Miracle-dz/UniFAR-FTUs huggingface dataset:
Shape-Based Generative Modeling for de Novo Drug Design

In this work, we propose a machine learning approach to generate novel molecules starting from a seed compound, its three-dimensional (3D) shape, and its pharmacophoric features. The pipeline draws inspiration from generative models used in image analysis and represents a first example of the de novo design of lead-like molecules guided by shape-based features. A variational autoencoder is used to perturb the 3D representation of a compound, followed by a system of convolutional and recurrent neural networks that generate a sequence of SMILES tokens. The generative design of novel scaffolds and functional groups can cover unexplored regions of chemical space that still possess lead-like properties.
Antrodia cinnamomea, a Treasured Medicinal Mushroom, Induces Growth Arrest in Breast Cancer Cells, T47D Cells: New Mechanisms Emerge

Reported cases of breast cancer have skyrocketed in the last decades with recent advances in examination techniques. Brest cancer has become the second leading cause of mortality among women worldwide, urging the scientific community to develop or find new drugs from natural sources with potent activity and a reasonable safety profile to tackle this ailment. Antrodia cinnamomea (AC) is a treasured medicinal fungus which has attracted attention due to its potent hepatoprotective and cytotoxic activities. We evaluated the antiproliferative activity of the ethanol extract of artificially cultured AC (EEAC) on breast cancer cells (T47D cells) in vivo and in vitro. Ethanol extract of artificially cultured AC inhibited T47D cells’ proliferation mediated by cell cycle arrest at G1 phase as well induced autophagy. Immunoblotting assay confirmed that EEAC not only decreased the expression of the cell-cycle-related proteins but also increased the expression of transcription factor FOXO1, autophagic marker LC3 II, and p62. Ethanol extract of artificially cultured AC mediated endoplasmic reticulum stress by promoting the expression of IRE1 (inositol-requiring enzyme 1α), GRP78/Bip (glucose regulating protein 78), and CHOP (C/EBP homologous protein). Apart from previous studies, HDACs (histone deacetylases) activity was inhibited as demonstrated by a cell-free system, immunoblotting, and immunofluorescence assays following EEAC treatment. The in vivo studies demonstrated that EEAC decreased tumor volume and inhibited tumor growth without any significant side effects. High performance liquid chromatography profile demonstrated similar triterpenoids compared to the profile of wild AC ethanol extract. The multiple targets of EEAC on breast cancer cells suggested that this extract may be developed as a potential dietary supplement targeting this debilitating disease.
An Entropy-Based Method for Identifying Mutual Exclusive Driver Genes in Cancer

Cancer in essence is a complex genomic alteration disease which is caused by the somatic mutations during the lifetime. According to previous researches, the first step to overcome cancer is to identify driver genes which can promote carcinogenesis. However, it is still a big challenge to precisely and efficiently extract the cancer related driver genes because the nature of cancer is heterogeneous and there exists tremendously irrelevant passenger mutations which have no function impact on the cancer's development. In this work, we proposed a novel entropy-based method namely EntroRank to identify driver genes by integrating the subcellular localization information and mutual exclusive of variation frequency into the network. EntroRank can take into full consideration different properties of driver genes. Considering the modularity of driver genes, the mutated genes in the network were first clustered into different subgroups according to their located compartments. After that, the structural entropy of the gene in the subgroup was employed to measure its indispensability. Considering mutual exclusive property between driver genes in the modules, relative entropy was utilized to measure the degree of mutual exclusive between two mutated genes in terms of their variation frequency. We applied our method to three different cancers including lung, prostate, and breast cancer. The results show our method not only detect the well-known important drivers but also prioritiz the rare unknown driver genes. Besides, EntroRank can identify driver genes having mutual exclusive property. Compared with other existing methods, our method achieves a better performance for most of cancer types in terms of Precision, Recall, and Fscore.
Tensioned Wire–Assisted Intramedullary Nail Treatment of Proximal Tibia Shaft Fractures: A Technical Trick

Summary: Proximal tibia shaft fractures are often challenging to manage because of their intrinsic tendency toward valgus and apex anterior deformity. In recent years, intramedullary nailing (IMN) has become more frequently used to treat these injuries, allowing for biologic advantages such as load-sharing, immediate weight-bearing, and avoidance of disruption of periosteal blood supply. Several adjunctive techniques, such as semiextended positioning, blocking screws, and external fixation, have been developed to assist with fracture reduction during IMN. We describe a new adjunctive reduction technique—tensioned wire–assisted IMN—for the treatment of proximal tibia shaft fractures. We have found that tensioned wire assistance facilitates fracture reduction during IMN, does not interfere with intraoperative image intensification, and is compatible with both standard nailing instrumentation and additional adjunctive techniques. We present tensioned wire nailing as a technical trick for anatomic and stable reduction of proximal tibia fractures and compare a cohort of proximal tibia shaft fractures managed with and without tensioned wire assistance.
Preferences for family involvement in care among consumers with serious mental illness.

OBJECTIVE Despite robust evidence of efficacy, family services for individuals diagnosed as having serious mental illness are of limited availability and drastically underutilized. This underutilization may be due to a mismatch between consumer and family preferences and the services offered. This study is the first systematic report on preferences expressed by consumers with serious mental illness for family involvement. METHODS The study enrolled 232 mental health consumers with serious mental illness who had contact with family but did not have any family regularly involved in their mental health care. Consumers were recruited from outpatient mental health clinics at three large medical centers in two Veterans Integrated Service Networks. Interviews elicited demographic characteristics, treatment preferences regarding family involvement, and perceived benefits and barriers to involvement. Chart diagnoses and measures of symptom severity, family functioning, and contact were collected. RESULTS Seventy-eight percent (171 of 219) of the consumers wanted family members to be involved in their care, and many desired involvement through several methods. Consumers were concerned with the impact of involvement on both themselves and their family member. The consumer's degree of perceived benefit of family involvement significantly predicted the degree of desire for family involvement after analyses controlled for service need (family conflict, family-related quality of life, and symptom severity), enabling factors (family contact and family capacity), demographic variables (age, gender, race, living with family, and marital status), and barriers perceived by the consumer. CONCLUSIONS The extent of overall support for family involvement in care coupled with the heterogeneity of preferred modes and concerns and anticipated benefits underscore the imperative to offer diverse family services and to elicit consumers' preferences regarding whether and how to involve their families.
Development of a Quality Score for the Home Food Environment Using the Home-IDEA2 and the Healthy Eating Index-2010

The home food environment (HFE) is an important factor in the development of food preferences and habits in young children, and the availability of foods within the home reflects dietary intake in both adults and children. Therefore, it is important to consider the holistic quality of the HFE. The purpose of this study was to apply the Healthy Eating Index (HEI; a measure of diet quality in conformance to the Dietary Guidelines for Americans) algorithm to the Home-IDEA2, a valid and reliable food inventory checklist, to develop a Home-IDEA2 HEI Score. After an initial score was developed, it was psychometrically tested for content, criterion, and construct validity. Content validity testing resulted in 104 foods being retained. Internal criterion testing demonstrated that 42 foods (40%) changed component scores by >5%; however, no single food changed a total Home-IDEA2 HEI score by >5%. Testing of hypothetical HFEs resulted in a range of scores in the expected directions, establishing sensitivity to varied HFEs. This study resulted in a validated methodology to assess the overall quality of the HFE, thus contributing a novel approach for examining home food environments. Future research can test interventions modifying the HFE quality to improve individual dietary intake.
Regions of homozygosity as risk factors for multiple myeloma

Genomic regions of homozygosity (ROH), detectable in outbred populations, have been implicated as determinants of inherited risk. To examine whether ROH is associated with risk of multiple myeloma (MM), we performed whole‐genome homozygosity analysis using single‐nucleotide polymorphism genotype data from 2,282 MM cases and 5,197 controls, with replication in an additional 878 MM cases and 7,083 controls. Globally, the distribution of ROH between cases and controls was not significantly different. However, one ROH at chromosome 9q21, harboring the B‐cell transcription factor gene KLF9, showed evidence of a consistent association and may therefore warrant further investigation as a candidate risk factor for MM. Overall, our analysis provides little support for a homozygosity signature being a significant factor in MM risk.
The Interaction between Genetic Polymorphisms in FTO and TCF7L2 Genes and Dietary Intake with Regard to Body Mass and Composition: An Exploratory Study

In contrast to the large number of genetic studies on obesity, there has been significantly less nutrigenetics investigation of the interaction between diet and single nucleotide polymorphisms (SNPs) in obesity, especially within Eastern Mediterranean populations. The aim of this study was to evaluate the potential interactions between three candidate SNPs, namely, rs1558902 and rs9939609 in the fat mass and obesity (FTO) gene and the rs7903146 variant of the Transcription factor 7 like 2 (TCF7L2) gene, and macronutrient intake with regard to obesity, body fat, and muscle composition. Three hundred and eight healthy Lebanese adults were included in this study. Data collection included a questionnaire for demographics and lifestyle in addition to a detailed dietary assessment using a culture-specific 80-item semi-quantitative food frequency questionnaire. This was coupled with anthropometric measurements and peripheral blood withdrawal for DNA and genotyping using Taqman allele discrimination assays. The two FTO candidate SNPs were not associated with risk of obesity in this population sample, yet there was a trend, though not a significant one, towards lower muscle mass among carriers of the risk allele of either FTO SNPs. To our knowledge, these results have not been previously reported. As for the TCF7L2 rs7903146 variant, results were congruent with the literature, given that individuals who were homozygous for the risk allele had significantly higher body mass index (BMI) and body fat despite lower intakes of saturated fat. Similar interactions, though not significant, were shown with muscle mass, whereby individuals who were homozygous for the risk allele had lower muscle mass with higher intakes of saturated fat, a result that, to our knowledge, has not been previously reported.
Hetero-tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies.

OBJECTIVE To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies. METHOD In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software. RESULTS Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have showed one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds. CONCLUSION In silico docking studies revealed that nitrogen containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds were emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.
Human Müller stem cell (MIO-M1) transplantation in a rat model of glaucoma: survival, differentiation, and integration.

PURPOSE Stem cell transplantation is a potential treatment strategy for neurodegenerative diseases such as glaucoma. The Müller stem cell line MIO-M1 can be differentiated to produce retinal neurons and glia. The survival, migration, differentiation, and integration of MIO-M1 cells were investigated in a rat model of glaucoma. The effect of modulating the retinal environment with either chondroitinase ABC or erythropoietin was also studied. METHODS Intraocular pressure was chronically increased unilaterally by using a laser glaucoma model in adult rats. EGFP-transduced MIO-M1 cells were transplanted into the vitreous or subretinal space of glaucomatous or untreated eyes. Oral immune suppressants were administered to reduce xenograft rejection. Survival, migration, differentiation, and integration of grafted cells were assessed by immunohistochemistry. RESULTS Transplanted cells survived for 2 to 3 weeks in vivo, although microglia/macrophage infiltration and a reduction in graft survival were seen by 4 weeks. Grafted cells displayed a migratory phenotype with an elongated bipolar shape often oriented toward the retina. Transplanted cells expressed markers such as PSA-NCAM, GFAP, and beta-III-tubulin. The host retina was resistant to MIO-M1 migration, but modification of the local environment with erythropoietin or chondroitinase ABC facilitated retinal infiltration by MIO-M1 cells. CONCLUSIONS The results demonstrate that differentiating MIO-M1 cells within the glaucomatous eye produced cells that expressed neuronal and glial cell markers. The retina was relatively resistant to transplant integration, and long-term xenograft survival was limited. However, local modulation of the retinal environment enhanced the integration of MIO-M1 cells into the glaucomatous retina.
Model-Based Chemical Exchange Saturation Transfer MRI for Robust z-Spectrum Analysis

This paper introduces a novel, model-based chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), in which asymmetric spectra of interest are directly estimated from complete or incomplete measurements by incorporating subspace-based spectral signal decomposition into the measurement model of CEST MRI for a robust z-spectrum analysis. Spectral signals are decomposed into symmetric and asymmetric components. The symmetric component, which varies smoothly, is delineated by the linear superposition of a finite set of vectors in a basis trained from the simulated (Lorentzian) signal vectors augmented with data-driven signal vectors, while the asymmetric component is to be inherently lower than or equal to zero due to saturation transfer phenomena. Spectral decomposition is performed directly on the measured spectral data by solving a constrained optimization problem that employs the linearized spectral decomposition model for the symmetric component and the weighted Frobenius norm regularization for the asymmetric component while utilizing additional spatial sparsity and low-rank priors. The simulations and in vivo experiments were performed to demonstrate the feasibility of the proposed method as a reliable molecular MRI.
Differential Efficacy of Neurofeedback in Children with ADHD Presentations

Training in neurofeedback (NF) reduces the symptomatology associated with attention deficit with hyperactivity disorder (ADHD). However, ADHD differs in terms of the type of presentation, i.e., inattentive (ADHD-I), impulsive/hyperactive (ADHD-HI), or combined (ADHD-C). This study examines the efficacy of NF in ADHD presentations. Participants were 64 students (8–12 years old). Cortical activation, executive control, and observed symptomatology by parents were assessed. Results indicated that ADHD-C and ADHD-HI demonstrated greater improvements than ADHD-I. It was concluded that this kind of training produces an improvement and that it is necessary to explore it further in terms of the protocol used.
Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease--FLAVURS: a randomized controlled trial.

BACKGROUND Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥ 1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION These data support recommendations to increase F&V intake to ≥ 6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD.
High Carbon Monoxide Levels from Charcoal Combustion Mask Acute Endothelial Dysfunction Induced by Hookah (Waterpipe) Smoking in Young Adults

Background: Hookah smoking is marketed to youth as a harmless alternative to cigarettes. Although cigarette smoking acutely impairs endothelial function, the effect of smoking fruit-flavored hookah tobacco is unknown. Because charcoal traditionally is used to heat the hookah tobacco in the waterpipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products: not only carbon-rich nanoparticles, oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide (CO), a putative vasodilator molecule. Methods: To test the acute effect of hookah smoking on endothelial function, in young adult hookah smokers (n=30, age 26±1 years, mean±SE), we measured plasma nicotine, exhaled CO, and brachial artery flow-mediated dilation (FMD) before and after charcoal-heated hookah smoking. To remove the effect of charcoal combustion, the same measurements were performed when the same flavored hookah tobacco product was heated electrically (n=20). As a positive internal control, we studied age-matched cigarette smokers (n=15) who smoked 1 cigarette. To isolate the effect of the CO boost on FMD, hookah smokers (n=8) inhaled a 0.1% CO gas mixture to approximate their CO boost achieved with charcoal-heated hookah smoking. Results: Nicotine levels increased similarly with all types of smoking, whereas exhaled CO increased 9- to 10-fold more after charcoal-heated hookah than after either electrically heated hookah or cigarette smoking. FMD did not decrease after smoking charcoal-heated hookah but instead increased by +43±7% (P<0.001). In contrast, FMD decreased by –27±4% (P<0.001) after smoking electrically heated hookah, comparable to the decrease after cigarette smoking. FMD increased markedly by 138±71% (P<0.001) after breathing CO gas, 2.8 times more than the increase induced in the same subjects after smoking charcoal-heated hookah (P<0.001), despite comparable increases in exhaled CO (24±1 versus 28±3 ppm, hookah versus CO). Conclusions: Smoking hookah tobacco, similar to cigarette tobacco, acutely impairs endothelial function. With traditional charcoal-heated hookah smoking, the acute endothelial dysfunction is masked by high levels of carbon monoxide, a potent vasodilator molecule generated by charcoal combustion. With respect to large-artery endothelial function, smoking hookah is not harmless. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifiers: NCT 03616002 and NCT 03067701.