bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis
Authors: Ren Yun Hong , Zhao Feng Juan , Mo Han Yue , Jia Rong Rong , Tang Juan , Zhao Xin Hua , Wei Jue Ling , Huo Rong Rui , Li Qiu Qin , You Xue Mei 
Published: August 2019

ObjectivesLiver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.DesignAn updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sourcesEligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteriaThe association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesisRelevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.ResultsThe systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).ConclusionLow LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.
Complementary therapies for clinical depression: an overview of systematic reviews
Authors: Haller Heidemarie , Anheyer Dennis , Cramer Holger , Dobos Gustav 
Published: August 2019

ObjectivesAs clinical practice guidelines vary widely in their search strategies and recommendations of complementary and alternative medicine (CAM) for depression, this overview aimed at systematically summarising the level 1 evidence on CAM for patients with a clinical diagnosis of depression.MethodsPubMed, PsycInfo and Central were searched for meta-analyses of randomised controlled clinical trials (RCTs) until 30 June 2018. Outcomes included depression severity, response, remission, relapse and adverse events. The quality of evidence was assessed according to Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) considering the methodological quality of the RCTs and meta-analyses, inconsistency, indirectness, imprecision of the evidence and the potential risk of publication bias.ResultsThe literature search revealed 26 meta-analyses conducted between 2002 and 2018 on 1–49 RCTs in major, minor and seasonal depression. In patients with mild to moderate major depression, moderate quality evidence suggested the efficacy of St. John’s wort towards placebo and its comparative effectiveness towards standard antidepressants for the treatment for depression severity and response rates, while St. John’s wort caused significant less adverse events. In patients with recurrent major depression, moderate quality evidence showed that mindfulness-based cognitive therapy was superior to standard antidepressant drug treatment for the prevention of depression relapse. Other CAM evidence was considered as having low or very low quality.ConclusionsThe effects of all but two CAM treatments found in studies on clinical depressed patients based on low to very low quality of evidence. The evidence has to be downgraded mostly due to avoidable methodological flaws of both the original RCTs and meta-analyses not following the Consolidated Standards of Reporting Trials and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Further research is needed.
Prevalence of hospitalisation caused by adverse drug reactions at an internal medicine ward of a single centre in Japan: a cross-sectional study
Authors: Komagamine Junpei , Kobayashi Masaki 
Published: August 2019

ObjectivesFew studies have investigated the prevalence of adverse drug reactions (ADRs) leading to hospitalisation in Japan. The aim of this study was to determine the prevalence of ADRs leading to hospitalisation and to evaluate the preventability of these ADRs in Japan.DesignA single-centre cross-sectional study using electronic medical records.SettingAcute care hospital.ParticipantsAll 1545 consecutive hospital admissions to an internal medicine ward due to acute medical illnesses from April 2017 to May 2018. The median patient age was 79 years (IQR 66–87), and the proportion of women was 47.9%.Outcome measuresThe primary outcome was the proportion of hospitalisations caused by ADRs among all hospitalisations. All suspected cases of ADRs were independently evaluated by two reviewers, and disagreements were resolved by discussion. The causality assessment for ADRs was performed by using the WHO-Uppsala Monitoring Committee criteria. The contribution of ADRs to hospitalisation and their preventability were evaluated based on the Hallas criteria.ResultsOf the 1545 hospitalisations, 153 hospitalisations (9.9%, 95% CI 8.4% to 11.4%) were caused by 200 ADRs. Cardiovascular agents (n=46, 23.0%), antithrombic agents (n=33, 16.5%), psychotropic agents (n=29, 14.5%) and non-steroidal anti-inflammatory drugs (n=24, 12.0%) accounted for approximately two-thirds of all ADRs leading to hospitalisation. Of 153 hospitalisations caused by ADRs, 102 (66.7%) were judged to be preventable.ConclusionsSimilar to other countries, one in every ten hospitalisations is caused by ADRs according to data from an internal medicine ward of a Japanese hospital. Most of these hospitalisations are preventable. Some efforts to minimise hospitalisations caused by ADRs are needed.
Mutaba’ah—Mother and Child Health Study: protocol for a prospective cohort study investigating the maternal and early life determinants of infant, child, adolescent and maternal health in the United Arab Emirates
Authors: Al Haddad Amal , Ali Nasloon , Elbarazi Iffat , Elabadlah Haba , Al-Maskari Fatima , Narchi Hassib , Brabon Christel , Ghazal-Aswad Saad , AlShalabi Fatima M , Zampelas Antonis , Loney Tom , Blair Iain , Ahmed Luai A 
Published: August 2019

IntroductionEarly life exposures, particularly environmental and parental lifestyle factors, have a major influence on children’s health and development. Due to increasing interest in the early life developmental origins of diseases, many birth cohorts have been established. These studies constitute a repository of data which researchers use over many years to investigate emerging research questions. However, no such databank or cohort study is available in the United Arab Emirates (UAE). This project aims to establish a prospective mother and child cohort study in Al Ain (Abu Dhabi, UAE) to investigate the maternal and early life determinants of infant, child, adolescent and maternal health of the Emirati population.Methods and analysisDuring the period 2017–2021, this study aims to recruit 10 000 pregnancies at approximately 12 weeks of gestation from hospitals and clinics in Al Ain city. For each mother/newborn pair, an initial dataset will be collected including anthropometric, physiological and biochemical measurements, medical interventions, circumstances of pregnancy, delivery details and neonatal and perinatal growth and health using a combination of questionnaires, interviews and medical record extractions. Baseline data will act as the starting point from which the children will be followed up and re-surveyed at intervals throughout their life course until the age of 16 years, to explore how familial, socioeconomic and lifestyle factors interact with genetic and environmental factors to influence health outcomes and achievements later in life.Ethics and disseminationEthical approval has been granted by the United Arab Emirates University Human Research Ethics Committee and the ethical committees of the participating institutions. Results will be widely disseminated via peer-reviewed manuscripts, conference presentations, media outlets and reports to relevant authorities.
Randomised controlled trial of a theory-based intervention to prompt front-line staff to take up the seasonal influenza vaccine
Authors: Schmidtke Kelly Ann , Nightingale Peter G , Reeves Katharine , Gallier Suzy , Vlaev Ivo , Watson Samuel I , Lilford Richard J 
Published: August 2019

ObjectiveTo evaluate the effectiveness of reminder letters informed by social normative theory (a type of ‘nudge theory’) on uptake of seasonal influenza vaccination by front-line hospital staff.DesignIndividually randomised controlled trial.SettingA large acute care hospital in England.ParticipantsFront-line staff employed by the hospital (n=7540) were randomly allocated to one of four reminder types in a factorial design.InterventionsThe standard letter included only general information directing the staff to take up the vaccine. A second letter highlighted a type of social norm based on peer comparisons. A third letter highlighted a type of social norm based on an appeal to authority. A fourth letter included a combination of the social norms.Main outcome measureThe proportion of hospital staff vaccinated on-site.ResultsVaccine coverage was 43% (812/1885) in the standard letter group, 43% (818/1885) in the descriptive norms group, 43% (814/1885) in the injunctive norms group and 43% (812/1885) in the combination group. There were no statistically significant effects of either norm or the interaction. The OR for the descriptive norms factor is 1.01 (0.89–1.15) in the absence of the injunctive norms factor and 1.00 (0.88–1.13) in its presence. The OR for the injunctive norms factor is 1.00 (0.88–1.14) in the absence of the descriptive norms factor and 0.99 (0.87–1.12) in its presence.ConclusionsWe find no evidence that the uptake of the seasonal influenza vaccination is affected by reminders using social norms to motivate uptake.
Assessment of rectalChlamydia trachomatisviable load in women by viability-PCR
Authors: Janssen Kevin J H , Wolffs Petra , Lucchesi Mayk , Dukers-Muijrers Nicole H T M , Hoebe Christian J P A 
Published: August 2019

ObjectivesIn recent years, studies have demonstrated frequent rectalChlamydia trachomatis(CT) detection in women, irrespective of reported anal sex or rectal symptoms. However, the clinical relevance and public health implication of rectal CT detection in women remain under debate. Therefore, evaluating CT viability may provide more insight into the relevance of standard routine nucleic acid amplification test (NAAT)–positive results.MethodsIn this cross-sectional explorative study, a convenience sample of female patients at our STI clinic aged 18 years or older, diagnosed with vaginal and/or rectal CT, were invited to participate. On return for treatment, rectal CT-diagnosed women were instructed to self-collect rectal swab samples before being treated. Standard COBAS 4800 CT/NG routine NAAT testing was applied for CT diagnosis. Rectal viable CT load was evaluated by using viability-PCR (V-PCR).Results53 women with rectal CT were included in this study; 86.8% (46/53) had a quantifiable rectal total CT load. Of women with quantifiable samples, 52.2% (24/46) had viable CT detected from rectal swabs by V-PCR, with a mean rectal viable CT load of 3.31 log10CT/mL (range 1.16–6.22). No statistically significant difference (p=0.73) was observed in the mean rectal viable CT load of women with an indication for rectal testing (n=9) and without (n=15), 3.20 log10CT/mL (range 2.06–4.36) and 3.38 log10CT/mL (range 1.16–6.22), respectively. CT culture yielded positive test results from rectal swabs in 22.6% (12/53) of rectal CT NAAT-diagnosed women. Of women with viable rectal CT by V-PCR (n=24), 50% (12/24) were positive by CT culture.ConclusionsOverall, the detection of high rectal viable CT loads in this study indicates that rectal CT in some women might represent a currently ongoing infection rather than just the presence of remnant DNA from dead bacteria or only contamination from an active vaginal CT infection.
Molecular diversity of
Treponema pallidum
subspecies
pallidum
isolates in Amsterdam, the Netherlands
Authors: Zondag Helene C A , Cornelissen Akke R , van Dam Alje P , Bruisten Sylvia M 
Published: August 2019

Objectives

The prevalence of syphilis, caused by the spirochete
Treponema pallidum
subsp
. pallidum
(TPA), remains high despite the availability of effective antibiotics. In the Netherlands, most syphilis cases are found among men who have sex with men (MSM). We studied the distribution of TPA strain types by molecular characterisation and related this to available characteristics. In addition, resistance to macrolides was assessed.

Methods

TPA DNA was extracted from 136 genital ulcer swab or skin lesions samples deriving from 135 patients diagnosed with syphilis in 2016 and 2017 at the Public Health Service in Amsterdam, the Netherlands. Molecular typing was done according to the enhanced CDC method (E-CDC), in which three genetic regions of the
arp
,
tpr
and
tp0548
genes are analysed by gel electrophoresis of the
arp
and
tpr
regions and by sequence analysis for the
tp0548
region. Part of the 23S rDNA locus was sequenced to determine the presence of macrolide resistance-associated mutations.

Results

Full E-CDC strain types could be determined for 99/136 (73%) DNA samples, which tested positive in a diagnostic PCR targeting the
polA
gene. Types differed within one patient of whom two samples were available. No association was found between the demographic and clinical characteristics and the TPA types. The most prevalent type was 14d/g, found in 23 of the 99 (23%) fully typed samples. Part of the 23S rDNA locus was successfully sequenced for 93/136 (68%) samples and 83 (88%) contained the A2058G mutation. No A2059G mutation was found.

Conclusions
A broad strain distribution was found. Few subtypes were clonally expanded, and most other subtypes were rare. Detection of the most prevalent strain type, 14d/g, is in concordance with other TPA typing studies. The high prevalence of genetic macrolide resistance indicates that azithromycin is not an alternative treatment option.
Immune Activation in Mismatch Repair–Deficient Carcinogenesis: More Than Just Mutational Rate
Authors: Willis Jason A. , Reyes-Uribe Laura , Chang Kyle , Lipkin Steven M. , Vilar Eduardo 
Published: August 2019

Abstract
Mismatch repair (MMR)–deficient colorectal cancers (dMMR colorectal cancer) are characterized by the expression of highly immunogenic neoantigen peptides, which stimulate lymphocytic infiltration as well as upregulation of inflammatory cytokines. These features are key to understanding why immunotherapy (specifically PD-1 and/or CTLA-4 checkpoint blockade) has proved to be highly effective for the treatment of patients with advanced dMMR colorectal cancer. Importantly, preclinical studies also suggest that this correlation between potent tumor neoantigens and the immune microenvironment is present in early (premalignant) stages of dMMR colorectal tumorigenesis as well, even in the absence of a high somatic mutation burden. Here, we discuss recent efforts to characterize how neoantigens and the tumor immune microenvironment coevolve throughout the dMMR adenoma-to-carcinoma pathway. We further highlight how this preclinical evidence forms the rational basis for developing novel immunotherapy-based colorectal cancer prevention strategies for patients with Lynch syndrome.
TFEB Mediates Immune Evasion and Resistance to mTOR Inhibition of Renal Cell Carcinoma via Induction of PD-L1
Authors: Zhang Cai , Duan Yaqi , Xia Minghui , Dong Yuting , Chen Yufei , Zheng Lu , Chai Shuaishuai , Zhang Qian , Wei Zhengping , Liu Na , Wang Jing , Sun Chaoyang , Tang Zhaohui , Cheng Xiang , Wu Jie , Wang Guoping , Zheng Fang , Laurence Arian , Li Bing , Yang Xiang-Ping 
Published: August 2019

Abstract

Purpose:
Despite the FDA approval of mTOR inhibitors (mTORi) for the treatment of renal cell carcinoma (RCC), the benefits are relatively modest and the few responders usually develop resistance. We investigated whether the resistance to mTORi is due to upregulation of PD-L1 and the underlying molecular mechanism.

Experimental Design:
The effects of transcription factor EB (TFEB) on RCC proliferation, apoptosis, and migration were evaluated. Correlation of TFEB with PD-L1 expression, as well as effects of mTOR inhibition on TFEB and PD-L1 expression, was assessed in human primary clear cell RCCs. The regulation of TFEB on PD-L1 was assessed by chromatin immunoprecipitation and luciferase reporter assay. The therapeutic efficacies of mTORi plus PD-L1 blockade were evaluated in a mouse model. The function of tumor-infiltrating CD8+ T cells was analyzed by flow cytometry.

Results:
TFEB did not affect tumor cell proliferation, apoptosis, and migration. We found a positive correlation between TFEB and PD-L1 expression in RCC tumor tissues, primary tumor cells, and RCC cells. TFEB bound to PD-L1 promoter in RCCs and inhibition of mTOR led to enhanced TFEB nuclear translocation and PD-L1 expression. Simultaneous inhibition of mTOR and blockade of PD-L1 enhanced CD8+ cytolytic function and tumor suppression in a xenografted mouse model of RCC.

Conclusions:
These data revealed that TFEB mediates resistance to mTOR inhibition via induction of PD-L1 in human primary RCC tumors, RCC cells, and murine xenograft model. Our data provide a strong rationale to target mTOR and PD-L1 jointly as a novel immunotherapeutic approach for RCC treatment.
Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study
Authors: Lamprea‐Montealegre Julio A. , Zelnick Leila R. , Shlipak Michael G. , Floyd James S. , Anderson Amanda H. , He Jiang , Christenson Rob , Seliger Stephen L. , Soliman Elsayed Z. , Deo Rajat , Ky Bonnie , Feldman Harold I. , Kusek John W. , deFilippi Christopher R. , Wolf Myles S. , Shafi Tariq , Go Alan S. , Bansal Nisha , Appel Lawrence J. , Lash James P. , Rao Panduranga S. , Rahman Mahboob , Townsend Raymond R. 
Published: August 2019

Background

We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (
AF
) in a prospective study of
chronic kidney disease
patients.

Methods and Results

The study sample was 3053 participants with
chronic kidney disease
in the multicenter
CRIC
(Chronic Renal Insufficiency Cohort) study who were not identified as having
AF
at baseline. Cardiac biomarkers, measured at baseline, were NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin T, galectin‐3, growth differentiation factor‐15, and soluble
ST
‐2. Incident AF (“
AF
event”) was defined as a hospitalization for AF. During a median follow‐up of 8 years, 279 (9%) participants developed a new
AF
event. In adjusted models, higher baseline log‐transformed NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was associated with incident
AF
(adjusted hazard ratio [
HR
] per
SD
higher concentration: 2.11; 95%
CI
, 1.75, 2.55), as was log‐high‐sensitivity troponin T (
HR
1.42; 95%
CI
, 1.20, 1.68). These associations showed a dose–response relationship in categorical analyses. Although log‐soluble
ST
‐2 was associated with
AF
risk in continuous models (
HR
per
SD
higher concentration 1.35; 95%
CI
, 1.16, 1.58), this association was not consistent in categorical analyses. Log‐galectin‐3 (
HR
1.05; 95%
CI
, 0.91, 1.22) and log‐growth differentiation factor‐15 (
HR
1.16; 95%
CI
, 0.96, 1.40) were not significantly associated with incident AF.

Conclusions

We found strong associations between higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and high‐sensitivity troponin T concentrations, and the risk of incident
AF
in a large cohort of participants with
chronic kidney disease
. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of
AF
in patients with
chronic kidney disease
.
Tropical Deep Convection Impact on Southern Winter Stationary Waves and Its Modulation by the Quasi-Biennial Oscillation
Authors: Peña-Ortiz Cristina , Manzini Elisa , Giorgetta Marco A. 
Published: August 2019

Abstract
The impact of tropical deep convection on southern winter stationary waves and its modulation by the quasi-biennial oscillation (QBO) have been investigated in a long (210 year) climate model simulation and in ERA-Interim reanalysis data for the period 1979–2018. Model results reveal that tropical deep convection over the region of its climatological maximum modulates high-latitude stationary planetary waves in the southern winter hemisphere, corroborating the dominant role of tropical thermal forcing in the generation of these waves. In the tropics, deep convection enhancement leads to wavenumber-1 eddy anomalies that reinforce the climatological Rossby–Kelvin wave couplet. The Rossby wave propagates toward the extratropical southern winter hemisphere and upward through the winter stratosphere reinforcing wavenumber-1 climatological eddies. As a consequence, stronger tropical deep convection is related to greater upward wave propagation and, consequently, to a stronger Brewer–Dobson circulation and a warmer polar winter stratosphere. This linkage between tropical deep convection and the Southern Hemisphere (SH) winter polar vortex is also found in the ERA-Interim reanalysis. Furthermore, model results indicate that the enhancement of deep convection observed during the easterly phase of the QBO (E-QBO) gives rise to a similar modulation of the southern winter extratropical stratosphere, which suggests that the QBO modulation of convection plays a fundamental role in the transmission of the QBO signature to the southern stratosphere during the austral winter, revealing a new pathway for the QBO–SH polar vortex connection. ERA-Interim corroborates a QBO modulation of deep convection; however, the shorter data record does not allow us to assess its possible impact on the SH polar vortex.