Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging alters phenotypic traits of thyroid dysfunction in male mice with divergent effects on complex systems but preserved thyroid hormone action in target organs.

Clinical manifestation of hyperthyroidism and hypothyroidism vary with age, with an attenuated, oligosymptomatic presentation of thyroid dysfunction (TD) in older patients. We asked, whether in rodents TD phenotypes are influenced by age and whether this involves changes in systemic and/or organ thyroid hormone (TH) signaling. Chronic hyper- or hypothyroidism was induced in male mice at different life stages (5, 12, 20 months). TH excess resulted in pronounced age-specific body weight changes (increase in youngest and decrease in old mice), neither explained by changes in food intake (similar increase at all ages), nor by thermogenic gene expression in brown adipose tissue (BAT) or TH serum concentrations. Relative increase in body temperature and activity were more pronounced in old compared to young hyperthyroid mice. An attenuated hypothyroid state was found in old mice for locomotor activity and in heart and BAT on functional (less bradycardia) and gene expression level (heart and BAT). In contrast, decrease in body weight was pronounced in old hypothyroid mice. Thus, age has divergent impact on features of TD in mice, whereby effects on highly complex systems, such as energy homeostasis are not proportional to serum TH state, in contrast to organ-specific responses in heart and BAT.
Prevalence Of Diabetic Complications In Newly Diagnosed Type 2 Diabetes Patients In Pakistan: Findings From National Registry.

Background This study was conducted to assess the prevalence of micro- and macrovascular complications in patients with newly diagnosed type 2 diabetes (T2DM) in Pakistan. Methods In this multicentre, observational, cross-sectional disease registry, patients (aged ≥18 years) who were diagnosed at enrolment with T2DM, defined by fasting blood glucose (FBG) ≥126 mg/dL and/or glycated haemoglobin (HbA1c) ≥6.5%, were enrolled. Microvascular complications were ascertained by objective examination while macrovascular complications were identified from patients' medical history. Descriptive statistics were used for data analysis. Results Data from 891 patients were analysed in the study. Mean [±standard deviation (SD)] HbA1c, FBG, and random blood glucose were 9.9% (±2.2%), 193.4 (±74.0) mg/dL, and 294.3 (±72.7) mg/dL, respectively. Obesity (n=689, 77.3%) and familial history of diabetes (n=575, 64.3%) were the most common risk factors for T2DM. Overall prevalence of micro- and macrovascular complications was 68.6% [n=611, 95% confidence interval (CI): 65.4-71.5] and 9.0% (n=80, 95% CI: 7.3-11.0), respectively. Neuropathy, nephropathy, and retinopathy were reported in 59.6% (95% CI: 56.3-62.8), 24.4% (95% CI: 21.6-27.2), and 15.9% (95% CI: 13.7-18.5) of the patients, respectively. Oral antidiabetic agents and insulin were prescribed to 839 (94.2%) and 140 (15.7%) patients, respectively. All study patients received education on T2DM management, mostly from the investigators, and also from diabetes educators and nurses. Conclusion The prevalence of micro- and macrovascular complications of T2DM is high, indicating a delay in diagnosis of disease. In order to counter the burden of diabetic complications, optimum strategies for screening of the general population are required.
Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy

Abstract Aims To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification. Methods and results This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat (n = 537) and non-febuxostat groups (n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively (P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592–0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562–0.987; P = 0.041). Conclusion Febuxostat lowers uric acid and delays the progression of renal dysfunction. Registration ClinicalTrials.gov (NCT01984749).
The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births

Background In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates. Methods and findings We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015–23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015–2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2–49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2–369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data. Conclusions This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.
Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases

Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Injury to OLs causes myelin loss. In demyelinating diseases, such as multiple sclerosis, the remyelination is hindered principally due to a failure of the oligodendrocyte precursor cells (OPCs) to differentiate into mature OLs. To identify inducers of OPC to OL differentiation, a high‐throughput screening based on myelin basic protein expression using neural progenitor cells‐derived OPCs has been performed and, PD0325901—an MEK (MAPK kinase) inhibitor—is found to significantly enhance OPC to OL differentiation in a dose‐ and time‐dependent manner. Other MEK inhibitors also display similar effect, indicating blockade of MAPK–ERK signaling is sufficient to induce OPC differentiation into OLs. PD0325901 facilitates the formation of myelin sheaths in OPC–neuron co‐culture in vitro. And in experimental autoimmune encephalomyelitis model and cuprizone‐induced demyelination model, PD0325901 displays significant therapeutic effect by promoting myelin regeneration. Our results suggest that targeting the MAPK–ERK pathway might be an intriguing way to develop new therapies for demyelinating diseases.
Positioning the Value of Dietary Carbohydrate, Carbohydrate Quality, Glycemic Index, and GI Labelling to the Canadian Consumer for Improving Dietary Patterns

The objectives of this qualitative study was to: (1) understand Canadian consumers’ knowledge and perception of dietary carbohydrates, carbohydrate quality, and the glycemic index (GI); and (2) determine Canadian’s receptiveness to GI labelling to assist with identifying and consuming foods of higher carbohydrate quality. Focus groups were recruited in Vancouver, Toronto, and Montreal and grouped according to body mass index (BMI) (NBW, normal body weight; PO, previously obese; and OW/OB, overweight/obese) and diagnosis with prediabetes and diabetes (PO (Vancouver) and OW/OB (Montreal and Toronto). Subjects in all groups linked excess consumption of carbohydrate with weight gain. PO and OW/OB groups were conflicted between perceived negative consequences and feelings of pleasure associated with carbohydrate consumption. Subjects were largely unfamiliar with the term ‘carbohydrate quality’, but were often associated with classifying carbohydrates as ‘good’ or ‘bad’. The concept of the GI resonated well across groups after exposure to corresponding educational materials. However, NBW groups largely felt that the GI was irrelevant to their dietary choices as they did not have a history of diabetes. PO and OW/OB groups associated the GI with diabetes management. The concept of a GI labelling program to help facilitate healthier carbohydrate choices was well received across all groups, especially when the low GI was interpreted as giving permission to consume foods they enjoyed eating. Results suggest that the GI could be used as a consumer-facing labelling program in Canada and assist with de-stigmatizing carbohydrate foods by helping to facilitate the consumption of carbohydrate foods that align with healthy dietary patterns.
The Time is Now to Control Typhoid

Time to Control Typhoid • CID 2019:68 (Suppl 2) • S47 Correspondence: K. M. Neuzil, Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, 685 West Baltimore St. HSF1-Room 480, Baltimore, MD 21201 (kneuzil@som.umaryland.edu). Clinical Infectious Diseases 2019;68(S2):S47–9 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/cid/ciy1115 The Time is Now to Control Typhoid
Impact of drug consumption rooms on risk practices and access to care in people who inject drugs in France: the COSINUS prospective cohort study protocol

Introduction The high prevalence of hepatitis C and the persistence of HIV and hepatitis C virus (HCV) risk practices in people who inject drugs (PWID) in France underlines the need for innovative prevention interventions. The main objective of this article is to describe the design of the COSINUS cohort study and outline the issues it will explore to evaluate the impact of drug consumption rooms (DCR) on PWID outcomes. Secondary objectives are to assess how DCR (a) influence other drug-related practices, such as the transition from intravenous to less risky modes of use, (b) reduce drug use frequency/quantity, (c) increase access to treatment for addiction and comorbidities (infectious, psychiatric and other), (d) improve social conditions and (e) reduce levels of violence experienced and drug-related offences. COSINUS will also give us the opportunity to investigate the impact of other harm reduction tools in France and their combined effect with DCR on reducing HIV-HCV risk practices. Furthermore, we will be better able to identify PWID needs. Methods and analysis Enrollment in this prospective multi-site cohort study started in June 2016. Overall, 680 PWID in four different cities (Bordeaux, Marseilles, Paris and Strasbourg) will be enrolled and followed up for 12 months through face-to-face structured interviews administered by trained staff to all eligible participants at baseline (M0), 3 month (M3), 6 month (M6) and 12 month (M12) follow-up visits. These interviews gather data on socio-demographic characteristics, past and current drug and alcohol consumption, drug-use related practices, access to care and social services, experience of violence (as victims), offences, other psychosocial issues and perception and needs about harm reduction interventions and services. Longitudinal data analysis will use a mixed logistic model to assess the impact of individual and structural factors, including DCR attendance and exposure to other harm reduction services, on the main outcome (HIV-HCV risk practices). Ethics and dissemination This study was reviewed and approved by the institutional review board of the French Institute of Medical Research and Health (opinion number: 14–166). The findings of this cohort study will help to assess the impact of DCR on HIV-HCV risk practices and other psycho-social outcomes and trajectories. Moreover, they will enable health authorities to shape health and harm reduction policies according to PWID needs. Finally, they will also help to improve current harm reduction and therapeutic interventions and to create novel ones.
Identification of Two Novel R2R3-MYB Transcription factors, PsMYB114L and PsMYB12L, Related to Anthocyanin Biosynthesis in Paeonia suffruticosa

Flower color is a charming phenotype with very important ornamental and commercial values. Anthocyanins play a critical role in determining flower color pattern formation, and their biosynthesis is typically regulated by R2R3-MYB transcription factors (TFs). Paeonia suffruticosa is a famous ornamental plant with colorful flowers. However, little is known about the R2R3-MYB TFs that regulate anthocyanin accumulation in P. suffruticosa. In the present study, two R2R3-MYB TFs, namely, PsMYB114L and PsMYB12L, were isolated from the petals of P. suffruticosa ‘Shima Nishiki’ and functionally characterized. Sequence analysis suggested that PsMYB114L contained a bHLH-interaction motif, whereas PsMYB12L contained two flavonol-specific motifs (SG7 and SG7-2). Subsequently, the in vivo function of PsMYB114L and PsMYB12L was investigated by their heterologous expression in Arabidopsis thaliana and apple calli. In transgenic Arabidopsis plants, overexpression of PsMYB114L and of PsMYB12L caused a significantly higher accumulation of anthocyanins, resulting in purple-red leaves. Transgenic apple calli overexpressing PsMYB114L and PsMYB12L also significantly enhanced the anthocyanins content and resulted in a change in the callus color to red. Meanwhile, gene expression analysis in A. thaliana and apple calli suggested that the expression levels of the flavonol synthase (MdFLS) and anthocyanidin reductase (MdANR) genes were significantly downregulated and the dihydroflavonol 4-reductase (AtDFR) and anthocyanin synthase (AtANS) genes were significantly upregulated in transgenic lines of PsMYB114L. Moreover, the expression level of the FLS gene (MdFLS) was significantly downregulated and the DFR (AtDFR/MdDFR) and ANS (AtANS/MdANS) genes were all significantly upregulated in transgenic lines plants of PsMYB12L. These results indicate that PsMYB114L and PsMYB12L both enhance anthocyanin accumulation by specifically regulating the expression of some anthocyanin biosynthesis-related genes in different plant species. Together, these results provide a valuable resource with which to further study the regulatory mechanism of anthocyanin biosynthesis in P. suffruticosa and for the breeding of tree peony cultivars with novel and charming flower colors.
Evaluating visual analytics for health informatics applications: a systematic review from the American Medical Informatics Association Visual Analytics Working Group Task Force on Evaluation

OBJECTIVE This article reports results from a systematic literature review related to the evaluation of data visualizations and visual analytics technologies within the health informatics domain. The review aims to (1) characterize the variety of evaluation methods used within the health informatics community and (2) identify best practices. METHODS A systematic literature review was conducted following PRISMA guidelines. PubMed searches were conducted in February 2017 using search terms representing key concepts of interest: health care settings, visualization, and evaluation. References were also screened for eligibility. Data were extracted from included studies and analyzed using a PICOS framework: Participants, Interventions, Comparators, Outcomes, and Study Design. RESULTS After screening, 76 publications met the review criteria. Publications varied across all PICOS dimensions. The most common audience was healthcare providers (n = 43), and the most common data gathering methods were direct observation (n = 30) and surveys (n = 27). About half of the publications focused on static, concentrated views of data with visuals (n = 36). Evaluations were heterogeneous regarding setting and measurements used. DISCUSSION When evaluating data visualizations and visual analytics technologies, a variety of approaches have been used. Usability measures were used most often in early (prototype) implementations, whereas clinical outcomes were most common in evaluations of operationally-deployed systems. These findings suggest opportunities for both (1) expanding evaluation practices, and (2) innovation with respect to evaluation methods for data visualizations and visual analytics technologies across health settings. CONCLUSION Evaluation approaches are varied. New studies should adopt commonly reported metrics, context-appropriate study designs, and phased evaluation strategies.
Infectious complications of laparoscopic and robotic hysterectomy: a systematic literature review and meta-analysis

Objective We performed a systematic review of the literature and meta-analysis of the infectious complications of hysterectomy, comparing robotic-assisted hysterectomy to conventional laparoscopic-assisted hysterectomy. Methods We searched PubMed, CINAHL, CDSR, and EMBASE through July 2018 for studies evaluating robotic-assisted hysterectomy, laparoscopic-assisted hysterectomy, and infectious complications. We employed random-effect models to obtain pooled OR estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooled ORs were calculated separately based on the reason for hysterectomy (eg, benign uterine diseases, endometrial cancer, and cervical cancer). Results Fifty studies were included in the final review for the meta-analysis with 176 016 patients undergoing hysterectomy. There was no statistically significant difference in the number of infectious complication events between robotic-assisted hysterectomy and laparoscopic-assisted hysterectomy (pooled OR 0.97; 95 % CI 0.74 to 1.28). When we performed a stratified analysis, similar results were found with no statistically significant difference in infectious complications comparing robotic-assisted hysterectomy to laparoscopic-assisted hysterectomy among patients with benign uterine disease (pooled OR 1.10; 95 % CI 0.70 to 1.73), endometrial cancer (pooled OR 0.97; 95 % CI 0.55 to 1.73), or cervical cancer (pooled OR 1.09; 95 % CI 0.60 to 1.97). Conclusion In our meta-analysis the rate of infectious complications associated with robotic-assisted hysterectomy was no different than that associated with conventional laparoscopic-assisted hysterectomy.
Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

Postmenopausal osteoporosis is characterized by the occurrence of fragility fracture with an increase in morbidity and mortality. Recently, microRNAs (miRNAs) have raised interest as regulators of translational repression, mediating a number of key processes, including bone tissue in both physiological and diseased states. The aim of this study was to examine the serum levels of 32 preselected miRNAs with reported function in bone and their association with osteoporotic fracture. We performed cross‐sectional and longitudinal analyses from the OFELY Cohort. Serum levels of the miRNAs were quantified by qRT‐PCR in 682 women: 99 premenopausal and 583 postmenopausal women, with 1 and 122 women with prevalent fragility fractures in each group, respectively. We have collected clinical variables (such as age, prevalent, and incident fractures), bone turnover markers (BTMs), BMD by dual X‐ray absorptiometry, and bone microarchitecture with HRpQCT. We observed a number of miRNAs to be associated with fragility fractures (prevalent or incident), BTMs, BMD, and microarchitecture. This effect, however, was negated after age adjustment. This may be because age was also strongly associated with the serum levels of the 32 miRNAs (correlation coefficient up to 0.49), confirming previous findings. In conclusion, in a well‐characterized prospective cohort with a sizeable sample size, we found no evidence that these 32 preselected miRNAs were not associated with BTMs, BMD, microarchitecture, and or fragility fractures. © 2019 American Society for Bone and Mineral Research.
Longitudinal Associations between Emotion Regulation and Adiposity in Late Adolescence: Indirect Effects through Eating Behaviors

The prevalence of obesity among U.S. youth continues to increase, with many adolescents engaging in unhealthy eating behaviors. Increasingly, research points to the role of self-regulation in obesity development, yet existing work has largely focused on young children and/or clinical adult populations. This multi-method longitudinal study (N = 153) utilized a path analysis to delineate links between emotion regulation (age 15), emotional eating and dietary restraint (age 16), and adiposity (% body fat) using a BodPod for body composition assessment (age 19). Emotion regulation was negatively associated with emotional eating (β = −0.30, p < 0.001) and positively associated with dietary restraint (β = 0.15, p < 0.05) at age 16, but was not associated with age 19 adiposity (β = −0.01, p = ns). Emotional eating was positively associated with adiposity (β = 0.24, p < 0.01). Indirect effects suggested that emotional eating, but not dietary restraint, at age 16 serves as a mechanism that helps explain the associations between emotion regulation and adiposity four years later. Results from this study suggest that both emotion regulation and emotional eating represent promising targets for that should be included in future interventions aimed at preventing adolescent obesity.