Miracle-dz/UniFAR-FTUs huggingface dataset:
Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats

Abstract There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.
Two Rye Genes Responsible for Abnormal Development of Wheat–Rye Hybrids Are Linked in the Vicinity of an Evolutionary Translocation on Chromosome 6R

The post-zygotic reproductive isolation (RI) in plants is frequently based on the negative interaction of the parental genes involved in plant development. Of special interest is the study of such types of interactions in crop plants, because of the importance of distant hybridization in plant breeding. This study is devoted to map rye genes that are incompatible with wheat, determining the development of the shoot apical meristem in wheat–rye hybrids. Linkage analysis of microsatellite loci, as well as genes of embryo lethality (Eml-R1) and hybrid dwarfness (Hdw-R1) was carried out in hybrids of Chinese Spring wheat with recombinant inbred lines as well as interline rye hybrids. Eml-R1 and Hdw-R1 could be mapped proximal and distal of two closely linked EST-SSR markers, Xgrm902 and Xgrm959, on rye chromosome 6R. Both rye genes are located on a segment of chromosome 6R that contains a breakpoint of evolutionary translocation between the ancestral chromosomes of homeologous groups 6 and 3. The obtained results are discussed in relation to genes interacting in developmental pathways as a class of causal genes of RI.
Influence of SIRT1 polymorphisms for diabetic foot susceptibility and severity

Abstract The present study aimed to explore the influence of sirtuin 1 (SIRT1) polymorphisms (rs12778366 and rs3758391) on diabetic foot (DF) susceptibility and severity in patients with type 2 diabetes mellitus (T2DM). This case–control study recruited 142 patients with DF, 148 patients with T2DM, and 148 healthy controls. SIRT1 gene polymorphisms were sequenced by polymerase chain reaction (PCR) and direct sequencing method. The relative expression of SIRT1 mRNA was estimated using quantitative real-time PCR (qRT-PCR) assay. Odds ratio (OR) with 95% confidence interval (95% CI) were used to represent the association of SIRT1 polymorphisms with DF susceptibility and severity. The results were adjusted using logistic regression analysis. C allele of rs12778366 polymorphism was significantly correlated with reduced DF susceptibility which deriving from healthy controls (adjusted OR = 0.364, 95% CI = 0.158–0.835) so was patients with T2DM (P = .047, OR = 0.591, 95%CI = 0.349–0.998), but the results became nonsignificant adjusted by clinical features (adjusted OR = 0.654, 95% CI = 0.391–1.094). We failed to find any significant association between rs3758391 polymorphisms and T2DM, DF susceptibility. No significant association has been discovered between SIRT1 polymorphisms and DF severity or characteristics. In addition, compared to healthy control and T2DM cases, patients with DF exhibited significant downregulation of SIRT1. The 2 studied polymorphisms had no effects on its gene expression (P > .05 for all). SIRT1 rs12778366 polymorphism C allele might act as a protective factor for DF onset.
A bilayer scaffold prepared from collagen and carboxymethyl cellulose for skin tissue engineering applications

Abstract Treatment of chronic skin wound such as diabetic ulcers, burns, pressure wounds are challenging problems in the medical area. The aim of this study was to design a bilayer skin equivalent mimicking the natural one to be used as a tissue engineered skin graft for use in the treatments of problematic wounds, and also as a model to be used in research related to skin, such as determination of the efficacy of transdermal bioactive agents on skin cells and treatment of acute skin damages that require immediate response. In this study, the top two layers of the skin were mimicked by producing a multilayer construct combining two different porous polymeric scaffolds: as the dermis layer a sodium carboxymethyl cellulose (NaCMC) hydrogel on which fibroblasts were added, and as the epidermis layer collagen (Coll) or chondroitin sulfate-incorporated collagen (CollCS) on which keratinocytes were added. The bilayer construct was designed to allow cross-talk between the two cell populations in the subsequent layers and achieves paracrine signalling. It had interconnected porosity, high water content, appropriate stability and elastic moduli. Expression of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF) and Interleukin 8 (IL-8), and the production of collagen I, collagen III, laminin and transglutaminase supported the attachment and proliferation of cells on both layers of the construct. Attachment and proliferation of fibroblasts on NaCMC were lower compared to performance of keratinocyte on collagen where keratinocytes created a dense and a stratified layer similar to epidermis. The resulting constructs succesfully mimicked in vitro the natural skin tissue. They are promising as grafts for use in the treatment of deep wounds and also as models for the study of the efficacy of bioactive agents on the skin.
Using smartphone-based virtual patients to assess the quality of primary healthcare in rural China: protocol for a prospective multicentre study

Introduction Valid and low-cost quality assessment tools examining care quality are not readily available. The unannounced standardised patient (USP), the gold standard for assessing quality, is costly to implement while the validity of clinical vignettes, as a low-cost alternative, has been challenged. Computerised virtual patients (VPs) create high-fidelity and interactive simulations of doctor-patient encounters which can be easily implemented via smartphone at low marginal cost. Our study aims to develop and validate smartphone-based VP as a quality assessment tool for primary care, compared with USP. Methods and analysis The study will be implemented in primary health centres (PHCs) in rural areas of seven Chinese provinces, and physicians practicing at township health centres and village clinics will be our study population. The development of VPs involves three steps: (1) identifying 10 VP cases that can best represent rural PHCs’ work, (2) designing each case by a case-specific development team and (3) developing corresponding quality scoring criteria. After being externally reviewed for content validity, these VP cases will be implemented on a smartphone-based platform and will be tested for feasibility and face validity. This smartphone-based VP tool will then be validated for its criterion validity against USP and its reliability (ie, internal consistency and stability), with 1260 VP/USP-clinician encounters across the seven study provinces for all 10 VP cases. Ethics and dissemination Sun Yat-sen University: No. 2017-007. Study findings will be published and tools developed will be freely available to low-income and middle-income countries for research purposes.
Misconceptions and issues regarding allometric scaling during the drug development process

ABSTRACT Introduction: Allometry is the study of size and its consequences. The simple hypothesis of allometric scaling is that all physiological parameters are proportional to body size or body mass. This review examines the development of theory-based allometry or fixed exponents (0.75 and 1.0 for basal metabolic rate and volume, respectively) and the evidence for or against the theory. The main focus of this report is to show the readers that there is enough evidence from experimental data that negate the concept of theory-based allometry in biology, physiology, and pharmacokinetics. Areas covered: In this review, the history of the development of theoretical allometry and the strong evidence against theory-based allometry demonstrated by experimental data is provided. During drug development, allometry is applied to both inter-species (from animals to humans) and intra-species (adults to children) scaling. These two forms of allometric scaling in the context of theory-based allometry are discussed and provide insight on scientific progress that refute theory-based allometry. Expert opinion: Theory-based allometry is a mere theory and experimental data and real-life observations strongly negate the existence of such a theory. Pharmacostatistical and physiological models based on theory-based allometry can be misleading and incorrect because the theory-based allometric exponent 0.75 is not universal. The exponents of allometry are data dependent and are not fixed in the universe.
Survey: Anaphora With Non-nominal Antecedents in Computational Linguistics: a Survey

This article provides an extensive overview of the literature related to the phenomenon of non-nominal-antecedent anaphora (also known as abstract anaphora or discourse deixis), a type of anaphora in which an anaphor like “that” refers to an antecedent (marked in boldface) that is syntactically non-nominal, such as the first sentence in “It’s way too hot here. That’s why I’m moving to Alaska. ” Annotating and automatically resolving these cases of anaphora is interesting in its own right because of the complexities involved in identifying non-nominal antecedents, which typically represent abstract objects such as events, facts, and propositions. There is also practical value in the resolution of non-nominal-antecedent anaphora, as this would help computational systems in machine translation, summarization, and question answering, as well as, conceivably, any other task dependent on some measure of text understanding. Most of the existing approaches to anaphora annotation and resolution focus on nominal-antecedent anaphora, classifying many of the cases where the antecedents are syntactically non-nominal as non-anaphoric. There has been some work done on this topic, but it remains scattered and difficult to collect and assess. With this article, we hope to bring together and synthesize work done in disparate contexts up to now in order to identify fundamental problems and draw conclusions from an overarching perspective. Having a good picture of the current state of the art in this field can help researchers direct their efforts to where they are most necessary. Because of the great variety of theoretical approaches that have been brought to bear on the problem, there is an equally diverse array of terminologies that are used to describe it, so we will provide an overview and discussion of these terminologies. We also describe the linguistic properties of non-nominal-antecedent anaphora, examine previous annotation efforts that have addressed this topic, and present the computational approaches that aim at resolving non-nominal-antecedent anaphora automatically. We close with a review of the remaining open questions in this area and some of our recommendations for future research.
Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis

Rationale: Frontometaphyseal dysplasia (FMD) is a dominant X-linked rare disease caused by mutations of FLNA. The distinctive features of FMD include skeletal dysplasia, facial dysmorphism, extremities anomalies, deafness, cleft palate and eye anterior segment anomalies, yet none of the complications, such as acro-osteolysis, keratitis, xerosis or poikiloderma, have been reported in FMD. Patient concerns: A 29-year-old mother and her 7-year-old daughter, both presented with congenital glaucoma, craniofacial dysmorphism, xerosis and poikiloderma, were admitted to our hospital in 2011. Additionally, the mother also suffered from acro-osteolysis, keratitis, camptodactyly of hands and metastatic cutaneous squamous cell carcinoma (SCC) which turned out to be fatal 5 years later. In 2017, keratitis and acro-osteolysis were noticed in the daughter as well. Radiography showed bowed long bones with thickening cortex, and distal phalangeal osteolysis. Diagnoses: Whole genome sequencing (WGS) was conducted in 2016, resulting in 71491 single-nucleotide polymorphisms and 7616 indels shared by patients while the father was taken as control. A FLNA variant was classified likely pathogenic, supporting the diagnoses of FMD. In addition, though our patients’ symptoms were highly consistent with xeroderma pigmentosum variant, a mild subtype of xeroderma pigmentosum (XP) with merely accumulated UV-induced lesions like xerosis and poikiloderma limited to sun-exposure sites, higher risks of cutaneous neoplasms and absence of classical XP features, WGS didn’t find supportive genetical evidence, but 2 HERC2 variants were assigned highest suspicion in both XP and SCC by bioinformatical analyses. Interventions: Anti-inflammatory treatment, sunscreens and moisturizers were administered. Outcomes: The daughter's cutaneous lesions developed slowly during the 6-year follow-up, but the keratitis seriously weakened her sight. Lessons: To our knowledge, it's the first report of cases carrying FMD, keratitis, xerosis, poikiloderma and acro-osteolysis simultaneously, and 3 likely pathogenic variants were identified. Whole genome/exon sequencing is recommended as a common test for patients with rare phenotypes.
Arts-based interventions to promote transition outcomes for young people with long-term conditions: A review

Objectives To conduct a systematic review of arts-based interventions promoting transition from paediatric to adult services for young people (Note: The term young people refers to adolescents and young adults.) with long-term conditions and to explore their effectiveness. Interventions Arts-based interventions included studies of young people who were actively participating in the intervention rather than passive observers. Visual arts interventions included film/video production, time-based media, photography, animation, sculpture, audio, installation, sound recordings, painting, textiles, print, mixed media, multimedia. Arts-based interventions included creative writing, poetry, dance, choreography and storytelling. Main outcome measures We included all outcome measures relevant to transition and any chronic condition. These included: self-care knowledge and skills, autonomy, continuity of care, adherence to treatment and attendance at appointments. Results Seven studies reported arts-based interventions promoting outcomes that are relevant to transition. These studies showed that arts-based interventions may influence young people with long-term conditions self-esteem, confidence and self-expression. The findings must be treated with caution as the evidence was weak with studies using qualitative measures and of poor methodological quality. Conclusions There is a need for further research of arts-based interventions for children and adolescents with long-term conditions that incorporate objective measurements or validated tools to assess outcomes relevant to the transition process.
Green Tea Quality Evaluation Based on Its Catechins and Metals Composition in Combination with Chemometric Analysis

Green tea infusions are one of the most popular beverages consumed across the world, especially is Asian countries. Green tea quality is primarily based on catechin content, however, the concentration of elements could also significantly influence its biological properties and thus quality and safety. The main purpose of the present study was the evaluation of catechin, antioxidant activity and metal content (K, Na, Ca, Mg, Fe, Mn, Cu, Zn, Cr, Pb, Cd and Ni) in different green tea types cultivated in Japan, Sri Lanka, South Korea, India, China and Japan. The chemical analysis of samples was performed using LC-ESI-Q-TOF-MS for organic constituents and atomic absorption spectrometry (flame and electrothermal) method for inorganic ones. The obtained results were subjected to chemometric elaboration. EGC (213 mg/100 mL of the tea infusion in South Korean Jeoncha) and EGCG (124 mg/100 mL in Japanese Sencha) were the dominant catechins in all green tea samples. Chinese and Indian green tea samples contained the highest concentration of toxic heavy metals, however these values were far below appropriate limitations for green teas. PCA revealed significant similarities between Japanese samples and Korean Jeoncha. In general the latter one was evaluated to have the best quality based on the investigated parameters.
PaPro1 and IDC4, Two Genes Controlling Stationary Phase, Sexual Development and Cell Degeneration in Podospora anserina

Filamentous fungi frequently undergo bistable phenotypic switches. Crippled Growth of Podospora anserina is one such bistable switch, which seems to rely upon the mis-activation of a self-regulated PaMpk1 MAP kinase regulatory pathway. Here, we identify two new partners of this pathway: PaPro1, a transcription factor orthologous to Sordaria macrospora pro1 and Neurospora crassa ADV-1, and IDC4, a protein with an AIM24 domain. Both PaPro1 and IDC4 regulate stationary phase features, as described for the other actors of the PaMpk1 signaling pathway. However, PaPro1 is also involved in the control of fertilization by activating the transcription of the HMG8 and the mating type transcription factors, as well as the sexual pheromones and receptor genes. The roles of two components of the STRIPAK complex were also investigated by inactivating their encoding genes: PaPro22 and PaPro45. The mutants of these genes were found to have the same phenotypes as PaPro1 and IDC4 mutants as well as additional phenotypes including slow growth, abnormally shaped hyphae, pigment accumulation and blockage of the zygotic tissue development, indicating that the STRIPAK complex regulates, in addition to the PaMpk1 one, other pathways in P. anserina. Overall, the mutants of these four genes confirm the model by which Crippled Growth is due to the abnormal activation of the PaMpk1 MAP kinase cascade.
Central and peripheral pain sensitization during an ultra-marathon competition

Abstract Background and aims The participation in ultra-marathons and other ultra-endurance events has increased exponentially over the past decade. There is insufficient data on variation in pain mechanisms in exercise overall but especially in the ultra-endurance athlete population. To further understand peripheral and central pain sensitization we have investigated pressure pain threshold and conditioned pain modulation during three separate ultra-marathon competitions. Methods Each ultra-marathon investigated was held in the state of Florida, USA, over flat, sandy and paved surfaces under generally warm to hot, humid conditions. Pressure pain threshold was measured utilizing a Baseline © Dolorimeter. The blunt end of the dolorimeter stylus was placed onto the distal dominant arm, equidistant between the distal radius and ulna, three times in a blinded manner to insure that the testing technician did not influence the subject’s responses. Conditioned pain modulation was measured immediately after the PPT measures by placing the non-dominant hand in a cool water bath maintained at 15°C. The same dolorimeter measurement was repeated two more times on the dominant arm while the non-dominant hand remained in the water. Data was analyzed with a paired t-test. Results Pressure pain threshold was significantly decreased (p<0.05) at 25, 50 and 100 miles. Conditioned pain modulation was also significantly decreased (p<0.05) at 25, 50 and 100 miles of an ultra-marathon competition. Conclusions Together these data suggest an increased peripheral and/or central pain sensitization starting at 25 miles and continuing throughout an ultra-marathon competition run in these conditions. This is the first study that provides evidence of a decreased peripheral pain threshold and decreased central pain inhibition from ultra-marathon running. Decreases in both the peripheral pain threshold and central inhibition may result from nociceptor plasticity, central sensitization or a combination of both. Implications Based on previous research that has indicated a central sensitization resulting from inflammation and the well-documented inflammatory response to the rigors of ultra-marathon competition, we suggest the decreased peripheral pain threshold and decreased descending pain inhibition results from this inflammatory response of running an ultra-marathon.
Revisiting Arthroscopic Partial Meniscectomy for Degenerative Tears in Knees With Mild or No Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE The purpose of this systematic review and meta-analysis was to evaluate the efficacy of arthroscopic partial meniscectomy (APM) for symptomatic degenerative meniscal tear (DMT) in knees with mild or no osteoarthritis. STUDY DESIGN A systematic review and meta-analysis. METHODS MEDLINE, EMBASE, and Cochrane databases were systematically searched. The inclusion criteria were as follows: (1) English language, (2) randomized controlled trial (RCT), (3) comparison between APM and other treatment modalities as a primary objective, and (4) complete DMT in knees with mild or no osteoarthritis. Mild or no arthritis was defined as Kellgren-Lawrence grade 0 to 2 or Ahlbäck 0 to 1 on radiography. Statistical analysis of functional activity and pain after APM and conservative treatment or sham operation was performed using R version 3.3. 1. RESULTS Five articles were included in the final analysis, and they were all RCTs. Four studies compared clinical results of APM with those for physical therapy, and one study compared APM with sham operation. The functional activity was not better in the APM group (296 cases) than in the conservative treatment or sham operation group (284 cases) (I: 0%, small level of heterogeneity). Pain was not reduced significantly in the APM group compared with that in the conservative treatment or sham operation group (I: 0∼90%, high level of heterogeneity). CONCLUSIONS This systematic review and meta-analysis of high-quality literature provides relatively strong evidence that APM did not improve functional activity or reduce pain compared with the results with conservative treatment or sham operation in knees with mild or no osteoarthritis.