bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients
Authors: Shao Shih-Chieh , Chang Kai-Cheng , Lin Swu-Jane , Chien Rong-Nan , Hung Ming-Jui , Chan Yuk-Ying , Kao Yang Yea-Huei , Lai Edward Chia-Cheng 
Published: February 2020

Abstract
Background
Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors.

Method
We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors.

Results
We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (− 1.0 vs. − 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (− 1.5 vs. − 1.0 kg; P = 0.008), SBP (− 2.5 vs. − 0.7 mmHg; P < 0.001) and ALT values (− 4.1 vs. − 0.0 U/l; P < 0.001) and smaller declines in eGFR values (− 2.0 vs. − 3.5 ml/min/1.73 m2; P < 0.001) when compared to DPP4 inhibitors.

Conclusion
SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients’ cardio-metabolic disease risks.
Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis
Authors: Lin Chun-Yan , Pang Ai-Ping , Zhang Yue , Qiao Jianjun , Zhao Guang-Rong 
Published: February 2020

Abstract
Background
Lincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic and widely used for the treatment of the infective diseases caused by Gram-positive bacteria. The mechanisms of lincomycin biosynthesis have been deeply explored in recent years. However, the regulatory effects of LmbU that is a transcriptional regulator in lincomycin biosynthetic (lmb) gene cluster have not been fully addressed.

Results
LmbU was used to search for homologous LmbU (LmbU-like) proteins in the genomes of actinobacteria, and the results showed that LmbU-like proteins are highly distributed regulators in the biosynthetic gene clusters (BGCs) of secondary metabolites or/and out of the BGCs in actinomycetes. The overexpression, inactivation and complementation of the lmbU gene indicated that LmbU positively controls lincomycin biosynthesis in S. lincolnensis. Comparative transcriptomic analysis further revealed that LmbU activates the 28 lmb genes at whole lmb cluster manner. Furthermore, LmbU represses the transcription of the non-lmb gene hpdA in the biosynthesis of l-tyrosine, the precursor of lincomycin. LmbU up-regulates nineteen non-lmb genes, which would be involved in multi-drug flux to self-resistance, nitrate and sugar transmembrane transport and utilization, and redox metabolisms.

Conclusions
LmbU is a significant pleiotropic transcriptional regulator in lincomycin biosynthesis by entirely activating the lmb cluster and regulating the non-lmb genes in Streptomyces lincolnensis. Our results first revealed the pleiotropic regulatory function of LmbU, and shed new light on the transcriptional effects of LmbU-like family proteins on antibiotic biosynthesis in actinomycetes.
Organ-on-a-chip: recent breakthroughs and future prospects
Authors: Wu Qirui , Liu Jinfeng , Wang Xiaohong , Feng Lingyan , Wu Jinbo , Zhu Xiaoli , Wen Weijia , Gong Xiuqing 
Published: February 2020

AbstractThe organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.
A randomized controlled trial examining consumers’ perceptions and opinions on using different versions of a FoodFlip© smartphone application for delivery of nutrition information
Authors: Ahmed Mavra , Oh Angela , Vanderlee Lana , Franco-Arellano Beatriz , Schermel Alyssa , Lou Wendy , L’Abbé Mary R. 
Published: February 2020

Abstract
Background
Food labelling is a common intervention to improve diets, where the back-of-pack Nutrition Information Panel (or Nutrition Facts table (NFt)) provides comprehensive nutrition information on food packages. However, many consumers find it difficult and time-consuming to identify healthier foods using the NFt. As a result, different interpretative nutrition rating systems (INRS) may enable healthier food choices and it is essential that consumers have the tools to allow for easily accessible nutrition information. The objective of this study was to examine consumers’ perceptions of different (INRS) for delivery of nutrition information using different versions of a smartphone app, FoodFlip©.

Methods
This study was part of a larger randomized controlled trial examining consumer perceptions of different INRS on food products. A nationally representative commercial sample of 2008 Canadians were randomized to one of four INRS intervention groups: 1) traffic light, 2) health star rating, 3) ‘high-in’ warning labels or 4) no INRS (NFt only; control) and asked to scan or enter 20 products into FoodFlip© from a list of food products provided to them with varying levels of healthfulness. After completing the app task, participants were asked a series of 7-point Likert-scale and open-ended questions to provide opinions on the usability and functionality of the app.

Results
Of the survey sample of 1997 participants, 95% (n = 1907) completed the app task, with similar number of participants in each treatment group. The mean age was 40 ± 12 years with no differences in sociodemographic characteristics between treatment groups. The health star rating ranked significantly lower in comparison to the other treatment groups in terms of usefulness (OR, 95% CI -0.67, 0.52–0.85), believability (0.59, 0.46–0.75), and understanding (0.55, 0.44–0.71) (p < 0.001). The health star rating (1.20, 0.94–1.53) and control (NFt) (1,1,1) ranked significantly lower than the traffic light or the ‘high-in’ warning labels for their ability to compare the healthfulness of products (p < 0.001).

Conclusion
This study demonstrated Canadian consumers’ preference for a nutrient-specific system (i.e. traffic light or ‘high-in’ warning labels). The app, which was liked by majority of the participants for its functionality and usability, has the potential to support healthy dietary decision making and may also encourage reformulation.

Trial registration
NCT03290118 (Clinicaltrials.gov).
Are social conflicts at work associated with depressive symptomatology? Results from the population-based LIFE-Adult-Study
Authors: Zuelke Andrea E. , Roehr Susanne , Schroeter Matthias L. , Witte A. Veronica , Hinz Andreas , Engel Christoph , Enzenbach Cornelia , Thiery Joachim , Loeffler Markus , Villringer Arno , Riedel-Heller Steffi G. 
Published: February 2020

Abstract
Background
Psychosocial stressors in the workplace can be detrimental to mental health. Conflicts at work, e.g. aggression, hostility or threats from coworkers, supervisors or customers, can be considered a psychosocial stressor, possibly increasing risk for depressive symptoms. Existing studies, however, differ in the assessment of social conflicts, i.e. as individual- or job-level characteristics. Here, we investigated the association between conflicts at work assessed as objective job characteristics, and depressive symptomatology, using data from a large population-based sample. Additionally, we investigated gender differences and the impact of personality traits and social resources.

Methods
We used data from the population-based LIFE-Adult-Study from Leipzig, Germany. Information on conflicts at work, assessed as job characteristics, were drawn from the Occupational Information Network, depressive symptoms were assessed via the Center for Epidemiological Studies Depression Scale. Multilevel linear regression models with individuals and occupations as levels of analysis were applied to investigate the association between conflicts at work and depressive symptoms.

Results
Our sample included 2164 employed adults (age: 18–65 years, mean: 49.3, SD: 7.9) in 65 occupations. No association between conflicts s at work and depressive symptomatology was found (men: b = − 0.14; p = 0.74, women: b = 0.17, p = 0.72). Risk for depression was mostly explained by individual-level factors like e.g. neuroticism or level of social resources. The model showed slightly higher explanatory power in the female subsample.

Conclusion
Conflicts at work, assessed as objective job characteristics, were not associated with depressive symptoms. Possible links between interpersonal conflict and impaired mental health might rather be explained by subjective perceptions of social stressors and individual coping styles.
Markers of immune activation: novel biomarkers to predict the early-warning indicator of patients with papillary thyroid carcinoma
Authors: Lu Hongsheng , Zhang Lihong , Dai Yuechu , Ruan Yanyun , Cao Xuequan , Cai Xiaobo , Ruan Sihan , Chen Qi 
Published: February 2020

Abstract
Background
Papillary thyroid carcinoma (PTC) is an indolent tumor that is exploding with increasing thyroid nodules (TN). Environmental carcinogens, lifestyle changes increased the incidence of thyroid carcinoma. With the development of B-ultrasound imaging, more and more thyroid cancer has been found. There has been a debate about whether thyroid cancer is overtreated.

Methods
The expression of T cell subsets and plasma cytokines in 191 patients, including 79 patients with PTC (PTC group), 58 patients with thyroid nodules (TN group) and 54 healthy individuals (HP group) were analyzed by flow cytometry.

Results
High levels of natural killer cells (NK) were detected in PTC and TN groups than in HP group. High activities of CD8+HLA-DR+ and CD8+CD38+ showed a gradual upward trend from HP group to PTC group. The rise in the levels of TNF-α in PTC patients’ was evident when compared with HP group. CD8+CD38+ showed a significant correlation with lymph node metastasis. CD8+CD38+ co-expression was higher in Nx stage than N0 stage, while the proportion of IL-10 was dramatically decreased in the Nx stage.

Conclusions
These results indicated that CD8+CD38+ might act as a biomarker of PTC lymph node metastasis. The combination of CD8+HLA-DR+, CD8+CD38+ and TNF-α can be used as useful biomarkers for the early-warning indicator of PTC.
The results of using a tendon autograft as a new rotator cable for patients with a massive rotator cuff tear: a technical note and comparative outcome analysis
Authors: Veen Egbert J. D. , Diercks Ronald L. , Landman Ellie B. M. , Koorevaar Cornelis T. 
Published: February 2020

Abstract
Background
Several surgical reconstructive options are available to treat massive rotator cuff tears (MRCTs). The rotator cable has an important function and we evaluated the clinical result after arthroscopic reconstruction of the rotator cable with an autograft tendon.

Methods
A prospective pilot study was performed with inclusion of four patients, average age of 64 years, with an irreparable MRCT. The patients underwent an arthroscopic reconstruction of the rotator cable with the use of the long head of biceps tendon autograft, except for one which was reconstructed with a hamstring tendon. Pre- and postsurgically, the Constant-Murley Score (CMS), Western Ontario Rotator Cuff Index (WORC), Simple Shoulder Test (SST), visual analog scale (VAS) scores, and an MRI was performed. Clinical results of the study group were compared with clinical results of comparable cohort of patients with a MRCT, treated non-operatively with physiotherapy.

Results
The CMS score increased after surgery in three of the four patients. The improvement of CMS score was comparable to the improvement of the CMS score encountered in a comparable cohort. The MRI at 12 months follow-up showed that the reconstructed rotator cable was disintegrated in all patients and the rotator cuff was detached and retracted.

Conclusions
In our pilot study, arthroscopic reconstruction of the rotator cable using a tendon autograft failed over time and showed no clinical benefit in comparison to the non-operative treatment with physiotherapy.

Trial registration
The regional Medical Ethical Committee (Zwolle) gave approval at 14th of October 2016 and assigned no. 16.06100.
Chinese herbal medicine for gout: a review of the clinical evidence and pharmacological mechanisms
Authors: Chi Xiansu , Zhang Hongxiu , Zhang Shuo , Ma Ke 
Published: February 2020

AbstractGout is a common arthritis condition due to disorders of purine metabolism and decreased uric acid excretion. Although researchers have carried out various studies on this disease, there are no effective drugs for patients with gout. In traditional Chinese medicine (TCM), gout pertains the category of Bi pattern due to qi stagnation in the meridians and collaterals. Chinese herbal medicinals has been employed to treat Bi patterns since the ancient China. In recent decades, classical TCM formulas and agents isolated from some Chinese herbal medicinals have been applied to treat gout and have achieved satisfactory effect. In this review, we focus on recent studies of gout in which TCM formulas were applied to treat animal models or to treat patients, and summarize the mechanism of gout from TCM perspective, the clinical application, pharmacological mechanism and the chemical compounds of TCM formulas in treating gout. In conclusion, through this study, we summarized the application principle of TCM formulas in gout treatment and some key issues of current research, and we hope this study will provide some references for applying TCM formulas to treat gout and will lay a foundation for the development of novel formulas for gout treatments.
Machine learning application for development of a data-driven predictive model able to investigate quality of life scores in a rare disease
Authors: Spiga Ottavia , Cicaloni Vittoria , Fiorini Cosimo , Trezza Alfonso , Visibelli Anna , Millucci Lia , Bernardini Giulia , Bernini Andrea , Marzocchi Barbara , Braconi Daniela , Prischi Filippo , Santucci Annalisa 
Published: February 2020

AbstractBackgroundAlkaptonuria (AKU) is an ultra-rare autosomal recessive disease caused by a mutation in the homogentisate 1,2-dioxygenase (HGD) gene. One of the main obstacles in studying AKU, and other ultra-rare diseases, is the lack of a standardized methodology to assess disease severity or response to treatment. Quality of Life scores (QoL) are a reliable way to monitor patients’ clinical condition and health status. QoL scores allow to monitor the evolution of diseases and assess the suitability of treatments by taking into account patients’ symptoms, general health status and care satisfaction. However, more comprehensive tools to study a complex and multi-systemic disease like AKU are needed. In this study, a Machine Learning (ML) approach was implemented with the aim to perform a prediction of QoL scores based on clinical data deposited in the ApreciseKUre, an AKU- dedicated database.MethodData derived from 129 AKU patients have been firstly examined through a preliminary statistical analysis (Pearson correlation coefficient) to measure the linear correlation between 11 QoL scores. The variable importance in QoL scores prediction of 110 ApreciseKUre biomarkers has been then calculated using XGBoost, with K-nearest neighbours algorithm (k-NN) approach. Due to the limited number of data available, this model has been validated using surrogate data analysis.ResultsWe identified a direct correlation of 6 (age, Serum Amyloid A, Chitotriosidase, Advanced Oxidation Protein Products, S-thiolated proteins and Body Mass Index) out of 110 biomarkers with the QoL health status, in particular with the KOOS (Knee injury and Osteoarthritis Outcome Score) symptoms (Relative Absolute Error (RAE) 0.25). The error distribution of surrogate-model (RAE 0.38) was unequivocally higher than the true-model one (RAE of 0.25), confirming the consistency of our dataset. Our data showed that inflammation, oxidative stress, amyloidosis and lifestyle of patients correlates with the QoL scores for physical status, while no correlation between the biomarkers and patients’ mental health was present (RAE 1.1).ConclusionsThis proof of principle study for rare diseases confirms the importance of database, allowing data management and analysis, which can be used to predict more effective treatments.
Nowhere to go: disclosure and help-seeking behaviors for survivors of violence against women and girls in South Sudan
Authors: Murphy Maureen , Ellsberg Mary , Contreras-Urbina Manuel 
Published: February 2020

Abstract
Background
Despite high rates of violence against women and girls (VAWG) in conflict and humanitarian contexts, many survivors do not tell anyone about their experience or seek help from support r services (e.g. health, legal, psychosocial support, police).

Methods
This paper examines disclosure and help seeking behaviours of survivors of non-partner sexual violence (NPSV) and intimate partner violence (IPV) among women and girls aged 15–64 from three sites in South Sudan. It seeks to understand how exposure to armed conflict is associated with disclosure and help seeking practices.

Results
For NPSV, respondents for whom an incident of sexual violence occurred during conflict had twice the odds of telling someone about their experience (aOR: 2.2; 95%CI: 1.3–3.7; p < 0.01) and three times the odds of seeking help (aOR: 3.1; 95%CI: 1.7–5.9, p < .001), compared to respondents for whom the incident of violence did not occur during conflict. Age, the identity of the perpetrator, working status of the woman, poverty and location also affected disclosure and help seeking behaviours for survivors of NPSV. For IPV, exposure to conflict increased the odds a respondent would tell someone about her experience (aOR 1.7; 95%CI 1.2–2.5; p < .01), but was not associated with seeking support services. The severity of IPV affected both disclosure and help seeking behaviours, with the odds of disclosing IPV increasing if the respondent experienced both physical and sexual IPV (compared to only sexual violence), had been injured, thought their well-being was affected, was afraid of their partner, or was controlled by their partner. However, not all these factors were subsequently associated with help seeking behaviours for survivors of IPV and respondents who reported they were sometimes afraid of their partner had reduced odds of seeking help, compared to those who were never afraid of their partners.

Conclusions
These findings are important as, prior to this analysis, it was unclear how experiencing conflict-related VAWG would influence disclosure and help seeking. Given the findings of this paper, it is important that the international community consider how to reduce barriers to reporting and help seeking for non-conflict-related forms of violence in these settings.
Preoperative serum levels of HE4 and CA125 predict primary optimal cytoreduction in advanced epithelial ovarian cancer: a preliminary model study
Authors: Feng Li-yuan , Liao Sheng-bin , Li Li 
Published: February 2020

Abstract
Objective
The aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters.

Methods
Clinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction.

Results
Optimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was: logit p = 0.12 age − 2.38 preoperative serum CA125 level − 1.86 preoperative serum HE4 level-2.74 histological type-3.37. AUC of the logistic model in the validation group was 0.71(95%CI 0.54–0.88, P = 0.025). Sensitivity and specificity were 1.00 and 0.44, respectively.

Conclusion
Age, preoperative serum CA125 level and preoperative serum HE4 level are important non-invasive predictors of primary optimal surgical cytoreduction in advanced epithelial ovarian cancer. Our PIV and logistic model can be used for assessment before expensive and complex predictive methods including laparoscopy and diagnostic imaging. Further future clinical validation is needed.