bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of YggS in Vitamin B6 Homeostasis in Salmonella enterica Is Informed by Heterologous Expression of Yeast SNZ3
Authors: Vu Huong N. , Ito Tomokazu , Downs Diana M. 
Published: September 2020

ABSTRACT
YggS (COG0325) is a pyridoxal 5′-phosphate (PLP)-binding protein proposed to be involved in homeostasis of B6 vitamers. In Salmonella enterica, lack of yggS resulted in phenotypes that were distinct and others that were similar to those of a yggS mutant of Escherichia coli. Like other organisms, yggS mutants of S. enterica accumulate endogenous pyridoxine 5′-phosphate (PNP). Data herein show that strains lacking YggS accumulated ∼10-fold more PLP in growth medium than a parental strain. The deoxyxylulose 5-phosphate-dependent biosynthetic pathway for PLP and the PNP/pyridoxamine 5′-phosphate (PMP) oxidase credited with interconverting B6 vitamers were replaced with a single PLP synthase from Saccharomyces cerevisiae. The impact of a yggS deletion on the intracellular and extracellular levels of B6 vitamers in this restructured strain supported a role for PdxH in PLP homeostasis and led to a general model for YggS function in PLP-PMP cycling. Our findings uncovered broader consequences of a yggS mutation than previously reported and suggest that the accumulation of PNP is not a direct effect of lacking YggS but rather a downstream consequence.
IMPORTANCE Pyridoxal 5′-phosphate (PLP) is an essential cofactor for enzymes in all domains of life. Perturbations in PLP or B6 vitamer content can be detrimental, notably causing B6-dependent epilepsy in humans. YggS homologs are broadly conserved and have been implicated in altered levels of B6 vitamers in multiple organisms. The biochemical activity of YggS, expected to be conserved across domains, is not yet known. Herein, a simplified heterologous pathway minimized metabolic variables and allowed the dissection of this system to generate new metabolic knowledge that will be relevant to understanding YggS.
Intentional weight loss as a predictor of type 2 diabetes occurrence in a general adult population
Authors: Sares-Jäske Laura , Knekt Paul , Eranti Antti , Kaartinen Niina E , Heliövaara Markku , Männistö Satu 
Published: September 2020

IntroductionObservational and intervention studies have verified that weight loss predicts a reduced type 2 diabetes (T2D) risk. At the population level, knowledge on the prediction of self-report intentional weight loss (IWL) on T2D incidence is, however, sparse. We studied the prediction of self-report IWL on T2D incidence during a 15-year follow-up in a general adult population.Research design and methodsThe study sample from the representative Finnish Health 2000 Survey comprised 4270 individuals, aged 30–69 years. IWL was determined with questions concerning dieting attempts and weight loss during the year prior to baseline. Incident T2D cases during a 15-year follow-up were drawn from national health registers. The strength of the association between IWL and T2D incidence was estimated with the Cox model.ResultsDuring the follow-up, 417 incident cases of T2D occurred. IWL predicted an increased risk of T2D incidence (HR 1.44; 95% CI 1.11 to 1.87, p=0.008) in a multivariable model. In interaction analyses comparing individuals with and without IWL, a suggestively elevated risk emerged in men, the younger age group, among less-educated people and in individuals with unfavorable values in several lifestyle factors.ConclusionsSelf-report IWL may predict an increased risk of T2D in long-term, probably due to self-implemented IWL tending to fail. The initial prevention of weight gain and support for weight maintenance after weight loss deserve greater emphasis in order to prevent T2D.
Trends and determinants of home delivery in Ethiopia: further multivariate decomposition analysis of 2005–2016 Ethiopian Demographic Health Surveys
Authors: Tiruneh Sofonyas Abebaw , Lakew Ayenew Molla , Yigizaw Seblewongel Tigabu , Sisay Malede Mequanent , Tessema Zemenu Tadesse 
Published: September 2020

ObjectiveThis study aimed to assess the trends and factors that had contributed to the change in home delivery in Ethiopia over the last decade.Design, setting and analysisA nationally representative repeated cross-sectional survey was conducted using 2005, 2011 and 2016 Ethiopian Demographic and Health Surveys. Multivariate decomposition logistic regression analysis was employed to identify significant factors that have been contributed to the change in home delivery. Level of statistical significance was declared at a two-sided p value <0.05.Outcome measureTrends of home delivery.ParticipantsA total of 33 482 women were included.ResultsHome delivery has been decreased by 21% over the last decade in Ethiopia. In the last decade, 39% of the decrements in home delivery attributed to change in women’s compositional characteristics. Antenatal care visits, educational status of the women and husband, birth order, religion, wealth index and distance from a health facility were the main sources of compositional change factors for the change of home delivery. Behavioural changes towards health facility delivery contributed approximately two-thirds of the decline of home delivery in Ethiopia. Antenatal care visits, birth order and religion have significantly contributed to the change of home delivery resulted from behavioural changes towards healthcare facility utilisation over the last decade.ConclusionDespite the importance of health facility delivery, a significant number of women still deliver at home in Ethiopia. Women’s compositional characteristics and behaviour changes were significantly associated with the change in home delivery. Multisectoral educational intervention is needed to change women’s attitudes towards home delivery. Antenatal care coverage and healthcare facility coverage should increase thereby to improve healthcare facility based-delivery practice. Further research needs to be done to explore the potential barriers of health facility delivery from a religious perspective.
Randomised cross-over trial of vildagliptin and pioglitazone as add-on therapy in patients with type 2 diabetes: predicting Which One is Right Here (WORTH) study protocol
Authors: Yeu Rui Qian , Brandon Rebecca , Jiang Yannan , Griffiths Dale , Smallman Kate , Moffitt Allan , Doherty Glenn , Paul Ryan , Harré Hindmarsh Jennie , Merriman Tony R , Macaskill-Smith Kerry , Orr-Walker Brandon , Murphy Rinki 
Published: September 2020

IntroductionThere is emerging evidence for stratified glucose-lowering responses to certain oral medications for type 2 diabetes (T2D) by individual characteristics. The objective of this study was to test whether glycaemic response to representative treatments of dipeptidyl peptidase-4 inhibitors (vildagliptin) and thiazolidinediones (pioglitazone) varies according to ethnicity, gender, baseline obesity, triglyceride level or genetic variation.MethodsThis is a multicentre, two-period, two-treatment, open-label, randomised cross-over trial of vildagliptin and pioglitazone as second-line or third-line therapy in patients with T2D who have suboptimal glycaemic control on metformin and/or sulfonylurea therapy. It is conducted in New Zealand with a target of 300 patients (40% with Māori or Pacific ancestry) eligible if aged ≥18 and ≤80 years, with T2D for more than 1 year, on stable doses of metformin and/or sulfonylurea for at least 3 months, with HbA1c between 59 and 110 mmol/mol inclusive. Participants are assigned to complete 4 months of vildagliptin 50 mg per day or pioglitazone 30 mg per day, followed by 4 months of the other medications in randomly allocated sequences. Participant characteristics, including ethnicity, obesity, lipid profile and candidate genotypes are collected at baseline. Primary outcome variable is on treatment HbA1c. Secondary outcomes include weight change, frequency of side effects and patient preference.Ethics and disseminationEthical approval of the trial has been obtained from the New Zealand Health and Disability Ethics Committee (18/STH/242). The trial commenced in February 2019 and recruitment is expected to be completed by March 2020. Results will be reported in articles submitted to peer-reviewed journals, as well as in presentations at national and international meetings.Trial registration numberACTRN12618001907235.
Study protocol for the international Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS): understanding lupus and the role of type I interferon gene signature
Authors: Hammond Edward R , Tummala Raj , Berglind Anna , Syed Farhat , Wang Xia , Desta Barnabas , Nab Henk 
Published: September 2020

IntroductionThe Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status.Methods and analysisSPOCS is an international, multicentre, prospective, observational cohort study designed to follow patients through biannual study visits during a 3-year observation period. Patients ≥18 years old with a physician diagnosis that meets the American College of Rheumatology or Systemic Lupus International Collaborating Clinics SLE classification criteria will be included. SPOCS will comprehensively analyse clinical features, disease progression and treatment, SLE outcomes, health status assessments and quality of life, and healthcare resource utilisation of patients with moderate to severe SLE. A four-gene test will be used to measure IFNGS status; scores will be compared with a pre-established cut-off. Patients will be stratified by low or high IFNGS expression levels. Enrolment began in June 2017, and study completion is expected in 2022. The total number of anticipated patients was initially planned for 1500 patients and was amended to 900 patients owing to slow accrual of eligible patients.Ethics and disseminationThe ethics committee/institutional review board/independent ethics committee at each study site approved the SPOCS protocol prior to study initiation (protocol number: D3461R00001, version 3.0, 26 June 2019). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.Trial registration numberNCT03189875.
Effects of coenzyme Q10 on endothelial and cardiac function in patients undergoing haemodialysis: study protocol for a pilot randomised controlled trial
Authors: Xu Yongxing , Li Xinlou , Zuo Xiaowen , Jia Huaping , Han Enhong , Liang Fugui , Xie Lei , Gao Jianjun 
Published: September 2020

IntroductionEndothelial and cardiac dysfunction are highly prevalent and are associated with cardiovascular morbidity and mortality among patients undergoing dialysis. For patients undergoing dialysis, no study has explored the effect of supplementation of coenzyme Q10 (CoQ10) on endothelial function. To our best of knowledge, only two small sample studies focused on the efficacy of supplementation of CoQ10 on cardiac function. However, the effect of CoQ10 supplementation on cardiac function remains uncertain in patients who undergo haemodialysis. The aim of this study is to explore whether CoQ10 supplementation can improve endothelial and cardiac function in patients undergoing haemodialysis.Methods and analysisThis is a pilot randomised controlled study. Eligible patients undergoing haemodialysis in our haemodialysis centre will be randomly allocated to the CoQ10 and control groups. The follow-up time is 12 months. The primary outcome is to assess the change of brachial artery endothelial-dependent flow-mediated dilation, left ventricular systolic function, diastolic function and Myocardial Performance Index at 12 months from baseline. Secondary outcomes are death or hospitalisation due to cardiovascular events, all-cause mortality, change of CoQ10 concentration, the ratio of ubiquinol to ubiquinone, the change of oxidative stress markers (including malondialdehyde and 8-hydroxy-deoxyguanosine) and Left Ventricular Mass Index.Ethics and disseminationRisks associated with CoQ10 are minor, even at doses as high as 1800 mg according to previous studies. The trial has received ethics approval from the Medical Ethics Committee for Clinical Trials of Drugs, the 306th Hospital of Chinese PLA. The results of the study are expected to be published in a peer-reviewed journal and presented at academic conferences.Trial registration numberChiCTR1900022258.
Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study
Authors: Sundbøll Jens , Szépligeti Szimonetta Komjáthiné , Adelborg Kasper , Szentkúti Péter , Gregersen Hans , Sørensen Henrik Toft 
Published: September 2020

ObjectivesTo assess the risks of myocardial infarction, stroke, peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter and heart failure in patients with constipation compared with a general population cohort.DesignPopulation-based matched cohort study.SettingAll Danish hospitals and hospital outpatient clinics from 2004 to 2013.ParticipantsPatients with a constipation diagnosis matched on age, sex and calendar year to 10 individuals without constipation from the general population.Main outcomes measuresComorbidity-adjusted and medication-adjusted hazard ratios (aHRs) for cardiovascular outcomes based on Cox regression analysis.Results83 239 patients with constipation were matched to 832 384 individuals without constipation. The median age at constipation diagnosis was 46.5% and 41% were men. Constipation was strongly associated with venous thromboembolism (aHR 2.04, 95% CI 1.89 to 2.20), especially splanchnic venous thrombosis (4.23, 95% CI 2.45 to 7.31). Constipation was also associated with arterial events, including myocardial infarction (1.24, 95% CI 1.14 to 1.35), ischaemic stroke (1.50, 95% CI 1.41 to 1.60), haemorrhagic stroke (1.46, 95% CI 1.26 to 1.69), peripheral artery disease (1.34, 95% CI 1.20 to 1.50), atrial fibrillation or atrial flutter (1.27, 95% CI 1.20 to 1.34) and heart failure (1.52, 95% CI 1.42 to 1.62). The associations were strongest during the first year after the constipation diagnosis and strengthened with an increased number of laxative prescriptions.ConclusionsConstipation was associated with an increased risk of several cardiovascular diseases, in particular venous thromboembolism.
Age distribution and types of breast lesions among Afghan women diagnosed by fine needle aspiration cytology (FNAC) at a tertiary care centre in Afghanistan: a descriptive cross-sectional study
Authors: Saadaat Ramin , Abdul-Ghafar Jamshid , Haidary Ahmed Maseh , Rahmani Soma , Atta Nooria 
Published: September 2020

ObjectivesIn Afghanistan, breast diseases are a common reason for women to visit hospitals. This is the first study in Afghanistan aimed to describe the age distribution and types of breast diseases among patients diagnosed by fine needle aspiration cytology.DesignDescriptive cross-sectional study.SettingFrench Medical Institute for Mothers and Children, Kabul, Afghanistan.ParticipantsThe study included 650 patients with breast lesions between 1 April 2015 and 1 April 2019.ResultsThe mean age of diagnosis was 35.38 (SD ±13.11) years, ranging from 15 to 75 years. The most common diagnosis was cancer (24% of all cases). The second most common diagnosed lesion was fibroadenoma, constituting 22.4%, and the third most common lesion was fibrocystic changes, with 15.4% of cases. Inflammatory conditions were diagnosed in 9.7% of cases, granulomatous inflammation in 9.1%, lesions only suspicious for malignancy in 5.5%, lipoma in 2.8% and miscellaneous benign lesions in 11.1%. Cancer was diagnosed at the youngest age of 20 years. Cancer was more common on the left side (62%), and only one case (0.9%) was bilateral.ConclusionOur study showed that cancer was the most commonly diagnosed lesion and was reported at younger ages too. This suggests that physicians should not ignore any breast lump in younger patients and that the possibility of cancer must be considered. Further country-wide studies are suggested to assess breast cancer and associated risk factors.
Person-centred eHealth intervention for patients on sick leave due to common mental disorders: study protocol of a randomised controlled trial and process evaluation (PROMISE)
Authors: Cederberg Matilda , Ali Lilas , Ekman Inger , Glise Kristina , Jonsdottir Ingibjörg H , Gyllensten Hanna , Swedberg Karl , Fors Andreas 
Published: September 2020

IntroductionThe number of people dealing with common mental disorders (CMDs) is a major concern in many countries, including Sweden. Sickness absence resulting from CMDs is often long-lasting and advancing return to work is a complex process impacted by several factors, among which self-efficacy appears to be an important personal resource. Person-centred care (PCC) has previously shown positive effects on self-efficacy however this needs to be further investigated in relation to patients with CMDs and in an eHealth context.Methods and analysisThis study is an open randomised controlled trial comparing a control group receiving standard care with an intervention group receiving standard care plus PCC by telephone and a digital platform. The primary outcome measure is a composite score of changes in sick leave and self-efficacy. Participants will include 220 primary care patients on sick leave due to CMDs and data will mainly be collected through questionnaires at baseline and 3, 6, 12 and 24 months from the inclusion date. Inclusion is ongoing and expected to be completed during the fall of 2020. A process and health economic evaluation will also be conducted.Ethics and disseminationThis study was approved by the Regional Ethical Review Board in Gothenburg, Sweden. Results will be published in peer-reviewed scientific journals and presented at national and international scientific conferences. This project is part of a broader research programme conducted at the Gothenburg Centre for Person-Centred Care (GPCC), where extensive work is undertaken to disseminate knowledge on and implementation of PCC.Trial registration numberNCT03404583.
Sex differences in prevalence and determinants of hypertension among adults: a cross-sectional survey of one rural village in Bangladesh
Authors: Islam Jessica Yasmine , Zaman M Mostafa , Ahmed Jasim Uddin , Choudhury Sohel Reza , Khan Hasanuzzaman , Zissan Tashfin 
Published: September 2020

ObjectivePrevention of mortality due to cardiovascular disease (CVD) through control of hypertension is a public health priority in Bangladesh. Our objective was to assess sex differences in prevalence and determinants of hypertension among adults in one rural area of Bangladesh.Study designCross-sectional.Setting and participantsFrom January 2014 to December 2015, we conducted a cross-sectional study of 2600 men and women aged ≥18 years located in one rural district of Bangladesh. We collected data on demographics, behavioural factors, physical measurements and health history.Primary outcome measuresOur primary outcome was hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mm Hg).ResultsThe average age of participants was 41.6 years and 53.7% were women. Hypertension prevalence was 6.9% (95% CI 5.9 to 7.9), and was significantly higher among women (8.9%) than men (4.5%). The highest prevalence of hypertension was observed among women aged ≥60 years at 21.3% (95% CI 16.6 to 26.7). A higher proportion of men with hypertension were aware of their condition (72.2%) compared with women (52.4%). Determinants of hypertension included older age, higher education, current tobacco use, increasing body mass index, and hyperglycaemia.ConclusionOur research suggests that hypertension prevalence is higher among women than men in rural Bangladesh. Sex-specific interventions should be developed to inform adults of the necessary lifestyle changes that may reduce the risk of hypertension and subsequent CVDs.
Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes
Authors: Halter Mary , Drennan Vari , Wang Chao , Wheeler Carly , Gage Heather , Nice Laura , de Lusignan Simon , Gabe Jonathan , Brearley Sally , Ennis James , Begg Phil , Parle Jim 
Published: September 2020

ObjectivesTo compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training.DesignMixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates.SettingThree emergency departments in England.ParticipantsThe records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation.Primary and secondary outcome measuresThe primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience.ResultsRe-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients’ charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role.ConclusionsPhysician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.