI, although the data were noted to be conflicting and significantly heterogeneous. Further study is recommended to ascertain whether a therapeutic window exists for magnesium in severe TBI.
Thrombectomy for acute ischemic stroke in the elderly: a ‘real world’ experience
Authors: Alawieh Ali , Chatterjee Arindam , Feng Wuwei , Porto Guilherme , Vargas Jan , Kellogg Ryan , Turk Aquilla S , Turner Raymond D , Imran Chaudry M , Spiotta Alejandro M
Published: April 2018

Introduction

Completed randomized trials on endovascular thrombectomy (ET) did not independently assess the efficacy of ET in the elderly (≥80 years old) who were often excluded or under-represented in trials. There were also inconsistent criteria for patient selection in this population across the different trials. This work evaluates outcomes after ET for acute ischemic stroke (AIS) in the elderly at a high volume stroke center.

Methods

We reviewed all cases of AIS that underwent a direct aspiration first pass technique (ADAPT) thrombectomy for large vessel occlusions between March 2013 and October 2017 while comparing outcomes in the elderly with younger counterparts. We also reviewed AIS cases in elderly patients undergoing medical management who were matched to the ET counterparts by demographics, comorbidities, baseline deficits, and stroke severity.

Results

Of 560 patients undergoing ET for AIS, 108 patients were in the elderly group (≥80 years of age), and had a significantly lower likelihood of functional independence (defined as a modified Rankin Scale score of 0–2) at 90 days compared with younger patients (20.5% vs 44.4%, P<0.001), and higher mortality rates (34.3% vs 20%, P<0.001). When compared with patients undergoing medical management, elderly patients did not have a significant improvement in rates of good outcomes (20.5% vs 19.5%, P>0.05), and had significantly higher rates of hemorrhage (40.7% vs 9.3%, P<0.001). We also identified baseline stroke severity and the incidence of hemorrhage as two independent predictors of outcome in the elderly patients.

Conclusions

ET in the elderly did not show a similar benefit to younger patients when compared with medical management. These findings emphasize the need for more optimal selection criteria for the elderly population to improve the risk to benefit ratio of ET.
Symptoms at lung cancer diagnosis are associated with major differences in prognosis
Authors: Athey Victoria L , Walters Stephen J , Rogers Trevor K
Published: April 2018

We report a cohort study of survival of patients with lung cancer presenting to a single multidisciplinary team between 1997 and 2011, according to symptoms at presentation. The overall median survival of the 3800 lung cases was 183 days (95% CI 171 to 195). There was a statistically significant difference in survival between the 12 symptom groups identified both without and with adjustment for the prognostic variables of age, gender and histology (P<0.001). Compared with the cough-alone symptom group, the risks of dying or HRs were significantly higher for the groups presenting with breathlessness (HR 1.86, 95% CI 1.54 to 2.24, n=359), systemic symptoms (HR 1.91, 95% CI 1.48 to 2.45, n=95), weight loss (HR 2.46, 95% CI 1.90 to 3.18, n=106), chest pain (HR 1.96, 95% CI 1.56 to 2.45, n=159), cough with breathlessness (HR 1.59 95% CI 1.28 to 1.98, n=177), neurological symptoms (HR 3.07, 95% CI 2.45 to 3.84, n=155) and other symptom combinations (HR 2.05, 95% CI 1.75 to 2.40, n=1963). Cough may deserve particular prominence in public health campaigns.
First report of prion‐related protein gene (PRNT) polymorphisms in cattle
Authors: Kim Yong‐Chan , Jeong Byung‐Hoon
Published: April 2018

Prion diseases are caused by structural changes in normal prion protein (PrPC). The prion gene family includes four members: prion protein (PRNP), prion‐like protein (PRND), shadow of PRNP (SPRN) and prion‐related protein (PRNT). Genetic association studies of prion diseases and the other genes in the prion gene family, except for PRNT, have been performed in cattle. Our previous studies indicated that the distribution of PRNP promoter polymorphisms related with bovine spongiform encephalopathy susceptibility is significantly different in Hanwoo (Korean native cattle) and Holstein cattle. However, PRNT polymorphisms have not been reported thus far in cattle. Hence, we examined the PRNT single nucleotide polymorphisms (SNPs) in 315 Hanwoo and 140 Holstein cattle. We found a total of two SNPs, PRNT c.‐87C>T and PRNT c.‐37G>C, in the 5’ untranslated region of exon 2. The c.‐87C>T and c.‐37G>C genotype (P<0.0001) and allele (P<0.0001) frequencies exhibited significant differences in the distribution between Hanwoo and Holstein cattle. In addition, the c.‐37G<C polymorphism was not found in Hanwoo. Interestingly, we did not find any polymorphisms in the ORF of bovine PRNT, which is in contrast with the highly polymorphic ovine PRNT ORF region. This is the first genetic research of the PRNT gene in cattle.
Multiyear variations in High Arctic river temperatures in response to climate variability
Authors: Bolduc Christopher , Lamoureux Scott F.
Published: April 2018

Water temperature measurements (2004–2016) from two small rivers in the High Arctic were analyzed to determine the effects of climate variability on thermal regime and the sensitivity to climate change. The East and West rivers (unofficial names) drain similar watersheds (11.6 and 8.0 km2, respectively) and are located at the Cape Bounty Arctic Watershed Observatory (CBAWO), Melville Island, Canada (74°55′N, 109°35′W). Differences in seasonal timing of river temperatures were evident when comparing the coldest and warmest years of the study period, and across different discharge conditions. Snowmelt runoff is characterized by uniformly cold water (∼0–1 °C) over a wide range of discharge conditions, followed by warming water temperatures during flow recession. The rivers showed varying sensitivity to mid-summer air temperature conditions in a given year, with warmer years indicating high correlation (r2 = 0.794–0.929), whereas colder years showed reduced correlation (r2 = 0.368–0.778). River temperatures reached levels which are reported to negatively affect fish and other cold-water aquatic species (>18 °C) with greater frequency and duration during the warmest years. These results provide a basis to further enhance prediction of river thermal conditions to assess ecosystem health in a river system and to refine insights into the effects of climate change on High Arctic aquatic ecosystems.
Service load deflection of tilt-up concrete wall panels
Authors: Bischoff Peter H.
Published: April 2018

The suitability of using CSA A23.3-14 to compute service load deflection of slender concrete wall panels is evaluated. Calculation of deflection using an effective moment of inertia with a reduced cracking moment is reviewed for beams, slabs, and tilt-up wall panels. While the procedure adopted by A23.3 for computing deflection works reasonably well for beams and slabs with reinforcing ratios as low as 0.4%, computed values do not correlate well with existing tests on slender walls and can underestimate deflection significantly. Deflection of slabs with very low reinforcement ratios (less than 0.4%) is also likely to be underestimated. Revisions to A23.3 are proposed for computing deflection.
Factorization of differential expansion for non-rectangular representations
Authors: Morozov A.
Published: April 2018

Factorization of the differential expansion (DE) coefficients for colored HOMFLY-PT polynomials of antiparallel double braids, originally discovered for rectangular representations [Formula: see text], in the case of rectangular representations [Formula: see text], is extended to the first non-rectangular representations [Formula: see text] and [Formula: see text]. This increases chances that such factorization will take place for generic [Formula: see text], thus fixing the shape of the DE. We illustrate the power of the method by conjecturing the DE-induced expression for double-braid polynomials for all [Formula: see text]. In variance with the rectangular case, the knowledge for double braids is not fully sufficient to deduce the exclusive Racah matrix [Formula: see text] — the entries in the sectors with nontrivial multiplicities sum up and remain unseparated. Still, a considerable piece of the matrix is extracted directly and its other elements can be found by solving the unitarity constraints.
Dielectric properties of single wall carbon nanotubes-based gelatin phantoms
Authors: Altarawneh M. M. , Alharazneh G. A. , Al-Madanat O. Y.
Published: April 2018

In this work, we report the dielectric properties of Single wall Carbon Nanotubes (SWCNTs)-based phantom that is mainly composed of gelatin and water. The fabricated gelatin-based phantom with desired dielectric properties was fabricated and doped with different concentrations of SWCNTs (e.g., 0%, 0.05%, 0.10%, 0.15%, 0.2%, 0.4% and 0.6%). The dielectric constants (real [Formula: see text] and imaginary [Formula: see text] were measured at different positions for each sample as a function of frequency (0.5–20[Formula: see text]GHz) and concentrations of SWCNTs and their averages were found. The Cole–Cole plot ([Formula: see text] versus [Formula: see text] was obtained for each concentration of SWCNTs and was used to obtain the static dielectric constant [Formula: see text], the dielectric constant at the high limit of frequency [Formula: see text] and the average relaxation time [Formula: see text]. The measurements showed that the fabricated samples are in good homogeneity and the SWCNTs are dispersed well in the samples as an acceptable standard deviation is achieved. The study showed a linear increase in the static dielectric constant [Formula: see text] and invariance of the average relaxation time [Formula: see text] and the value of [Formula: see text] at room temperature for the investigated concentrations of SWCNTs.
Structure of the crust and upper mantle beneath the Parnaíba Basin, Brazil, from wide-angle reflection–refraction data
Authors: Soares José E. P. , Stephenson Randell , Fuck Reinhardt A. , de Lima Marcus V. A. G. , de Araújo Vitto C. M. , Lima Flávio T. , Rocha Fábio A. S. , da Trindade Cíntia R.
Published: April 2018

The Parnaíba Basin is a Phanerozoic intracontinental basin within the South America plate, lying on top of and within Precambrian terranes. The Parnaíba Basin Analysis Program wide-angle reflection–refraction (WARR) lies east–west and is 1150 km long profile crossing the basin and its margins. The WARR results show that the crust and uppermost mantle along the profile consist of the Amazonian Craton and Borborema Province, and the Grajaú and Teresina domains comprising the Parnaíba block hidden below the sedimentary cover of the basin itself. The lithospheric characteristics of the Parnaíba block and their differences from the adjacent Precambrian Amazonian Craton and Borborema Province elucidate some aspects of the present day existence of the sedimentary basin covering it. Important elements include the presence of a high mantle velocity and high-velocity lowermost crustal region, interpreted as linked to the intrusion of mafic material into the crust underlying the Grajaú domain, and indications that the crust in this area has been intruded since its consolidation in the Neoproterozoic. It is tentatively proposed that magmatism is related to the inferred thinning of the lower crust of the Teresina and Borborema segments of the profile, with this, in turn, linked to Cretaceous extensional tectonics and the opening of the South Atlantic Ocean.
Lysosomes and Brain Health
Authors: Sharma Jaiprakash , di Ronza Alberto , Lotfi Parisa , Sardiello Marco
Published: April 2018

One of the fundamental properties of the cell is the capability to digest and remodel its own components according to metabolic and developmental needs. This is accomplished via the autophagy-lysosome system, a pathway of critical importance in the brain, where it contributes to neuronal plasticity and must protect nonreplaceable neurons from the potentially harmful accumulation of cellular waste. The study of lysosomal biogenesis and function in the context of common and rare neurodegenerative diseases has revealed that a dysfunctional autophagy-lysosome system is the shared nexus where multiple, interconnected pathogenic events take place. The characterization of pathways and mechanisms regulating the lysosomal system and autophagic clearance offers unprecedented opportunities for the development of polyvalent therapeutic strategies based on the enhancement of the autophagy-lysosome pathway to maintain cellular homeostasis and achieve neuroprotection.
SILAC-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys
Authors: Wang Junlong , Xu Shimeng , Gao Jing , Zhang Linqiang , Zhang Zhiguo , Yang Wenhui , Li Yunhai , Liao Shasha , Zhou Hu , Liu Pingsheng , Liang Bin
Published: April 2018

Type 2 diabetes mellitus (T2DM) is a severe metabolic disorder that affects more than 10% of the population worldwide. Obesity is a major cause of insulin resistance and contributes to the development of T2DM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. The nonhuman primate rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individuals of spontaneously diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with a high body mass index at the beginning, but gradually lost their body weight during one year of observation. Furthermore, we performed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. In total, 3,509 proteins were identified and quantified, of which 185 proteins displayed an altered expression level. Gene ontology analysis revealed that the expression of proteins involved in fatty acids β-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation and branched chain amino acid (BCAA) degradation were upregulated in diabetic monkeys. In addition, we observed mild apoptosis in the liver of diabetic monkeys, suggesting liver injury at the late onset of diabetes. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids β-oxidation in obese monkey to BCAA degradation in diabetic monkeys.
A mathematical analysis of adaptations to the metabolic fate of fructose in essential fructosuria subjects
Authors: Allen Richard J. , Musante Cynthia J.
Published: April 2018

Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during “first-pass” liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration. Here we develop and use a mathematical model to investigate the adaptations to altered fructose metabolism in people with EF. First, the model is calibrated to fit available data in normal healthy subjects. Then, to mathematically represent EF subjects, we systematically implement metabolic adaptations such that model simulations match available data for this phenotype. We hypothesize that these modifications represent the major metabolic adaptations present in these subjects. This modeling approach suggests that several other aspects of fructose metabolism, beyond hepatic KHK deficiency, are altered and contribute to the etiology of this benign condition. Specifically, we predict that fructose absorption into the portal vein is altered, peripheral metabolism is slowed, renal reabsorption of fructose is mostly ablated, and alternate pathways for hepatic metabolism of fructose are upregulated. Moreover, these findings have implications for drug discovery and development, suggesting that the therapeutic targeting of fructose metabolism could lead to unexpected metabolic adaptations, potentially due to a physiological response to high-fructose conditions.
The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet
Authors: Shidfar Farzad , Bahrololumi Samaneh Sadat , Doaei Saeid , Mohammadzadeh Assieh , Gholamalizadeh Maryam , Mohammadimanesh Ali
Published: April 2018

Background. Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD). Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet.Methods. This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m2) and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil) or the control group (with normal consumption of oil) for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured.Findings. A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study (P= 0.004). In the olive oil group, both enzymes decreased compared to baseline measurements (P<0.01). There were significant differences in the ALT and AST levels between the two groups (P<0.02). The severity of liver steatosis did not change significantly during the study.Conclusion. The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.
Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome
Authors: Wang Yueli , Li Xiaoyan , Li Rongjuan , Yang Ya , Du Jie
Published: April 2018

Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation sequencing (NGS) technologies, 3 novel frameshift pathogenic mutations which are cosegregated with affected subjects in 3 pedigrees were identified. These novel mutations provide important diagnostic and therapeutic insights for precision medicine in MFS, especially regarding the lethal cardiovascular events.
Mapping the Structure-Function Relationship in Glaucoma and Healthy Patients Measured with Spectralis OCT and Humphrey Perimetry
Authors: Jaumandreu Laia , Muñoz–Negrete Francisco J. , Oblanca Noelia , Rebolleda Gema
Published: April 2018

Purpose. To study the structure-function relationship in glaucoma and healthy patients assessed with Spectralis OCT and Humphrey perimetry using new statistical approaches. Materials and Methods. Eighty-five eyes were prospectively selected and divided into 2 groups: glaucoma (44) and healthy patients (41). Three different statistical approaches were carried out: (1) factor analysis of the threshold sensitivities (dB) (automated perimetry) and the macular thickness (μm) (Spectralis OCT), subsequently applying Pearson’s correlation to the obtained regions, (2) nonparametric regression analysis relating the values in each pair of regions that showed significant correlation, and (3) nonparametric spatial regressions using three models designed for the purpose of this study. Results. In the glaucoma group, a map that relates structural and functional damage was drawn. The strongest correlation with visual fields was observed in the peripheral nasal region of both superior and inferior hemigrids (r=0.602 and r=0.458, resp.). The estimated functions obtained with the nonparametric regressions provided the mean sensitivity that corresponds to each given macular thickness. These functions allowed for accurate characterization of the structure-function relationship. Conclusions. Both maps and point-to-point functions obtained linking structure and function damage contribute to a better understanding of this relationship and may help in the future to improve glaucoma diagnosis.