Miracle-dz/UniFAR-FTUs huggingface dataset:
Obesity is Associated with Shorter Telomere Length in Prostate Stromal Cells in Men with Aggressive Prostate Cancer

This study investigates a potential mechanism underlying the association between obesity and prostate cancer death. Among men with aggressive prostate cancer, obesity was associated with shorter telomeres prostate cancer associated stromal cells, and shorter CAS telomeres have been associated with an increased risk of prostate cancer death. In our prior studies, obesity was associated with shorter telomeres in prostate cancer-associated stromal (CAS) cells, and shorter CAS telomeres were associated with an increased risk of prostate cancer death. To determine whether the association between obesity and shorter CAS telomeres is replicable, we conducted a pooled analysis of 790 men who were surgically treated for prostate cancer, whose tissue samples were arrayed on five tissue microarray (TMA) sets. Telomere signal was measured using a quantitative telomere-specific FISH assay and normalized to 4′,6-diamidino-2-phenylindole for 351 CAS cells (mean) per man; men were assigned their median value. Weight and height at surgery, collected via questionnaire or medical record, were used to calculate body mass index (BMI; kg/m2) and categorize men as normal (<25), overweight (25 ≤ BMI < 30), or obese (≥30). Analyses were stratified by grade and stage. Men were divided into tertiles of TMA- (overall) or TMA- and disease aggressiveness- (stratified) specific distributions; short CAS telomere status was defined by the bottom two tertiles. We used generalized linear mixed models to estimate the association between obesity and short CAS telomeres, adjusting for age, race, TMA set, pathologic stage, and grade. Obesity was not associated with short CAS telomeres overall, or among men with nonaggressive disease. Among men with aggressive disease (Gleason≥4+3 and stage>T2), obese men had a 3-fold increased odds of short CAS telomeres (OR: 3.06; 95% confidence interval: 1.07–8.75; Ptrend = 0.045) when compared with normal weight men. Telomere shortening in prostate stromal cells may be one mechanism through which lifestyle influences lethal prostate carcinogenesis. Prevention Relevance: This study investigates a potential mechanism underlying the association between obesity and prostate cancer death. Among men with aggressive prostate cancer, obesity was associated with shorter telomeres prostate cancer associated stromal cells, and shorter CAS telomeres have been associated with an increased risk of prostate cancer death.
Computational and training requirements for interatomic potential based on artificial neural network for estimating low thermal conductivity of silver chalcogenides.

We examined the estimation of thermal conductivity through molecular dynamics simulations for a superionic conductor, α-Ag2Se, using the interatomic potential based on an artificial neural network (ANN potential). The training data were created using the existing empirical potential of Ag2Se to help find suitable computational and training requirements for the ANN potential, with the intent to apply them to first-principles calculations. The thermal conductivities calculated using different definitions of heat flux were compared, and the effect of explicit long-range Coulomb interaction on the conductivities was investigated. We clarified that using a rigorous heat flux formula for the ANN potential, even for highly ionic α-Ag2Se, the resulting thermal conductivity was reasonably consistent with the reference value without explicitly considering Coulomb interaction. It was found that ANN training including the virial term played an important role in reducing the dependency of thermal conductivity on the initial values of the weight parameters of the ANN.
DNA polymerase and mismatch repair exert distinct microsatellite instability signatures in normal and malignant human cells.

Although replication repair deficiency, either by mismatch repair deficiency (MMRD) and/or loss of DNA polymerase proofreading, can cause hypermutation in cancer, microsatellite instability (MSI) is considered a hallmark of MMRD alone. By genome-wide analysis of tumors with germline and somatic deficiencies in replication repair, we reveal a novel association between loss of polymerase proofreading and MSI, especially when both components are lost. Analysis of indels in microsatellites (MS-indels) identified five distinct signatures (MS-sigs). MMRD MS-sigs are dominated by multi-base losses, while mutant-polymerase MS-sigs contain primarily single-base gains. MS-deletions in MMRD tumors depend on the original size of the microsatellite and converge to a preferred length, providing mechanistic insight. Finally, we demonstrate that MS-sigs can be a powerful clinical tool for managing individuals with germline MMRD and replication repair deficient cancers, as they can detect the replication repair deficiency in normal cells and predict their response to immunotherapy.
Grey matter volume abnormalities in the first depressive episode of medication-naïve adult individuals: a systematic review of voxel based morphometric studies

Abstract Background To identify the reliable and consistent grey matter volume (GMV) abnormalities associated with major depressive disorder (MDD), we excluded the influence of confounding clinical characteristics, comorbidities and brain degeneration on brain morphological abnormalities by inclusion of non-comorbid and non-geriatric drug-naïve MDD individuals experiencing first episode depressive. Methods The PubMed, Scopus, Web of Science, Science Direct and Google scholar databases were searched for papers published in English up to April 2020. Results A total of 21 voxel based morphometric (VBM) studies comparing 845 individuals in the first depressive episode and medication-naïve with 940 healthy control subjects were included. The results showed a grey matter volumes reductions in the orbitofrontal cortex (OFC), prefrontal cortex (PFC), frontal and temporal gyri, temporal pole, insular lobe, thalamus, basal ganglia, cerebellum, hippocampus, cingulate cortex, and amygdala. In addition, increased grey matter volumes in the postcentral gyrus, superior frontal gyrus, insula, basal ganglia, thalamus, amygdala, cuneus, and precuneus differentiated the first depressive episode in medication-naïve individuals from healthy subjects. Conclusion The present systematic review provided additional support for the involvement of grey matter structural abnormalities in limbic-cortical circuits as possibly specific structural abnormalities in the early stage of MDD. Key points Distinct brain regions in MDD patients might be associated with the early stages of illness, and thus it is critical to study the causal relationship between brain structures and the onset of the disease to improve the evaluation in clinic. Grey matter alterations in the fronto-limbic networks in the first episode, medication-naïve MDD might suggest that these abnormalities may play an important role in the neuropathophysiology of MDD at its onset. First episode, medically naïve depressive patients show grey matter volume alterations in brain regions mainly associated with emotion regulation including parietal–temporal regions, PFC, insular lobe, thalamus, basal ganglia, cerebellum and limbic structures that may be specific changes in early stage of MDD. Genotype–diagnosis interaction effects on brain morphology in the cortico-limbic-striatal circuits, including the PFC, amygdala, hippocampus and striatum that might be implicated in the dysfunctional regulation of emotion in first-episode MDD patients. Future longitudinal and prospective studies should be conducted to identify the core structural brain changes in people at-risk for MDD and explore the association of their brain volumes with symptom onset.
Radiation therapy and immunotherapy in breast cancer treatment: preliminary data and perspectives

ABSTRACT Introduction: The discovery of the major role of the immune system in the tumor process has led to the development of therapeutic strategies with immunotherapy. The potential systemic role of radiotherapy, (RT) used for a long time for its local action, based on its impact on immunity, is now better understood. The combination of immunotherapy and radiation therapy is currently a field of sustained research programs and has shown successful results, in non-small cell lung cancer, for example. Breast cancer (BC) was wrongly considered poorly immunogenic and put aside during accelerating progress in this new area of treatment. Areas covered: This review provides an overview of pre-clinical and clinical rationales to associate immunotherapy with radiation therapy in the management of breast cancer. Expert opinion: Immunotherapy has been used only recently in breast cancer, but clinical trials have yet to determine the place of this treatment. RT may be useful to enhance the response of breast tumors to immunotherapy. This new approach in breast cancer management is currently based on limited data but should be further investigated, especially in triple-negative breast cancer and in the neoadjuvant setting.
STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.

BACKGROUND The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment-targets in 2015 for adult IBD patients. We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in two surveys and two voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale. RESULTS In the systematic-review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey (n=39 on Crohn's Disease (CD) and n=36 on ulcerative colitis (UC)) identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed (n=70). STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in CD and histological healing in UC are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This framework should be adapted to individual patients and local resources to improve outcomes.
Recommendations on the management of multiple myeloma in 2020

ABSTRACT With the introduction of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, major improvements have been achieved in the treatment of multiple myeloma (MM), with a significant impact on the outcome of this disease. Different treatment combinations are now in use and other therapies are being developed. Based on an extensive review of the recent literature, we propose practical recommendations on myeloma management, to be used by hematologists as a reference for daily practice.
Activation of Mechanoreflex, but not Central Command, Delays Heart Rate Recovery after Exercise in Healthy Men

Abstract This study tested the hypotheses that activation of central command and muscle mechanoreflex during post-exercise recovery delays fast-phase heart rate recovery with little influence on the slow phase. Twenty-five healthy men underwent three submaximal cycling bouts, each followed by a different 5-min recovery protocol: active (cycling generated by the own subject), passive (cycling generated by external force) and inactive (no-cycling). Heart rate recovery was assessed by the heart rate decay from peak exercise to 30 s and 60 s of recovery (HRR30s, HRR60s fast phase) and from 60 s-to-300 s of recovery (HRR60−300s slow phase). The effect of central command was examined by comparing active and passive recoveries (with and without central command activation) and the effect of mechanoreflex was assessed by comparing passive and inactive recoveries (with and without mechanoreflex activation). Heart rate recovery was similar between active and passive recoveries, regardless of the phase. Heart rate recovery was slower in the passive than inactive recovery in the fast phase (HRR60s=20±8vs.27 ±10 bpm, p<0.01), but not in the slow phase (HRR60−300s=13±8vs.10±8 bpm, p=0.11). In conclusion, activation of mechanoreflex, but not central command, during recovery delays fast-phase heart rate recovery. These results elucidate important neural mechanisms behind heart rate recovery regulation.
Popliteal artery aneurysms treatments: early midterm results of the use of endovascular stent grafts

Background/aim Popliteal artery aneurysms (PAAs) are abnormal bulgings, which account for 70% of all peripheral artery aneurysms. They are usually asymptomatic. In this study, we present our long-term results of endovascular stent grafts in the treatment of PAA in the light of literature data. Material and methods A total of 63 legs of 63 patients with PAA, who were treated with endovascular techniques in our clinic between July 2010 and July 2019, were retrospectively analyzed. All patients underwent color Doppler ultrasound (DUS), magnetic resonance angiography (MRA), or computed tomography angiography (CTA) to identify the diameter and length of PAAs, vessel tortuosity, the presence and degree of thrombus, and diameter in the healthy landing zone and to visualize tibioperoneal vascular structures. A Viabahn stent graft was inserted in all patients. Results 57 patients (90.5%) were males with a mean age of 76.35 ± 7 years. 24 patients (38.1%) were symptomatic, while 11 patients (17.5%) had a concomitant abdominal aortic aneurysm (AAA). The mean follow-up period was 46.05 ± 25.01 months. The primary patency rate was 79.3%. A graft thrombosis was observed in 13 patients (20.6%) during a mean follow-up period of 8.31 ± 5.91 months. The number of distal arteries was significantly lower in the patients with thrombosis than those without. Conclusions Endovascular treatment of PAA using stentgrafts is safe in selected cases. However, it is reasonable to avoid endovascular treatment due to an increased risk for thrombosis in patients with a low number of patent distal arteries or impaired distal flow.
Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota

ABSTRACT Introduction Autism spectrum disorder (ASD) is a neurodevelopmental disorder typical of early age, characterized by impaired communication, social interaction, and repetitive behaviors. ASD patients frequently suffer from gastrointestinal (GI) symptoms. Neuro-psychological functions, intestinal homeostasis, and functional GI disturbances are modulated by the gut microbiota through the so-called ‘microbiota-gut-brain axis’. Areas covered Literature regarding GI symptoms among the ASD community as well as the involvement and modulation of the gut microbiota in GI disturbances of ASD patients was searched. Constipation, diarrhea, reflux, abdominal bloating, pain, and discomfort are reported with variable prevalence. ASD is characterized by a reduction of Bacteroidetes/Firmicutes, of the abundance of Bacteroidetes and other imbalances. ASD patients with GI symptoms present microbial changes with plausible relation with deficiency of digestive enzymes, carbohydrate malabsorption, selective eating, bacterial toxins, serotonin metabolism, and inflammation. The strategies to mitigate the GI distress through the gut microbiota modulation comprise antimicrobials, probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. Expert opinion The modulation of the gut microbiota in ASD individuals with GI disturbances seems a promising target for the future medicine. A standardization of the research strategies for large-scale studies together with a focus on poorly explored fields is necessary to strengthen this hypothesis.
Early Hemodynamic Profile after Aortic Valve Replacement - A Comparison between Three Mechanical Valves

Introduction There are scarce data comparing different mechanical valves in the aortic position. The objective of this study was to compare the early hemodynamic changes after aortic valve replacement between ATS, Bicarbon, and On-X mechanical valves. Methods We included 99 patients who underwent aortic valve replacement with mechanical valves between 2017 and 2019. Three types of mechanical valves were used, On-X valve (n=45), ATS AP360 (n=32), and Bicarbon (n=22). The mean prosthetic valve gradient was measured postoperatively and after six months. Results Preoperative data were comparable between groups, and there were no differences in preoperative echocardiographic data. Pre-discharge echocardiography showed no difference between groups in the ejection fraction (P=0.748), end-systolic (P=0.764) and end-diastolic (P=0.723) diameters, left ventricular mass index (P=0.348), aortic prosthetic mean pressure gradient (P=0.454), and indexed aortic prosthetic orifice area (P=0.576). There was no difference in the postoperative aortic prosthetic mean pressure gradient between groups when stratified by valve size. The changes in the aortic prosthetic mean pressure gradient of the intraoperative period, at pre-discharge, and at six months were comparable between the three prostheses (P=0.08). Multivariable regression analysis revealed that female gender (beta coefficient -0.242, P=0.027), body surface area (beta coefficient 0.334, P<0.001), and aortic prosthetic size (beta coefficient -0.547, P<0.001), but not the prosthesis type, were independent predictors of postoperative aortic prosthetic mean pressure gradient. Conclusion The three bileaflet mechanical aortic prostheses (On-X, Bicarbon, and ATS) provide satisfactory early hemodynamics, which are comparable between the three valve types and among different valve sizes.
Monitoring electron energies during FLASH irradiations

When relativistic electrons are used to irradiate tissues, such as during FLASH pre-clinical irradiations, the electron beam energy is one of the critical parameters that determine the dose distribution. Moreover, during such irradiations, linear accelerators (linacs) usually operate with significant beam loading, where a small change in the accelerator output current can lead to beam energy reduction. Optimisation of the tuning of the accelerator’s radio frequency system is often required. We describe here a robust, easy-to-use device for non-interceptive monitoring of potential variations in the electron beam energy during every linac macro-pulse of an irradiation run. Our approach monitors the accelerated electron fringe beam using two unbiased aluminium annular charge collection plates, positioned in the beam path and with apertures (5 cm in diameter) for the central beam. These plates are complemented by two thin annular screening plates to eliminate crosstalk and equalise the capacitances of the charge collection plates. The ratio of the charge picked up on the downstream collection plate to the sum of charges picked up on the both plates is sensitive to the beam energy and to changes in the energy spectrum shape. The energy sensitivity range is optimised to the investigated beam by the choice of thickness of the first plate. We present simulation and measurement data using electrons generated by a nominal 6 MeV energy linac as well as information on the design, the practical implementation and the use of this monitor.
Cross-cultural differences in intercultural mindreading: Evidence from a sample of Palestinian, Italian, and German adolescents.

Despite the fact that the "Reading the Mind in the Eyes" Test (RMET) is now available in more than 20 languages, there are only very few cross-cultural researchers using this test, and these researchers generally focus on North American versus East Asian cultures. Considering that the RMET stimuli were selected and constructed in the United Kingdom, this research explored cross-cultural differences in intercultural mindreading with a large sample of adolescents from Palestine (PAL), Italy (ITA), and Germany (GER). In addition to significant main effects of age (younger < older) and gender (male < female), we found a significant main effect of country (PAL < ITA < GER) and a significant interaction between gender and country. Individualism was not related to mindreading in any of the three countries whereas collectivism was positively related in PAL, but not in ITA or GER, accounting only for a very small amount of the variance. Our results suggest that (a) there may be cultural ingroup effects on mindreading, (b) the known female superiority in mindreading may be moderated by cultural factors, and (c) depending on cultural factors, individualism and collectivism may be differently related to mindreading.
Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

Abstract Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. Methods We developed an enzyme‐linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO‐C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulphate sodium‐induced rat colitis model, the PRO‐C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO‐C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO‐C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO‐C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). Conclusion PRO‐C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO‐C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.