Miracle-dz/UniFAR-FTUs huggingface dataset:
Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

Toray Industries, Inc., Tokyo, Japan Department of Diabetes, Metabolism and Endocrinology, Chiba University Graduate School of Medicine, Chiba, Japan National Center for Geriatrics and Gerontology, Aichi, Japan Department of Internal Medicine and Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University, Iwate, Japan Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, Japan Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima, Japan Egusa Genshi Clinic, Hiroshima, Japan Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan Biomedical Informatics, Osaka University, Osaka, Japan Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan Department of Community Health Systems Nursing, Ehime University Graduate School of Medicine, Ehime, Japan Department of Vascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan Department of Vascular Surgery, Saitama Medical Center, Saitama, Japan Chief Health Management Department, Mitsui Chemicals Inc., Tokyo, Japan Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan Department of Neurology, Kita-Harima Medical Center, Hyogo, Japan Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kanagawa, Japan Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Tsukasa Health Care Hospital, Kagoshima, Japan Faculty of Nutrition, Division of Clinical Nutrition, Kobe Gakuin University, Hyogo, Japan Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women’s University, Tokyo, Japan 25 Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan Department of Medical Statistics, Toho University, Tokyo, Japan Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Laboratory Medicine, Jikei University Kashiwa Hospital, Chiba, Japan Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan Department of Obstetrics and Gynecology, Aichi Medical University, Aichi, Japan 31 Department of Community Medicine, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan Rinku General Medical Center, Osaka, Japan
Continuous Code Quality: Are We (Really) Doing That?

Continuous Integration (CI) is a software engineering practice where developers constantly integrate their changes to a project through an automated build process. The goal of CI is to provide developers with prompt feedback on several quality dimensions after each change. Indeed, previous studies provided empirical evidence on a positive association between properly following CI principles and source code quality. A core principle behind CI is Continuous Code Quality (also known as CCQ, which includes automated testing and automated code inspection) may appear simple and effective, yet we know little about its practical adoption. In this paper, we propose a preliminary empirical investigation aimed at understanding how rigorously practitioners follow CCQ. Our study reveals a strong dichotomy between theory and practice: developers do not perform continuous inspection but rather control for quality only at the end of a sprint and most of the times only on the release branch. Preprint [https://doi.org/10.5281/zenodo.1341036]. Data and Materials [http://doi.org/10.5281/zenodo.1341015].
TDO2 Overexpression Is Associated with Cancer Stem Cells and Poor Prognosis in Esophageal Squamous Cell Carcinoma

Objective: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. Methods: TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). Results: TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. Conclusion: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.
Does testing enhance learning in continuing medical education?

Background There has been growing interest in using theory-driven research to develop and evaluate continuing medical education (CME) activities. Within health professions education, testing has been shown to promote learning in a variety of different contexts, an effect referred to as test-enhanced learning (TEL). However, the extent to which TEL generalizes to CME remains unclear. The purpose of this study was to investigate whether physicians who received two intervening tests following a CME event would experience a TEL effect relative to physicians who received additional study material to review without testing. Methods Forty-nine physicians were recruited during a local CME activity. Physicians were randomized to either a) the test group (n=26), where participants completed two 20 multiple-choice question (MCQ) quizzes related to the lecture content or b) the study group (n=23), where participants studied the same information without testing. Testing and studying occurred independently during the CME activity, and then four weeks later online. At eight weeks, participants completed a final 20-item MCQ online test. A between-subjects t-test was used to compare performance on the final test as a function of the initial educational activity (test group vs. study group). Results Performance on the final MCQ test was equivalent for both test (Mean (SD): 75% (9.9)) and study-only (77% (7.3)) conditions (t(47) = 0.94, p=0.35). Conclusion The null findings in the present study are contrary to previous findings demonstrating TEL among novice learner populations. The lack of TEL highlights several programmatic considerations that should be factored in before implementing TEL as a part of CME.
‘My blood pressure is low today, do you have the heating on?’ The association between indoor temperature and blood pressure

Objectives: The independent association of indoor temperature with blood pressure (BP) is poorly understood and is not routinely considered in hypertension diagnosis or research. Questions remain as to whether the effect of indoor temperature on BP is confounded or modified by other factors. Methods: This study used data from the Health Survey for England 2014, consisting of 4659 community-dwelling adults aged 16 years and over, interviewed from January to December. Multivariable regression models were used to determine whether indoor temperature was related to levels of BP, and whether these relationships were confounded by other factors, including mean monthly outdoor temperature. Results: After controlling for confounding variables, a 1°C decrease in indoor temperature was associated with rises of 0.48 mmHg (95% confidence interval: −0.72 to −0.25) in SBP and 0.45 mmHg (95% confidence interval: −0.63 to −0.27) in DBP. The magnitude of association of indoor temperature with DBP and SBP was modified by physical activity. The indoor temperature–BP relationship was stronger in people who do not take physical activity regularly than people who exercise regularly. Conclusion: The size of the independent association between indoor temperature and BP suggests it should be considered in the clinical management of hypertension and in hypertension research. Room temperature should also be considered as a modifiable risk factor in hypertension-related mortality and morbidity.
Validation of a preclinical model for assessment of drug efficacy in melanoma

The aim of personalized medicine is to improve our understanding of the disease at molecular level and to optimize therapeutic management. In this context, we have developed in vivo and ex vivo preclinical strategies evaluating the efficacy of innovative drugs in melanomas. Human melanomas (n = 17) of different genotypes (mutated BRAF, NRAS, amplified cKIT and wild type) were successfully engrafted in mice then amplified by successive transplantations. The exhaustive characterization of patient-derived xenografts (PDX) at genomic level (transcriptomic and CGH arrays) revealed a similar distribution pattern of genetic abnormalities throughout the successive transplantations compared to the initial patient tumor, enabling their use for mutation-specific therapy strategies. The reproducibility of their spontaneous metastatic potential in mice was assessed in 8 models. These PDXs were used for the development of histoculture drug response assays (ex vivo) for the evaluation of innovative drug efficacy (BRAF and MEK inhibitors). The pharmacological effects of BRAF and MEK inhibitors were similar between PDX-derived histocultures and their corresponding PDX, on 2 models of BRAF and NRAS-mutated melanomas. These models constitute a validated, effective tool for preclinical investigation of new therapeutic agents, and improve therapeutic strategies in the treatment of metastatic melanoma.
Estimating the effects of variation in viremia on mosquito susceptibility, infectiousness, and R0 of Zika in Aedes aegypti

Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. Like most viral infections, ZIKV viremia varies over several orders of magnitude, with unknown consequences for transmission. To determine the effect of viral concentration on ZIKV transmission risk, we exposed field-derived Ae. aegypti mosquitoes to four doses (103, 104, 105, 106 PFU/mL) representative of potential variation in the field. We demonstrate that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected and infectious, as well as the rate at which virus spreads to the saliva, but found no effect on dissemination efficiency or mosquito mortality. We also demonstrate that determining infection using RT-qPCR approaches rather than plaque assays potentially over-estimates key pathogen parameters, including the time at which mosquitoes become infectious and viral burden. Finally, using these data to parameterize an R0 model, we demonstrate that variation in viremia substantially affects transmission risk.
Support for architectural smell refactoring

To preserve high quality of a project, it is necessary to perform many refactoring steps during the development and maintenance phases. Code refactoring received a great attention in the literature, often directed to the refactoring of code smells. While at the architectural level, architectural smells received less attention. One of the most common architectural smell which may affect many parts of a software application is the Cyclic Dependency smell. This position paper presents a tool prototype that suggests which path a developer could follow to remove Cyclic Dependency smells in Java applications. The tool has been developed as an extension of the Arcan tool for architectural smells detection. In this paper we describe how the tool identifies the path to follow for the refactoring of Cyclic Dependency on real projects. The tool has been thought only to suggest a possible refactoring approach which a developer could considerate to resolve Cyclic Dependency.
Two-Dimensional Band Structure in Honeycomb Metal–Organic Frameworks

Two-dimensional (2D) metal–organic frameworks (MOFs) have been recently proposed as a flexible material platform for realizing exotic quantum phases including topological and anomalous quantum Hall insulators. Experimentally, direct synthesis of 2D MOFs has been essentially confined to metal substrates, where the strong interaction with the substrate masks the intrinsic electronic properties of the MOF. In addition to electronic decoupling from the underlying metal support, synthesis on weakly interacting substrates (e.g., graphene) would enable direct realization of heterostructures of 2D MOFs with inorganic 2D materials. Here, we demonstrate synthesis of 2D honeycomb MOFs on epitaxial graphene substrate. Using low-temperature scanning tunneling microscopy (STM) and atomic force microscopy (AFM) complemented by density-functional theory (DFT) calculations, we show the formation of a 2D band structure in the MOF decoupled from the substrate. These results open the experimental path toward MOF-based designer electronic materials with complex, engineered electronic structures.
Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. ABSTRACT The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. Studies evaluating the relationship between treatment efficacy and in vitro susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than Candida albicans and Candida glabrata, and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on in vitro susceptibility are growing, particularly for C. albicans and C. glabrata. Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.
Influence of Dental Restorations on Oxidative Stress in Gingival Crevicular Fluid

Biocompatibility of dental materials (DM) can be evaluated by gingival crevicular fluid (GCF) oxidative stress (OS) status. The goal of the study was to ascertain influence of dental caries degree, teeth position, and type and amount of applied DM on GCF OS profile. For this purpose, we tested six DMs that were sealed in one session: amalgam (Amg), composites: Tetric EvoCeram and Beautifil (BF), phosphate cement—zinc phosphate and polycarboxylate cements—zinc polycarboxylate cements, and glass ionomer cement (GIC). The study included 88 dental outpatients. Follow-up was scheduled at 7th and 30th day. Oxidative stress parameters (malondialdehyde (MDA) and glutathione (GSH) levels and total superoxide dismutase (tSOD) activity) were measured before (0th day) and after the treatment (7th and 30th day) in GCF. Control teeth were mirror-positioned healthy teeth. The DM accomplished the following effects (listed in descending order): increase of GSH in GCF was realized by ZPoC > BF > GIC > Amg; tSOD activity increase by ZPoC > BF > Amg; and MDA decrease by ZPoC > ZPhC > Amg > TEC. Dental caries provokes insignificant rise of OS in GCF. ZPoC and ZPhC showed the highest antioxidant effect, contrary to GIC. Restorations with antioxidant properties may reduce gum diseases initiated by caries lesion, what is of great clinical relevance in dentistry.
Generalized Canonical Polyadic Tensor Decomposition

Tensor decomposition is a fundamental unsupervised machine learning method in data science, with applications including network analysis and sensor data processing. This work develops a generalized canonical polyadic (GCP) low-rank tensor decomposition that allows other loss functions besides squared error. For instance, we can use logistic loss or Kullback-Leibler divergence, enabling tensor decomposition for binary or count data. We present a variety statistically-motivated loss functions for various scenarios. We provide a generalized framework for computing gradients and handling missing data that enables the use of standard optimization methods for fitting the model. We demonstrate the flexibility of GCP on several real-world examples including interactions in a social network, neural activity in a mouse, and monthly rainfall measurements in India.
Early life trauma increases threat response of peri‐weaning rats, reduction of axo‐somatic synapses formed by parvalbumin cells and perineuronal net in the basolateral nucleus of amygdala

Early life trauma is a risk factor for life‐long disorders related to emotional processing, but knowledge underlying its enduring effect is incomplete. This study was motivated by the hypothesis that early life trauma increases amygdala‐dependent threat responses via reduction in inhibition by parvalbumin (PV) interneurons and perineuronal nets (PNN) supporting PV cells, thus increasing excitability of the basolateral amygdala (BLA). From postnatal day (PN) 8–12, rat pups of both sexes were reared under normal bedding or under insufficient nest‐building materials to induce maternal‐to‐infant maltreatment trauma (Scarcity‐Adversity Model, SAM). At weaning age of PN23, the SAM group exhibited increased threat responses to predator odor. The SAM‐induced increase in threat response was recapitulated in normally reared PN22–23 rats that were unilaterally depleted of PNN in the BLA by the enzymes, chondroitinase‐ABC plus hyaluronidase at PN19–20. Light and electron microscopic analysis of the BLA revealed that anterior‐to‐mid levels of SAM group's BLAs exhibited decreased PNN intensity and decreased axo‐somatic synapses between PV‐to‐principal pyramidal‐like neurons and PV‐to‐PV. PV and PNN densities (cells/mm2) in the BLA of both control (CON) and SAM groups were still low at PN12 and SAM delayed the ontogenetic rise of PV intensity and PNN density. Moreover, PV cell density in the anterior‐to‐mid BLA correlated negatively with threat response of CON animals, but not for SAM animals. Thus, reduction of PNN‐supported, PV‐mediated somatic inhibition of pyramidal cells provides a mechanistic support for the enduring effect of early life maltreatment manifested as increasing innate threat response at weaning.
Exploring genetic diversity in an Italian horse native breed to develop strategies for preservation and management

Genetic diversity is a key factor for both adaptation and response to selection. The loss of genetic diversity causes a decrease in individual fitness, and it has a dramatically negative effect on population lifespan in the long term. This study aimed at exploring the genetic diversity at pedigree level of the Bardigiano horse breed, which is a native breed from Italy shaped for living in rural areas. In 1977, the Bardigiano studbook was founded to preserve the breed and for improving its use for riding and draft purposes. Pedigree data contained 9,469 horses, of which 3,416 were alive. Demographic and genetic parameters were estimated on subpopulations to evaluate potential genetic diversity differences among breeding and nonbreeding animals, and animals showing different breeding values (EBVs) for an index combining 18 conformation traits. Throughout the studied period, inbreeding steadily increased, reaching in the last birth year cohort a mean value equal to 0.10. The rate of inbreeding per generation, assuming a mean generation interval of 8.74 years, was equal to 1.64%. Moreover, significant differences on both average relatedness and inbreeding among horses with high and low EBVs were shown. Our study unravelled the state of genetic diversity in the Bardigiano breed, highlighting that breeding strategies for optimizing the contribution of breeding animals in the coming generations are needed to ensure long-term survival of the Bardigiano horse breed.
Effects of Alternative Redox Partners and Oxidizing Agents on CYP154C8 Catalytic Activity and Product Distribution

CYP154C8 catalyzes the hydroxylation of diverse steroids, as has previously been demonstrated, by using an NADH‐dependent system including putidaredoxin and putidaredoxin reductase as redox partner proteins carrying electrons from NADH. In other reactions, CYP154C8 reconstituted with spinach ferredoxin and NADPH‐dependent ferredoxin reductase displayed catalytic activity different from that of the NADH‐dependent system. The NADPH‐dependent system showed multistep oxidation of progesterone and other substrates including androstenedione, testosterone, and nandrolone. (Diacetoxyiodo)benzene was employed to generate compound I (FeO3+), actively supporting the redox reactions catalyzed by CYP154C8. In addition to 16α‐hydroxylation, progesterone and 11‐oxoprogesterone also underwent hydroxylation at the 6β‐position in reactions supported by (diacetoxyiodo)benzene. CYP154C8 was active in the presence of high concentrations (>10 mm) of H2O2, with optimum conversion surprisingly being achieved at ≈75 mm H2O2. More importantly, H2O2 tolerance by CYP154C8 was evident in the very low heme oxidation rate constant (K) even at high concentrations of H2O2. Our results demonstrate that alternative redox partners and oxidizing agents influence the catalytic efficiency and product distribution of a cytochrome P450 enzyme. More importantly, these choices affected the type and selectivity of reaction catalyzed by the P450 enzyme.
Real-time implementation of the coupled neural mass and its application

The neural mass model is a self-oscillation network composed of two neural populations. In this study, we use the field-programmable gate array (FPGA) device to implement the neural mass model and the hardware implementation results are exactly the same as the MATLAB simulation results. The study reveals that dynamical characteristics of the neural population implemented on FPGA can meet the real-time computational requirements. Besides, we propose a control method of the robotic arm based on the oscillation dynamics of the network. For the implementation results of FPGA is real-time, it can be used to realize the robotic control. A closed-loop control system is realized by inputting the error signals of robotic arm into the neural network model and obtaining the feedback signal to arm joint for error elimination. The results show that the control method based on the neural mass model can quickly and effectively eliminate the angle errors.