Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of novel genetic models to dissect resistance to thyroid hormone receptor alpha in zebrafish.

BACKGROUND Patients with mutations of the thyroid hormone receptor  gene (THRA) show resistance to thyroid hormone (RTH). No amendable mouse models are currently available to elucidate deleterious effects of TR1 mutants during early development. Zebrafish with transient suppressed expression by morpholino knockdown and ectopic expression of TR1 mutants in the embryos have been reported. However, zebrafish with germline transmittable mutations have not been reported. The stable expression of thra mutants from embryos to adulthood facilitated the study of molecular actions of TR1 mutants during development. METHODS In contrast to human and mice, the thra gene is duplicated, thraa and thrab. Using CRISPR/Cas9-mediated targeted mutagenesis, we created dominant negative mutations in the two duplicated thra genes in zebrafish. We comprehensively analyzed the molecular and phenotypic characteristics of mutant fish during development. RESULTS Adult and juvenile homozygous thrab 1-bp ins (m/m) mutants exhibited severe growth retardation, but adult homozygous thraa 8-bp ins (m/m) mutants had very mild growth impairment. Expression of the growth hormone (gh1) and insulin-like growth factor 1 was markedly suppressed in homozygous thrab 1-bp ins (m/m) mutants. Decreased mRNA and protein levels of T3-regulated keratin genes and inhibited keratinocyte proliferation resulted in epidermis hypoplasia of adult and juvenile homozygous thrab 1-bp ins (m/m) mutants, but not homozygous thraa 8-bp ins (m/m) mutants. RNA-seq analysis showed that homozygous thrab 1-bp ins (m/m) mutation had global impact on the functions of the adult pituitary. However, no morphological defects, nor any changes in the expression of gh1 and keratin genes were observed in the embryos and early larvae. Thus, mutations of either the thraa or thrab gene did not affect initiation of embryogenesis. But the mutation of the thrab gene, but not the thraa gene, is detrimental in post-larva growth and skin development. CONCLUSIONS The thra duplicated genes are essential to control temporal coordination in post-larva growth and development in a tissue-specific manner. We uncovered novel functions of the duplicated thra genes in zebrafish in development. These mutant zebrafish could be used as a model for further analysis of TR1 mutant actions and for rapid screening of therapeutics for RTH.
The Effect of Sodium Bicarbonate Supplementation on the Decline in Gross Efficiency During a 2000-m Cycling Time Trial.

BACKGROUND Gross efficiency (GE) declines during high-intensity exercise. Increasing extracellular buffer capacity might diminish the decline in GE and thereby improve performance. PURPOSE To examine if sodium bicarbonate (NaHCO3) supplementation diminishes the decline in GE during a 2000-m cycling time trial. METHODS Sixteen male cyclists and 16 female cyclists completed 4 testing sessions including a maximal incremental test, a familiarization trial, and two 2000-m GE tests. The 2000-m GE tests were performed after ingestion of either NaHCO3 supplements (0.3 g/kg body mass) or placebo supplements (amylum solani, magnesium stearate, and sunflower oil capsules). The GE tests were conducted using a double-blind, randomized, crossover design. Power output, gas exchange, and time to complete the 2000-m time trials were recorded. Capillary blood samples were analyzed for blood bicarbonate, pH, and lactate concentration. Data were analyzed using magnitude-based inference. RESULTS The decrement in GE found after the 2000-m time trial was possibly smaller in the male and female groups after NaHCO3 than with placebo ingestion, with the effect in both groups combined being unclear. The effect on performance was likely trivial for males (placebo 164.2 [5.0] s, NaHCO3 164.3 [5.0] s; Δ0.1; ±0.6%), unclear for females (placebo 178.6 [4.8] s, NaHCO3 178.0 [4.3] s; Δ-0.3; ±0.5%), and very likely trivial when effects were combined. Blood bicarbonate, pH, and lactate concentration were substantially elevated from rest to pretest after NaHCO3 ingestion. CONCLUSIONS NaHCO3 supplementation results in an unclear effect on the decrease in GE during high-intensity exercise and in a very likely trivial effect on performance.
Reliability of the Functional Threshold Power in Competitive Cyclists

Abstract Functional threshold power (FTP) is defined as the highest power that a cyclist can maintain in a quasi-steady state without fatigue for approximately 1 hour. To improve practicality, a 20-minute time-trial test was proposed, where FTP is represented by 95% of the mean power produced. It is preceded by a specific 45-min warm-up, with periods of low intensity, fast accelerations, and a 5-min time-trial. Thus, the aim of this study was to determine the reliability of this protocol, including the reliability of the warm-up, pacing strategy, and FTP determination. For this purpose, 25 trained cyclists performed a familiarization and two other tests separated by seven days. The coefficient of variation (CV [%]), intraclass correlation coefficient (ICC), and change in the mean between test and retest were calculated. The results show that the 20-min time-trial was reliable (CV=2.9%, ICC=0.97), despite a less reliable warm-up (CV=5.5%, ICC=0.84). The changes in the mean between the test and retest were trivial to small for all measurements, and the pacing strategy was consistent across all trials. These results suggest that FTP determination with a 20-min protocol was reliable in trained cyclists.
M06-SX screened-exchange density functional for chemistry and solid-state physics

Significance Density functionals with Hartree–Fock exchange have been widely used for a wide range of chemical applications, but the nonlocal character of exchange makes long-range exchange computationally expensive for solid-state calculations with periodic boundary conditions, and full exchange is nonphysical for condensed-phase systems. Here, we present a screened-exchange (SX) density functional, M06-SX, that is especially designed to have good accuracy for both solid-state physics and chemical applications with less computational cost than full Hartree–Fock exchange. The M06-SX functional gives accuracy comparable to functionals with full Hartree–Fock exchange for predicting chemical properties of molecules, while also being practical with good accuracy for plane wave calculations on band gaps and lattice constants of solids. Screened-exchange hybrid density functionals are especially recommended for solid-state systems because they combine the advantages of hybrid functionals with the correct physics and lower computational cost associated with the attenuation of Hartree–Fock exchange at long range. We present a screened-exchange hybrid functional, M06-SX, that combines the functional form of the local revM06-L functional with a percentage of short-range nonlocal Hartree–Fock exchange. The M06-SX functional gives good results not only for a large set of training data but also for several databases quite different from the training data. The mean unsigned error (MUE) of the M06-SX functional is 2.85 kcal/mol for 418 atomic and molecular energies (AME418) in Minnesota Database 2019, which is better than all five other screened-exchange hybrid functionals tested in this work. The M06-SX functional also gives especially good results for semiconductor band gaps, molecular dissociation energies, noncovalent interactions, barrier heights, and electronic excitation energies excluding long-range charge transfer excitations. For the LC18 lattice constants database, the M06-SX functional gives an MUE of only 0.034 Å. Therefore, the M06-SX functional is well suited for studying molecular chemistry as well as solid-state physics.
Innovations in Electrodermal Activity Data Collection and Signal Processing: A Systematic Review

The electrodermal activity (EDA) signal is an electrical manifestation of the sympathetic innervation of the sweat glands. EDA has a history in psychophysiological (including emotional or cognitive stress) research since 1879, but it was not until recent years that researchers began using EDA for pathophysiological applications like the assessment of fatigue, pain, sleepiness, exercise recovery, diagnosis of epilepsy, neuropathies, depression, and so forth. The advent of new devices and applications for EDA has increased the development of novel signal processing techniques, creating a growing pool of measures derived mathematically from the EDA. For many years, simply computing the mean of EDA values over a period was used to assess arousal. Much later, researchers found that EDA contains information not only in the slow changes (tonic component) that the mean value represents, but also in the rapid or phasic changes of the signal. The techniques that have ensued have intended to provide a more sophisticated analysis of EDA, beyond the traditional tonic/phasic decomposition of the signal. With many researchers from the social sciences, engineering, medicine, and other areas recently working with EDA, it is timely to summarize and review the recent developments and provide an updated and synthesized framework for all researchers interested in incorporating EDA into their research.
Preventing and reducing ‘coercion’ in mental health services: an international scoping review of English‐language studies

This article discusses initiatives aimed at preventing and reducing ‘coercive practices’ in mental health and community settings worldwide, including in hospitals in high‐income countries, and in family homes and rural communities in low‐ and middle‐income countries. The article provides a scoping review of the current state of English‐language empirical research. It identifies several promising opportunities for improving responses that promote support based on individuals’ rights, will and preferences. It also points out several gaps in research and practice (including, importantly, a gap in reviews of non‐English‐language studies). Overall, many studies suggest that efforts to prevent and reduce coercion appear to be effective. However, no jurisdiction appears to have combined the full suite of laws, policies and practices which are available, and which taken together might further the goal of eliminating coercion.
Influence of Pneumonia on the Survival of Patients with COPD

Background: Pneumonia is a frequent infection. Chronic obstructive pulmonary disease (COPD) can present with comorbidities, including pneumonia. It is known that COPD worsens the evolution of pneumonia, but few studies describe the impact of pneumonia on COPD evolution. This study analyzes the influence of pneumonia on the survival of COPD patients. Methods: Observational study of a cohort of 273 patients with COPD who attended spirometry in 2011, with a prospective follow-up of six years. Patients were divided into two groups according to their acquisition of pneumonia during follow-up. The difference in survival between the two groups was analyzed. Results: Survival was lower in the group with pneumonia compared with that without pneumonia (p = 0.000), both globally and after stratification by COPD phenotype. Pneumonia (Hazard Ratio -HR- 2.65; 95% Confidence Interval -CI- 1.57–4.48), advanced age (HR 1.08; 95% CI 1.03–1.09), and high Charlson index (HR 1.31; 95% CI 1.17–1.47) were identified as risk factors independently associated with mortality, while a high body mass index (HR 0.92; 95% CI 0.87–0.96) was identified as a protective factor. Conclusions: Pneumonia is associated with worse prognosis in COPD patients. It is important to take into account this comorbidity for a comprehensive care of these patients.
Consistency of Effect of Docetaxel-Containing Adjuvant Chemotherapy in Patients with Early Stage Breast Cancer Independent of Nodal Status: Meta-Analysis of 12 Randomized Clinical Trials.

Background Up to now taxanes have been extensively evaluated in the treatment of node-positive early-stage breast cancers (ESBC). Recently, more data have become available in patients with node-negative as well as node-positive ESBC treated with docetaxel-based regimens. We conducted a meta-analysis of randomized ESBC trials in order to evaluate the efficacy of adjuvant docetaxel-based regimens in terms of disease-free survival (DFS), overall survival (OS), and whether treatment effects are maintained across different nodal status subpopulations. Methods Studies including at least 100 patients and presented or published before December 31, 2008 were retrieved by searching the MEDLINE, CANCERLIT, and Cochrane Library databases and the proceedings of major conferences. Outcomes recorded were DFS and OS. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model in a random effect model. In trials including both node-positive and node-negative breast cancers, and with nodal status as a clear stratification factor at randomization, HR were extracted for each subpopulation separately. A HR less than 1 indicated that docetaxel was superior to the no-taxane regimen. Results Twelve randomized phase III studies were included in the meta-analysis (20 698 patients). Three subsets of trials/strata were used: node-positive (10 trials or strata, 14 787 patients), node-negative (4 trials/strata, 4 274 patients), or combination of both (2 trials, 1 637 patients). Overall, the pooled HR estimate [95% CI] for DFS was 0.81 [0.74;0.89] ( P ) in favor of docetaxel-based chemotherapy. The results are the same for node-positive (HR=0.84 [0.77;0.91]) and node-negative breast cancer (HR=0.84 [0.72;0.99]). The overall estimated HR for OS was 0.81 [0.72;0.91] ( P ). Results by nodal status subpopulations are awaited. Conclusion This meta-analysis of 12 recent randomized phase III trials shows that adjuvant docetaxel-based chemotherapy compared to regimens without taxanes is associated with an improvement in DFS and OS independent of nodal status. Other analyses will also be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 605.
Vedolizumab and etrolizumab for ulcerative colitis: twins or simple cousins?

ABSTRACT Introduction: Vedolizumab is a monoclonal antibody that selectively blocks α4β7 integrin and has already been approved for use in patients with moderate-to-severe ulcerative colitis both as first and second line. Etrolizumab is a monoclonal antibody still being tested, which acts with a dual mechanism by selectively inhibiting both α4β7 and αEβ7 integrins. Areas covered: This review provides an overview of the literature data of vedolizumab and etrolizumab, in order to define their role in the treatment of patients with moderate-to-severe ulcerative colitis. Expert opinion: Etrolizumab and vedolizumab block the α4β7 integrin with a similar action mechanism. However, the inhibition of αEβ7 integrin by etrolizumab distinguishes the two anti-integrins making them ‘cousin’ drugs. Phase 3 clinical trials are needed to confirm the promising etrolizumab’s efficacy data and to resolve any doubts about its safety, allowing a clearer comparison with vedolizumab.
Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity

Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.
Modeling the effect of prolonged ethanol exposure on global gene expression and chromatin accessibility in normal 3D colon organoids

In this study we aimed to explore the potential biological effect of ethanol exposure on healthy colon epithelial cells using normal human colon 3D organoid “mini-gut” cultures. In numerous published studies ethanol use has been shown to be an environmental risk factor for colorectal cancer (CRC) development; however, the influence of ethanol exposure on normal colon epithelial cell biology remains poorly understood. We investigated the potential molecular effects of ethanol exposure in normal colon 3D organoids in a small pilot study (n = 3) using RNA-seq and ATAC-seq. We identify 1965 differentially expressed genes and 2217 differentially accessible regions of chromatin in response to ethanol treatment. Further, by cross-referencing our results with previously published analysis in colorectal cancer cell lines, we have not only validated a number of reported differentially expressed genes, but also identified several novel candidates for future investigation. In summary, our data highlights the potential importance for the use of normal colon 3D organoid models as a novel tool for the investigation of the relationship between the effects of environmental risk factors associated with colorectal cancer and the molecular mechanisms through which they confer this risk.
Effect of feeding different sources of selenium on growth performance and antioxidant status of broilers

ABSTRACT 1. This study was conducted to determine the effect of different sources of selenium (Se) on breast and liver tissue deposition, apparent metabolisable energy (AME), growth performance and antioxidant status of broilers, measured as Se content in liver and breast tissues and glutathione peroxidase (GSH-Px) in blood, when used in 0–35 d broiler chicken diets. 2. A total of 200 male Ross 308 broilers were used in the feeding trial, which comprised two dietary phases, a starter from 0 to 21 d and finisher from 21 to 35 d of age. Four treatments with 10 replications each were used. A control diet (C) was formulated that was sufficient in protein and energy (230 and 215 g/kg of crude protein and 12.67 and 13.11 MJ/kg of metabolisable energy, respectively), for both phases, but contained background Se only from the feed ingredients. Diet 2 (IS) was supplemented with 10.35 g/t inorganic, elemental source of Se. Diet 3 (SY) was supplemented with 136.36 g/t selenised yeast, an organic source derived from Saccharomyces cerevisiae. Diet 4 (SS) was supplemented with 0.666 g/t sodium selenite, an inorganic source. 3. Birds fed the SY diet consumed less and weighed less than those fed IS or C (P < 0.05; 0–35 d of age), but there was no difference compared to birds fed SS diets. There were no differences in FCR or dietary AME between broilers fed different Se sources. All diets containing supplementary Se increased concentrations in the liver and breast muscle, and for GSH-Px levels in blood compared to birds fed the C diet (P < 0.001). Birds fed SY diets had greater Se levels in liver and breast tissues compared to birds fed any of the other diets (P < 0.001). 4. Diets supplemented with Se had variable effects on broiler growth performances and antioxidant status. Feeding Se from a yeast source has higher transfer into breast tissues. Feeding different sources and levels of Se to birds in a more challenging situation to induce oxidative stress may bring more conclusive results.
Body mass index in psoriatic patients with or without familial psoriasis

Psoriasis is a chronic inflammatory disease caused by both genetic and environmental factors. The occurrence of psoriasis in family members indicates a genetic predisposition, while obesity is also a major contributor to psoriasis. We examined whether patients with versus without familial psoriasis were obese at the onset of psoriasis. Clinical information, including age at onset, age at first visit and body mass index (BMI) at first visit, was extracted from the Fukuoka University Psoriasis Registry. To compare BMI, patients aged 10 years or older who visited the clinic within 3 years of onset were selected. Familial psoriasis was observed in 27 patients (15 male, 12 female) out of 428 individuals (264 male, 164 female) with psoriasis, accounting for 6.3% of cases. Age at onset was younger for both men and women with familial psoriasis (34 ± 17 and 40 ± 15 years, respectively) relative to those with non‐familial psoriasis (48 ± 19 and 53 ± 19 years, respectively). We examined age‐ and sex‐adjusted average values of BMI at initial presentation after onset of psoriasis, finding that patients with familial psoriasis had lower BMI (22.0 kg/m2 [95% confidence interval, 21.8–22.4]) than those with non‐familial psoriasis (23.2 [23.1–23.3], P < 0.001). Individuals with a family history of psoriasis should be considered to be at risk for developing the disease even if obesity is not present.
Synthesis of highly branched hollow trimetallic PdAgCu nanoparticles

An aqueous, room temperature, and surfactant-less synthetic route based on galvanic replacement and co-reduction is reported to yield PdAgCu nanoparticles (NPs) with a high density of sharp and branched tips. The PdAgCu NPs are of high-purity, uniform size and more than 90% of them adopt branched tips. Besides, the PdAgCu NPs exhibit hollow interiors, well-alloyed nature, and a tuneable localized surface plasmon resonance peak in the near infrared region. Their morphology and optical property are facilely controlled by adjusting the precursor molar ratio, amounts of AgNP seeds and Cl− ions in the growth solution. The proposed synthetic approach is anticipated to offer an attractive avenue for facile synthesis of other multi-metallic and branched NPs with controlled properties.