Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of candidate gene FAM183A and novel pathogenic variants in known genes: High genetic heterogeneity for autosomal recessive intellectual disability

The etiology of intellectual disability (ID) is heterogeneous including a variety of genetic and environmental causes. Historically, most research has not focused on autosomal recessive ID (ARID), which is a significant cause of ID, particularly in areas where parental consanguinity is common. Identification of genetic causes allows for precision diagnosis and improved genetic counseling. We performed whole exome sequencing to 21 Turkish families, seven multiplex and 14 simplex, with nonsyndromic ID. Based on the presence of multiple affected siblings born to unaffected parents and/or shared ancestry, we consider all families as ARID. We revealed the underlying causative variants in seven families in MCPH1 (c.427dupA, p.T143Nfs*5), WDR62 (c.3406C>T, p.R1136*), ASPM (c.5219_5225delGAGGATA, p.R1740Tfs*7), RARS (c.1588A>G, p.T530A), CC2D1A (c.811delG, p.A271Pfs*30), TUSC3 (c.793C>T, p.Q265*) and ZNF335 (c.808C>T, p.R270C and c.3715C>A, p.Q1239K) previously linked with ARID. Besides ARID genes, in one family, affected male siblings were hemizygous for PQBP1 (c.459_462delAGAG, p.R153Sfs*41) and in one family the proband was female and heterozygous for X-chromosomal SLC9A6 (c.1631+1G>A) variant. Each of these variants, except for those in MCPH1 and PQBP1, have not been previously published. Additionally in one family, two affected children were homozygous for the c.377G>A (p.W126*) variant in the FAM183A, a gene not previously associated with ARID. No causative variants were found in the remaining 11 families. A wide variety of variants explain half of families with ARID. FAM183A is a promising novel candidate gene for ARID.
An experimental test of the Community Assembly by Trait Selection (CATS) model

The Community Assembly by Trait Selection (CATS) model of community assembly predicts species abundances along environmental gradients in relatively undisturbed vegetation. Here we ask whether this model, when calibrated with data from natural plant communities, can predict the abundances of five dominant grass species (Bouteloua gracilis, Elymus elymoides, Festuca arizonica, Muhlenbergia montana, and Poa fendleriana) in a greenhouse experiment that manipulated light and soil properties. To address this question, we used generalized additive models (GAMs) to model community-weighted mean (CWM) seed mass, mean Julian flowering date, and specific root length (SRL) as non-linear functions of two environmental variables (soil pH and pine basal area) in natural vegetation. The model-fitted CWM traits were then used as constraints in the CATS model to predict the relative abundance of the five grass species that were seeded in a mixture at equal densities into a 2×2 factorial experiment with soil parent material and light level as crossed factors. Light was the most important factor influencing seedling community composition, especially the abundances of Bouteloua gracilis and Poa fendleriana. The model-predicted relative abundances were significantly correlated with the observed relative abundances, and the model accurately predicted the dominant species in every treatment. P. fendleriana was correctly predicted to be the most abundant species in both shade treatments and the sun-basalt treatment, and B. gracilis was correctly predicted to be the most abundant species in the sun-limestone treatment. Our results provide experimental evidence that environmental filtering of the species pool occurs in the early stages of community assembly (including germination, emergence, and early growth), and that trait-based models calibrated with data from natural plant communities can be used to predict the outcome of the early stages of community assembly under experimental conditions.
The Effectiveness of Nutrition Education for Overweight/Obese Mother with Stunted Children (NEO-MOM) in Reducing the Double Burden of Malnutrition

(1) Background: In households experiencing the double burden of malnutrition, stunted children are in a better position for growth improvement when parents are able to direct their resources to support nutrition requirements. This study assesses the effectiveness of maternal nutrition education to reduce child stunting. (2) Methods: This was a Randomized Controlled Trial involving pairs of overweight/obese mothers with stunted children aged 2 to 5 years old in urban Indonesia. Methods: Seventy-one mother-child pairs were randomly assigned to receive either a 12-week nutrition education or printed educational materials. Mixed factorial ANOVA was used to test for between-group differences over time in relation to child’s height, weight, maternal self-efficacy, outcome expectation, and caloric intake. (3) Results: Across groups, there was a significant effect of time on child height and weight but no significant differences were observed between-groups. Maternal self-efficacy, outcome expectations in providing animal protein for the children (p-value = 0.025) and mother’s total caloric intake (p-value = 0.017) favored the intervention group over the comparison group. (4) Conclusions: The behavioral intervention produced strong improvement in maternal self-efficacy to engage in physical activity, eat fruits and vegetables and to provide children with growth-promoting animal protein, but did not significantly influence child height gain.
Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A Randomized Controlled Trial

OBJECTIVE To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODS We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35–70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). RESULTS Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo −0.08 [95% CI −0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0–0.7]; P = 0.05), despite a decrease in fat mass (MAD −2.38 kg [−3.10 to −1.66]; P < 0.001) and an increase in lean mass (MAD 2.08 kg [1.52–2.64]; P < 0.001). Testosterone therapy reduced subcutaneous (MAD −320 cm3 [−477 to −163]; P < 0.001) but not visceral abdominal adipose tissue (MAD 140 cm3 [−89 to 369]; P = 0.90). CONCLUSIONS Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.
Household structure and its association with sexual risk behaviours and sexual health outcomes: evidence from a British probability sample survey

Objectives Economic and social changes over the last 20 years have led to changes in the living situations of young people in Britain. A person’s home-life context might influence their sexual behaviour, with implications for their sexual healthcare needs; we investigated this hypothesis. Methods Britain’s third National Survey of Sexual Attitudes and Lifestyles, a probability sample survey undertaken in 2010–2012, interviewed 15 162 men and women aged 16–74 years in Britain (with 3869 aged 16–24 years). We examined household structure by gender and age group. We then focused on sexually experienced young people (aged 16–24 years), and used multivariable models to explore associations between household structure, sexual risk behaviours and sexual health outcomes, independent of confounders including age, relationship status, employment and area of residence. Results Young people were most likely to be living with parents (women 57.1% (95% CI 54.5% to 59.6%) and men 68.7% (95% CI 65.4% to 71.8%)) or non-relatives (women 10.5% (95% CI 8.5% to 12.9%) and men 12.6% (95% CI 10.1% to 15.6%)). Among the 81.3% of young people who were sexually experienced, compared with young women living with parents (reference category), young women living alone or with non-relatives had a higher likelihood of reporting ≥2 sexual partners (adjusted OR 1.54 (95% CI 1.03 to 2.31); 1.76 (95% CI 1.03 to 3.00), respectively). Women living alone were also more likely to have had unsafe sex (2.04 (95% CI 1.38 to 3.02)). Despite these differences in sexually transmitted infection (STI) risk, there was no difference in sexual healthcare-seeking behaviour. Young men and women living with partners reported lower levels of sexual risk behaviours. Conclusions Our study suggests household structure may influence the sexual behaviour of young people in Britain. Given changes in their living arrangements, the role of household structure in sexual health research should be further investigated, and also considered as a possible marker for STI risk in clinical consultations.
The meaning of learning to live with medically unexplained symptoms as narrated by patients in primary care: A phenomenological–hermeneutic study

Background Although research about medically unexplained symptoms (MUS) is extensive, problems still affect a large group of primary care patients. Most research seems to address the topic from a problem-oriented, medical perspective, and there is a lack of research addressing the topic from a perspective viewing the patient as a capable person with potential and resources to manage daily life. The aim of the present study is to describe and interpret the experiences of learning to live with MUS as narrated by patients in primary health-care settings. Methods A phenomenological–hermeneutic method was used. Narrative interviews were performed with ten patients suffering from MUS aged 24–61 years. Data were analysed in three steps: naive reading, structural analysis, and comprehensive understanding. Findings The findings revealed a learning process that is presented in two themes. The first, feeling that the symptoms overwhelm life, involved becoming restricted and dependent in daily life and losing the sense of self. The second, gaining insights and moving on, was based on subthemes describing the patients’ search for explanations, learning to take care of oneself, as well as learning to accept and becoming mindful. The findings were reflected against Antonovsky's theory of sense of coherence and Kelly's personal construct theory. Possibilities and obstacles, on an individual as well as a structural level, for promoting patients’ capacity and learning were illuminated. Conclusions Patients suffering from MUS constantly engage in a reflective process involving reasoning about and interpretation of their symptoms. Their efforts to describe their symptoms to healthcare professionals are part of this reflection and search for meaning. The role of healthcare professionals in the interpretative process should be acknowledged as a conventional and necessary care activity.
Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 1

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose–response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies.
Music structure determines heart rate variability of singers

Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Coupling of heart rate variability (HRV) to respiration is called Respiratory sinus arrhythmia (RSA). This coupling has a subjective as well as a biologically soothing effect, and it is beneficial for cardiovascular function. RSA is seen to be more marked during slow-paced breathing and at lower respiration rates (0.1 Hz and below). In this study, we investigate how singing, which is a form of guided breathing, affects HRV and RSA. The study comprises a group of healthy 18 year olds of mixed gender. The subjects are asked to; (1) hum a single tone and breathe whenever they need to; (2) sing a hymn with free, unguided breathing; and (3) sing a slow mantra and breathe solely between phrases. Heart rate (HR) is measured continuously during the study. The study design makes it possible to compare above three levels of song structure. In a separate case study, we examine five individuals performing singing tasks (1–3). We collect data with more advanced equipment, simultaneously recording HR, respiration, skin conductance and finger temperature. We show how song structure, respiration and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously. Implications concerning the effect on wellbeing and health are discussed as well as the question how this inner entrainment may affect perception and behavior.
Terlipressin for the treatment of acute variceal bleeding

Background and aim: Acute variceal bleeding (AVB) is life-threatening. We aimed to systematically review the current evidence regarding the efficacy and safety of terlipressin for AVB in liver cirrhosis. Methods: We searched the PubMed, EMBASE, and Cochrane Library databases. The reference list was also hand-searched. Using a random-effect model, we combined the data obtained according to the different time points when the events developed. Odds ratio (OR) and weighted mean difference (WMD) were calculated. Quality of evidence was evaluated by the GRADE methodology. Results: Thirty randomized controlled trials with 3344 patients were included. Compared with no vasoactive drug, terlipressin significantly improved the control of bleeding within 48 hours (OR = 2.94, P = .0008) and decreased the in-hospital mortality (OR = 0.31, P = .008). Compared with somatostatin, terlipressin had a significantly higher risk of complications (OR = 2.44, P = .04). Compared with octreotide, terlipressin had a significantly inferior control of bleeding within 24 hours (OR = 0.37, P = .007). Compared with vasopressin, terlipressin had a significantly lower risk of complications (OR = 0.15, P = .02). Compared with terlipressin combined with endoscopic variceal ligation, terlipressin alone had significantly higher 5-day treatment failure (OR = 14.46, P = .01) and transfusion requirements within 49 to 120 hours (WMD = 1.20, P = .002). No outcome was significantly different between terlipressin and sclerotherapy. Compared with balloon tamponade, terlipressin significantly decreased the 30-day rebleeding (OR = 0.05, P = .001) and transfusion requirements (WMD = −2.70, P = .02). Quality of evidence was very low to moderate. Conclusion: Our findings were in accordance with the current recommendations regarding terlipressin for the treatment of AVB in cirrhosis. However, due to low quality of evidence, further studies are recommended.
Temporal Sequence of Hearing Impairment and Cognition in the Baltimore Longitudinal Study of Aging.

Background Hearing impairment (HI) could be a risk factor for cognitive decline, but cognition could plausibly also affect psychoacoustic assessment of hearing with audiometry. We examined the temporal sequence of hearing and cognitive function among non-demented, community-dwelling older adults. Methods Hearing and cognition were assessed between 2012-2015 and two years thereafter in 313 non-demented participants aged ≥60 years in the Baltimore Longitudinal Study of Aging. Poorer hearing was defined by pure-tone average (PTA) of 0.5-4 kHz tones in the better-hearing ear. Cognitive measures with either visual or auditory inputs were Trail-making Test Part B (TMT-B), Digit Symbol Substitution Test (DSST), California Verbal Learning Test (CVLT) immediate recall, short-delay, and long-delay, Digit Span Forward/Backward, Benton Visual Retention Test, and Mini Mental State Examination (MMSE). We used linear regression models for cross-sectional associations at each time point and autoregressive, cross-lagged models to evaluate whether baseline HI (time 1) predicted cognitive performance two years after baseline (time 2) and vice versa. Results Cross-sectionally, there were no associations between poorer hearing and cognitive performance. Longitudinally, poorer hearing was associated with declines in CVLT immediate (β=-0.073, SE=0.032, p=0.024), short-delayed (β=-0.134, SE=0.043, p=0.002), long-delayed (β=-0.080, SE=0.032, p=0.012) recall, and Digit Span Forward (β=-0.074, SE=0.029, p=0.011). ) from time 1 to time 2. Cognitive performance at time 1 did not predict change in hearing status at time 2. Conclusions Audiometric HI predicted short-term cognitive declines in both CVLT and auditory stimuli for attention.
Stent graft versus balloon angioplasty for failing dialysis-access grafts.

BACKGROUND The leading cause of failure of a prosthetic arteriovenous hemodialysis-access graft is venous anastomotic stenosis. Balloon angioplasty, the first-line therapy, has a tendency to lead to subsequent recoil and restenosis; however, no other therapies have yet proved to be more effective. This study was designed to compare conventional balloon angioplasty with an expanded polytetrafluoroethylene endovascular stent graft for revision of venous anastomotic stenosis in failing hemodialysis grafts. METHODS We conducted a prospective, multicenter trial, randomly assigning 190 patients who were undergoing hemodialysis and who had a venous anastomotic stenosis to undergo either balloon angioplasty alone or balloon angioplasty plus placement of the stent graft. Primary end points included patency of the treatment area and patency of the entire vascular access circuit. RESULTS At 6 months, the incidence of patency of the treatment area was significantly greater in the stent-graft group than in the balloon-angioplasty group (51% vs. 23%, P<0.001), as was the incidence of patency of the access circuit (38% vs. 20%, P=0.008). In addition, the incidence of freedom from subsequent interventions at 6 months was significantly greater in the stent-graft group than in the balloon-angioplasty group (32% vs. 16%, P=0.03 by the log-rank test and P=0.04 by the Wilcoxon rank-sum test). The incidence of binary restenosis at 6 months was greater in the balloon-angioplasty group than in the stent-graft group (78% vs. 28%, P<0.001). The incidences of adverse events at 6 months were equivalent in the two treatment groups, with the exception of restenosis, which occurred more frequently in the balloon-angioplasty group (P<0.001). CONCLUSIONS In this study, percutaneous revision of venous anastomotic stenosis in patients with a prosthetic hemodialysis graft was improved with the use of a stent graft, which appears to provide longer-term and superior patency and freedom from repeat interventions than standard balloon angioplasty. (ClinicalTrials.gov number, NCT00678249.)
Molecular characterization of Peste des petits ruminants viruses in the Marmara Region of Turkey

Abstract Recent outbreaks of Peste des petits ruminants (PPR) in the Marmara region of Turkey including the European part of Thrace is important due to its proximity to Europe (Greece and Bulgaria) and the potential threat of spread of PPR into mainland Europe. In order to investigate the circulation of PPRV in the region suspect clinical and necropsy samples were collected from domestic sheep (n = 211) in the Marmara region of Turkey between 2011 and 2012. PPR virus (PPRV) genome was detected in 10.4% (22 out of 211) of sheep samples by real‐time RT‐PCR, and PPR virus was isolated from lungs of two sheep that died from infection. Of the 22 positive samples nine were used for partial N‐gene amplification and sequencing. The phylogenetic analyses indicated that the virus belongs to lineage IV, the same lineage that is circulating in eastern and central part of Turkey since its first official report in 1999. In addition, samples from 100 cattle were collected to investigate potential subclinical circulation of PPRV. However all were found to be negative by real‐time RT‐PCR, and also in serological tests indicating the large ruminants were likely not exposed or infected with the virus. The impact of these findings on the potential threat of spread of PPR to Europe including the first PPR outbreak in Europe in Bulgaria on 23rd June 2018 is discussed.