Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Functional and Structural Connectivity of the Human Hand-Knob Supported by Intraoperative Findings

Fine motor skills rely on the control of hand muscles exerted by a region of primary motor cortex (M1) that has been extensively investigated in monkeys. Although neuroimaging enables the exploration of this system also in humans, indirect measurements of brain activity prevent causal definitions of hand motor representations, which can be achieved using data obtained during brain mapping in tumor patients. High-frequency direct electrical stimulation delivered at rest (HF-DES-Rest) on the hand-knob region of the precentral gyrus has identified two sectors showing differences in cortical excitability. Using quantitative analysis of motor output elicited with HF DES-Rest, we characterized two sectors based on their excitability, higher in the posterior and lower in the anterior sector. We studied whether the different cortical excitability of these two regions reflected differences in functional connectivity (FC) and structural connectivity (SC). Using healthy adults from the Human Connectome Project (HCP), we computed FC and SC of the anterior and the posterior hand-knob sectors identified within a large cohort of patients. The comparison of FC of the two seeds showed that the anterior hand-knob, relative to the posterior hand-knob, showed stronger functional connections with a bilateral set of parietofrontal areas responsible for integrating perceptual and cognitive hand-related sensorimotor processes necessary for goal-related actions. This was reflected in different patterns of SC between the two sectors. Our results suggest that the human hand-knob is a functionally and structurally heterogeneous region organized along a motor-cognitive gradient. SIGNIFICANCE STATEMENT The capability to perform complex manipulative tasks is one of the major characteristics of primates and relies on the fine control of hand muscles exerted by a highly specialized region of the precentral gyrus, often termed the “hand-knob” sector. Using intraoperative brain mapping, we identify two hand-knob sectors (posterior and anterior) characterized by differences in cortical excitability. Based on resting-state functional connectivity (FC) and tractography in healthy subjects, we show that posterior and anterior hand-knob sectors differ in their functional connectivity (FC) and structural connectivity (SC) with frontoparietal regions. Thus, anteroposterior differences in cortical excitability are paralleled by differences in FC and SC that likely reflect a motor (posterior) to cognitive (anterior) organization of this cortical region.
A size‐adaptive 32‐channel array coil for awake infant neuroimaging at 3 Tesla MRI

Functional magnetic resonance imaging (fMRI) during infancy poses challenges due to practical, methodological, and analytical considerations. The aim of this study was to implement a hardware‐related approach to increase subject compliance for fMRI involving awake infants. To accomplish this, we designed, constructed, and evaluated an adaptive 32‐channel array coil.
Global climate change, diet, and the complex relationship between human host and microbiome: Towards an integrated picture

Dietary changes can alter the human microbiome with potential detrimental consequences for health. Given that environment, health, and evolution are interconnected, we ask: Could diet‐driven microbiome perturbations have consequences that extend beyond their immediate impact on human health? We address this question in the context of the urgent health challenges posed by global climate change. Drawing on recent studies, we propose that not only can diet‐driven microbiome changes lead to dysbiosis, they can also shape life‐history traits and fuel human evolution. We posit that dietary shifts prompt mismatched microbiome‐host genetics configurations that modulate human longevity and reproductive success. These mismatches can also induce a heritable intra‐holobiont stress response, which encourages the holobiont to re‐establish equilibrium within the changed nutritional environment. Thus, while mismatches between climate change‐related genetic and epigenetic configurations within the holobiont increase the risk and severity of diseases, they may also affect life‐history traits and facilitate adaptive responses. These propositions form a framework that can help systematize and address climate‐related dietary challenges for policy and health interventions.
Ternary Zn–Mn–Sn alloy electrodeposition from an ionic liquid based on choline chloride

Zinc–manganese–tin (Zn–Mn–Sn) ternary alloys have been successfully prepared, for the first time, by electrochemical deposition from a choline chloride-based ionic liquid. The influence of electrolyte composition and electrodeposition potential on the ternary Zn–Mn–Sn alloy surface morphology, composition and corrosion resistance were investigated and contrasted with the characteristics of binary Zn–Mn and Zn–Sn electrodeposits. It was found that the composition of the plating bath and deposition potential have a significant influence on the alloy content, morphology and corrosion properties of the Zn–Mn–Sn alloys. The content of Sn in the ternary alloy increased with a decrease in electrodeposition potential and an increase in concentration of Sn2+ in the electrolyte. The corrosion studies showed that the Zn–Mn–Sn alloys have a synergistic property combining the barrier behaviour afforded by Sn and the strong passive behaviour of Mn, while the sacrificial characteristics are still preserved.
Neuronal Mechanisms Underlying Opioid Induced Respiratory Depression: Our Current Understanding.

Opioid induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within the U.S., the rate of death from opioid abuse since the early 1990's has grown disproportionally, prompting the classification as a nationwide "epidemic". Since this time, we have begun to unravel many fundamental cellular and systems-level mechanisms associated with opioid-related death. However, factors such as individual vulnerability, neuromodulatory compensation, and redundancy of opioid effects across central and peripheral nervous systems have created a barrier to a concise, integrative view of OIRD. Within this review, we bring together multiple perspectives in the field of OIRD to create an overarching viewpoint of what we know, and where we view this essential topic of research going forward into the future.
Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study.

BACKGROUND An investigation for the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted. METHODS In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the eGFR with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer, and driving) were investigated in 329,758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567,460). The findings were replicated with the 321,024 UK white British Biobank participants in the allele-score-based one-sample MR. RESULTS A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR. CONCLUSION Physical activity and television watching causally affect kidney function in the general population.
Development and validation of 3‐CpG methylation prognostic signature based on different survival indicators for colorectal cancer

Abnormal DNA methylation is considered a vital hallmark to regulate gene expression and influence the development and progression of colorectal cancer (CRC). Although CRC‐related methylation prognostic models have been developed, their clinical application is limited due to the lack of external validation and extension to other survival evaluation indicators. Therefore, this study aimed to develop and validate novel methylation prognostic models correlated with different survival indicators for individualized prognosis prediction for CRC patients. The prognostic‐related CpG sites of methylation‐driven genes screened by the MethylMix algorithm were identified and validated in The Cancer Genome Atlas (TCGA) CRC methylation data and our methylation data. The prognostic models correlated with different survival evaluation indicators (overall survival [OS] and disease‐free survival [DFS]) were developed and validated in the TCGA CRC dataset (N = 376) and our independent CRC dataset (N = 227). We utilized the combination of selected 3‐CpG methylation sites in three genes (DAPP1, FAM3D, and PIGR) to construct a prognostic risk‐score model. In the training dataset, Kaplan–Meier survival analysis demonstrated that high‐risk patients had significantly poorer survival than low‐risk patients (pOS = .0014; pDFS < .001). Then, the 3‐CpG methylation signature was successfully validated as an independent predictor in the testing data set (pOS = .016; pDFS = .016). A prognostic nomogram was constructed and validated. Additionally, mediation analysis revealed the direct effect of the methylation signature on CRC prognosis (pOS = 9.149e−06; pDFS = .001). In summary, our study revealed that the 3‐CpG methylation signature might be a potential prognostic indicator to facilitate individualized survival prediction for CRC patients.
Selective inhibition of JAK3 signaling is sufficient to reverse alopecia areata

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) are key intracellular mediators in the signal transduction of many cytokines and growth factors. Common γ chain cytokines and interferon-γ that use the JAK/STAT pathway to induce biological responses have been implicated in the pathogenesis of alopecia areata (AA), a T cell–mediated autoimmune disease of the hair follicle. We previously showed that therapeutic targeting of JAK/STAT pathways using the first-generation JAK1/2 inhibitor, ruxolitinib, and the pan-JAK inhibitor, tofacitinib, was highly effective in the treatment of human AA, as well as prevention and reversal of AA in the C3H/HeJ mouse model. To better define the role of individual JAKs in the pathogenesis of AA, in this study, we tested and compared the efficacy of several next-generation JAK-selective inhibitors in the C3H/HeJ mouse model of AA, using both systemic and topical delivery. We found that JAK1-selective inhibitors as well as JAK3-selective inhibitors robustly induced hair regrowth and decreased AA-associated inflammation, whereas several JAK2-selective inhibitors failed to restore hair growth in treated C3H/HeJ mice with AA. Unlike JAK1, which is broadly expressed in many tissues, JAK3 expression is largely restricted to hematopoietic cells. Our study demonstrates inhibiting JAK3 signaling is sufficient to prevent and reverse disease in the preclinical model of AA.
The Combination of Venetoclax and Ixazomib Selectively and Efficiently Kills HIV-Infected Cell Lines but Has Unacceptable Toxicity in Primary Cell Models

A cure for HIV would require eliminating cells that contain the virus in a latent form from the body. Current antiretroviral medications are unable to rid the body of latently infected cells. Here, we show that a combination of investigational agents—ixazomib plus venetoclax—which reactivate latent virus and predispose infected cells to apoptosis may reduce latent virus in a T cell model, but at the expense of nonspecific toxicity in primary cells. ABSTRACT The antiapoptotic protein BCL2 inhibits death of HIV-infected cells. Previously, we showed that the BCL2 inhibitor venetoclax selectively kills acutely HIV-infected cells and reduces HIV DNA in latently infected CD4 T cells ex vivo after reactivation with anti-CD3/anti-CD28. However, there is a need to identify a combination therapy with venetoclax and a clinically relevant latency reversal agent. Ixazomib is an oral proteasome inhibitor which we have shown reactivates latent HIV and predisposes reactivated cells to cell death. Here, we determined that the combination of venetoclax and ixazomib kills more latently HIV-infected cells and leads to greater reduction in HIV replication than either treatment alone in vitro in a T cell model. However, combination treatment of ex vivo CD4 T cells from antiretroviral therapy (ART)-suppressed, HIV-positive participants resulted in unanticipated and unacceptable nonspecific toxicity in primary cells. Therefore, while we show proof of concept that multiple agents can enhance selective killing of HIV-infected cells, the combination of venetoclax and ixazomib has unacceptable toxicity in primary cells, and so further investigation is needed to identify a clinically relevant latency reversal agent to combine with venetoclax as a novel strategy to reduce the size of the HIV reservoir. IMPORTANCE A cure for HIV would require eliminating cells that contain the virus in a latent form from the body. Current antiretroviral medications are unable to rid the body of latently infected cells. Here, we show that a combination of investigational agents—ixazomib plus venetoclax—which reactivate latent virus and predispose infected cells to apoptosis may reduce latent virus in a T cell model, but at the expense of nonspecific toxicity in primary cells.
Exploring change in cognitive-behavioral therapy for generalized anxiety disorder-A two-arms ABAB crossed-therapist randomized clinical implementation trial.

OBJECTIVE There is little evidence-based knowledge of how psychotherapists should handle both sudden gains and more gradual session-by-session changes, either in general or in individuals suffering from generalized anxiety disorder. METHODS Using an ABAB crossed-therapist randomized clinical implementation trial design (N = 80 patients and 20 therapists), we contrasted a Prolonged Focus on Change (PFC, N = 40) implementation with a State-Of-The-Art (SOTA, N = 40) implementation. Both implementations were based on a widely used cognitive behavioral therapy approach (Mastery of your Anxiety and Worry package) with the only difference that in the PFC implementation, the therapists were instructed to systematically explore eventual changes at the beginning of the therapy sessions. RESULTS Based on a 3-level hierarchical linear model, PFC implementation showed faster symptom reduction in worry over therapy (i.e., linear change) and a decelerated (quadratic) change until 12-month follow-up in comparison to the SOTA implementation. CONCLUSION These findings provide clinically useful information about potential short-term and long-term effects of exploring occurring change in GAD populations. Randomized clinical implementation trial designs are a step forward allowing to experimentally investigate basic psychotherapeutic strategies in process-based psychotherapy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Assessment of risk of malignancy by application of the proposed Sydney system for classification and reporting lymph node cytopathology

Fine‐needle aspiration cytology (FNAC) is one of the most commonly used techniques for evaluating lymphadenopathy. Recently, the Sydney system was proposed for assessing the performance, classification, and reporting of lymph node (LN) cytopathology. The present study was conducted to assess the risk of malignancy associated with each of the diagnostic categories of the proposed Sydney system.
eHealth Literacy of Medical and Health Science Students and Factors Affecting eHealth Literacy in an Ethiopian University: A Cross-Sectional Study

Abstract Background eHealth literacy is individual's ability to look for, understand, and evaluate health information from electronic sources. Integrating eHealth literacy to the health system could help lower health care costs and ensure health equity. Despite its importance, the eHealth literacy level in Ethiopia has not been studied on medical and health science students, who are important parties in the health system. Understanding their level of eHealth literacy augments practice of health care, efficiency in education, and use of eHealth technologies. Objective This research study aims to determine eHealth literacy level and identify its associated factors among medical and health science students in University of Gondar (UoG). Methods An institution-based cross-sectional study was conducted from March to May 2019 among undergraduate medical and health science students in the UoG. Stratified multistage sampling was used. The eHealth literacy scale was used to measure eHealth literacy. A binary logistic regression model was fitted to measure association between eHealth literacy and the independent variables. Results A total of 801 students participated in this study with a 94.6% of response rate. The majority (60%) were male and previously lived-in urban areas (68%). The mean eHealth literacy score was 28.7 and 60% of the participants possessed high eHealth literacy. Using health-specific Web sites (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI]: 1.86–4.33), having higher Internet efficacy (AOR = 2.26, 95% CI: 1.56–3.26), perceived usefulness of the Internet (AOR = 3.33, 95% CI: 1.95–5.69), medical app use (AOR = 1.70, 95% CI: 1.13–2.55), being female (AOR = 1.55, 95% CI: 1.08–2.22), and being health informatics student (AOR = 2.02, 95% CI: 1.149–3.148) affect a high eHealth literacy level. Conclusion The level of eHealth literacy in this study was moderate. Using specific reputable health Web sites, using smartphone medical applications, and Internet efficacy determine eHealth literacy significantly.
Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results.

This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed or refractory classical Hodgkin lymphoma. In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2-4. In part 3, both study drugs were dosed same day for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (N=91) was 85%, with 67% achieving a complete response. At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI]: 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns.
Characterizing the cytotoxic effects and several antimicrobial phytocompounds of Argemone mexicana

Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries by indigenous communities in Mexico and Western parts of the United States. This plant has been exploited to treat a wide variety of ailments, with reported antimicrobial and antioxidant properties, as well as cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the germination conditions of A. mexicana are described and the cytotoxic activities of different parts (seeds, leaves, inner vs. outer roots) of the plant from methanol or hexane extracts are preliminarily characterized against cells of seven unique organisms. When comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Additionally, using the MTT colorimetric assay, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC (oncogene) and APC (tumor suppressor) mRNA levels help elucidate how the A. mexicana root methanol extract may be affecting colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and subsequent nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, have been identified. The roots were found to possess both phytocompounds, while the leaf lacked chelerythrine. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial and anticancer drug discovery has plateaued.
Methylphenidate use in geriatric depression: A systematic review

Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression.