Miracle-dz/UniFAR-FTUs huggingface dataset:
TRIM28 variants and Wilms' tumour predisposition

TRIM28 was recently identified as a Wilms' tumour (WT) predisposition gene, with germline pathogenic variants identified in around 1% of isolated and 8% of familial WT cases. TRIM28 variants are associated with epithelial WT, but the presence of other tumour components or anaplasia does not exclude the presence of a germline or somatic TRIM28 variant. In children with WT, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour. Therefore, loss of TRIM28 (KAP1/TIF1beta) protein expression in tumour tissue by immunohistochemistry is an effective strategy to identify patients carrying pathogenic TRIM28 variants. TRIM28 is a ubiquitously expressed corepressor that binds transcription factors in a context‐, species‐, and cell‐type‐specific manner to control the expression of genes and transposable elements during embryogenesis and cellular differentiation. In this review, we describe the inheritance patterns, histopathological and clinical features of TRIM28‐associated WT, as well as potential underlying mechanisms of tumourigenesis during embryonic kidney development. Recognizing germline TRIM28 variants in patients with WT can enable counselling, genetic testing, and potential early detection of WT in other children in the family. A further exploration of TRIM28‐associated WT will help to unravel the diverse and complex mechanisms underlying WT development. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Taurine attenuates the damage of lupus nephritis mouse via inactivation of the NF-κB pathway.

BACKGROUND Taurine is an organic amino acid and a major constituent of bile. With its contribution to various cellular functions, it has demonstrated therapeutic effects in a wide range of diseases. Since there is a lack of literature investigating taurine as a treatment for lupus nephritis (LN), here we examined the potential of taurine as a treatment for LN. METHODS Experiments were carried out using MRL/lpr mice as a model of LN, and C57BL/6 mice were used as negative controls. At 12 weeks old, MRL/lpr mice were divided into four groups and treated with 0, 50 and 100 mg/kg body weight taurine for 5 days. Enalapril is used as a positive control drug. All animals were sacrificed after treatment. LN-induced damage was assessed by proteinuria, blood urea nitrogen (BUN) and serum creatinine (CRE) levels. The degree of inflammation was assessed by inducible nitric oxide synthase (iNOS), interleukin-4 (IL-4), IL-10, and tumor necrosis factor-α (TNF-α) levels. The degree of oxidative stress was assessed by malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (Gpx) levels. Hematoxylin and eosin (HE) staining and TUNEL staining assessed histopathological damage and apoptosis, respectively. The levels of Bcl-2, Bax, caspase-3, caspase-9, and NF-κB p65 were detected by western blot. RESULTS The data indicated that taurine administration improved kidney functions, reversed cell death, suppressed oxidative stress, and importantly, adjusted the immune response of LN mice to a more balanced state. CONCLUSIONS These results provide a novel strategy for LN therapy, which may overcome the disadvantages of traditional immunosuppression and hormone treatments with greater efficacy and fewer side effects.
Occupational Therapy Interventions in Adults with Multiple Sclerosis or Amyotrophic Lateral Sclerosis: A Scoping Review

This scoping review aims to describe occupational therapy interventions carried out with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) patients in occupational therapy. A peer review of the literature was conducted in different databases: Pubmed, Scopus, Web of Science and Embase, and in some occupational therapy journals. A search of the literature published was carried out before December 2019. The inclusion criteria were as follows: (1) articles evaluating the intervention of occupational therapy in MS or ALS including experimental, randomized, nonrandomized and exploratory studies; (2) written in English or Spanish; (3) adult population (over 18 years old). The initial search identified 836 articles of which we included 32 divided into four areas of intervention: fatigue-targeted interventions, cognitive interventions, physical interventions and others. Only 16 studies were carried out exclusively by occupational therapists. Most occupational therapy interventions are aimed at fatigue and physical rehabilitation. The majority of the studies in our review included MS patients, with little representation from the ALS population. These interventions have shown an improvement in perceived fatigue, manual dexterity, falls prevention and improvement in cognitive aspects such as memory, communication, depression and quality of life in the MS and ALS populations.
Temperature and Concentration Dependence of Human Whole Blood and Protein Drying Droplets

The drying of bio-colloidal droplets can be used in many medical and forensic applications. The whole human blood is the most complex bio-colloid system, whereas bovine serum albumin (BSA) is the simplest. This paper focuses on the drying characteristics and the final morphology of these two bio-colloids. The experiments were conducted by varying their initial concentrations, and the solutions were dried under various controlled substrate temperatures using optical and scanning electron microscopy. The droplet parameters (the contact angle, the fluid front, and the first-order image statistics) reveal the drying process’s unique features. Interestingly, both BSA and blood drying droplets’ contact angle measurements show evidence of a concentration-driven transition as the behavior changes from non-monotonic to monotonic decrease. This result indicates that this transition behavior is not limited to multi-component bio-colloid (blood) only, but may be a phenomenon of a bio-colloidal solution containing a large number of interacting components. The high dilution of blood behaves like the BSA solution. The ring-like deposition, the crack morphology, and the microstructures suggest that the components have enough time to segregate and deposit onto the substrate under ambient conditions. However, there is insufficient time for evaporative-driven segregation to occur at elevated temperatures, as expected.
Zinc Based Metal-Organic Frameworks as Ofloxacin Adsorbents in Polluted Waters: ZIF-8 vs. Zn3(BTC)2

Two different zinc-based metal-organic frameworks (MOFs) were investigated to remove one of the most used fluoroquinolone antibiotic, Ofloxacin (OFL), from polluted water. The most common zeolitic imidazolate framework-8 (ZIF-8) and the green Zn(II) and benzene-1,3,5-tri-carboxylate (Zn3(BTC)2) were prepared through a facile synthetic route and characterized by means of Fourier-Transform Infrared (FT-IR) Spectroscopy, X-ray Powder Diffraction (XRPD), and Scanning Electron Microscopy (SEM) analyses. The two MOFs were compared in terms of both adsorption and kinetic aspects under real conditions (tap water, natural pH). Results showed that OFL was adsorbed in remarkable amounts, 95 ± 10 and 25.3 ± 0.8 mg g−1 on ZIF-8 and Zn3(BTC)2, respectively, following different mechanisms. Specifically, a Langmuir model well described the ZIF-8 profile, while for Zn3(BTC)2, cooperative adsorption occurred. Moreover the kinetic results were quite different, pseudo-second-order and sigmoidal, respectively. The suitability of ZIF-8 and Zn3(BTC)2 as adsorbent phases for water depollution was tested on tap water samples spiked with OFL 10 µg L−1. The obtained removal efficiencies, of 88% for ZIF-8 and 72% for Zn3(BTC)2, make these materials promising candidates for removing fluoroquinolone antibiotics (FQs) from polluted waters, notwithstanding their limited reusability in tap water, as demonstrated by in-depth characterization of the two MOFs after usage.
The effectiveness and safety of cariprazine in schizophrenia patients with negative symptoms and insufficient effectiveness of previous antipsychotic therapy: an observational study

Supplemental Digital Content is available in the text. The aim of the study was to examine the effectiveness and safety of cariprazine in routine psychiatric settings on schizophrenia patients with negative symptoms who have been treated with antipsychotics previously but without sufficient success. This was an open-label, flexible-dose, 16-week, observational study in Latvia. The primary outcome measure was an array of anamnesis-based clinical questions on schizophrenia symptoms rated on a seven-point scale. Other outcome measurements were the clinical global impression improvement (CGI-I) and severity (CGI-S) scales. Safety parameters included spontaneous reports of adverse events and specific assessments of extrapyramidal side-effects. A mixed model for repeated measures was fit to the data to evaluate the mean change from baseline for all visits. A total of 116 patients enrolled in the study (completion: 83%). Change from baseline to termination in symptom control was statistically significant (−7.3; P < 0.001), with the most improvement in negative symptoms (−6.3; P < 0.001). Over 70% of patients improved minimally or much based on the CGI-I scores at the final visit, and the CGI-S scores indicated an overall improvement in severity from moderately to mildly ill. 40% of patients experienced treatment-emergent adverse events. Over 70% of doctors were satisfied with the effectiveness and tolerability of cariprazine. Cariprazine significantly improved negative symptoms in schizophrenia patients.
Cancer Risk in Normal Weight Individuals with Metabolic Obesity: A Narrative Review

Obesity represents one of the most significant public health challenges worldwide. Current clinical practice relies on body mass index (BMI) to define the obesity status of an individual, even though the index has long been recognized for its limitations as a measure of body fat. In normal BMI individuals, increased central adiposity has been associated with worse health outcomes, including increased risks of cardiovascular disease and metabolic disorders. The condition leading to these outcomes has been described as metabolic obesity in the normal weight (MONW). More recent evidence suggests that MONW is associated with increased risk of several obesity-related malignancies, including postmenopausal breast, endometrial, colorectal, and liver cancers. In MONW patients, the false reassurance of a normal range BMI can lead to lost opportunities for implementing preventive interventions that may benefit a substantial number of people. A growing body of literature has documented the increased risk profile of MONW individuals and demonstrated practical uses for body composition and biochemical analyses to identify this at-risk population. In this review, we survey the current literature on MONW and cancer, summarize pathophysiology and oncogenic mechanisms, highlight potential strategies for diagnosis and treatment, and suggest directions for future research.
Gestational iron deficiency anemia is associated with preterm birth, fetal growth restriction, and postpartum infections

Abstract Objectives Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. Methods We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. Results Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. Conclusions Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system.
Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study

Background. Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients. Methods. All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients. Results. T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001). Conclusions. This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.
Dating Violence Victimization among Adolescents in Europe: Baseline Results from the Lights4Violence Project

Dating violence (DV) among adolescents is a public health issue because of its negative health consequences. In this study, we aimed to analyse the prevalence and the psychosocial and socioeconomic risk and protective factors associated DV among male and female adolescents in Europe. It was performed a cross-sectional study based on a non-probabilistic sample of 1555 students aged 13–16 years (2018–2019). The global prevalence of DV victimization was significantly greater among girls than boys (girls: 34.1%, boys: 26.7%; p = 0.012). The prevalence of DV in both girls and boys was greater for those over age 15 (girls: 48.5% p < 0.001; boys: 35.9%; p = 0.019). There was an increased likelihood of DV victimization among girls whose fathers did not have paid employment (p = 0.024), who suffered abuse in childhood, and reported higher Benevolent Sexism [PR (CI 95%): 1.01 (1.00–1.03)] and machismo [1.02 (1.00–1.05)]. In the case of boys, the likelihood of DV increased with abuse in childhood (p = 0.018), lower parental support [0.97 (0.96–0.99)], high hostile sexism scores (p = 0.019), lower acceptance of violence (p = 0.009) and high machismo (p < 0.001). Abuse in childhood was shown to be the main factor associated with being a victim of DV in both population groups, as well as sexism and machismo attitudes. These results may contribute to future DV prevention school programs for both, teenagers and children of elementary school ages.
A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909)

Background Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. Methods A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Discussion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. Trial registration NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: “A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma”. Version 1.0/Nov. 21, 2019.
St Andrew's COVID-19 surgery safety study: hand trauma.

INTRODUCTION Adaptation is vital to ensure successful healthcare recovery during the COVID-19 pandemic. Hand trauma represents the most common acute emergency department presentation internationally. This study prospectively evaluates the COVID-19 related patient risk, when undergoing management within one of the largest specialist tertiary referral centres in Europe, which rapidly implemented national COVID-19 safety guidelines. MATERIALS AND METHODS A prospective cohort study was undertaken in all patients referred to the integrated hand trauma service, during the UK COVID-19 pandemic peak (April-May 2020); all were evaluated for 30-day COVID-19 related death. Random selection was undertaken for patients with hand trauma who either underwent non-operative (control group) or operative (surgery group) management; these groups were prospectively followed-up within a controlled cohort study design and telephoned at 30 days following first intervention (control group) or postoperatively (surgery group). RESULTS Of 731 referred patients (566 operations), there were no COVID-19 related deaths. Both groups were matched for sex, age, ethnicity, body mass index, comorbidities, smoking, preoperative/first assessment COVID-19 symptoms, pre- and postoperative/first assessment isolation and positive COVID-19 contact (p > 0.050). There were no differences in high service satisfaction (10/10 compared with 10/10; p = 0.067) and treatment outcome (10/10 compared with 10/10; p = 0.961) scores, postoperative/first assessment symptoms (1%, 1/100 compared with 0.8%, 2/250; p = 1.000) or proportion of positive tests (7.1%, 1/14 compared with 2.2%, 2/92; p = 0.349), between the control (n = 100) and surgery (n = 250) groups. CONCLUSION These data support continued and safe service provision and no increased risk to patients who require surgical management. Such findings are vital for healthcare providers when considering service adaptations to reinstate patient treatment.
Inflammation-Related Changes in Mood Disorders and the Immunomodulatory Role of Lithium

Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder (BD). Molecular biology studies have indicated an involvement of the immune system in the pathogenesis of mood disorders, and showed their correlation with altered levels of inflammatory markers and energy metabolism. Previous reports, including meta-analyses, also suggested the role of microglia activation in the M1 polarized macrophages, reflecting the pro-inflammatory phenotype. Lithium is an effective mood stabilizer used to treat both manic and depressive episodes in bipolar disorder, and as an augmentation of the antidepressant treatment of depression with a multidimensional mode of action. This review aims to summarize the molecular studies regarding inflammation, microglia activation and energy metabolism changes in mood disorders. We also aimed to outline the impact of lithium on these changes and discuss its immunomodulatory effect in mood disorders.
Evaluation of the volatile and chiral composition in Pistacia lentiscus L. essential oil

In the present research, the chemical composition of the volatiles present in the fresh leaves and twigs of Pistacia lentiscus L. was determined by using GC–FID and GC–MS. In past years the oil was employed in the perfumery, food and pharmaceutical industries, while recently it has been re-evaluated as a flavouring in alcoholic beverages and chewing gums, due to the natural production of the exudate called ‘mastic gum’. The present study was carried out on Sicilian plants with the aim of integrating the already existing information on the chemical composition of the oil. The oil samples were obtained using traditional hydrodistillation (HD) and simultaneous distillation and extraction (SDE). For the first time, the enantiomeric distribution of 17 chiral couples by means of enantioselective multidimensional gas chromatography (Es-MDGC), was determined. The results showed that more compounds were detected in the SDE extract (96 components) than in the HD extract (62 components). Several minor components contained in the HD product probably contribute significantly to its aromatic properties and could be useful for chemotaxonomic characterization. P. lentiscus L. leaf and twig oil, although not considered until now, could be employed as a flavour contributor or as food preservative. Copyright © 2008 John Wiley & Sons, Ltd.