Miracle-dz/UniFAR-FTUs huggingface dataset:
The genetic legacy of the Yaghnobis: A witness of an ancient Eurasian ancestry in the historically reshuffled central Asian gene pool.

OBJECTIVES The Yaghnobis are an ethno-linguistic minority historically settled along the Yaghnob River in the Upper-Zarafshan Valley in Tajikistan. They speak a language of Old Sogdian origin, which is the only present-day witness of the Lingua Franca used along the Silk Road in Late Antiquity. The aim of this study was to reconstruct the genetic history of this community in order to shed light on its isolation and genetic ancestry within the Euro-Asiatic context. MATERIALS AND METHODS A total of 100 DNA samples were collected in the Yaghnob and Matcha Valleys during several expeditions and their mitochondrial, Y-chromosome and autosomal genome-wide variation were compared with that from a large set of modern and ancient Euro-Asiatic samples. RESULTS Findings from uniparental markers highlighted the long-term isolation of the Yaghnobis. Mitochondrial DNA ancestry traced an ancient link with Middle Eastern populations, whereas Y-chromosome legacy showed more tight relationships with Central Asians. Admixture, outgroup-f3, and D-statistics computed on autosomal variation corroborated Y-chromosome evidence, pointing respectively to low Anatolian Neolithic and high Steppe ancestry proportions in Yaghnobis, and to their closer affinity with Tajiks than to Iranians. DISCUSSION Although the Yaghnobis do not show evident signs of recent admixture, they could be considered a modern proxy for the source of gene flow for many Central Asian and Middle Eastern groups. Accordingly, they seem to retain a peculiar genomic ancestry probably ascribable to an ancient gene pool originally wide spread across a vast area and subsequently reshuffled by distinct demographic events occurred in Middle East and Central Asia.
Reliability of Zephyr Bioharness and Fitbit Charge Measures of Heart Rate and Activity at Rest, During the Modified Canadian Aerobic Fitness Test, and Recovery

Abstract Nazari, G, MacDermid, JC, Sinden, KE, Richardson, J, and Tang, A. Reliability of Zephyr Bioharness and Fitbit Charge measures of heart rate and activity at rest, during the modified Canadian Aerobic Fitness Test, and recovery. J Strength Cond Res 33(2): 559–571, 2019—The purpose of this study was to determine the intrasession and intersession reliability of Zephyr Bioharness (ZB) and Fitbit Charge variables in both healthy men and women at rest, during the Modified Canadian Aerobic Fitness Test (mCAFT), and throughout recovery. Stratified convenience and snowball sampling were used to recruit 60 participants (30 women, 48 ± 15 years) and (30 men, 48 ± 15 years) from McMaster University student, staff, and faculty population. At rest, intrasession average heart rate (b·min−1). Intraclass correlation coefficients (ICCs) and Standard Error of Measurement [SEM] for Zephyr ranged from (0.94–0.97) [1.17–1.70] to (0.92–0.97) [1.45–2.10] for Fitbit Charge. During the mCAFT, the Zephyr ICCs and (SEM) ranged from 0.31–0.99 (1.28–8.10) to 0.45–0.99 (1.45–8.71) for the Fitbit Charge. Throughout the recovery, the ICCs and (SEM) ranged from 0.44–0.98 (1.26–10.47) to 0.45–0.98 (1.15–11.90) for Zephyr and Fitbit devices, respectively. At rest, intersession ICCs (SEM) for Zephyr and Fitbit ranged from 0.90–0.94 (1.73–2.37) to 0.88–0.94 (1.83–2.67), respectively. At mCAFT, the Zephyr ICCs (SEM) ranged from 0.91–0.97 (3.12–4.64) to 0.85–0.98 (3.28–4.88) for the Fitbit. Throughout the recovery, the ICCs (SEM) ranged from 0.93–0.97 (2.65–4.66) to 0.76–0.91 (3.17–4.67) for Zephyr and Fitbit devices, respectively. To conclude, both the ZB and Fitbit Charge devices demonstrated excellent reliability measures throughout the 3 phases. The findings from our study add to the existing pool of literature regarding the reliability parameters of wearable devices and suggest that stable and consistent measures of heart rate and physical activity can be obtained using ZB and Fitbit Charge devices among healthy male and female participants at rest, during a standardized submaximal fitness test (mCAFT), and throughout recovery.
Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy

Abstract Mitochondrial dysfunction and oxidative stress are underlying contributors to Parkinson’s disease (PD). The reduction of aberrant proteins and dysfunctional mitochondria through constitutive autophagy is essential for neuronal survival. We investigated the neuroprotective effects of the natural red wine extract, resveratrol, on the Complex I inhibitor, rotenone-induced oxidative stress SH-SY5Y cellular model. With rotenone exposure, cellular reactive oxygen species (ROS), apoptosis and cell death increased at both 6 and 18 h; at the same time, mitochondrial membrane potential (ΔΨm) and the balance of mitochondrial dynamic proteins were disrupted, resulting with fragmented mitochondria. Rotenone was also noted to elevate autophagy initiation but downregulate the autophagy flux. Pretreatment with resveratrol to rotenone exposed cells lowered cellular ROS, apoptosis, and increased survival rates. Resveratrol administration also recovered rotenone induced ΔΨm, mitochondria dynamics alteration, and elongated fragmented mitochondria. Both autophagic induction and autophagic flux were enhanced with resveratrol pre-treatment which is compatible with cellular survival. The mitogen-activated protein kinase (MEK) inhibitor, U0126, abolished the rescuing effect of resveratrol on rotenone treated neurons through the inhibition of autophagy flux. Thus, our work implies that the neuroprotective effect of resveratrol works in part through modulation of mitochondria dynamics and upregulating autophagic flux via the MEK/extracellular signal-regulated kinase (ERK) signalling pathway.
Feasibility and initial efficacy of project-based treatment for people with ABI.

BACKGROUND Communication impairments are common and pervasive for people a long time following acquired brain injury (ABI). These impairments have a significant impact on a person's quality of life (QOL) post-injury. Project-based treatment is a treatment approach that could have an impact on communication skills and QOL for people with ABI a long-term post-injury. This treatment is embedded in a context of meaningful activities chosen by people with ABI, whereby, as a group, they work collaboratively to achieve a tangible end product. AIMS To evaluate the feasibility and initial efficacy of project-based treatment on improving the communication skills and QOL for people with ABI. METHODS & PROCEDURES An exploratory controlled trial with alternate allocation of groups, and follow-up at 6-8 weeks, was completed. Twenty-one people with chronic ABI were recruited in groups of two to three from community settings, allocated to either a TREATMENT (n = 11) or WAITLIST group (n = 10). Participants attended a 20-h group-based treatment over 6 weeks where they worked towards achieving a project that helped others. To determine feasibility, four criteria were used: demand, implementation, practicality and acceptability. A range of communication and QOL outcomes was used to determine a fifth feasibility criterion, initial efficacy. Some of these criteria were additionally used to evaluate the feasibility of the outcomes. OUTCOMES & RESULTS All participants received the treatment as allocated with high attendance and no dropouts. The treatment was feasible to deliver as intended and was highly acceptable to participants. Medium and large effect sizes were found from pre- to post-treatment, and from pre-treatment to follow-up for measures of conversation, perceived communicative ability and QOL. CONCLUSIONS & IMPLICATIONS Project-based treatment is feasible with indications of initial efficacy for both communication skills and QOL. The treatment provides a promising new approach for improving communication skills and QOL in people with chronic acquired brain injuries in the community setting.
Providing Assistance for Older Adult Financial Exploitation Victims: Implications for Clinical Gerontologists

ABSTRACT Background and Objective: Despite the growth of financial exploitation research in the past decade, almost none has focused on older urban adults, and especially urban African Americans. The Success After Financial Exploitation (SAFE) program provides individual financial coaching to older urban adults. Methods: We use community education, delivered separately to older adults and to the professionals who serve them, to raise awareness about financial exploitation (FE) and to motivate referrals for financial coaching. This paper describes the program and methodology, and uses case examples and preliminary research to investigate the intersection of FE and physical and mental health functioning. Results: SAFE participants were able to repair their credit scores, reduce new financial burdens, and even recover monies they had lost due to FE. Case examples illustrate how financial scams and identity theft impacts urban older adults. Participants were assessed prior to the provision of services, and SAFE participants performed poorer on executive functioning tasks than participants in the control group. They also reported more physical health problems and anxiety and depressive symptoms. SAFE participants also had significantly higher risk scores on a financial decision-making scale. Conclusion: Study findings advance our understanding of the impacts of FE on cognitive functioning, mental health, and financial decision-making. Clinical Implications: Clinicians need to be more attuned to the financial health of their older clients, who, if they are struggling with financial exploitation, may also be suffering from problems with cognitive functioning and physical and mental health.
Improving Dietary Protein Quality Reduces the Negative Effects of Physical Inactivity on Body Composition and Muscle Function.

Background Brief periods of physical inactivity can compromise muscle health. Increasing dietary protein intake is potentially beneficial but complicated by difficulties reconciling anabolic potential with a realistic food volume and energy intake. We sought to determine whether increasing dietary protein quality could reduce the negative effects of physical inactivity. Methods Twenty healthy, older men and women completed 7 days of bed rest followed by 5 days of rehabilitation. Volunteers consumed a mixed macronutrient diet (MIXED: N = 10; 68 ± 2 years; 1,722 ± 29 kcal/day; 0.97 ± 0.01 g protein/kg/day) or an isoenergetic, whey-augmented, higher protein quality diet (WHEY: N = 10; 69 ± 1 years; 1,706 ± 23 kcal/day; 0.90 ± 0.01 g protein/kg/day). Outcomes included body composition, blood glucose, insulin, and a battery of physical function tests. Results During bed rest, both groups experienced a 20% reduction in knee extension peak torque (p < .05). The WHEY diet partially protected leg lean mass (-1,035 vs. -680 ± 138 g, MIXED vs. WHEY; p = .08) and contributed to a greater loss of body fat (-90 vs. -233 ± 152 g, MIXED vs. WHEY; p < .05). Following rehabilitation, knee extension peak torque in the WHEY group fully recovered (-10.0 vs. 2.2 ± 4.1 Nm, MIXED vs. WHEY; p = .05). Blood glucose, insulin, aerobic capacity, and Short Physical Performance Battery (SPPB) changes were similar in both dietary conditions (p > .05). Conclusions Improving protein quality without increasing total energy intake has the potential to partially counter some of the negative effects of bed rest in older adults.
Synthesis and characterization of rGO-graft-poly(trimethylene carbonate) for nerve regeneration conduits

Graphene-graft-polymer has been used to improve the compatibility between graphene and a polymer matrix, and to further enhance electrical, mechanical and biological properties of polymer/graphene composites. In this study, poly(trimethylene carbonate) (PTMC) was successfully grafted onto graphene surface via ‘grafting from’ method. Reduced graphene oxide (rGO) initiator was synthesized by azido ethanol reaction with graphene oxide (GO) at high temperature. This resulted in thermal reduction of the GO and stable hydroxyl groups on the graphene surface. Subsequently, rGO initiator was used for the ring-opening polymerization of TMC monomer. rGO-graft-PTMC composites with PTMC molecular weights of 430, 480, 2150 and 7030 g mol−1 were successfully synthesized using different amounts of TMC. Single layer graphene nanosheets remained after graft polymerization by this method. rGO-graft-PTMC dispersions in chloroform were stable. The rGO-graft-PTMC composites with PTMC molecular weights of 430–7030 g mol−1 had electrical conductivities ranging from 0.2 to 0.016 s cm−1. To investigate the biocompatibility of rGO-graft-PTMC, PTMC-based films containing rGO-graft-PTMC were prepared and used in cell culturing experiments. The composite films showed good biocompatibility with PC12 neuronal cells. It is concluded that rGO-graft-PTMC composite is a promising material for the preparation of nerve regeneration conduits.
Prenatal stress decreases sperm quality, mature follicles and fertility in rats

ABSTRACT Prenatal stress disrupts reproductive function in females and males. These alterations have primarily been related to maternal corticosteroid fetal programming due to the stress response, affecting the fetus and causing long-lasting effects. The aim of this study was to investigate the influence of prenatal stress on male and female fertility. Dams were exposed to stress by immersion in cold water twice a day for the last week of gestation (days 15–21). In the adulthood, sperm quality, mature follicles, sexual hormones and fertility were assessed in female and male progeny. The results in prenatally stressed females showed lower body weight, longer estrous cycles, lower estradiol and progesterone, and lower number of pups. In prenatally stressed males, lower body weight, increased testicular cell death, as well as decreased testosterone levels, sperm quality, and fertility were observed. Aside from these effects, corticosterone levels in prenatally stressed males and females increased. These results show that prenatal stress can markedly influence infertility in adult female and male progeny. Abbreviations: 3β-HSD: 3β hydroxysteroid dehydrogenase; CRH: corticotropin releasing hormone; DEX: dexamethasone; ERα: estrogen receptor alpha; H-E: hematoxylin-eosine; HPA: hypothalamus-pituitary-adrenal; KISS: Kisspeptin; ORW: ovarian relative weight; PBS: phosphates; PS: prenatally stressed; PRW: prostatic relative weight; ROS: reactive oxygen species; SRW: seminal relative weight; TdT: terminal deoxynucleotidyl transferase; TUNEL: terminal deoxynucleotidyl transferase dUTP Nick-end labelling; TRW: testicular relative weight; URW: uterine relative weight
Upregulation of miR-183-5p predicts worse survival in patients with renal cell cancer after surgery.

OBJECTIVE Renal cell carcinoma (RCC) is one of the most common genitourinary cancers, and advanced RCC usually leads to poor prognosis. Therefore, identifying novel biomarkers for predicting the progression and prognosis of RCC is essential. The present study aims to evaluate the clinical value of miR-183-5p in RCC development and prognosis after surgery. MATERIALS AND METHODS We enrolled a total of 284 patients who received partial or radical nephrectomy from April 2003 to May 2013 at a single institution. The clinical and pathological characteristics of the patients were collected, including age, gender, tumor size, tumor stage, as well as follow-up information. The expression levels of miR-183-5p of all the patients were calculated from FFPE specimens. Cox regression analyses were performed to approve the effect of miR-183-5p expression on patient survival. Kaplan-Meier method was used to analyze the patient survival curves. RESULTS After controlling for gender, age, tumor size and tumor stage in the multivariate analysis, we found that high expression of miR-183-5p was independently associated lower overall survival (HR = 0.550, 95% CI = 0.364-0.832, p= 0.005). The Kaplan-Meier analysis also showed that patients with high expression of miR-183-5p had a significantly poor prognosis (p= 0.006). These results was verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA). CONCLUSION Our results indicated that the high miR-183-5p expression is an independent factor for predicting RCC's worse prognosis.
T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy

Across clinical trials, T cell expansion and persistence following adoptive cell transfer (ACT) have correlated with superior patient outcomes. Herein, we undertook a pan-cancer analysis to identify actionable ligand-receptor pairs capable of compromising T cell durability following ACT. We discovered that FASLG, the gene encoding the apoptosis-inducing ligand FasL, is overexpressed within the majority of human tumor microenvironments (TMEs). Further, we uncovered that Fas, the receptor for FasL, is highly expressed on patient-derived T cells used for clinical ACT. We hypothesized that a cognate Fas-FasL interaction within the TME might limit both T cell persistence and antitumor efficacy. We discovered that genetic engineering of Fas variants impaired in the ability to bind FADD functioned as dominant negative receptors (DNRs), preventing FasL-induced apoptosis in Fas-competent T cells. T cells coengineered with a Fas DNR and either a T cell receptor or chimeric antigen receptor exhibited enhanced persistence following ACT, resulting in superior antitumor efficacy against established solid and hematologic cancers. Despite increased longevity, Fas DNR–engineered T cells did not undergo aberrant expansion or mediate autoimmunity. Thus, T cell–intrinsic disruption of Fas signaling through genetic engineering represents a potentially universal strategy to enhance ACT efficacy across a broad range of human malignancies.
Effectiveness of direct contact intervention with people with mental illness to reduce stigma in nursing students

People with mental illnesses are at a higher risk than the general population of suffering from somatic diseases. However, they receive less attention from healthcare services. Some studies have indicated that this situation can be partially explained by the stigmatizing attitudes of health professionals, including nurses. With the objective to improve future nursing professionals' attitudes towards people with mental illnesses, an intervention involving direct contact with people who had lived experience with mental illnesses was designed and its effectiveness was measured. It consisted of a single 90-min session involving a mental health professional, a person with a mental illness, and a family member of someone with a mental illness. The intervention was based on a structured script where they described their experiences with the illness and their history of recovery, and then, they had a discussion with the attendees. The effectiveness of this approach was measured through a quasi-experimental study with a pretest-post-test design. The differences in the scores obtained in the AQ-27-E questionnaire before and after the intervention indicated that there was a decrease in fear, feelings of danger, avoidance, segregation, and coercive attitudes, while positive feelings increased, including a tendency to help and compassion. These results are important for clinical practice because this intervention could improve the quality of care provided to people with mental illnesses.
Investigation of the skin microbiome: swabs vs. biopsies

Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota.
Genomic profiling of combined hepatocellular‐cholangiocarcinoma reveals similar genetics to hepatocellular carcinoma

Combined hepatocellular‐cholangiocarcinomas (CHC) are mixed tumours with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components. CHC prognosis is similar to intrahepatic CC (ICC) and worse than HCC; staging and treatment generally follow ICC algorithms. However, the molecular biology of CHC remains poorly characterised. We performed capture‐based next‐generation sequencing of 20 CHC and, for comparison, 10 ICC arising in cirrhosis. Intratumour heterogeneity was assessed by separately sequencing the HCC and CC components of nine CHC. CHC demonstrated molecular profiles similar to HCC, even in the CC component. CHC harboured recurrent alterations in TERT (80%), TP53 (80%), cell cycle genes (40%; CCND1, CCNE1, CDKN2A), receptor tyrosine kinase/Ras/PI3‐kinase pathway genes (55%; MET, ERBB2, KRAS, PTEN), chromatin regulators (20%; ARID1A, ARID2) and Wnt pathway genes (20%; CTNNB1, AXIN, APC). No CHC had alterations in IDH1, IDH2, FGFR2 or BAP1, genes typically mutated in ICC. TERT promoter mutations were consistently identified in both HCC and CC components, supporting TERT alteration as an early event in CHC evolution. TP53 mutations were present in both components in slightly over half the TP53‐altered cases. By contrast, focal amplifications of CCND1, MET and ERRB2, as well as Wnt pathway alterations, were most often exclusive to one component, suggesting that these are late events in CHC evolution. ICC in cirrhosis demonstrated alterations similar to ICC in non‐cirrhotic liver, including in IDH1 or IDH2 (30%), CDKN2A (40%), FGFR2 (20%), PBRM1 (20%), ARID1A (10%) and BAP1 (10%). TERT promoter and TP53 mutation were present in only one ICC each. Our data demonstrate that CHC genetics are distinct from ICC (even in cirrhosis) and similar to HCC, which has diagnostic utility and implications for treatment. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Comparative analyses identify genomic features potentially involved in the evolution of birds-of-paradise

Abstract The diverse array of phenotypes and courtship displays exhibited by birds-of-paradise have long fascinated scientists and nonscientists alike. Remarkably, almost nothing is known about the genomics of this iconic radiation. There are 41 species in 16 genera currently recognized within the birds-of-paradise family (Paradisaeidae), most of which are endemic to the island of New Guinea. In this study, we sequenced genomes of representatives from all five major clades within this family to characterize genomic changes that may have played a role in the evolution of the group's extensive phenotypic diversity. We found genes important for coloration, morphology, and feather and eye development to be under positive selection. In birds-of-paradise with complex lekking systems and strong sexual dimorphism, the core birds-of-paradise, we found Gene Ontology categories for “startle response” and “olfactory receptor activity” to be enriched among the gene families expanding significantly faster compared to the other birds in our study. Furthermore, we found novel families of retrovirus-like retrotransposons active in all three de novo genomes since the early diversification of the birds-of-paradise group, which might have played a role in the evolution of this fascinating group of birds.