bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study
Authors: Chen Yung-Hsuan , Chen Yen-Fu , Chen Chung-Yu , Shih Jin-Yuan , Yu Chong-Jen 
Published: October 2019

Abstract

Background
Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations often develop brain metastases. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) has shown the effectiveness; however, knowledge of the clinical factors associated with outcomes in NSCLC patients with EGFR mutations remains limited.

Methods
Treatment-naive patients diagnosed with advanced non-squamous NSCLC with brain metastases harboring EGFR mutations and treated with an EGFR-TKI as first-line therapy were enrolled with analysis of their medical records.

Results
A total of 134 advanced NSCLC patients with brain metastases harboring EGFR mutations received an EGFR-TKI (gefitinib: 62, erlotinib: 49, and afatinib: 23) as the first-line therapy. Sixty-nine had exon 19 deletions (51.5%), and 56 (41.8%) had L858R mutations. There was no statistically significant difference in progression-free survival (PFS) and overall survival (OS) among the EGFR-TKIs. Significantly shorter OS was noted in patients with multiple brain metastases (hazard ratio [HR]: 2.43, p = 0.007), uncommon EGFR mutations (HR: 3.75, p = 0.009), and liver metastases. Thirty-eight patients (29.1%) received brain radiotherapy for brain metastases before disease progression, and had a significantly longer time until intracranial progression. However, the brain radiotherapy had no statistically significant impact on PFS or OS.

Conclusions
Patients with uncommon mutations, multiple brain metastases, and concomitant liver metastases tended to have shorter OS. Brain radiotherapy could delay the time to intracranial disease progression but had no impact on survival. The different first-line EGFR-TKIs achieved similar treatment responses in terms of PFS and OS in the EGFR-mutated NSCLC patients with brain metastases.
The use of PanDrugs to prioritize anticancer drug treatments in a case of T-ALL based on individual genomic data
Authors: Fernández-Navarro Pablo , López-Nieva Pilar , Piñeiro-Yañez Elena , Carreño-Tarragona Gonzalo , Martinez-López Joaquín , Sánchez Pérez Raúl , Aroca Ángel , Al-Shahrour Fátima , Cobos-Fernández María Ángeles , Fernández-Piqueras José 
Published: October 2019

AbstractBackgroundAcute T-cell lymphoblastic leukaemia (T-ALL) is an aggressive disorder derived from immature thymocytes. The variability observed in clinical responses on this type of tumours to treatments, the high toxicity of current protocols and the poor prognosis of patients with relapse or refractory make it urgent to find less toxic and more effective therapies in the context of a personalized medicine of precision.MethodsWhole exome sequencing and RNAseq were performed on DNA and RNA respectively, extracted of a bone marrow sample from a patient diagnosed with tumour primary T-ALL and double negative thymocytes from thymus control samples. We used PanDrugs, a computational resource to propose pharmacological therapies based on our experimental results, including lists of variants and genes. We extend the possible therapeutic options for the patient by taking into account multiple genomic events potentially sensitive to a treatment, the context of the pathway and the pharmacological evidence already known by large-scale experiments.ResultsAs a proof-of-principle we used next-generation-sequencing technologies (Whole Exome Sequencing and RNA-Sequencing) in a case of diagnosed Pro-T acute lymphoblastic leukaemia. We identified 689 disease-causing mutations involving 308 genes, as well as multiple fusion transcript variants, alternative splicing, and 6652 genes with at least one principal isoform significantly deregulated. Only 12 genes, with 27 pathogenic gene variants, were among the most frequently mutated ones in this type of lymphoproliferative disorder. Among them, 5 variants detected inCTCF, FBXW7, JAK1, NOTCH1andWT1genes have not yet been reported in T-ALL pathogenesis.ConclusionsPersonalized genomic medicine is a therapeutic approach involving the use of an individual’s information data to tailor drug therapy. Implementing bioinformatics platform PanDrugs enables us to propose a prioritized list of anticancer drugs as the best theoretical therapeutic candidates to treat this patient has been the goal of this article. Of note, most of the proposed drugs are not being yet considered in the clinical practice of this type of cancer opening up the approach of new treatment possibilities.
Early maladaptive schemas impact on long-term outcome in patients treated with group behavioral therapy for obsessive-compulsive disorder
Authors: Sunde Tor , Hummelen Benjamin , Himle Joseph A. , Walseth Liv Tveit , Vogel Patrick A. , Launes Gunvor , Haaland Vegard Øksendal , Haaland Åshild Tellefsen 
Published: October 2019

AbstractBackgroundSome studies have previously found that certain elevated early maladaptive schemas (EMSs) are negative predictors for outcome for patients with obsessive-compulsive disorder (OCD) treated with Cognitive-Behavioral Therapy (CBT) or Exposure and Response Prevention (ERP). The current study explores whether EMS were related to reductions in OCD symptom severity at long-term follow-up (Mean = 8 years) after group ERP for patients with OCD. The central hypothesis was that patients with no response to treatment or patients who relapsed during the follow-up period were more likely to have elevated pre-treatment EMSs compared to those who responded to initial treatment and maintained gains over time. We also investigated whether there were any differences in change over time of overall EMS between patients who were recovered versus patients who were not recovered at extended follow-up.MethodsYoung Schema Questionnaire –Short Form (YSQ-SF), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) were measured in 40 OCD patients in a general outpatient clinic before and after group ERP, after 12-months and at extended follow-up. To analyze the predictors, a multiple regression analyses was conducted. Changes in overall EMS was analyzed by mixed models procedures.ResultsThe major finding is that patients with high pre-treatment YSQ-SF total scores were less likely to respond to initial treatment or were more likely to relapse between post-treatment and the extended follow-up. The YSQ-SF total score at pre-treatment explained 10.5% of the variance of extended long-term follow-up outcome. The entire sample experienced a significant reduction in overall EMS over time with largest reduction from pre- to post-test. There were no statistically significant differences in total EMS change trajectories between the patients who were recovered at the extended follow-up compared to those who were not.ConclusionThe results from the present study suggest that patients with higher pre-treatment EMSs score are less likely to recover in the long-term after receiving group ERP for OCD. A combined treatment that also targets early maladaptive schemas may be a more effective approach for OCD patients with elevated EMS who don’t respond to standard ERP.
“He can send her to her parents”: The interaction between marriageability, gender and serious mental illness in rural Ethiopia
Authors: Hailemariam Maji , Ghebrehiwet Senait , Baul Tithi , Restivo Juliana L. , Shibre Teshome , Henderson David C. , Girma Eshetu , Fekadu Abebaw , Teferra Solomon , Hanlon Charlotte , Johnson Jennifer E. , Borba Christina P. C. 
Published: October 2019

AbstractBackgroundFor women in most low- and middle-income countries, the diagnosis with serious mental illness (SMI) leads to stigma and challenges related to starting or maintaining marriages. The purpose of this qualitative study was to explore perspectives on marriage, divorce and family roles of women with SMI in rural Ethiopia.MethodsA qualitative study was conducted in a rural setting of Butajira, South Central Ethiopia. A total of 39 in-depth interviews were carried out with service users (n = 11), caregivers (n = 12), religious leaders (n = 6), health extension workers (n = 4), police officers (n = 2), teachers (n = 2) and government officials (n = 2). Data were analyzed using a thematic approach.ResultsThree themes emerged. (1) Marriage and SMI: Chances of getting married for individuals with SMI in general was perceived to be lower: Individuals with SMI experienced various challenges including difficulty finding romantic partner, starting family and getting into a long-term relationship due to perceived dangerousness and the widespread stigma of mental illness. (2) Gendered experiences of marriageability: Compared to men, women with SMI experienced disproportionate levels of stigma which often continued after recovery. SMI affects marriageability for men with SMI, but mens' chances of finding a marital partner increases following treatment. For women in particular, impaired functioning negatively affects marriageability as ability to cook, care and clean was taken as the measure of suitability. (3) Acceptability of divorce and separation from a partner with SMI: Divorce or separation from a partner with SMI was considered mostly acceptable for men while women were mostly expected to stay married and care for a partner with SMI. For men, the transition from provider to dependent was often acceptable. However, women who fail to execute their domestic roles successfully were considered inept and would be sent back to their family of origin.ConclusionWomen with SMI or those married to partners with SMI are at greater disadvantage. Reducing vulnerabilities through stigma reduction efforts such as community outreach and mental health awareness raising programs might contribute for better social outcomes for women with SMI.
Population-based surveys and interventions for mental health literacy in China during 1997–2018: a scoping review
Authors: Lu Shurong , Oldenburg Brian , Li Wenjing , He Yanling , Reavley Nicola 
Published: October 2019

AbstractBackgroundThis scoping review maps population-based surveys and mental health literacy (MHL) interventions undertaken in China during 1997–2018 in order to identify research gaps.MethodFollowing Arksey and O’Malley’s framework for a scoping review, five English databases (Medline, PsycINFO, Cochrane library, Web of Science and CINAHL) and two Chinese ones (CNKI and WanFang) were systematically searched, identifying both reports of surveys and evaluation of interventions from Jan 1997 to Oct 2018.ResultsMHL research has developed rapidly in China in terms of numbers of studies and geographic coverage over the past two decades. There were 350 peer-reviewed publications included in this review, covering diverse settings and participants. Of these publications, 313 (89.4%) were published in Chinese-language journals and 37 in English-language journals; 303 (86.6%) reported on survey findings and 47 reported on the evaluation of MHL interventions. MHL research in China has mainly focused on the assessment of mental health-related knowledge and beliefs. Much less attention has been given to developing and evaluating relevant interventions. MHL related to general mental health and suicide were most commonly studied, with less focus on specific disorders, although some studies covered depression, psychosis and anxiety disorders. The majority of MHL tools utilized in the studies reported in this review were developed in China (n = 97, 80.2% ) and almost half of these studies (57.8%) did not provide enough details concerning psychometrics.ConclusionsMore interventions targeting the general public and aiming to improve MHL and promote behaviour change, are needed in China. These should be evaluated with high-quality study designs, such as randomised controlled trials. Proper validation of tools used for measuring MHL should also be addressed in future studies.
Cross-sectional analysis of self-reported sedentary behaviors and chronic knee pain among South Korean adults over 50 years of age in KNHANES 2013-2015
Authors: Lee Sook-Hyun , Son Chihyoung , Yeo Sujung , Ha In-Hyuk 
Published: October 2019

Abstract

Background
An increasing amount of evidence supports an association between sedentary behaviors and chronic knee pain. However, the association between the total daily duration of sedentary behavior and chronic knee pain in the general population remains unclear. We aimed to analyze the association between sedentary behavior and chronic knee pain in a study population representative of the general Korean population aged > 50 years while also considering the physical activity or body mass index (BMI).

Methods
This cross-sectional study used data from the 6th Korean National Health and Nutrition Examination Survey (KNHANES VI) of 2013–2015, which was completed by 22,948 Korean adult participants aged > 50 years. The participants were divided into two groups based on the status of the chronic knee pain. Data were analyzed using multivariable logistic regression after adjustment for age, sex, and individual factors.

Results
Longer sedentary behavior was correlated with chronic knee pain (p for trend = 0.02). Sedentary behavior exceeding 10 h/day was significantly associated with chronic knee pain (adjusted odds ratio, 1.28; p = 0.03). Participants with high levels of physical activity were less likely to suffer from chronic knee pain (adjusted odds ratio, 0.78; p = 0.00), and women with over 10 daily hours of sedentary behavior with high levels of physical activity were more likely to have chronic knee pain. A significant association was noted between chronic knee pain and obesity (≥30.0 kg/m2) individuals (adjusted odds ratio, 3.48; p = 0.04).

Conclusions
Longer duration of sedentary behaviors was correlated with chronic knee pain. Our study suggests the need to encourage reductions in overall sedentary behavior to < 10 h daily. A high physical activity level is recommended, particularly for women > 50 years and those with obesity.
Trends in working conditions and health across three cohorts of older workers in 1993, 2003 and 2013: a cross-sequential study
Authors: van der Noordt M. , Hordijk H. J. , IJzelenberg W. , van Tilburg T. G. , van der Pas S. , Deeg D. J. H. 
Published: October 2019

AbstractBackgroundOver the past decades, the number of older workers has increased tremendously. This study examines trends from 1993 to 2013 in physical, cognitive and psychological functioning among three successive cohorts of Dutch older workers. The contribution of the changes in physical and psychosocial work demands and psychosocial work resources to change in functioning is examined. Insight in health of the older working population, and in potential explanatory variables, is relevant in order to reach sustainable employability.MethodsData from three cohorts (observations in 1993, 2003 and 2013) of the Longitudinal Aging Study Amsterdam (LASA) were used. Individuals aged 55–65 with a paid job were included (N = 1307). Physical functioning was measured using the Timed Chair Stand Test, cognitive functioning by a Coding Task and psychological functioning by the positive affect scale from the CES-D. Working conditions were deduced from a general population job exposure matrix. Linear and logistic regression analyses were performed.ResultsFrom 1993 to 2013, time needed to perform the Timed Chair Stand Test increased with 1.3 s (95%CI = 0.89–1.71), to a mean of 11.5 s. Coding Task scores increased with 1.7 points (95%CI = 0.81–2.59), to a mean of 31 points. The proportion of workers with low positive affect increased non-significantly from 15 to 20% (p = 0.088). Only the improvement in cognitive functioning was associated with the change in working conditions. The observed decrease of physically demanding jobs and increase of jobs with higher psychosocial resources explained 8% of the improvement.ConclusionsChanges in working conditions may not contribute to improved physical and psychological functioning, but do contribute to improved cognitive functioning to some extent. Further adjustment of physical work demands and psychosocial work resources may help to reach sustainable employability of older workers.
Associations between occupational factors and self-rated health in the national Brazilian working population
Authors: Oenning Nágila Soares Xavier , de Goulart Bárbara Niegia Garcia , Ziegelmann Patrícia Klarmann , Chastang Jean-François , Niedhammer Isabelle 
Published: October 2019

Abstract

Background
The literature remains seldom on the topic of self-rated health (SRH) among the national working populations of emerging countries. The objectives of the study were to examine the associations of occupational factors with SRH in a national representative sample of the working population in Brazil.

Methods
This study relied on a cross-sectional sample of 36,442 workers, 16,992 women and 19,450 men. SRH was the studied health outcome. Sixteen occupational factors related to four topics were studied: employment characteristics, working time/hours, psychosocial work factors and physical and chemical work exposures. The associations between occupational factors and SRH were studied using logistic regression models with adjustment for sociodemographic characteristics (age, ethnicity and marital status). The analyses were performed for each gender separately and using weights.

Results
The prevalence of poor SRH was 26.71%, this prevalence being higher among women (29.77%) than among men (24.23%). The following risk factors for poor SRH were found among men and women: working as a self-employed worker, clerk/service worker, manual worker, part-time (≤ 20 h/week), exposure to work stress, exposure to high physical activity and exposure to sun. The risk factors for poor SRH among women only were: working as a domestic worker and exposure to noise, and among men, working in the agriculture sector.

Conclusions
Our study suggested that occupational factors related to both physical and psychosocial work environment may be associated with SRH in the working population in Brazil. Improving working conditions may be beneficial for health at work in Brazil.
Community-based aftercare following an emergency department presentation for attempted suicide or high risk for suicide: study protocol for a non-randomised controlled trial
Authors: Bliokas Vida V. , Hains Alex R. , Allan Jonathan A. , Lago Luise , Sng Rebecca 
Published: October 2019

AbstractBackgroundSuicide is a major public health issue worldwide. Those who have made a recent suicide attempt are at high risk for dying by suicide in the future, particularly during the period immediately following departure from a hospital emergency department. As such the transition from hospital-based care to the community is an important area of focus in the attempt to reduce suicide rates. There is a need for evaluation studies to test the effectiveness of interventions directed to this stage (termed ‘aftercare’ interventions).MethodsA controlled non-randomised two group (intervention vs treatment-as-usual control) design, using an intention-to-treat model, will evaluate the effectiveness of a suicide prevention aftercare intervention providing follow-up after presentations to a hospital emergency department as a result of a suicide attempt or high risk for suicide. The intervention is a community-based service, utilising two meetings with a mental health clinician and follow-up contacts by peer workers via a combination of face-to-face and telephone for four weeks, with the option of extension to 12 weeks. Seventy-five participants of the intervention service will be recruited to the study and compared to 1265 treatment-as-usual controls. The primary hypotheses are that over 12 months, those who participate in the aftercare follow-up intervention are less likely than controls to present to a hospital emergency department for a repeat suicide attempt or because of high risk for suicide, will have fewer re-presentations during this period and will have lower all-cause mortality. As a secondary aim, the impact of the intervention on suicide risk factors for those who participate in the service will be evaluated using pre- and post-intervention repeated measures of depression, anxiety, stress, hopelessness, belongingness, burdensomeness, and psychological distress. Enrolments into the study commenced on 1 November 2017 and are anticipated to cease in November 2019.DiscussionThe study aims to contribute to the understanding of effective interventions for individuals who have presented to a hospital emergency department as a result of a suicide attempt or at high risk for suicide and provide evidence in relation to interventions that incorporate peer-workers.Trial registrationACTRN12618001701213. Registered on 16 October 2018. Retrospectively registered.
Use of the kojA promoter, involved in kojic acid biosynthesis, for polyketide production in Aspergillus oryzae: implications for long-term production
Authors: Tamano Koichi , Kuninaga Mahoko , Kojima Naoshi , Umemura Myco , Machida Masayuki , Koike Hideaki 
Published: October 2019

Abstract

Background
Aspergillus oryzae, a useful industrial filamentous fungus, produces limited varieties of secondary metabolites, such as kojic acid. Thus, for the production of valuable secondary metabolites by genetic engineering, the species is considered a clean host, enabling easy purification from cultured cells. A. oryzae has been evaluated for secondary metabolite production utilizing strong constitutive promoters of genes responsible for primary metabolism. However, secondary metabolites are typically produced by residual nutrition after microbial cells grow to the stationary phase and primary metabolism slows. We focused on a promoter of the secondary metabolism gene kojA, a component of the kojic acid biosynthetic gene cluster, for the production of other secondary metabolites by A. oryzae.

Results
A kojA disruptant that does not produce kojic acid was utilized as a host strain for production. Using this host strain, a mutant that expressed a polyketide synthase gene involved in polyketide secondary metabolite production under the kojA gene promoter was constructed. Then, polyketide production and polyketide synthase gene expression were observed every 24 h in liquid culture. From days 0 to 10 of culture, the polyketide was continuously produced, and the synthase gene expression was maintained. Therefore, the kojA promoter was activated, and it enabled the continuous production of polyketide for 10 days.

Conclusions
The combined use of the kojA gene promoter and a kojA disruptant proved useful for the continuous production of a polyketide secondary metabolite in A. oryzae. These findings suggest that this combination can be applied to other secondary metabolites for long-term production.