Miracle-dz/UniFAR-FTUs huggingface dataset:
The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.
Adipose-Derived Stem Cell Exosomes as a Novel Anti-Inflammatory Agent and the Current Therapeutic Targets for Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA), a chronic inflammatory joint disorder, may not respond adequately to current RA treatments. Mesenchymal stem cells (MSCs) elicit several immunomodulatory and anti-inflammatory effects and, thus, have therapeutic potential. Specifically, adipose-derived stem cell (ADSC)-based RA therapy may have considerable potency in modulating the immune response, and human adipose tissue is abundant and easy to obtain. Paracrine factors, such as exosomes (Exos), contribute to ADSCs’ immunomodulatory function. ADSC-Exo-based treatment can reproduce ADSCs’ immunomodulatory function and overcome the limitations of traditional cell therapy. ADSC-Exos combined with current drug therapies may provide improved therapeutic effects. Using ADSC-Exos, instead of ADSCs, to treat RA may be a promising cell-free treatment strategy. This review summarizes the current knowledge of medical therapies, ADSC-based therapy, and ADSC-Exos for RA and discusses the anti-inflammatory properties of ADSCs and ADSC-Exos. Finally, this review highlights the expanding role and potential immunomodulatory activity of ADSC-Exos in patients with RA.
IgG Fusion Proteins for Brain Delivery of Biologics via Blood–Brain Barrier Receptor-Mediated Transport

The treatment of neurological disorders with large-molecule biotherapeutics requires that the therapeutic drug be transported across the blood–brain barrier (BBB). However, recombinant biotherapeutics, such as neurotrophins, enzymes, decoy receptors, and monoclonal antibodies (MAb), do not cross the BBB. These biotherapeutics can be re-engineered as brain-penetrating bifunctional IgG fusion proteins. These recombinant proteins comprise two domains, the transport domain and the therapeutic domain, respectively. The transport domain is an MAb that acts as a molecular Trojan horse by targeting a BBB-specific endogenous receptor that induces receptor-mediated transcytosis into the brain, such as the human insulin receptor (HIR) or the transferrin receptor (TfR). The therapeutic domain of the IgG fusion protein exerts its pharmacological effect in the brain once across the BBB. A generation of bifunctional IgG fusion proteins has been engineered using genetically engineered MAbs directed to either the BBB HIR or TfR as the transport domain. These IgG fusion proteins were validated in animal models of lysosomal storage disorders; acute brain conditions, such as stroke; or chronic neurodegeneration, such as Parkinson’s disease and Alzheimer’s disease. Human phase I–III clinical trials were also completed for Hurler MPSI and Hunter MPSII using brain-penetrating IgG-iduronidase and -iduronate-2-sulfatase fusion protein, respectively.
Equipping Youth to Think and Act Responsibly: The Effectiveness of the “EQUIP for Educators” Program on Youths’ Self-Serving Cognitive Distortions and School Bullying Perpetration

School bullying is a serious public health concern in many countries worldwide. Over recent decades, several effective anti-bullying prevention programs have been developed. This study aimed to evaluate the effectiveness of an adapted version of the “Equipping Youth to Help One Another (EQUIP) for Educators” (EfE) program in reducing adolescents’ engagement in school bullying perpetration by correcting their use of self-serving cognitive distortions (CDs). Furthermore, guided by the vantage sensitivity framework, we investigated whether the intervention effects varied depending on the adolescents’ gender and environmental sensitivity. A quasi-experimental pre-test/post-test with a control group design involved 354 Italian middle and high school adolescents (51.7% males; Mage = 14.86, SD = 2.54). Both the control (n = 187) and experimental group (n = 167) completed self-report questionnaires, before and after the intervention. Structural equation modeling revealed a significant moderated mediation effect: highly sensitive males participating in the EfE program decreased their engagement in bullying by reducing CDs, compared to females and those with low- and medium- sensitivity. These findings support the effectiveness of the EfE program in equipping youth to think and act more responsible and shed light on “why” and “for whom” the intervention might work better to counteract school bullying during adolescence.
Frailty Index and Cardiovascular Disease among Middle-Aged and Older Chinese Adults: A Nationally Representative Cross-Sectional and Follow-Up Study

Evidence for the association between the frailty index and cardiovascular disease (CVD) is inconclusive, and this association has not been evaluated in Chinese adults. We aim to examine the association between the frailty index and CVD among middle-aged and older Chinese adults. We conducted cross-sectional and cohort analyses using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). From 2011 to 2018, 17,708 participants aged 45 years and older were included in the CHARLS. The primary outcome was CVD events (composite of heart disease and stroke). Multivariable adjusted logistic regression and Cox proportional hazards models were used to estimate the association between the frailty index and CVD in cross-sectional and follow-up studies, respectively. A restricted cubic spline model was used to characterize dose–response relationships. A total of 16,293 and 13,580 participants aged 45 years and older were included in the cross-sectional and cohort analyses, respectively. In the cross-sectional study, the prevalence of CVD in robust, pre-frailty and frailty was 7.83%, 18.70% and 32.39%, respectively. After multivariable adjustment, pre-frailty and frailty were associated with CVD; ORs were 2.54 (95% confidence interval [CI], 2.28–2.84) and 4.76 (95% CI, 4.10–5.52), respectively. During the 7 years of follow-up, 2122 participants without previous CVD developed incident CVD; pre-frailty and frailty were associated with increased risk of CVD events; HRs were 1.53 (95% CI, 1.39–1.68) and 2.17 (95% CI, 1.88–2.50), respectively. Furthermore, a stronger association of the frailty index with CVD was observed in participants aged <55, men, rural community-dwellers, BMI ≥ 25, without hypertension, diabetes or dyslipidemia. A clear nonlinear dose–response pattern between the frailty index and CVD was widely observed (p < 0.001 for nonlinearity), the frailty index was above 0.08, and the hazard ratio per standard deviation was 1.18 (95% CI 1.13–1.25). We observed the association between the frailty index and CVD among middle-aged and elderly adults in China, independent of chronological age and other CVD risk factors. Our findings are important for prevention strategies aimed at reducing the growing burden of CVD in older adults.
Internationally Linked Firms and Productivity in Pakistan: A Look at the Top End of the Distribution

Abstract This paper examines productivity drivers for Pakistani publicly listed firms from 2012 to 2017, with a focus on policy and outcome measures of integration in upstream sectors. We find that increased import duties on intermediates, and reduced FDI in upstream services, are associated with a reduction in productivities downstream. Gains from lower input tariffs accrue to firms that cannot secure duty exemptions—domestic-oriented firms and smaller exporters. Gains from upstream services FDI accrue mostly to firms that are further from the productivity frontier. Our results suggest that productivity growth in Pakistan would benefit from increased exposure of upstream sectors to global markets.
Teaching in Orthopaedic Surgery: Effective Strategies for Educating the Modern Learner in a Modern Surgical Practice

Abstract Prioritizing the education of orthopaedic surgery residents and fellows is essential for the future of the field. This review highlights strategies that educators may find useful in improving their teaching skills for the modern orthopaedic surgery learner. Educators may benefit from focusing on active, effortful, and repetitive engagement in lecture; setting clear expectations to help track progress in clinic; and breaking skills into smaller steps in context of a framework when teaching procedural skills. Providing objective assessment and growth-oriented feedback helps establish a close rapport between educator and trainee while encouraging personal development. Through a remediation process that examines deficiency in core areas and equitability of the learning environment, the trainee and the educator may engage in a fair discussion that prevents trainees from falling behind. Finally, in the era of COVID-19, e-learning and virtual simulations have become increasingly used as effective modalities for teaching clinical knowledge and procedures to trainees. The medical education landscape has been changing at a rapid pace, and by evaluating and adapting to the novel educational models of today, the modern orthopaedic surgeon ensures a learning environment that is equitable, effective, and inspiring for the orthopaedic surgeon of tomorrow.
Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology

Background In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations. Methods A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose “Accept Completely” (Option A) or “Accept with Some Reservation” (Option B). Results The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients. Conclusion This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.
Liver Stiffness in Obese Hypothyroid Patients Taking Levothyroxine

Background and Objectives: Thyroid dysfunction is associated with non-alcoholic fatty liver disease, but its role in the progression of liver damage in obese patients remains unclear. In addition, several case reports have suggested the existence of a levothyroxine-induced liver injury, which has been poorly investigated. Our aim was to verify whether a difference in the prevalence of liver fibrosis exists in a population of obese individuals taking Levothyroxine. Materials and Methods: We conducted a cross-sectional study on a population of 137 obese individuals, of which 49 were on replacement therapy with Levothyroxine. We excluded those who had hypertriglyceridemia and diabetes mellitus. All participants underwent a liver stiffness assessment by transient elastography as well as biochemical measurements. In subjects with liver fibrosis, other cause of liver fibrosis were ruled out. Results: Participants taking Levothyroxine had a higher prevalence of liver fibrosis than those not taking Levothyroxine (30.6% vs. 2.3%; p < 0.001), and these results were obtained after we made an adjustment for age (Exp(B) = 18.9; 95% CI = 4.1–87.4; p < 0.001). The liver stiffness value differed significantly between groups (6.0 ± 3.6 and 5.1 ± 1.2, p = 0.033). Of those subjects taking Levothyroxine, there were no significant differences in the dose of medication (1.21 ± 0.36 vs. 1.07 ± 0.42; p = 0.240) and treatment duration (13.7 ± 7.43 vs. 11.13 ± 6.23; p = 0.380) between those with and without liver fibrosis. Conclusions: We found, for the first time, a greater prevalence of liver fibrosis in obese individuals taking Levothyroxine than in those not taking this medication. This finding needs to be confirmed by longitudinal population studies as well as by cellular studies.
Deeper engagement with live theater increases middle school students’ empathy and social perspective taking

Abstract Building on research showing social-emotional benefits from a single live theater performance, this study tests for significant differences in pre to post social-cognitive outcomes among a racially and economically diverse sample of young audiences who attended the same theater performance with or without additional pre- and post-show educational experiences. We extend previous work by experimentally manipulating and testing a common artistic educational intervention: deeper engagement strategies including facilitated discussions and pre-performance guides. We also refine previous investigations into generalized social and emotional skills by specifically examining foundational social-cognitive abilities: social perspective taking and empathy. This study utilizes a pre-post design with randomized control and treatment groups. Several significant findings suggest that when paired with educational pre- and post-show experiences, students’ social perspective taking and empathy can be positively impacted through a single live theater performance.
Powdery Mildew Resistance Genes in European Barley Cultivars Registered in the Czech Republic from 2016 to 2020

Barley is an important crop grown annually on about 55 Mha and intensively cultivated in Europe. In central and north-western Europe, spring and winter barley can be grown in similar environments which creates suitable conditions for the development of barley pathogens, including Blumeria graminis f. sp. hordei, the causal agent of powdery mildew. Apart from pesticide application, it can be controlled by inexpensive and environmentally-friendly genetic resistance. In this contribution, results of the resistance gene identification in 58 barley cultivars to powdery mildew are presented. In 56 of them their resistances were postulated and in two hybrid cultivars a recently developed method of gene identification was used. In total, 18 known resistance genes were found and several unknown genes were detected. In spring barley, a gene of durable resistance mlo is still predominant. MlVe found in winter SU Celly was the only new resistance gene recorded in barley cultivars registered in the Czech Republic in this time span. Since 2001 eight new genes of specific resistance have been identified in cultivars registered in the country and their response under field conditions is discussed, including the corresponding responses of the pathogen population due to directional selection. Different strategies for breeding spring and winter barley are recommended.
Investigation of the Genotoxic, Antigenotoxic and Antioxidant Profile of Different Extracts from Equisetum arvense L.

The present study investigated the cyto-genotoxic and antigenotoxic effects of four different extracts of Equisetum arvense L. (common name: field horsetail) on human lymphocytes. Specifically, Soxhlet’s prepared extracts from E. arvense L. , using different solvents (S1: methanol (MeOH)-, S2: ethanol (EtOH)-, S3: water-, and S4: ethanol/water (EtOH-W)-) were analyzed for (a) their total phenolic and flavonoid content (TPC and TFC, respectively), (b) their antioxidant activity (AA), via the DPPH, FRAP and ABTS assays, and (c) their cyto-genotoxic and/or protective efficiency against the mutagenic agent mitomycin C, via the Cytokinesis Block MicroNucleus assay. All extracts showed increased TPC, TFC, and AA values in almost all cases. S1, S3 and S4 demonstrated no cytotoxic potential, whereas S2 was cytotoxic only at the highest concentrations. Genotoxicity was not observed in the tested extracts. The highest antigenotoxic activity was observed for EtOH-W (S4) extract, which was found to be rich in flavonoids, flavonoid-O-glycosides, phytosterols, phenolic and fatty acids as well as in minerals and mainly in K, Ca, Mg, Si and P, as assessed by using various mass spectrometry techniques. Those findings confirm that E. arvense L. extracts could be valuable candidates for medicinal applications and pharmaceutical products, thus alleviating the effects of more conventional drugs.
Diabesity in Elderly Cardiovascular Disease Patients: Mechanisms and Regulators

Cardiovascular disease (CVD) is the leading cause of death in the world. In 2019, 550 million people were suffering from CVD and 18 million of them died as a result. Most of them had associated risk factors such as high fasting glucose, which caused 134 million deaths, and obesity, which accounted for 5.02 million deaths. Diabesity, a combination of type 2 diabetes and obesity, contributes to cardiac, metabolic, inflammation and neurohumoral changes that determine cardiac dysfunction (diabesity-related cardiomyopathy). Epicardial adipose tissue (EAT) is distributed around the myocardium, promoting myocardial inflammation and fibrosis, and is associated with an increased risk of heart failure, particularly with preserved systolic function, atrial fibrillation and coronary atherosclerosis. In fact, several hypoglycaemic drugs have demonstrated a volume reduction of EAT and effects on its metabolic and inflammation profile. However, it is necessary to improve knowledge of the diabesity pathophysiologic mechanisms involved in the development and progression of cardiovascular diseases for comprehensive patient management including drugs to optimize glucometabolic control. This review presents the mechanisms of diabesity associated with cardiovascular disease and their therapeutic implications.
Visual Functions Affecting Vision-Related Quality of Life Following Intravitreal Ranibizumab Therapy for Central Retinal Vein Occlusion

Visual functions that affect vision-related quality of life (VR-QoL) before and after intravitreal injection of ranibizumab in patients with cystoid macular edema secondary to central retinal vein occlusion (CRVO-CME) are poorly understood. This multicenter, open-label, single-arm prospective study included 23 treatment-naïve patients with CRVO-CME. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS), severity of metamorphopsia (M-CHARTS), amount of aniseikonia (New Aniseikonia Test), and stereopsis (Titmus Stereo Test and TNO stereotest) were examined every month from before treatment to 12 months after treatment. For VR-QoL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was provided to the patients before treatment and at 3, 6, and 12 months after treatment. Stepwise multiple regression analysis revealed that the BCVA of the fellow eye was related to the VFQ-25 composite score before treatment, and that the BCVA of the fellow eye and TNO values were related to the VFQ-25 composite score 12 months after treatment. Changes in LCS were significantly correlated with changes in the VFQ-25 composite score. In patients with CRVO-CME, visual acuity of the fellow eye had the strongest impact on VR-QoL. The contrast sensitivity of the affected eye and stereopsis were also associated with VR-QoL.
Influence of the COVID-19 Pandemic on Quality of Life, Mental Health, and Level of Physical Activity in Colombian University Workers: A Longitudinal Study

The COVID-19 pandemic has had a strong influence on people’s quality of life, and the different restrictive measures during the phases of the pandemic have had consequences for physical and mental health. This study determined the changes in health-related quality of life (HRQoL), sleep quality, depression symptoms (DS), and physical activity (PA) level of middle-aged Colombian university personnel during the COVID-19 pandemic. The analysis was performed following a longitudinal design on a sample of 354 people at four points before and during the pandemic. The International Physical Activity Questionnaire (IPAQ), the SF-12v2, the Pittsburgh Sleep Quality Index (PSQI), and the Zung Self-Rating Depression Scale (ZSDS) were included in an online survey. The measurements showed a decrease in quality of life with respect to PCS from 91.66 ± 10.78 to 83.64 ± 17.22 (p = 0.000) and MCS from 87.57 ± 12.23 to 80.90 ± 17.31, while poor sleep quality increased from 25.99% to 47.46% (p = 0.000), with DS reaching the peak during mandatory confinement (14.69%). Regarding the level of physical activity, the period of mandatory confinement inverted the proportion, highlighting active people as a minority (32.2%). In the multivariate analysis, we adjusted for age, sex, BMI, and socioeconomic level, discarding confounding effects and their interactions with the results obtained. In conclusion, this study showed that the pandemic has had a negative impact on sleep quality, HRQoL, DS, and PA level.