Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma adsorption in refractory chronic gouty arthritis flare: A case report

Background Along with uric acid, which is the primary driving factor of gout, downstream inflammatory mediators have been shown to be involved in the pathogenesis of gouty arthritis flares. Extracorporeal haemadsorption is an emerging technology for the treatment of dysregulated inflammatory states by effectively removing cytokines from the bloodstream. Whether haemadsorption was effective in refractory gout flares has not been reported in the literature. Case summary We report the case of a 52-year-old male who presented with refractory gouty arthropathy for 30 years. His uric acid levels were poorly controlled due to poor diet and treatment compliance. Tophi were found to have precipitated in multiple joints and subcutaneous tissue. In the last 2 years, his incidents of gouty flares had become more frequent, and resistant to the medications, including colchicine, allopurinol, febuxostat, glucocorticoids, and NSAID analgesics. He had experienced a triad of chills, high fever and arthritis for the past 2 weeks. Therefore, he took 2 mg colchicine twice daily for 2 weeks with no improvement in his pain. Proinflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were found to be remarkably elevated. Given that conventional treatment was unsuccessful, we tried to employ plasma adsorption (PA) to remove inflammatory cytokines. After 4 sessions, symptoms, such as fever, joint swelling and pain, were greatly improved. Meanwhile, the levels of proinflammatory factors such as IL-6 and TNF-α were found to be decreased, while the anti-inflammatory factor IL-10 remained the same during the course. He was followed up for 8 months and arthritis have flared up twice in response to a high-purine diet. Conclusion Our study suggests that plasma adsorption (PA) may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated. However, more clinical trials are needed to verify the efficacy and safety of the treatment. Core tip Chronic gouty arthritis flares are refractory to conventional treatment, such as uric acid-lowering drugs and NSAID analgesics. Due to the involvement of inflammatory cytokines, plasma adsorption was employed to alleviate flares by removing inflammatory mediators. Herein, we report a 52-year-old male who presented with refractory gouty arthropathy for 30 years, manifested with a triad of chills, high fever and arthritis. He underwent several sessions of plasma adsorption, and his symptoms soon improved, along with a drop in inflammatory mediators. We conclude that plasma adsorption may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated.
White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology

Introduction An inactivating mutation in the histidine decarboxylase gene (Hdc) has been identified as a rare but high-penetrance genetic cause of Tourette syndrome (TS). TS is a neurodevelopmental syndrome characterized by recurrent motor and vocal tics; it is accompanied by structural and functional abnormalities in the cortico-basal ganglia circuitry. Hdc, which is expressed both in the posterior hypothalamus and peripherally, encodes an enzyme required for the biosynthesis of histamine. Hdc knockout mice (Hdc-KO) functionally recapitulate this mutation and exhibit behavioral and neurochemical abnormalities that parallel those seen in patients with TS. Materials and methods We performed exploratory RNA-seq to identify pathological alterations in several brain regions in Hdc-KO mice. Findings were corroborated with RNA and protein quantification, immunohistochemistry, and ex vivo brain imaging using MRI. Results Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain ex vivo diffusion tensor imaging (DTI), which revealed reduced fractional anisotropy (FA) in the dorsal striatum. Discussion While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with tics. The Hdc-KO model may represent a powerful system in which to examine the developmental mechanisms underlying this abnormality.
How does bilingual experience influence novel word learning? Evidence from comparing L1-L3 and L2-L3 cognate status

Bilingual experience exerts a complex influence on novel word learning, including the direct effects of transferable prior knowledge and learning skill. However, the facilitation and interference mechanism of such influence has largely been tangled by the similarity of the previously learned word knowledge. The present study compared Chinese-English bilinguals’ paired-associate learning of nonwords in logographic and alphabetic writing systems. The logographic nonwords resemble the form and meaning of L1 Chinese words in varying degrees, being cognates, false cognates, or non-cognates of Chinese. The alphabetic nonwords resemble the form and meaning of L2 English words, being cognates, false cognates, or non-cognates of English. The learning sequence of logographic and alphabetic words was cross-balanced. The learning results were measured in production and recognition tasks. As for learning the logographic nonwords, both the recognition and production results showed that cognates were learned significantly faster than the non-cognates, and the false cognates were also learned significantly faster than the non-cognates. This suggests stronger facilitation rather than interference from L1 on novel word learning. As for learning the alphabetic nonwords, both the recognition and production results revealed that cognates were learned significantly faster than the non-cognates, but false cognates showed no advantage over the non-cognates. This indicates that interference from L2 is stronger than that from L1. Taken together, the results provide new evidence for the dissociable facilitation and interference effects of bilingual experience. These results carry potential educational implications in that learning novel words depends on substantial bilingual experience.
Urban–rural difference in the costs of disability and its effects on poverty among people with disabilities in China

The urban–rural difference in poverty is an important issue in China, particularly for people with disabilities. The extra costs of disability render this population susceptible to falling into poverty, where this can exacerbate the inequality among people with disabilities between urban and rural areas of the country. Previous studies have provided empirical evidence for the extra costs of disabilities in certain countries, but little scholarly attention has been devoted to the urban–rural gap in the costs of disability, particularly in countries like China that have a dual urban–rural system. This study explores changes in the extra costs of disability in China between urban and rural households with disabled members from 2008 to 2018 by using the standard of living approach. We apply the Foster–Greer–Thorbecke Poverty Index to measure the rates of poverty in urban and rural households with disabilities after considering the costs of disability. The results reveal that the costs of disability were not always lower for rural households than for urban households. At the same time, many rural households with disabled people were found to suffer from severe poverty owing to the high costs of their disabilities. The difference in health insurance and rehabilitation services between urban and rural China have led to an urban-rural gap in the costs of disability. This suggests that supplying more goods and services for disabled people in rural areas, especially free services, and raising the reimbursement due to them from their health insurance can help improve their standard of living.
Dinaciclib as an effective pan-cyclin dependent kinase inhibitor in platinum resistant ovarian cancer

Background Ovarian cancer (OC) is amongst the most lethal of common cancers in women. Lacking in specific symptoms in the early stages, OC is predominantly diagnosed late when the disease has undergone metastatic spread and chemotherapy is relied on to prolong life. Platinum-based therapies are preferred and although many tumors respond initially, the emergence of platinum-resistance occurs in the majority of cases after which prognosis is very poor. Upregulation of DNA damage pathways is a common feature of platinum resistance in OC with cyclin dependent kinases (CDKs) serving as key regulators of this process and suggesting that CDK inhibitors (CDKis) could be effective tools in the treatment of platinum resistant and refractory OC. Aim The aim of this study was to evaluate the efficacy of CDKis in platinum resistant OC models and serve as a predictor of potential clinical utility. Methods The efficacy of CDKi, dinaciclib, was determined in wildtype and platinum resistant cell line pairs representing different OC subtypes. In addition, dinaciclib was evaluated in primary cells isolated from platinum-sensitive and platinum-refractory tumors to increase the clinical relevance of the study. Results and conclusions Dinaciclib proved highly efficacious in OC cell lines and primary cells, which were over a thousand-fold more sensitive to the CDKi than to cisplatin. Furthermore, cisplatin resistance in these cells did not influence sensitivity to dinaciclib and the two drugs combined additively in both platinum-sensitive and platinum-resistant OC cells suggesting a potential role for pan-CDKis (CDKis targeting multiple CDKs), such as dinaciclib, in the treatment of advanced and platinum-resistant OC.
Supersymmetric Nonlinear Sigma Models as Gauge Theories

Supersymmetric nonlinear sigma models are obtained from linear sigma models by imposing supersymmetric constraints. If we introduce auxiliary chiral and vector superfields, these constraints can be expressed by D-terms and F-terms depending on the target manifolds. Auxiliary vector superfields appear as gauge fields without kinetic terms. If there are no D-term constraints, the target manifolds are always non-compact manifolds. When all the degrees of freedom in these non-compact directions are eliminated by gauge symmetries, the target manifold becomes compact. All supersymmetric nonlinear sigma models, whose target manifolds are the hermitian symmetric spaces, are successfully formulated as gauge theories.
Insight into genetic, biological, and environmental determinants of sexual-dimorphism in type 2 diabetes and glucose-related traits

There is growing evidence that sex and gender differences play an important role in risk and pathophysiology of type 2 diabetes (T2D). Men develop T2D earlier than women, even though there is more obesity in young women than men. This difference in T2D prevalence is attenuated after the menopause. However, not all women are equally protected against T2D before the menopause, and gestational diabetes represents an important risk factor for future T2D. Biological mechanisms underlying sex and gender differences on T2D physiopathology are not yet fully understood. Sex hormones affect behavior and biological changes, and can have implications on lifestyle; thus, both sex-specific environmental and biological risk factors interact within a complex network to explain the differences in T2D risk and physiopathology in men and women. In addition, lifetime hormone fluctuations and body changes due to reproductive factors are generally more dramatic in women than men (ovarian cycle, pregnancy, and menopause). Progress in genetic studies and rodent models have significantly advanced our understanding of the biological pathways involved in the physiopathology of T2D. However, evidence of the sex-specific effects on genetic factors involved in T2D is still limited, and this gap of knowledge is even more important when investigating sex-specific differences during the life course. In this narrative review, we will focus on the current state of knowledge on the sex-specific effects of genetic factors associated with T2D over a lifetime, as well as the biological effects of these different hormonal stages on T2D risk. We will also discuss how biological insights from rodent models complement the genetic insights into the sex-dimorphism effects on T2D. Finally, we will suggest future directions to cover the knowledge gaps.
A web-based psychoeducational simulation game for adults in stepfamilies (GSteps)—study protocol for a randomized controlled feasibility trial

Background Stepfamilies are a prevalent family form. However, less stable than nuclear, first marriage families due to the presence of risk factors such as the absence of social norms and the presence of stepchildren. Stepfamilies have unique educational needs regarding stepparenting and co-parenting issues. The development and documentation of psychoeducational intervention strategies can facilitate dissemination of ongoing studies and promote transparency. This article describes the background, design and protocol of a randomized controlled trial (RCT) evaluating the eficacy and feasibility of a web-based Psychoeducational Simulation Game (GSteps). Behavior-modeling video training (BMT) is used to demonstrate and promote relational skills, stepparenting and co-parenting effective strategies for adults in stepfamilies. A mental health professional will be available within the GSteps platform for clarification or emotional support. Methods/design A RCT design is presented to evaluate the outcomes of a self-administered, interactive and web-based psychoeducational Game targeting dyadic marital adjustment and interpersonal skills as the primary outcomes and remarriage beliefs, family function and stepparenting and co-parenting attitudes as the secondary outcomes. Other outcome measures include satisfaction with GSteps, participants’ knowledge learned after the intervention and a purposive sampling method will be used to access feasibility. The minimum required sample size is 112 participants (56 per condition) randomly allocated either to an experimental group (EG), receiving GSteps intervention, or to a wait-list control group (CG). A survey is conducted electronically. Assessments take place at baseline (T0), after the intervention (T1) and 1-month follow-up (T2). Discussion This protocol presents a RCT aimed at evaluating the efficacy of a web-based psychoeducational intervention (GSteps) designed for improving marital, stepparenting and co-parenting skills in adults who live in stepfamilies. The use of the protocol and results of intervention studies may guide the use and refinement of web-based psychoeducational intervention for stepfamilies. Additionally, GSteps may become a tool for health professionals to enhance stepfamily functioning, stepparenting skills, and marital adjustment of remarried adults.
Activation of farnesoid X receptor suppresses ER stress and inflammation via the YY1/NCK1/PERK pathway in large yellow croaker (Larimichthys crocea)

Unfolded protein responses from endoplasmic reticulum (ER) stress have been implicated in inflammatory signaling. The vicious cycle of ER stress and inflammation makes regulation even more difficult. This study examined effects of farnesoid X receptor (FXR) in ER-stress regulation in large yellow croakers. The soybean-oil-diet-induced expression of ER stress markers was decreased in fish with FXR activated. In croaker macrophages, FXR activation or overexpression significantly reduced inflammation and ER stress caused by tunicamycin (TM), which was exacerbated by FXR knockdown. Further investigation showed that the TM-induced phosphorylation of PERK and EIF2α was inhibited by the overexpression of croaker FXR, and it was increased by FXR knockdown. Croaker NCK1 was then confirmed to be a regulator of PERK, and its expression in macrophages is increased by FXR overexpression and decreased by FXR knockdown. The promoter activity of croaker NCK1 was inhibited by yin-yang 1 (YY1). Furthermore, the results show that croaker FXR overexpression could suppress the P65-induced promoter activity of YY1 in HEK293t cells and decrease the TM-induced expression of yy1 in macrophages. These results indicate that FXR could suppress P65-induced yy1 expression and then increase NCK1 expression, thereby inhibiting the PERK pathway. This study may benefit the understanding of ER stress regulation in fish, demonstrating that FXR can be used in large yellow croakers as an effective target for regulating ER stress and inflammation.
A quasi-static two-dimensional induction heating problem II. Numerical analysis

We consider a nonlinear elliptic–parabolic system which stems from the modelling of heat induction processes in which a sinusoidal electromagnetic field is applied at the boundary of the inductor. The magnetic field satisfies an elliptic equation whereas the temperature equation is parabolic. These two equations are coupled due to the Joule effect and to the conductivity dependence on temperature. A Galerkin method for our problem is analyzed and shown to yield error estimates in L2 and H1.
Confinement induces oxidative damage and synaptic dysfunction in mice

A confined environment is an enclosed area where entry or exit is highly restricted, which is a risk factor for a work crew’s mental health. Previous studies have shown that a crew is more susceptible to developing anxiety or depression in a confined environment. However, the underlying mechanism by which negative emotion is induced by confinement is not fully understood. Hence, in this study, mice were retained in a tube to simulate short-term confinement. The mice exhibited depressive-like behavior. Additionally, the levels of H2O2 and malondialdehyde in the prefrontal cortex were significantly increased in the confinement group. Furthermore, a label-free quantitative proteomic strategy was applied to analyze the abundance of proteins in the prefrontal cortex of mice. A total of 71 proteins were considered differentially abundant proteins among 3,023 identified proteins. Two differentially abundant proteins, superoxide dismutase [Mn] and syntaxin-1A, were also validated by a parallel reaction monitoring assay. Strikingly, the differentially abundant proteins were highly enriched in the respiratory chain, oxidative phosphorylation, and the synaptic vesicle cycle, which might lead to oxidative damage and synaptic dysfunction. The results of this study provide valuable information to better understand the mechanisms of depressive-like behavior induced by confined environments.
The impact of soluble HLA-G in IVF/ICSI embryo culture medium on implantation success

The HLA-G molecule is widely accepted as an important factor for pregnancy success. Its expression has been detected in the extravillous trophoblasts. Soluble HLA-G (sHLA-G) was found in the genital tract, pre-implanted embryos as well as in seminal fluid. In this study, we investigated the concentration of sHLA-G (sHLA-G1 and sHLA-G5) in media from 344 single cultured embryos following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The level of sHLA-G (U/ml) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. We correlated sHLA-G secretion with ovarian stimulation protocols, the type of embryo transfer (fresh or frozen cycle) and the quality of the embryos. The ovarian stimulation protocol affects the secretion of sHLA-G by the embryo. Embryos obtained from the long agonist protocol secreted more sHLA-G than those originating from the short antagonist protocol (p = 0.0001). Embryos whose transfer resulted in a clinical pregnancy and/or live birth secreted more sHLA-G compared to those whose transfer ended without pregnancy. This was particularly observable in embryos following the long ovarian stimulation protocol and from a frozen embryo cycle. In conclusion, sHLA-G secreted by the embryo has an impact on implantation and live birth and could be a developmental potential marker of the embryo. Its concentration depends on the ovarian stimulation protocol used.
Carbon, nitrogen, and oxygen stable isotopes in modern tooth enamel: A case study from Gorongosa National Park, central Mozambique

The analyses of the stable isotope ratios of carbon (δ13C), nitrogen (δ15N), and oxygen (δ18O) in animal tissues are powerful tools for reconstructing the feeding behavior of individual animals and characterizing trophic interactions in food webs. Of these biomaterials, tooth enamel is the hardest, most mineralized vertebrate tissue and therefore least likely to be affected by chemical alteration (i.e., its isotopic composition can be preserved over millions of years), making it an important and widely available archive for biologists and paleontologists. Here, we present the first combined measurements of δ13C, δ15N, and δ18O in enamel from the teeth of modern fauna (herbivores, carnivores, and omnivores) from the well-studied ecosystem of Gorongosa National Park (GNP) in central Mozambique. We use two novel methods to produce high-precision stable isotope enamel data: (i) the “oxidation-denitrification method,” which permits the measurement of mineral-bound organic nitrogen in tooth enamel (δ15Nenamel), which until now, has not been possible due to enamel’s low organic content, and (ii) the “cold trap method,” which greatly reduces the sample size required for traditional measurements of inorganic δ13Cenamel and δ18Oenamel (from ≥0.5 to ≤0.1 mg), permitting analysis of small or valuable teeth and high-resolution serial sampling of enamel. The stable isotope results for GNP fauna reveal important ecological information about the trophic level, dietary niche, and resource consumption. δ15Nenamel values clearly differentiate trophic level (i.e., carnivore δ15Nenamel values are 4.0‰ higher, on average, than herbivores), δ13Cenamel values distinguish C3 and/or C4 biomass consumption, and δ18Oenamel values reflect local meteoric water (δ18Owater) in the park. Analysis of combined carbon, nitrogen, and oxygen stable isotope data permits geochemical separation of grazers, browsers, omnivores, and carnivores according to their isotopic niche, while mixed-feeding herbivores cannot be clearly distinguished from other dietary groups. These results confirm that combined C, N, and O isotope analyses of a single aliquot of tooth enamel can be used to reconstruct diet and trophic niches. Given its resistance to chemical alteration, the analysis of these three isotopes in tooth enamel has a high potential to open new avenues of research in (paleo)ecology and paleontology.