Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Proteomic Analysis of Two Differently Extracted Coptis chinensis in the Treatment of Type 2 Diabetic Rats

Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese medicine due to its significant hypoglycemic and hypolipidemic effects. It was reported that CC powders are more effective than CC decoctions. In this study, a rat model of type 2 diabetes was established and treated with supercritical-extracted CC and gastric juice extracted CC, respectively. Body weight, fasting plasma insulin, insulin resistance index, and lipid profiles were measured along with oral glucose tolerance tests (OGTTs). In addition, the levels of plasma proteins were compared between type 2 diabetic rats and CC-treated rats using an iTRAQ-based quantitative proteomic analysis. The results showed that the plasma levels of triglyceride (TC), total cholesterol (TG), and low-density lipoprotein (LDL) in rats of both CC-treated groups were significantly decreased. In addition, the proteomic analysis identified 929 proteins, while 15 proteins were selected from these 929 proteins based on their expression levels and bioinformatic results. Among these 15 proteins, 9 proteins (IGF-1, Igfbp4, Igfbp-6, Igfals, C2, C4, Cfi, Prdx-2, and Prdx-3) were upregulated in the two CC-treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC-1, ApoC-3, ApoB-100, and ApoE) were downregulated. The functions of these proteins are associated with glucose metabolism, insulin action, immunity, inflammation, lipid metabolism, oxidation, and antioxidation. The two differently extracted CC did not show significant differences in terms of their treatment efficacy. This research expanded our understanding on the therapeutic effects and mechanisms of CC in the treatment of type 2 diabetes.
A tool for automatically selecting optimal model transformation chains

Developing model transformations can be a complex task and as such advanced reuse mechanisms are increasingly recognised as necessary for increasing both development productivity and quality of model transformations. Creating a new transformation by chaining existing ones is one of the possible ways to reuse existing transformations. However, chaining transformations can be an error prone and strenuous task especially in case of multiple potential chains. In this paper the CITRIC tool is presented as a solution to mitigate the problem of characterizing the multitude of transformation chains that can be defined by composing existing model transformations to bridge source and target metamodels that are of interest for the modeler. The tool is based on well-established algorithms, and it is able to support modelers when multiple transformation chains are available. The optimal chain is automatically selected based on two quality criteria i.e., metamodel coverage and information loss.
A European Whitefish Linkage Map and Its Implications for Understanding Genome-Wide Synteny Between Salmonids Following Whole Genome Duplication

Genomic datasets continue to increase in number due to the ease of production for a wider selection of species including non-model organisms. For many of these species, especially those with large or polyploid genomes, highly contiguous and well-annotated genomes are still rare due to the complexity and cost involved in their assembly. As a result, a common starting point for genomic work in non-model species is the production of a linkage map. Dense linkage maps facilitate the analysis of genomic data in a variety of ways, from broad scale observations regarding genome structure e.g., chromosome number and type or sex-related structural differences, to fine scale patterns e.g., recombination rate variation and co-localization of differentiated regions. Here we present both sex-averaged and sex-specific linkage maps for Coregonus sp. “Albock”, a member of the European whitefish lineage (C. lavaretus spp. complex), containing 5395 single nucleotide polymorphism (SNP) loci across 40 linkage groups to facilitate future investigation into the genomic basis of whitefish adaptation and speciation. The map was produced using restriction-site associated digestion (RAD) sequencing data from two wild-caught parents and 156 F1 offspring. We discuss the differences between our sex-averaged and sex-specific maps and identify genome-wide synteny between C. sp. “Albock” and Atlantic Salmon (Salmo salar), which have diverged following the salmonid-specific whole genome duplication. Our analysis confirms that many patterns of synteny observed between Atlantic Salmon and Oncorhynchus and Salvelinus species are also shared by members of the Coregoninae subfamily. We also show that regions known for their species-specific rediploidization history can pose challenges for synteny identification since these regions have diverged independently in each salmonid species following the salmonid-specific whole genome duplication. The European whitefish map provided here will enable future studies to understand the distribution of loci of interest, e.g., FST outliers, along the whitefish genome as well as assisting with the de novo assembly of a whitefish reference genome.
Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia

The disease known as late-onset Alzheimer’s disease is a neurodegenerative condition recognized as the single most commonform of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer’s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathogen Chlamydia pneumoniae. In this article, we review previously published data and recent results that support involvement of this unusual respiratory pathogen in disease induction and development. We further suggest several areas for future research that should elucidate details relating to those processes, and we argue for a change in the designation of the disease based on increased understanding of its clinical attributes.
Prevalence of vitamin D deficiency in Iran: A systematic review and meta-analysis

Background: The prevalence of vitamin D deficiency in the Iranian community is very high. Women and older people are at the higher risk of vitamin D deficiency. Aim: This study aimed to estimate the prevalence of vitamin D deficiency in Iran by combining the results of various studies. Methods: This was a systematic review and meta-analysis. Separate strategies were developed for search in national databases (Irandoc, Magiran, SID) and international databases (Web of Science, PubMed, and Scopus) using the keywords of “vitamin D deficiency,” “Iran,” and “prevalence. ” The titles and abstracts of the articles were screened and related full texts were appraised. Those articles that met inclusion criteria were selected for meta-analysis. The heterogeneity of the articles was assessed via the Chi-square test. They were combined using the random-effect approach. In addition, the groups were categorized and analyzed in terms of age and gender. Results: Of 639 articles, 30 articles with a sample size of 26,042 people were included for data analysis. The overall prevalence of vitamin D deficiency was reported as 0.56. Subgroup analysis showed that 0.64 of women and 0.44 of men were suffering from vitamin D deficiency. The prevalence of vitamin D deficiency in the age groups under 20, 20–50, and over 50 years was 0.56. 4, 0.72. 4, and 0.59. 8, respectively. Conclusions: The Iranian Ministry of Health is expected to design strategies to improve the status of vitamin D at the national level.
Culture-Negative Early-Onset Neonatal Sepsis — At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship

Sepsis is a leading cause of mortality and morbidity in neonates. Presenting clinical symptoms are unspecific. Sensitivity and positive predictive value of biomarkers at onset of symptoms are suboptimal. Clinical suspicion therefore frequently leads to empirical antibiotic therapy in uninfected infants. The incidence of culture confirmed early-onset sepsis is rather low, around 0.4–0.8/1000 term infants in high-income countries. Six to 16 times more infants receive therapy for culture-negative sepsis in the absence of a positive blood culture. Thus, culture-negative sepsis contributes to high antibiotic consumption in neonatal units. Antibiotics may be life-saving for the few infants who are truly infected. However, overuse of broad-spectrum antibiotics increases colonization with antibiotic resistant bacteria. Antibiotic therapy also induces perturbations of the non-resilient early life microbiota with potentially long lasting negative impact on the individual‘s own health. Currently there is no uniform consensus definition for neonatal sepsis. This leads to variations in management. Two factors may reduce the number of culture-negative sepsis cases. First, obtaining adequate blood cultures (0.5–1 mL) at symptom onset is mandatory. Unless there is a strong clinical or biochemical indication to prolong antibiotics physician need to trust the culture results and to stop antibiotics for suspected sepsis within 36–48 h. Secondly, an international robust and pragmatic neonatal sepsis definition is urgently needed. Neonatal sepsis is a dynamic condition. Rigorous evaluation of clinical symptoms (“organ dysfunction”) over 36–48 h in combination with appropriately selected biomarkers (“dysregulated host response”) may be used to support or refute a sepsis diagnosis.
“It’s Hard Work”: A Feminist Political Economy Approach to Reconceptualizing “Work” in the Cancer Context

Within mainstream cancer literature, policy documents, and clinical practice, “work” is typically characterized as being synonymous with paid employment, and the problem of work is situated within the “return to work” discourse. The work that patients perform in managing their health, care, and everyday life at times of illness, however, is largely overlooked and unsupported. Drawing on feminist political economy theory, we report on a qualitative study of 12 women living with cancer. Major findings show that the work of patienthood cut across multiple fields of practice and included both paid and unpaid labor. The most prevalent types of work included illness work, body work, identity work, everyday work, paid employment and/or the work of maintaining income, and coordination work. The findings of this study disrupt popular conceptualizations of work and illuminate the nuanced and often invisible work that cancer patients may encounter, and the health consequences and inequities therein.
Frailty and Exercise Training: How to Provide Best Care after Cardiac Surgery or Intervention for Elder Patients with Valvular Heart Disease

The aim of this literature review was to evaluate existing evidence on exercise-based cardiac rehabilitation (CR) as a treatment option for elderly frail patients with valvular heart disease (VHD). Pubmed database was searched for articles between 1980 and January 2018. From 2623 articles screened, 61 on frailty and VHD and 12 on exercise-based training for patients with VHD were included in the analysis. We studied and described frailty assessment in this patient population. Studies reporting results of exercise training in patients after surgical/interventional VHD treatment were analyzed regarding contents and outcomes. The tools for frailty assessment included fried phenotype frailty index and its modifications, multidimensional geriatric assessment, clinical frailty scale, 5-meter walking test, serum albumin levels, and Katz index of activities of daily living. Frailty assessment in CR settings should be based on functional, objective tests and should have similar components as tools for risk assessment (mobility, muscle mass and strength, independence in daily living, cognitive functions, nutrition, and anxiety and depression evaluation). Participating in comprehensive exercise-based CR could improve short- and long-term outcomes (better quality of life, physical and functional capacity) in frail VHD patients. Such CR program should be led by cardiologist, and its content should include (1) exercise training (endurance and strength training to improve muscle mass, strength, balance, and coordination), (2) nutrition counseling, (3) occupational therapy (to improve independency and cognitive function), (4) psychological counseling to ensure psychosocial health, and (5) social worker counseling (to improve independency). Comprehensive CR could help to prevent, restore, and reduce the severity of frailty as well as to improve outcomes for frail VHD patients after surgery or intervention.
The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care

Objective The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients. Methods Ninety-six patients (86% women), aged 18–25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale - IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11:00 hours and 30 minutes after lunch) during the waking hours of 1 day. Results After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale - IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p = .015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association. Conclusions In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.
iNOS promotes CD24+CD133+ liver cancer stem cell phenotype through a TACE/ADAM17-dependent Notch signaling pathway

Significance CD24+CD133+ liver cancer stem cells (LCSCs) express higher levels of the inducible nitric oxide synthase (iNOS) and possess self-renewal and tumor growth properties. iNOS is associated with more aggressive hepatocellular carcinoma (HCC), leading to the upregulation of Notch1 signaling. The activation of Notch1 by iNOS/NO is dependent on cGMP/PKG-mediated activation of TACE and upregulation of iRhom-2. The expression of iNOS, CD24, and CD133 correlates with the expression of activated TACE and Notch signaling in more aggressive human HCC. These findings have implications for understanding how LCSCs are regulated in the setting of chronic inflammation, where signals to upregulate iNOS are often present. Targeting iNOS could have therapeutic benefit in HCC. The inducible nitric oxide synthase (iNOS) is associated with more aggressive solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer stem cells promotes cancer progression and requires Notch cleavage by ADAM (a disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem cell markers CD24 and CD133 in the tumors of patients with HCC was associated with greater iNOS expression and worse outcomes. The expression of iNOS in CD24+CD133+ LCSCs, but not CD24−CD133− LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as well as accelerating HCC initiation and tumor formation in the mouse xenograft tumor model. iNOS/NO led to Notch1 signaling through a pathway involving the soluble guanylyl cyclase/cGMP/PKG-dependent activation of TACE/ADAM17 and up-regulation of iRhom2 in LCSCs. In patients with HCC, higher TACE/ADAM17 expression and Notch1 activation correlated with poor prognosis. These findings link iNOS to Notch1 signaling in CD24+CD133+ LCSCs through the activation of TACE/ADAM17 and identify a mechanism for how iNOS contributes to progression of CD24+CD133+ HCC.
COST-EFFECTIVENESS OF INTERVENTIONS BASED ON PHYSICAL ACTIVITY IN THE TREATMENT OF CHRONIC CONDITIONS: A SYSTEMATIC LITERATURE REVIEW

Objectives: The aim of this study is to review evidence on the cost-effectiveness of exercise-based interventions in the treatment of chronic conditions a decade after the publication of Roine et al. in 2009 (Roine E, Roine RP, Räsänen P, et al. Int J Technol Assess Health Care. 2009;25:427–454). Methods: We carried out a review of published articles in PUBMED and JSTOR between January 1, 2008, and December 31, 2016. Full economic evaluations of exercise programs targeting patients with a chronic condition were eligible for inclusion. Data on program, design, and economic characteristics were extracted using a predefined extraction form. The quality of the economic evaluations was appraised using the adjusted Consensus Health Economic Criteria List. Results: A total of 426 articles were identified and thirty-seven studies were selected. Eleven studies dealt with musculoskeletal and rheumatologic disorders, ten with cardiovascular diseases, six with neurological disorders, three with mental illnesses, three with cancers, and four with diabetes, respiratory diseases, or pelvic organ prolapse. In total, 60 percent of exercise programs were dominant or cost-effective. For musculoskeletal and rheumatologic disorders, 72 percent of programs were dominant or cost-effective while this was the case for 57 percent of programs for cardiovascular diseases using a nonsurgical comparator. Conclusions: There is clear evidence in favor of exercise-based programs for the treatment of musculoskeletal and rheumatologic disorders and, to a lesser extent, for the treatment of cardiovascular diseases. More research is needed to evaluate the cost-effectiveness of physical activity in the treatment of neurological disorders, mental illnesses, cancers, respiratory diseases, and diabetes/obesity.
Transesophageal Echocardiographic Measurements of the Superior Vena Cava for Predicting Fluid Responsiveness in Patients Undergoing Invasive Positive Pressure Ventilation

Preoperative fasting, water deprivation, and intraoperative fluid loss and redistribution result in hypovolemia in patients undergoing surgery. Some findings have indicated that the superior vena cava (SVC) diameter and variation, as determined by transesophageal echocardiography during surgery, do not reflect central venous pressure effectively. This study aimed to compare and correlate the SVC diameter and variation with the stroke volume variation for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation.
Stein Neural Sampler

We propose two novel samplers to produce high-quality samples from a given (un-normalized) probability density. The sampling is achieved by transforming a reference distribution to the target distribution with neural networks, which are trained separately by minimizing two kinds of Stein Discrepancies, and hence our method is named as Stein neural sampler. Theoretical and empirical results suggest that, compared with traditional sampling schemes, our samplers share the following three advantages: 1. Being asymptotically correct; 2. Experiencing less convergence issue in practice; 3. Generating samples instantaneously.
A scalable and efficient approach for compiling and analyzing commit history

Background: Researchers oftentimes measure quality metrics only in the changed files when analyzing software evolution over commit-history. This approach is not suitable for compilation and using program analysis techniques that require byte-code. At the same time, compiling the whole software not only is costly but may also leave us with many uncompilable and unanalyzed revisions. Aims: We intend to demonstrate if analyzing changes in a module results in achieving a high compilation ratio and a better understanding of software quality evolution. Method: We conduct a large-scale multi-perspective empirical study on 37838 distinct revisions of the core module of 68 systems across Apache, Google, and Netflix to assess their compilability and identify when the software is uncompilable as a result of a developer's fault. We study the characteristics of uncompilable revisions and analyze compilable ones to understand the impact of developers on software quality. Results: We achieve high compilation ratios: 98.4% for Apache, 99.0% for Google, and 94.3% for Netflix. We identify 303 sequences of uncompile commits and create a model to predict uncompilability based on commit metadata with an F1-score of 0.89 and an AUC of 0.96. We identify statistical differences between the impact of affiliated and external developers of organizations. Conclusions: Focusing on a module results in a more complete and accurate software evolution analysis, reduces the cost and complexity, and facilitates manual inspection.