Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of soy isoflavone intake on cardiovascular disease risk factors - potential role of equol

Isoflavones, the subclass of flavonoids found in soybeans, may reduce the risk of cardiovascular disease (CVD). However, the current evidence is inconsistent. The capability to produce the isoflavone metabolite equol in 20-60 % of the population might underlie the benefits of isoflavone intake on vascular health. In a retrospective analysis of a 12-month intervention containing isoflavones (100 mg isoflavones, as aglycones equivalents), postmenopausal women with Type 2 diabetes who were equol producers (EPs) had significantly lower diastolic blood pressure (BP), mean arterial BP and arterial stiffness (assessed by pulse wave velocity (PWV)) (mean change from baseline ()±SEM; -2.2±1.3 mmHg, -1.2±1.3 mmHg, -0.7±0.4 m/s, respectively, P<0.01) than non-EPs. Subsequently, an acute crossover double-blind study was conducted where EP and non-EP males at elevated heart disease risk were prospectively recruited (n=14 per group) to determine whether EP phenotype was associated with differential vascular responses. The effects of an isoflavone supplement (80mg; single-dose) on endothelial function, PWV and BP were assessed at baseline, and at the anticipated Tmax for plasma isoflavones (6h) and equol (24h). After isoflavone intake, EPs had significantly decreased PWV at 24h (±SEM: isoflavone -0.2±0.2, placebo +0.6±0.2; P<0.01). However, isoflavone intake had no effect on the vascular measures at the 6h and 24h timepoints. To further investigate the acute vascular effects of S-equol per se, synthetic S-equol supplements (40 mg) were consumed by non-EPs at the anticipated Tmax for plasma S-equol (2h) and this showed no significant vascular benefits. In conclusion, acute isoflavone intake improved arterial stiffness in male EPs at increased CVD risk, with the magnitude of change potentially equating to a 10-12% risk reduction in risk of CVD if sustained. Synthetic equol intake had no acute benefit on vascular health in non-EPs. These data suggest that the EP phenotype may partly predict the effectiveness of soy isoflavones on arterial stiffness. Further long term RCTs with prospectively recruited EPs are required to confirm the importance of equol production for cardiovascular health.
Cancer Care in Pakistan: A Descriptive Case Study

In this descriptive case study, we aimed to understand the experiences of cancer diagnosis, treatment, and palliative care in Pakistan. The case was limited to a hospital for cancer and hospice care in Karachi, Pakistan. Data collection included interviews with patients who had a cancer diagnosis, family members, healthcare providers, and unstructured observations. Two themes of suffering and late diagnosis were developed to describe the experiences of people with cancer. Suffering occurred as a result of poverty, social ideas about cancer, and physical suffering. Late diagnosis happened because of cultural ideas about health, low health literacy, and healthcare challenges, although both themes are interconnected. The findings illuminate three key pathways that will improve cancer diagnosis and palliative care in Pakistan: specifically, the need to (a) educate healthcare providers about cancer and palliative care, (b) eradicate corruption in healthcare, and (c) develop policies for universal access to health.
The Yin-Yang Relationship Between Essentialist and Non-essentialist Discourses Related to the Participation of Children of Migrants, and Its Implication for How to Research

There is a complex relationship between the essentialist and non-essentialist discourses that respectively fail to and succeed in recognising the potential for participation which the children of migrants bring with them into new cultural settings. These competing discourses curl around each other within the structures of educational settings and within all the people involved, including the children themselves. A yin-yang framework helps us to see the nature of this entwined relationship and the hybridity which is the key to untangling it. It helps researchers to understand that getting to the bottom of what is going on is not straightforward and requires that they reassess who they are and how they should proceed. Sometimes it takes unusual and unexpected circumstances, such as those brought about by the emergency of the COVID-19 pandemic to shake their thinking-as-usual and to see the unexpected.
Prognostic factors for treatment response and survival outcomes after first-line management of Stage 4 non-small cell lung cancer: A real-world Indian perspective

Background: Indian data on treatment outcomes and survival in advanced non-small cell lung cancer (NSCLC) remain scarce. Materials and Methods: A retrospective review of 537 advanced NSCLC patients treated at a tertiary care facility in North India from January 2008 to March 2018 was done to assess treatment response and survival in terms of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Median age of enrolled patients was 60 years (range: 26–89 years). The majority were males (78.2%) and smokers (66.5%). Adenocarcinoma (51.2%) was the most common pathological type. Most patients had good performance status (PS) (the Eastern Cooperative Oncology Group [ECOG] 0 or 1 in 55.7%) and received conventional chemotherapy (86.6%). ORR and DCR after 3–4 months of first-line treatment were 55.2% and 71.75%, respectively (n = 223). Never smokers had better ORR as well as DCR compared to chronic smokers whereas treatment with tyrosine kinase inhibitors achieved significantly better ORR, and patients with good PS had better DCR compared to those with poor PS. Median PFS (n = 455) was 7.0 months (95% confidence interval [CI]: 3.7–14.0) and median OS was 11.7 months (95% CI: 5.5–29.9 months). Good PS and nonsmoking status were independent predictors of better PFS on multivariate analysis. For OS, good PS, nonsmoking behavior, and treatment with epidermal growth factor receptor inhibitors were independent predictors. Conclusion: In advanced NSCLC, never-smokers, and patients with good baseline ECOG have favorable treatment and survival outcomes. Treatment with targeted therapy results in better ORR and OS but did not affect PFS.
Prediction performance of single index principal fitted component models

When dealing with large-p-small-n problems in regression analyses, a reduction of the dimensionality is always desired. A lofty goal is to reduce the dimension of the original design matrix without losing any regressive information. Utilizing the randomness property of the predictors, a sufficient reduction is obtained under a principal fitted component (PFC) model. Assuming that the sufficient reduction is of dimension one, we replace the original predictors vector with the dimension-reduced-predictors vector in a forward regression model to form the so called single index principal fitted component regression (PFCR) model. We conducted a simulation study to compare the prediction performances of the single index PFCR to forward dimension reduction models, including the partial least squares, LASSO and ridge regressions, under distinct scenarios.
Thyroid Hormone Receptor Agonist Promotes Hair Growth in Mice

Background Thyroxine is important to maintain the normal operation of the body. Both clinical and experimental results show thyroxine is closely related to hair growth, the mechanism of which is not fully understood. Purpose Investigate the effect of thyroxine receptor agonist, TDM10842, for dorsal hair growth in C3H mice and explore its underlying mechanism. Methods Depilated mice were applied with the TDM10842, vehicle of this drug and without any materials on dorsal skin. RNA‐sequencing (RNA‐seq) was employed to identify the change in gene expression of skin tissues. Quantitative real-time PCR (rt-PCR) and immunoblotting were conducted to validate key differentially expressed genes (DEGs) between different groups. Results The TDM group showed early induction of anagen. 857, 782, and 276 differentially expressed genes were identified between 3 groups. As a critical DEG in group TDM, Pclaf was positively related to the motivation of Wnt/beta-catenin and Hedgehog signaling pathways, with a high expression of Ki67 and cyclinD1. Conclusion TDM10842 accelerates the anagen entrance and the potential mechanism might be the activation of Wnt/beta-catenin and Hedgehog pathways. Pclaf serves as a critical molecule involved in pathway activation, and cyclinD1 is an important effector protein downstream of the pathways.
Internet of Things Technologies and Machine Learning Methods for Parkinson’s Disease Diagnosis, Monitoring and Management: A Systematic Review

Parkinson’s disease is a chronic neurodegenerative disease that affects a large portion of the population, especially the elderly. It manifests with motor, cognitive and other types of symptoms, decreasing significantly the patients’ quality of life. The recent advances in the Internet of Things and Artificial Intelligence fields, including the subdomains of machine learning and deep learning, can support Parkinson’s disease patients, their caregivers and clinicians at every stage of the disease, maximizing the treatment effectiveness and minimizing the respective healthcare costs at the same time. In this review, the considered studies propose machine learning models, trained on data acquired via smart devices, wearable or non-wearable sensors and other Internet of Things technologies, to provide predictions or estimations regarding Parkinson’s disease aspects. Seven hundred and seventy studies have been retrieved from three dominant academic literature databases. Finally, one hundred and twelve of them have been selected in a systematic way and have been considered in the state-of-the-art systematic review presented in this paper. These studies propose various methods, applied on various sensory data to address different Parkinson’s disease-related problems. The most widely deployed sensors, the most commonly addressed problems and the best performing algorithms are highlighted. Finally, some challenges are summarized along with some future considerations and opportunities that arise.
Statistical life prediction of a unidirectional carbon fiber/polypropylene laminates under creep bending load

Our developed accelerated testing methodology (ATM) based on matrix resin viscoelasticity for the long-term life prediction of carbon fiber reinforced plastics (CFRP) was applied to assess the statistical prediction of long-term creep failure time of a carbon fiber/polypropylene unidirectional (CF/PP) laminates under creep bending load. Results show that the statistical long-term creep failure times under an arbitrary constant bending load and temperature for the CF/PP laminates can be easily predicted from the statistical static strengths of the CF/PP laminates measured at several temperatures and the viscoelasticity of matrix PP.
Novel Dual-Rotor Single-Stator Coreless Permanent Magnet Machine With Dual-Flywheel

Permanent magnet (PM) machines have attracted much attention in the field of flywheel energy storage system (FESS) due to their merits of high power density and high efficiency. However, the flux generated by the PMs would cause large stator core loss during the idling state of FESS, which would reduce the energy conversion ratio and limit the application of FESS in long-term energy storage occasions. Addressing this issue, a novel dual-rotor single-stator coreless PM machine (DSSCPMM) with dual-flywheel is proposed in this article. The stator of the DSSCPMM is made of ceramic material, which can effectively eliminate the stator core loss. The rotor of the DSSCPMM contains inner and outer rotors, which are used as the flywheels and can be helpful to improve the energy storage density. First, the structure and operation principle of the proposed DSSCPMM are illustrated. Then, the influences of the key structure parameters and arrangement of PMs, winding configurations, and magnetization method on the electromagnetic performance of the proposed DSSCPMM are investigated. Finally, the optimized structure of the DSSCPMM is obtained and the efficiency is calculated. The result shows that the proposed DSSCPMM is a promising candidate for the application of FESS.
Cardiac Tissue-like 3D Microenvironment Enhances Route towards Human Fibroblast Direct Reprogramming into Induced Cardiomyocytes by microRNAs

The restoration of cardiac functionality after myocardial infarction represents a major clinical challenge. Recently, we found that transient transfection with microRNA combination (miRcombo: miR-1, miR-133, miR-208 and 499) is able to trigger direct reprogramming of adult human cardiac fibroblasts (AHCFs) into induced cardiomyocytes (iCMs) in vitro. However, achieving efficient direct reprogramming still remains a challenge. The aim of this study was to investigate the influence of cardiac tissue-like biochemical and biophysical stimuli on direct reprogramming efficiency. Biomatrix (BM), a cardiac-like extracellular matrix (ECM), was produced by in vitro culture of AHCFs for 21 days, followed by decellularization. In a set of experiments, AHCFs were transfected with miRcombo and then cultured for 2 weeks on the surface of uncoated and BM-coated polystyrene (PS) dishes and fibrin hydrogels (2D hydrogel) or embedded into 3D fibrin hydrogels (3D hydrogel). Cell culturing on BM-coated PS dishes and in 3D hydrogels significantly improved direct reprogramming outcomes. Biochemical and biophysical cues were then combined in 3D fibrin hydrogels containing BM (3D BM hydrogel), resulting in a synergistic effect, triggering increased CM gene and cardiac troponin T expression in miRcombo-transfected AHCFs. Hence, biomimetic 3D culture environments may improve direct reprogramming of miRcombo-transfected AHCFs into iCMs, deserving further study.
"They whispered me the answer" in Australia and the US: A comparative experimental study

Mismatches between grammaticality judgments of linguists and actual usage are surprisingly common, particularly where linguists invoke subtle contrasts such as between different types of dative transfer verbs or between different types of dative communication verbs. For example, as Levin's (1993) compendium of verb classes in the linguistic literature shows, linguists have judged verbs of manner of communication like mutter or whisper as ungrammatical in the double object form in contrast to the prepositional alternative (*whisper John the answer vs. whisper the answer to John), while they have judged verbs of communication by instrument like phone or text grammatical in each of the alternative structures (phone John the answer, phone the answer to John). Similarly, linguists have
-2548G>A LEP Polymorphism Is Positively Associated with Increased Leptin and Glucose Levels in Obese Saudi Patients Irrespective of Blood Pressure Status

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6–8.4), p = 0.001; 3.2 (1.2–8.6), p = 0.03; 3.5 (1.6–7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2–3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.
Novel insights based on the plasticity of γδ T cells in the tumor microenvironment

γδ T cells express unique T cell receptor (TCR) γ and TCR δ chains, with structural and functional heterogeneity. Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. Their advantage lies in the ability to perceive tumors with a low mutation load, thus establishing the first line of defense against pathogens. Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. Additionally, these cells show highly flexible and dynamic plasticity and are extremely easily polarized into regulatory phenotypes. This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. Effective immunity of the body is often manifested by counterbalance under mutual restriction. Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. It is hoped that the host immune status can be accurately predicted and gradually advance γδ T cell precise individualized medicine.
Effect of ITPA Polymorphism on Adverse Drug Reactions of 6-Mercaptopurine in Pediatric Patients with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

6-Mercaptopurine (6-MP) is a cornerstone of the maintenance regimen for pediatric acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphatase (ITPA) is considered a candidate pharmacogenetic marker that may affect metabolism and 6-MP-induced toxicities; however, the findings are inconsistent. Therefore, we attempted to evaluate the effect of ITPA 94C>A polymorphism on 6-MP-induced hematological toxicity and hepatotoxicity through a systematic review and meta-analysis. A literature search for qualifying studies was conducted using the PubMed, Web of Science, and Embase databases until October 2021. Overall, 10 eligible studies with 1072 pediatric ALL patients were included in this meta-analysis. The results indicated that ITPA 94C>A was significantly associated with 6-MP-induced neutropenia (OR 2.38, 95% CI: 1.56–3.62; p = 0.005) and hepatotoxicity (OR 1.98, 95% CI: 1.32–2.95; p = 0.0009); however, no significant association was found between the ITPA 94C>A variant and 6-MP-induced leukopenia (OR 1.75, 95% CI: 0.74–4.12; p = 0.20). This meta-analysis demonstrated that ITPA 94C>A polymorphism could affect 6-MP-induced toxicities. Our findings suggested that ITPA genotyping might help predict 6-MP-induced myelosuppression and hepatotoxicity.
Casting Into The Future: Effectiveness of a 3D-Printed Fishhook Removal Task Trainer

While participation in both recreational and commercial fisheries is common, it is not risk-free. Puncture wounds caused by fishhooks are commonly incurred by people who fish recreationally and commercially. Despite literature that details the challenges of treating fishhook injuries and specific techniques for fishhook removal, only a single publication focuses on teaching fishhook removal techniques to medical trainees and staff physicians. The aim of this technical report is to investigate the efficacy of using a 3D-printed task trainer for simulating and teaching fishhook removal techniques. To facilitate this, the 3D-printed Fishhook Emergency Removal Simulator (FISH-ER 3D) was designed by the Memorial University of Newfoundland (MUN) MED 3D Network and satellite research partner, Carbonear Institute for Rural Reach and Innovation by the Sea (CIRRIS). A sample of 22 medical residents and staff physicians were asked to evaluate the task trainer by way of a practical session, which was then followed by an evaluation survey. The overall realism of the 3D-printed task trainer components was ranked as “realistic” or “very realistic” by 86% of the evaluators. The majority of evaluators rated acquiring and performing various fishhook removal techniques using the simulator as “easy” or “somewhat easy”. Most evaluators found that using the task trainer increased user competence and confidence with fishhook removal techniques, and 100% of the evaluators rated the task trainer as a “very valuable” or “valuable” training tool. The results of this report demonstrate support for the FISH-ER 3D as an efficacious simulator for building competence in fishhook removal techniques.
The self as a stress-regulating factor: Core self-evaluations moderate the job demands-emotional exhaustion relationship

Abstract We examined whether core self-evaluations (CSE) are negatively associated with perceived job demands and emotional exhaustion (EE) (differential exposure hypothesis), as well as decrease the relationship between job demands and EE (differential reactivity hypothesis, DRH). This study is the first to examine the DRH with EE as strain outcome. Employees of diverse backgrounds (N = 296) completed a survey measuring each variable. Results from conditional process analyses corroborate both hypotheses. The more employees had high CSE (1) the less they perceived high job demands, (2) the less they had exhaustion symptoms, and (3) the less job demands were associated with exhaustion. Accordingly, CSE is a personal protective resource that must be taken into account in burnout-related interventions (e.g., using coaching practices tailored to favor high CSE).
Theoretical Investigation on the Hydrogen Evolution, Oxygen Evolution, and Oxygen Reduction Reactions Performances of Two-Dimensional Metal-Organic Frameworks Fe3(C2X)12 (X = NH, O, S)

Two-dimensional metal-organic frameworks (2D MOFs) inherently consisting of metal entities and ligands are promising single-atom catalysts (SACs) for electrocatalytic chemical reactions. Three 2D Fe-MOFs with NH, O, and S ligands were designed using density functional theory calculations, and their feasibility as SACs for hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) was investigated. The NH, O, and S ligands can be used to control electronic structures and catalysis performance in 2D Fe-MOF monolayers by tuning charge redistribution. The results confirm the Sabatier principle, which states that an ideal catalyst should provide reasonable adsorption energies for all reaction species. The 2D Fe-MOF nanomaterials may render highly-efficient HER, OER, and ORR by tuning the ligands. Therefore, we believe that this study will serve as a guide for developing of 2D MOF-based SACs for water splitting, fuel cells, and metal-air batteries.