Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Genetics and Complex Inheritance of Congenital Heart Disease

Congenital heart disease (CHD) is the most common congenital malformation and the leading cause of mortality therein. Genetic etiologies contribute to an estimated 90% of CHD cases, but so far, a molecular diagnosis remains unsolved in up to 55% of patients. Copy number variations and aneuploidy account for ~23% of cases overall, and high-throughput genomic technologies have revealed additional types of genetic variation in CHD. The first CHD risk genotypes identified through high-throughput sequencing were de novo mutations, many of which occur in chromatin modifying genes. Murine models of cardiogenesis further support the damaging nature of chromatin modifying CHD mutations. Transmitted mutations have also been identified through sequencing of population scale CHD cohorts, and many transmitted mutations are enriched in cilia genes and Notch or VEGF pathway genes. While we have come a long way in identifying the causes of CHD, more work is required to end the diagnostic odyssey for all CHD families. Complex genetic explanations of CHD are emerging but will require increasingly sophisticated analysis strategies applied to very large CHD cohorts before they can come to fruition in providing molecular diagnoses to genetically unsolved patients. In this review, we discuss the genetic architecture of CHD and biological pathways involved in its pathogenesis.
The Relevance of Plant-Derived Se Compounds to Human Health in the SARS-CoV-2 (COVID-19) Pandemic Era

Dietary selenium (Se)-compounds accumulated in plants are essential for human metabolism and normal physiological processes. Inorganic and organic Se species can be readily absorbed by the human body, but are metabolized differently and thus exhibit distinct mechanisms of action. They can act as antioxidants or serve as a source of Se for the synthesis of selenoproteins. Selenocysteine, in particular, is incorporated at the catalytic center of these proteins through a specific insertion mechanism and, due to its electronic features, enhances their catalytic activity against biological oxidants. Selenite and other Se-organic compounds may also act as direct antioxidants in cells due to their strong nucleophilic properties. In addition, Se-amino acids are more easily subjected to oxidation than the corresponding thiols/thioethers and can bind redox-active metal ions. Adequate Se intake aids in preventing several metabolic disorders and affords protection against viral infections. At present, an epidemic caused by a novel coronavirus (SARS-CoV-2) threatens human health across several countries and impacts the global economy. Therefore, Se-supplementation could be a complementary treatment to vaccines and pharmacological drugs to reduce the viral load, mutation frequency, and enhance the immune system of populations with low Se intake in the diet.
Small Molecule Drugs in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), mainly represented by Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development.
Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity

The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very-low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR-B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid-lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.
A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.
Optimized Aluminum Reflector for Enhancement of UVC Cathodoluminescence Based-AlGaN Materials with Carbon Nanotube Field Emitters

The far ultraviolet C (UVC) light sources based on carbon nanotube (CNT) field emitters as excitation sources have become promising light sources for sterilization, disinfection, and water purification. However, the low light extraction efficiency of UVC–CNT light sources still hinders the practical application of these structures. Herein, we report an optimized aluminum (Al) reflector to enhance the light extraction efficiency of UVC–CNT light sources. Optical analysis of UVC-CNT light sources covered by the Al reflectors with various thicknesses ranging from 30 to 150 nm was performed to realize the optimized reflector. The UVC-CNT light sources exhibit the highest light extraction efficiency when the Al reflector layer has an optimized thickness of 100 nm. For comparison, the cathodoluminescence (CL) spectra were recorded for UVC–CNT light sources with and without the optimized Al reflector. The measured light output power and the estimated power efficiency of the UVC–CNT light-source-tube with Al reflector were enhanced by about 27 times over the reference. This enhancement is mainly attributed to the outstanding reflection effect of the Al reflector.
Spatial Structure-Related Sensory Landmarks Recognition Based on Long Short-Term Memory Algorithm

Indoor localization is the basis for most Location-Based Services (LBS), including consumptions, health care, public security, and augmented reality. Sensory landmarks related to the indoor spatial structures (such as escalators, stairs, and corners) do not rely on active signal transmitting devices and have fixed positions, which can be used as the absolute positioning information to improve the performance of indoor localization effectively without extra cost. Specific motion patterns are presented when users pass these architectural structures, which can be captured by mobile built-in sensors, including accelerometers, gyroscopes, and magnetometers, to achieve the recognition of structure-related sensory landmarks. Therefore, the recognition of these landmarks can draw on the mature methods of Human Activity Recognition (HAR) with improvements. To this end, we improved a Long Short-Term Memory (LSTM) neural network to recognize different kinds of spatial structure-related sensory landmarks. Labels of structural sensory landmarks were proposed, and data processing methods (including interpolation, filter, and window length) were used and compared to achieve the highest recognition accuracy of 99.6%.
Mass Spectrometry-Based Proteomic and Immunoproteomic Analyses of the Candida albicans Hyphal Secretome Reveal Diagnostic Biomarker Candidates for Invasive Candidiasis

Invasive candidiasis (IC) is associated with high morbidity and mortality in hospitalized patients if not diagnosed early. Long-term use of central venous catheters is a predisposing factor for IC. Hyphal forms of Candida albicans (the major etiological agent of IC) are related to invasion of host tissues. The secreted proteins of hyphae are involved in virulence, host interaction, immune response, and immune evasion. To identify IC diagnostic biomarker candidates, we characterized the C. albicans hyphal secretome by gel-free proteomic analysis, and further assessed the antibody-reactivity patterns to this subproteome in serum pools from 12 patients with non-catheter-associated IC (ncIC), 11 patients with catheter-associated IC (cIC), and 11 non-IC patients. We identified 301 secreted hyphal proteins stratified to stem from the extracellular region, cell wall, cell surface, or intracellular compartments. ncIC and cIC patients had higher antibody levels to the hyphal secretome than non-IC patients. Seven secreted hyphal proteins were identified to be immunogenic (Bgl2, Eno1, Pgk1, Glx3, Sap5, Pra1 and Tdh3). Antibody-reactivity patterns to Bgl2, Eno1, Pgk1 and Glx3 discriminated IC patients from non-IC patients, while those to Sap5, Pra1 and Tdh3 differentiated between cIC and non-IC patients. These proteins may be useful for development of future IC diagnostic tests.
RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers

Simple Summary High mammographic density (MD) is a significant risk factor for the development of breast cancer, as is inheritance of mutations in BRCA1 or BRCA2 tumour suppressor genes. High MD combined with BRCA1/2 gene mutations synergistically increases breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD or exacerbate the inherent tissue stiffness that high MD creates. The molecular basis for this additive effect therefore remains unclear. Our data indicate that the combinatory effect of high MD and BRCA mutations on breast cancer risk may be a product of repression of the tumour suppressor gene RASSF1A, in regions of increased tissue stiffness. Abstract High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in BRCA1/2 gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (RASSF1A), a gene that is also directly regulated by tissue stiffness. High MD combined with BRCA1/2 mutations further increase breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD. The molecular basis for this additive effect therefore remains unclear. We studied the interplay between MD, stiffness, and BRCA1/2 mutation status in human mammary tissue obtained after prophylactic mastectomy from women at risk of developing BC. Our results demonstrate that RASSF1A expression increased in MCF10DCIS.com cell cultures with matrix stiffness up until ranges corresponding with BiRADs 4 stiffnesses (~16 kPa), but decreased in higher stiffnesses approaching malignancy levels (>50 kPa). Similarly, higher RASSF1A protein was seen in these cells when co-cultivated with high MD tissue in murine biochambers. Conversely, local stiffness, as measured by collagen I versus III abundance, repressed RASSF1A protein expression in BRCA1, but not BRCA2 gene mutated tissues; regional density as measured radiographically repressed RASSF1A in both BRCA1/2 mutated tissues. The combinatory effect of high MD and BRCA mutations on breast cancer risk may be due to RASSF1A gene repression in regions of increased tissue stiffness.
Associations between Psychosocial Variables, Availability of Physical Activity Resources in Neighborhood Environment, and Out-of-School Physical Activity among Chinese Adolescents

This study aimed to evaluate the relationship between psychosocial variables (peer support, parental support, autonomous motivation, and controlled motivation), availability of physical activity resources in a neighborhood environment, and out-of-school moderate to vigorous physical activity (MVPA) among Chinese adolescents. The questionnaire of Family Life, Activity, Sun, Health, and Eating (FLASHE) Study was used to collect information on demographics, socioeconomic status, psychosocial variables, available physical activity resources in the neighborhood environment, and minutes of out-of-school MVPA. ANOVA analysis and multiple regression analysis were performed. The mean age of the 3833 adolescents included in our analysis was 14.7 years old (SD = 1.7). Peer support (b = 9.35, 95% CI: 7.55–11.15), autonomous motivation (b = 6.46, 95% CI: 4.09–8.82), parental support (b = 3.90, 95% CI: 1.75–6.07), and availability of physical activity resources in neighborhood environment (b = 3.18, 95% CI: 1.99–4.36) were significantly associated with out-of-school MVPA (p < 0.05). Controlled motivation was insignificantly related to minutes of out-of-school MVPA. Boys spent more time on out-of-school MVPA than girls (p < 0.001) and had a high level of peer support, parental support, and motivation (p < 0.05). Our findings suggest that interventions targeting the out-of-school MVPA among Chinese adolescents should focus on the psychosocial variables and neighborhood environment.
Psychometric Suitability of Adaptations to the Special Judo Fitness Test for Athletes With Visual Impairment

This study aimed to test the reliability, sensitivity, construct and logical validity of an adapted Special Judo Fitness Test (SJFT) for judo athletes with visual impairment . Twenty judo athletes with visual impairments performed both the adapted SJFT with tactile and sonorous stimuli (experimental conditions) and the typically administered SJFT (standard condition). We used analyses of variance (ANOVAs) with repeated-measures to compare the groups’ SJFT performances, and one-way ANOVAs to compare different visual ability classes of athletes (B1, B2 and B3). We used t-tests to compare SJFT variables between elite and sub-elite groups. We set statistical significance for all tests at p < 0.05. The standard SJFT showed excellent test-retest reliability for number of throws and overall index (ICC = 0.91–0.95), and both sonorous and tactile sensitivity adaptations of the SJFT showed medium sensitivity for detecting performance changes. The number of throws and SJFT index were higher with the sonorous adaptation of the test, compared to the tactile and standard versions (p < 0.001). Athletes who were blind (B1) presented similar performances to athletes who were partially sighted (B2 and B3) only on the SJFT with the sonorous stimulus. Moreover, only the sonorous SJFT adaptation discriminated between the performances of elite and sub-elite athletes (p < 0.001). In conclusion, both SJFT adaptations showed excellent reliability and medium sensitivity on test-retest, but, only the SJFT with the sonorous stimulus seemed valid for assessing judo athletes with varying degrees of visual impairment, and only the sonorous stimulus SJFT discriminated elite from sub-elite athletes.
Differential Effects of Resistance- and Endurance-Based Exercise Programs on Muscular Fitness, Body Composition, and Cardiovascular Variables in Young Adult Women: Contextualizing the Efficacy of Self-Selected Exercise Modalities

There is an evident lack of research simultaneously investigating endurance training (ET) and resistance training (RT) with regard to their potential influence on fitness and health status in young women. This study aimed to determine the effects of RT and ET three times a week over an eight-week period on anthropometric/body composition indices, blood pressure (BP), and muscular fitness in apparently healthy young women who participated in a self-preferred program. The sample of participants comprised 57 young healthy women (23.9 ± 3.08 years, 165.5 ± 5.8 cm, 66.8 ± 7.2 kg) divided into ET (n = 18), RT (n = 19), and non-exercising (C) (n = 20) groups. The variables consisted of anthropometric/body composition indices (body mass, BMI, body fat, and lean body mass), muscular fitness variables (lower body strength, upper body strength, abdominal strength, dynamometric force, and flexibility), and cardiovascular parameters (resting heart rate and systolic and diastolic BP). A pre- and post-testing design, with factorial analysis of variance for repeated measurements (ANOVA: Group × Measurement), including a consecutive post hoc test, was applied. The ANOVA indicated a similar improvement in body composition (increase in lean body mass and decrease in body fat percentage), resting heart rate, and flexibility in both of the exercise groups, with no significant changes in the C group. RT improved the participants’ strength and force capacities to a greater extent than ET. BP showed a trend of improvement in both of the training groups, but without statistically significant pre- to post-changes. Correlation analysis calculated with variables of pre- to post-differences (VDs) indicated poor associations between VDs, indicating relative independence of the obtained effects for the different variables in each training group. Although this investigation comprised apparently healthy young women, numerous positive changes indicated the efficacy of both programs in a relatively short period of time. While the participants in this study self-selected training programs, the evidenced positive effects can be at least partially related to this fact.
Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood–retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.
Nanocelluloses: Sources, Pretreatment, Isolations, Modification, and Its Application as the Drug Carriers

The ‘Back-to-nature’ concept has currently been adopted intensively in various industries, especially the pharmaceutical industry. In the past few decades, the overuse of synthetic chemicals has caused severe damage to the environment and ecosystem. One class of natural materials developed to substitute artificial chemicals in the pharmaceutical industries is the natural polymers, including cellulose and its derivatives. The development of nanocelluloses as nanocarriers in drug delivery systems has reached an advanced stage. Cellulose nanofiber (CNF), nanocrystal cellulose (NCC), and bacterial nanocellulose (BC) are the most common nanocellulose used as nanocarriers in drug delivery systems. Modification and functionalization using various processes and chemicals have been carried out to increase the adsorption and drug delivery performance of nanocellulose. Nanocellulose may be attached to the drug by physical interaction or chemical functionalization for covalent drug binding. Current development of nanocarrier formulations such as surfactant nanocellulose, ultra-lightweight porous materials, hydrogel, polyelectrolytes, and inorganic hybridizations has advanced to enable the construction of stimuli-responsive and specific recognition characteristics. Thus, an opportunity has emerged to develop a new generation of nanocellulose-based carriers that can modulate the drug conveyance for diverse drug characteristics. This review provides insights into selecting appropriate nanocellulose-based hybrid materials and the available modification routes to achieve satisfactory carrier performance and briefly discusses the essential criteria to achieve high-quality nanocellulose.