Miracle-dz/UniFAR-FTUs huggingface dataset:
Ferroptosis in inflammatory arthritis: A promising future

Ferroptosis is a kind of regulatory cell death (RCD) caused by iron accumulation and lipid peroxidation, which is characterized by mitochondrial morphological changes and has a complex regulatory network. Ferroptosis has been gradually emphasized in the pathogenesis of inflammatory arthritis. In this review, we summarized the relevant research on ferroptosis in various inflammatory arthritis including rheumatoid arthritis (RA), osteoarthritis, gout arthritis, and ankylosing spondylitis, and focused on the relationship between RA and ferroptosis. In patients with RA and animal models of RA, there was evidence of iron overload and lipid peroxidation, as well as mitochondrial dysfunction that may be associated with ferroptosis. Ferroptosis inducers have shown good application prospects in tumor therapy, and some anti-rheumatic drugs such as methotrexate and sulfasalazine have been shown to have ferroptosis modulating effects. These phenomena suggest that the role of ferroptosis in the pathogenesis of inflammatory arthritis will be worth further study. The development of therapeutic strategies targeting ferroptosis for patients with inflammatory arthritis may be a promising future.
Enriched environment ameliorates propagation of tau pathology and improves cognition in rat model of tauopathy

Introduction The typical symptoms of Alzheimer’s disease (AD) are cognitive impairment, disrupted spatial orientation, behavioral and psychiatric abnormalities, and later motor deficits. Neuropathologically, AD is characterized by deposits of pathological forms of endogenous proteins – amyloid-β, and neurofibrillary tau protein pathology. The latter closely correlates with brain atrophy and clinical impairment. Pharmacological therapies for these pathologies are largely absent, raising the question whether non-pharmacological interventions could be efficacious. Environmental factors can play a role in the manifestation of AD. It is unknown whether enriched environment (EE) can ameliorate the propagation of protein aggregates or their toxic components. Methods We injected insoluble tau extracts from human brains with AD (600 or 900 ng per animal) into hippocampi of SHR72 transgenic rats that express non-mutated truncated human tau 151-391/4R, but usually do not develop hippocampal tangles. The rats had either standard housing, or could access an EE 5×/week for 3 months. Behavioral analysis included the Morris Water Maze (MWM). Histological analysis was used to assess the propagation of tau pathology. Results Animals exposed to EE performed better in the MWM (spatial acquisition duration and total distance, probe test); unexposed animals improved over the course of acquisition trials, but their mean performance remained below that of the EE group. Enriched environment abrogated tau propagation and hippocampal tangle formation in the 600 ng group; in the 900 ng group, tangle formation was ∼10-fold of the 600 ng group, and unaffected by EE. Conclusion Even a small difference in the amount of injected human AD tau can cause a pronounced difference in the number of resulting tangles. EE leads to a noticeably better spatial navigation performance of tau-injected animals. Furthermore, EE seems to be able to slow down tau pathology progression, indicating the possible utility of similar interventions in early stages of AD where tangle loads are still low.
Effect of intraoperative dexmedetomidine on hepatic ischemia-reperfusion injury in pediatric living-related liver transplantation: A propensity score matching analysis

Background Hepatic ischemia-reperfusion injury (HIRI) is largely unavoidable during liver transplantation (LT). Dexmedetomidine (DEX), an α2-adrenergic agonist, exerts a variety of organ-protective effects in pediatric populations. However, evidence remains relatively limited about its hepatoprotective effects in pediatric living-related LT. Methods A total of 121 pediatric patients undergoing living-related LT from June 2015 to December 2018 in our hospital were enrolled. They were classified into DEX or non-DEX groups according to whether an infusion of DEX was initiated from incision to the end of surgery. Primary outcomes were postoperative liver graft function and the severity of HIRI. Multivariate logistic regression and propensity score matching (PSM) analyses were performed to identify any association. Results A 1:1 matching yielded 35 well-balanced pairs. Before matching, no significant difference was found in baseline characteristics between groups except for warm ischemia time, which was longer in the non-DEX group (44 [38–50] vs. 40 [37–44] min, p = 0.017). After matching, the postoperative peak lactic dehydrogenase levels decreased significantly in the DEX group than in the non-DEX group (622 [516–909] vs. 970 [648–1,490] IU/L, p = 0.002). Although there was no statistical significance, a tendency toward a decrease in moderate-to-extreme HIRI rate was noted in the DEX group compared to the non-DEX group (68.6% vs. 82.9%, p = 0.163). Patients in the DEX group also received a significantly larger dosage of epinephrine as postreperfusion syndrome (PRS) treatment (0.28 [0.17–0.32] vs. 0.17 [0.06–0.30] µg/kg, p = 0.010). However, there were no significant differences between groups in PRS and acute kidney injury incidences, mechanical ventilation duration, intensive care unit, and hospital lengths of stay. Multivariate analysis revealed a larger graft-to-recipient weight ratio (odds ratio [OR] 2.657, 95% confidence interval [CI], 1.132–6.239, p = 0.025) and intraoperative DEX administration (OR 0.333, 95% CI, 0.130–0.851, p = 0.022) to be independent predictors of moderate-to-extreme HIRI. Conclusion This study demonstrated that intraoperative DEX could potentially decrease the risk of HIRI but was associated with a significant increase in epinephrine requirement for PRS in pediatric living-related LT. Further studies, including randomized controlled studies, are warranted to provide more robust evidence.
Effects of Postural Education Program (PEPE Study) on Daily Habits in Children

The current randomized controlled trial aimed to investigate the effects of a postural education program on daily life habits related to low back pain (LBP) in children. Reducing the disease burden of unspecific LBP in children is of major public health relevance, as children with episodes of LBP tend to experience chronic back pain in adulthood. The study was performed in Majorca (Spain), with 253 primary school children aged between 10 and 12 years. The sample was selected from different clusters (schools) using convenience sampling and randomly distributed into an experimental group (5 schools) or a control group (5 schools). Individual postural items did not improve after the intervention in the experimental group, nor did they improve in the control group. Neither did they improve postural habits score in both groups after the intervention. In conclusion, this telematic intervention has not managed to improve postural habits in children. Nevertheless, there is a lack of evidence to determine whether it is feasible to carry out telematics intervention that promotes lifestyle changes in children.
The role of interleukin-1β in type 2 diabetes mellitus: A systematic review and meta-analysis

Type 2 diabetes mellitus (T2DM) is a multifactorial non-communicable disease that is characterized by insulin resistance and chronic sub-clinical inflammation. Among the emerging inflammatory markers observed to be associated with β-cell damage is interleukin 1β (IL1β), a proinflammatory cytokine that modulates important metabolic processes including insulin secretion and β-cell apoptosis. The present systematic review and meta-analysis gathers available evidence on the emerging role of IL1β in T2DM. PubMed and Embase were searched for human studies that assessed 1L1β in T2DM individuals from 2016-2021. Thirteen studies (N=2680; T2DM=1182, controls=1498) out of 523 were included in the systematic review and only 3 studies in the meta-analysis. Assays were the most commonly used quantification method and lipopolysaccharides as the most common stimulator for IL1β upregulation. Random and fixed effects meta-analysis showed non-significant mean differences of IL1β concentrations between the T2DM and controls. Given the high heterogeneity and small subset of studies included, caution is advised in the interpretation of results. The present systematic review and meta-analysis highlights the limited evidence available that could implicate 1L1β as a potent biomarker for T2DM. Standardization of 1L1β assays with larger sample sizes are encouraged in future observational and prospective studies.
Comparison of three validated PD-L1 immunohistochemical assays in urothelial carcinoma of the bladder: interchangeability and issues related to patient selection

Different programmed cell death-ligand 1 (PD-L1) assays and scoring algorithms are being used in the evaluation of PD-L1 expression for the selection of patients for immunotherapy in specific settings of advanced urothelial carcinoma (UC). In this paper, we sought to investigate three approved assays (Ventana SP142 and SP263, and Dako 22C3) in UC with emphasis on implications for patient selection for atezolizumab/pembrolizumab as the first line of treatment. Tumors from 124 patients with invasive UC of the bladder were analyzed using tissue microarrays (TMA). Serial sections were stained with SP263 and SP142 on Ventana Benchmark Ultra and with 22C3 on Dako Autostainer Link 48. Stains were evaluated independently by two observers and scored using the combined positive score (CPS) and tumor infiltrating immune cells (IC) algorithms. Differences in proportions (DP), overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen κ were calculated for all comparable cases. Good overall concordance in analytic performance was observed for 22C3 and SP263 with both scoring algorithms; specifically, the highest OPA was observed between 22C3 and SP263 (89.6%) when using CPS. On the other hand, SP142 consistently showed lower positivity rates with high differences in proportions (DP) compared with 22C3 and SP263 with both CPS and IC, and with a low PPA, especially when using the CPS algorithm. In conclusion, 22C3 and SP263 assays show comparable analytical performance while SP142 shows divergent staining results, with important implications for the selection of patients for both pembrolizumab and atezolizumab.
Herpes simplex virus 1 as an oncolytic viral therapy for refractory cancers

The need for efficacious and non-toxic cancer therapies is paramount. Oncolytic viruses (OVs) are showing great promise and are introducing new possibilities in cancer treatment with their ability to selectively infect tumor cells and trigger antitumor immune responses. Herpes Simplex Virus 1 (HSV-1) is a commonly selected OV candidate due to its large genome, relative safety profile, and ability to infect a variety of cell types. Talimogene laherparevec (T-VEC) is an HSV-1-derived OV variant and the first and only OV therapy currently approved for clinical use by the United States Food and Drug Administration (FDA). This review provides a concise description of HSV-1 as an OV candidate and the genomic organization of T-VEC. Furthermore, this review focuses on the advantages and limitations in the use of T-VEC compared to other HSV-1 OV variants currently in clinical trials. In addition, approaches for future directions of HSV-1 OVs as cancer therapy is discussed.
Word reading skills in autism spectrum disorder: A systematic review

A growing body of research suggests that children with autism spectrum disorder (ASD) are at risk of reading and learning difficulties. However, there is mixed evidence on their weaknesses in different reading components, and little is known about how reading skills characterize in ASD. Thereby, the current study aimed to systematically review the research investigating this function in children with ASD. To this purpose, we reviewed 24 studies that compared (1) children with ASD and children with typical development (TD) in word and nonword reading performance, (2) children with ASD and normative data of word and nonword reading tests, and (3) the results obtained by children with ASD in word and nonword reading tests. Most of the comparisons (62%) contrasting the reading performance of children with ASD and children with TD did not find significant differences between groups in both word and nonword reading. However, all the comparisons that reported standardized results showed that children with ASD had scores that fell within population norms. Regarding the third comparison of interest, about 54% of the studies presented data for both word and nonword reading, but only one study tested the difference between them and showed that children with ASD had higher levels of word than of nonword reading. Despite these results, the heterogeneous and small samples do not allow to draw sound conclusions regarding the strategies that children with ASD use to read words. As consequence, the nature of reading difficulties presented by children with ASD are still unknown, requiring future research conducted with larger and well-characterized samples of ASD and TD, using homogeneous specific tasks designed to assess word reading strategies.
Predictive value of the systemic immune-inflammation index for cancer-specific survival of osteosarcoma in children

Background Osteosarcoma (OS) is the primary malignant bone tumor that most commonly affects children and adolescents. Recent years effective chemotherapy have improved the 5-year survival in osteosarcoma patients to up to 60%-70%. Still, there is a lack of novel therapeutic strategies to enhance further survival. Our study aimed to evaluate the clinical significance of pretreatment inflammatory-based parameters, including PLT, NLR, and SII, as prognostic indicators of survival in pediatric osteosarcoma patients. Methods A total of 86 pediatric osteosarcoma patients between 2012 and 2021 in the Department of Orthopedics or tumor Surgery of Children's Hospital affiliated to Chongqing Medical University were retrospectively analyzed. The clinicopathological variables and systematic inflammatory biomarkers, including NLR, PLR and SII, was performed by the A Receiver operating characteristic (ROC) curve and Cox proportional risk regression model. According to the results of multivariate analysis, a prognostic nomogram was generated, and the concordance index (C-index) was calculated to predict the performance of the established nomogram. The survival curve was plotted by the Kaplan-Meier method. Results Univariate analysis showed that TNM stage, tumor size, NLR value, PLR value, SII value, neutrophil count and platelet count were related to CSS (p < 0.05). According to multivariate analysis, only TNM stage (p = 0.006) and SII values (p = 0.015) were associated with poor prognosis.To further predict survival in pediatric osteosarcoma patients, multivariate Cox regression analysis was used to predict cancer-specific survival at 1, 3 and 5 years. And constructed a nomogram model to predict children's CSS. The C-index of the nomogram is 0.776 (95%CI, 0.776–0.910), indicating that the model has good accuracy. Conclusion Preoperative SII and TNM staging are independent prognostic markers for pediatric osteosarcoma patients. SII may be used in conjunction with TNM staging for individualized treatment of pediatric osteosarcoma patients in future clinical work.
Mesophilic Argonaute-based isothermal detection of SARS-CoV-2

Coronavirus disease (COVID-19), caused by SARS-CoV-2 infection and its mutations, has spread rapidly all over the world and still requires sensitive detection to distinguish mutations. CRISPR-based diagnosis has been regarded as a next-generation detection method; however, it has some limitations, such as the need for specific recognition sequences and multiple enzymes for multiplex detection. Therefore, research on the exploration and development of novel nucleases helps to promote specific and sensitive diagnoses. Prokaryotic Argonaute (Ago) proteins exert directed nuclease activity that can target any sequence. Recently, thermophilic Agos have been developed as new detection techniques achieving multiplexity for multiple targets using a single enzyme, as well as accurate recognition of single-base differential sequences. In this study, to overcome the requirement for high reaction temperature of thermophilic Ago-based methods, we expanded the mining of mesophilic Agos to achieve CRISPR-like isothermal detection, named mesophilic Ago-based isothermal detection method (MAIDEN). The principle of MAIDEN uses mesophilic Ago cleavage combined with reverse transcription, which can provide single-strand DNA as a substrate and allow cleavage of fluorescence probes to sense SARS-CoV-2 at moderate temperature. We first mined and optimized the mesophilic Ago and the fluorescence reporter system and then selected a compatible reverse transcription reaction. Furthermore, we optimized MAIDEN into a one-step reaction that can detect SARS-CoV-2 RNA at the nanomolar concentration at a constant temperature of 42°C within 60 min. Therefore, MAIDEN shows advantageous portability and easy-to-implement operation, avoiding the possibility of open-lid contamination. Our study was the first attempt to demonstrate that mesophilic Agos can be harnessed as diagnostic tools, and MAIDEN was easily extended to detect other pathogens in a rapid and efficient manner.
Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity

Many variants of SARS-CoV-2 have emerged around the world. It is therefore important to understand its global viral evolution and the corresponding mutations associated with transmissibility and severity. In this study, we analyzed 112 whole genome sequences of SARS-CoV-2 collected from patients at Juntendo University Hospital in Tokyo and the genome data from entire Japan deposited in Global Initiative on Sharing Avian Influenza Data (GISAID) to examine the relationship of amino acid changes with the transmissibility and the severity of each strain/lineage. We identified 12 lineages, including B.1. 1.284, B.1. 1.214, R.1, AY.29, and AY.29. 1, which were prevalent specifically in Japan. B.1. 1.284 was most frequently detected in the second wave, but B.1. 1.214 became the predominant lineage in the third wave, indicating that B.1. 1.214 has a higher transmissibility than B.1. 1.284. The most prevalent lineage during the fourth and fifth wave was B.1. 1.7 and AY.29, respectively. In regard to the severity of identified lineages, B.1. 1.214 was significantly lower than the reference lineage, B.1. 1.284. Analysis of the genome sequence and other traits of each lineage/strain revealed the mutations in S, N, and NSPs that increase the transmissibility and/or severity. These mutations include S: M153T, N: P151L, NSP3: S543P, NSP5: P108S, and NSP12: A423V in B.1. 1.284; S: W152L and E484K in R.1; S: H69del, V70del, and N501Y in the Alpha strain; S: L452R, T478K, and P681R in the Delta strain. Furthermore, it is suggested that the transmissibility of B.1. 1.214 could be enhanced by the mutations N: M234I, NSP14: P43L, and NSP16: R287I. To address the issue of the virus evolution, it is necessary to continuously monitor the genomes of SARS-CoV-2 and analyze the effects of mutations for developing vaccines and antiviral drugs effective against SARS-CoV-2 variants.
Association between dietary acid load and cancer risk and prognosis: An updated systematic review and meta-analysis of observational studies

Epidemiological studies have suggested that dietary acid load (DAL) might be related to the risk and prognosis of cancer, whereas the evidence is contentious. Several high-quality observational studies have been published following a prior systematic review with only one study included. Consequently, we conducted an updated systematic review and meta-analysis to comprehensively investigate the relationship between DAL and cancer risk and prognosis. A systematic literature search was conducted in the PubMed, Embase, and Web of Science databases from inception to 26 October 2021. Summary relative risks (RRs) with 95% CIs were calculated using a random-effects model. Publication bias, subgroup, meta-regression, and sensitivity analyses were also conducted. Ten observational studies (six cohorts and four case–control studies) with 227,253 participants were included in this systematic review and meta-analysis. The summary RRs revealed a statistically significant associations between DAL and cancer risk (RR = 1.58, 95% CI = 1.23–2.05, I2 = 71.9%, n = 7) and prognosis (RR = 1.53, 95% CI = 1.10–2.13, I2 = 77.1%, n = 3). No evidence of publication bias was observed in the current analysis. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, study design, study quality, study population, participants’ gender, age of participants, cancer type, DAL assessment indicator, and adjustment of potential confounding parameters. No evidence of heterogeneity between subgroups was indicated by meta-regression analyses. The high DAL might be associated with an increased risk of cancer, as well as a poor prognosis of cancer. More high-quality prospective studies are warranted to further determine the associations between DAL and risk and prognosis for specific cancers.
Influence of discrimination perception on career exploration of higher vocational students: Chain mediating effect test

Explore the influence mechanism of discrimination perception on higher vocational Students’ career exploration, it provides empirical evidence for promoting vocational college Students’ career exploration and career development. Using the questionnaire survey method, 893 higher vocational students from four higher vocational colleges in Jiangsu Province were investigated by using the Discrimination Perception Scale, the Core Self-Evaluation Scale (CSES), the Chinese version of the Acceptance and Action Questionnaire, the Chinese version of the Cognitive Fusion Questionnaire (CFQ) and the Career Exploration Scale (CES). The data were analyzed using SPSS26.0 and Amos23.0, and the results showed that discrimination perception was significantly negatively correlated with core self-evaluation, psychological flexibility and career exploration (r = −0.487, −0.497, −0.326, p < 0.01), core self-evaluation was significantly positively correlated with psychological flexibility and career exploration (r = 0.518, 0.352, p < 0.01), and psychological flexibility was significantly positively correlated with career exploration (r = 0.386, p < 0.01); Core self-evaluation and psychological flexibility mediated the effect between discrimination perception and career exploration with effect sizes of −0.054 and −0.061, respectively; Core self-evaluation and psychological flexibility mediated the chain effect between discrimination perception and career exploration of higher vocational students with effect sizes of −0.030. Therefore, discrimination perception not only directly influences career exploration of higher vocational students, but also indirectly influences career exploration of higher vocational students through the separate mediating effects of core self-evaluation and psychological flexibility and the chain mediating effects of core self-evaluation and psychological flexibility. Accordingly, the following suggestions are put forward, which should pay attention to the cultivation of core self-evaluation and psychological flexibility of higher vocational students, strengthen the teaching quality and improve the image of vocational colleges.