Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging technologies to study glial cells

Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several technological breakthroughs were achieved, allowing “glio‐scientists” to address new challenging biological questions. These technical developments make it possible to study the roles of specific cell types with medium or high‐content workflows and perform fine analysis of their mutual interactions in a preserved environment. This review illustrates the potency of several cutting‐edge experimental approaches (advanced cell cultures, induced pluripotent stem cell (iPSC)‐derived human glial cells, viral vectors, in situ glia imaging, opto‐ and chemogenetic approaches, and high‐content molecular analysis) to unravel the role of glial cells in specific brain functions or diseases. It also illustrates the translation of some techniques to the clinics, to monitor glial cells in patients, through specific brain imaging methods. The advantages, pitfalls, and future developments are discussed for each technique, and selected examples are provided to illustrate how specific “gliobiological” questions can now be tackled.
Validation process of Toronto Exremity Salvage Score in Italian: A quality of life measure for patients with extremity bone and soft tissue tumors

Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross‐cultural adaptation and validation in Italian, testing test‐retest reliability, construct validity, and responsiveness.
HIV therapeutic vaccines aimed at intensifying combination antiretroviral therapy

ABSTRACT Introduction: Although successful at suppressing HIV replication, combination antiretroviral therapy (cART) only partially restores immune functions and fails to reduce the latent HIV reservoir, thus requiring novel interventions for its intensification. Areas covered: Here are reviewed therapeutic vaccine candidates that are being developed to this goal. Among them, the Tat vaccine has been shown to promote immune restoration, including CD4+ T-cell recovery in low immunological responders, and to reduce the virus reservoirs well beyond what achieved with long-term suppressive cART. Expert opinion: The authors propose the Tat vaccine as a promising vaccine candidate for cART intensification toward HIV reservoirs depletion, functional cure, and eradication strategies, suggesting that targeting a key protein in the virus life cycle is pivotal to success.
Psychosocial Interventions for Family Carers of People With Dementia: A Systematic Review and Meta-Analysis

Objective:This study aimed to review and synthesize findings of the effectiveness of psychosocial interventions aimed at improving outcomes for family carers of people with dementia. Method: A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the following databases: Cochrane, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Excerpta Medica Database (EMBASE), and Applied Social Sciences Index and Abstracts (ASSIA). RevMan 5 software was used to conduct meta-analysis and subgroup analysis using a random-effects model. Results: The search yielded 22 high-quality intervention articles that were suitable for further meta-analysis. Meta-analysis revealed that psychosocial interventions have a small to moderate significant effect on carer burden (standardized mean difference [SMD] = −0.34, confidence interval [CI] = [−0.59, −0.09]), depression (SMD = −0.36, CI = [−0.60, −0.13]), and general health (SMD = 0.34, CI = [0.18, 0.51]). Discussion: Psychosocial interventions had a positive impact on carer outcomes; however, these results should be interpreted with caution, given the significant level of heterogeneity in study designs. Future research could examine contextual and implementation mechanisms underlying psychosocial interventions to develop effective support systems for family carers of people with dementia.
Effects of a 12-week yoga versus a 12-week educational film intervention on symptoms of restless legs syndrome and related outcomes: an exploratory randomized controlled trial.

STUDY OBJECTIVES To assess the effects of a yoga versus educational film (EF) program on restless legs syndrome (RLS) symptoms and related outcomes in adults with RLS. METHODS Forty-one community-dwelling, ambulatory nonpregnant adults with moderate to severe RLS were randomized to a 12-week yoga (n = 19) or EF program (n = 22). In addition to attending classes, all participants completed practice/treatment logs. Yoga group participants were asked to practice at home 30 minutes per day on nonclass days; EF participants were instructed to record any RLS treatments used on their daily logs. Core outcomes assessed pretreatment and posttreatment were RLS symptoms and symptom severity (International RLS Study Group Scale (IRLS) and RLS ordinal scale), sleep quality, mood, perceived stress, and quality of life (QOL). RESULTS Thirty adults (13 yoga, 17 EF), aged 24 to 73 (mean = 50.4 ± 2.4 years), completed the 12-week study (78% female, 80.5% white). Post-intervention, both groups showed significant improvement in RLS symptoms and severity, perceived stress, mood, and QOL-mental health (P ≤ .04). Relative to the EF group, yoga participants demonstrated significantly greater reductions in RLS symptoms and symptom severity (P ≤ .01), and greater improvements in perceived stress and mood (P ≤ .04), as well as sleep quality (P = .09); RLS symptoms decreased to minimal/mild in 77% of yoga group participants, with none scoring in the severe range by week 12, versus 24% and 12%, respectively, in EF participants. In the yoga group, IRLS and RLS severity scores declined with increasing minutes of homework practice (r = .7, P = .009 and r = .6, P = .03, respectively), suggesting a possible dose-response relationship. CONCLUSIONS Findings of this exploratory RCT suggest that yoga may be effective in reducing RLS symptoms and symptom severity, decreasing perceived stress, and improving mood and sleep in adults with RLS. CLINICAL TRIAL REGISTRATION Registry: Clinicaltrials.gov; Title: Yoga vs. Education for Restless Legs: a Feasibility Study; Identifier: NCT03570515; URL: https://clinicaltrials.gov/ct2/show/NCT03570515.
Developmentally informed behaviour change techniques to enhance self-regulation in a health promotion context: a conceptual review

ABSTRACT Self-regulation (SR), or the ability to manage thoughts, emotions, and behaviours in order to achieve a desired goal, is seen as underlying positive health behaviours. In adults, behaviour change techniques (BCTs) are recommended to promote SR across health domains; although establishing healthy habits early in life is important, studies of SR and health in children are rare. This conceptual review provides guidance on developmental considerations for applying BCTs to enhance SR capacity in children and youth with the goal of fostering positive behavioural health trajectories early in the lifespan. Key considerations include the nature of developmental changes in SR and interaction among SR processes; temporal associations between SR and health behaviours; and relevance of health goals for children and youth. Building on a meta-review of BCT’s used to promote SR in adults and youth, this conceptual review highlights key SR milestones to consider in behaviour change-focused interventions from early childhood through adolescence and provides an overview of social-ecologic influences on SR development and associations between SR and health behaviours across these age periods. Implications for and examples of using developmentally-informed BCTs in interventions to enhance SR in children and youth are noted and suggestions for future research are discussed.
Data Integrity in Global Clinical Trials: Discussions From Joint US Food and Drug Administration and UK Medicines and Healthcare Products Regulatory Agency Good Clinical Practice Workshop

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials. Regulatory agencies conduct GCP inspections to verify the integrity of data generated in clinical trials and to assure the protection of human research subjects, in addition to ensuring that clinical trials are conducted according to the applicable regulations. The first joint GCP workshop of the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA‐UK) was held in October 2018 and provided the agencies’ perspectives on the importance of data quality management practices on data integrity. Regulatory perspectives on data blinding to minimize introduction of bias, and the role of audit trails in assessing data integrity in global clinical trials were discussed. This paper summarizes considerations of both agencies on these topics, along with case examples.
An Overview on Predicting Protein Subchloroplast Localization by using Machine Learning Methods.

The chloroplast is a type of subcellular organelle of green plants and eukaryotic algae, which plays an important role in the photosynthesis process. Since the function of a protein correlates with its location, knowing its subchloroplast localization is helpful for elucidating its functions. However, due to the large number of chloroplast proteins, it is costly and time-consuming to design biological experiments to recognize subchloroplast localizations of these proteins. To address this problem, during the past ten years, twelve computational prediction methods have been developed to predict protein subchloroplast localization. This review summarizes the research progress in this area. We hope the review could provide important guide for further computational study on protein subchloroplast localization.
Efficacy of leflunomide combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy

Abstract Objective To evaluate the clinical efficacy and safety of leflunomide (LEF) combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy (PMN) and changes in anti-PLA2R antibody titers after treatment. Methods Sixty patients with nephrotic syndrome, biopsy-proven MN and anti-PLA2R antibody positivity were included in this study conducted from December 2017 to February 2019. The patients were randomly divided into an experimental group (n = 30) and a control group (n = 30). The patients in the experimental group were treated with LEF combined with prednisone, whereas the patients in the control group were treated with cyclophosphamide (CTX) combined with prednisone. We assessed 24-h urinary protein and serum albumin levels, kidney function markers, blood lipid levels and anti-PLA2R antibody titers before and after treatment. Adverse reactions during treatment were recorded. Results After 16 weeks of treatment, there were 2 cases of complete remission and 6 cases of partial remission in the experimental group, with a total effective rate of 26.67%. In the control group, there were 4 cases of complete remission and 8 cases of partial remission, with a total effective rate of 40% (p > .05). After 24 weeks of treatment, the total effective rates of the experimental and control groups were 66.67% and 76.67%, respectively (p > .05). There were no significant differences in 24-h urinary protein, serum albumin, kidney function marker or blood lipid levels between the two groups after treatment (p > .05). However, there were fewer adverse reactions in the experimental group than in the control group (p < .05). After treatment, serum anti-PLA2R antibody titers were clearly decreased in patients with complete remission and partial remission (p < .05), but these levels remained relatively high in patients without remission (p > .05). Conclusion LEF combined with prednisone has a certain efficacy for the treatment of PLA2R-associated PMN and provokes few adverse reactions. A large-sample randomized double-blind controlled study with a long follow-up period is needed to verify the efficacy of LEF combined with prednisone.
Rs11655237 polymorphism of LINC00673 affects the prognosis of cervical cancer by interfering with the interaction between LINC00673 and microRNA‐1231

Single‐nucleotide polymorphism (SNP) in long noncoding RNAs (lncRNAs) is known to disrupt the binding between lncRNAs and microRNAs. In this paper, we aimed to explore the role of LINC00673 rs11655237 SNP in the survival of cervical cancer (CC). Real‐time polymerase chain reaction and western‐blot analysis were used to detect expressions of LINC00673 and microRNA‐1231 (miR‐1231) in CC patients with different rs11655237 SNP genotypes. And the expression of LINC00673, miR‐1231, and IFNAR1 was measured in mice and cells treated with exosomes carrying GG, GA, and AA rs11655237 genotypes. Compared with patients carrying the rs11655237 A allele of LINC00673 rs11655237 SNP, patients carrying the G allele showed higher overall survival and higher miR‐1231 expression. In addition, the expression of miR‐1231 was the highest in patients carrying the GG genotype and the lowest in patients carrying the AA genotype. Furthermore, the exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP reduced tumor growth in mice, while the inhibitory effect of rs11655237 A allele was much stronger than that of the rs11655237 G allele. Additionally, exosome treatment upregulated the expression of LINC000673 and IFNAR1 while downregulating the expression of miR‐1231. Interestingly, the A allele of rs11655237 generated a binding site for miR‐1231 and subsequently affected the expression of IFNAR1, a target gene of miR‐1231 containing a miR‐1231 binding site in its 3′‐untranslated region. Cells transfected with exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP achieved higher LINC000673 and IFNAR1 expression along with lower miR‐1231 expression. Therefore, rs11655237 can be used as a prognostic biomarker for CC.
Design Rules for Improving the Cycling Stability of High-Performance Donor-Acceptor-Type Electrochromic Polymers.

Although high-performance donor-acceptor (D-A)-type polymers have received much attention as an important class of electrochromic materials, the related studies have mostly focused on the influence of D and A units on the band gap, onset potential, and switching time, leaving the effect of D-A structures on cycling lifetime underexplored. Herein, we design and synthesize a series of poly(aryl amino sulfone)s (PAASs) as D-A polymers with TPA-based donor units and the sulfone moiety as the acceptor unit. As a result, we present new rules to design and develop D-A structure polymers with high EC cycling stability: (1) the electron donating and withdrawing abilities of donor and acceptor should be balanced during the electrochemical cycle process, and this balance can be measured by the ratio of Jred/Jox; (2) the donor-acceptor structure should benefit to generate lower Eonset. By these design rules, the best-performing polymer PAAS-TPPA-OMe exhibits excellent long-term cycling stability (over 3,900 cycles), low onset potential (0.26 V), fast switching time (6.0/4.3 s for the electrochromic process), high contrast (87% at 688 nm and 94% at 928 nm), and high coloration efficiency (500 cm2 C-1 at 688 nm and 1131 cm2 C-1 at 928 nm).
Central administration of REV‐ERBα agonist promotes opposite responses on energy balance in fasted and fed states

The REV‐ERBα receptor has a recognised role in the regulation of the circadian rhythm system. However, recent evidence suggests that it also contributes to energy balance regulation. Both expression and function of REV‐ERBα can be influenced by the energy status of the body. Considering the possibility of the involvement of REV‐ERBα in the regulation of energy balance, which is critically regulated by the hypothalamus, and based on the impact of intermittent fasting, the present study evaluated the effects of central administration of REV‐ERBα agonist on energy balance in rats exposed to 24 hours of fasting or ad lib. feeding conditions. Initially, 24‐hour fasted rats received an acute i.c. v. administration of agonist at doses of 1, 5, 10 or 15 μg per rat and feed efficiency was evaluated. Because 10 μg was a sufficient dose to affect feed efficiency, subsequent experiments used this dose to assess effects of agonist on the following parameters: energy expenditure induced by physical activity and locomotor activity, time spent in physical activity over 24 hours, and glucose and insulin tolerance. In fasted rats, the agonist promoted increased food intake and feed efficiency, with a greater body weight gain associated with less time spent in locomotor activity, suggesting a reduction in energy expenditure induced by physical activity. Furthermore, a reduction in glucose tolerance was noted. By contrast, free‐fed rats exhibited reduced food intake and feed efficiency with decreased body weight gain along with an increase in locomotor activity and physical activity‐dependent energy expenditure. Thus, i.c. v. administration of REV‐ERBα agonist regulates energy balance depending on the energy status of the organism; that is, it promotes a positive energy balance in the fasted state and a negative energy balance in the fed state. These results may be useful in understanding the underlying mechanisms of energy balance disorders and intermittent fasting for body weight control.
Increased long‐term risk for hypertension in kidney donors – a retrospective cohort study

Kidney donors may be at increased risk of end‐stage renal disease and premature mortality. Elevated blood pressure after donation may contribute to the increased risks. In this cohort study, we have assessed long‐term risk for the development of hypertension in kidney donors compared to a control group potentially eligible as donors. Follow‐up data were obtained from previous living kidney donors. A healthy control group with baseline assessment from similar time periods as the donor nephrectomies was selected. Hypertension was defined as blood pressure >140/90, use of blood pressure medication, or established diagnosis of hypertension. Stratified logistic regression was used to estimate risk of hypertension at follow‐up, adjusted for systolic blood pressure at baseline, age at follow‐up, time since donation/baseline, gender, smoking at baseline, and BMI at baseline. A total of 368 donors (36%) had hypertension at follow‐up, and 241 of these (23%) were using blood pressure medication. In adjusted stratified logistic regression analyses, odds ratio for hypertension was significantly increased (1.25, 95% confidence interval 1.12–1.39, P < 0.001) in donors compared with controls. Kidney donors appear to be at increased long‐term risk for hypertension compared with healthy controls. This finding supports regular follow‐up of blood pressure in kidney donors.
Sense of coherence and hypertensive target organ damage.

OBJECTIVES This study was designed to compare the level of sense of coherence in hypertensive patients with arterial stiffness or leftventricular hypertrophy and in hypertensive individuals without such health complications. METHODS The study group consisted of 93 participants. All of them were asked to undergo the following procedures: clinical assessment, echocardiography (to diagnose hypertensive cardiac damage), pulse wave velocity measurement (to assess vascular damage) and psychological testing (to measure their level of comprehensibility, manageability, meaningfulness, and sense of coherence). RESULTS Patients with hypertensive vascular damage (high pulse wave velocity) had higher levels of comprehensibility and sense of coherence than other hypertensive subjects. At the same time, there were no significant differences in the level of sense of coherence (and all of its dimensions) between individuals with and people without hypertensive left ventricular hypertrophy. CONCLUSIONS The findings of this study suggest, that the sense of coherence may not be strongly associated with good somatic health. They may also contribute to the discussion about diagnostic usefulness of the SOC-29 method as a single tool. We believe that the level of sense of coherence should be taken into consideration in further studies on the development of hypertensive TOD.
Evolution of Machine Learning Algorithms in the Prediction and Design of Anticancer Peptides.

Peptides act as promising anticancer agents due to their ease of synthesis and modifications, enhanced tumor penetration, and less systemic toxicity. However, only limited success has been achieved so far, as experimental design and synthesis of anticancer peptides (ACPs) are prohibitively costly and time-consuming. Furthermore, sequential increase in the protein sequence data via high-throughput sequencing makes it difficult to identify ACPs only through experimentation, that often involves months or years of speculation and failure. All these limitations could be conquered by applying machine learning (ML) approaches, which is a field of artificial intelligence that automates analytical model building for rapid and accurate outcome predictions. Recently, ML approaches hold great promise in the rapid discovery of ACPs, which could be witnessed by the growing number of ML-based anticancer prediction tools. In this review, we aim to provide a comprehensive view on the existing ML approaches for ACP predictions. Initially, we will briefly discuss the currently available ACP databases. This is followed by the main text, where state-of-the-art ML approaches working principles and their performances based on the ML algorithms are reviewed. Lastly, we discuss on the limitations and future directions of the ML methods in the prediction of ACPs.