Miracle-dz/UniFAR-FTUs huggingface dataset:
An Online, Person-Centered, Risk Factor Management Program to Prevent Cognitive Decline: Protocol for A Prospective Behavior-Modification Blinded Endpoint Randomized Controlled Trial.

BACKGROUND Several modifiable risk factors for dementia have been identified, although the extent to which their modification leads to improved cognitive outcomes remains unclear. OBJECTIVE The primary aim is to test the hypothesis that a behavior modification intervention program targeting personalized risk factors prevents cognitive decline in community-dwelling, middle-aged adults with a family history of dementia. METHODS This is a prospective, risk factor management, blinded endpoint, randomized, controlled trial, where 1510 cognitively normal, community-dwelling adults aged 40-70 years old will be recruited. Participants will be screened for risk factors related to vascular health (including physical inactivity), mental health, sleep, and cognitive/social engagement. The intervention is an online person-centered risk factor management program: BetterBrains. Participants randomized to intervention will receive telehealth-based person-centered goal setting, motivational interviewing, and follow-up support, health care provider communication and community linkage for management of known modifiable risk factors of dementia. Psychoeducational health information will be provided to both control and intervention groups. RESULTS The primary outcome is favorable cognitive performance at 24-months post-baseline, defined as the absence of decline on one or more of the following cognitive tests: (a) Cogstate Detection, (b) Cogstate One Card Learning, (c) Cogstate One Back, and (d) Cognitive Function Instrument total score. CONCLUSION We will test the hypothesis that the BetterBrains intervention program can prevent cognitive decline. By leveraging existing community services and using a risk factor management pathway that tailors the intervention to each participant, we maximize likelihood for engagement, long-term adherence, and for preserving cognitive function in at-risk individuals.
Tbx4 function during hindlimb development reveals a mechanism that explains the origins of proximal limb defects

ABSTRACT We dissect genetically a gene regulatory network that involves the transcription factors Tbx4, Pitx1 and Isl1 acting cooperatively to establish the hindlimb bud, and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of murine limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects observed in Tbx4 mutant mice result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing an explanation for the origins of proximally biased limb defects.
Effect of a theory-based educational intervention for enhancing nutrition and physical activity among Iranian women: a randomised control trial

Abstract Objective: The relative contribution of health promotion models (HPM) to improve health-related behaviours in intervention programmes is still limited. Here, we tested whether Pender’s HPM operationalised in the educational intervention was effective to modify nutrition and physical activity (PA) behaviours among Iranian women. Design: A randomised controlled field trial evaluating the efficacy of an educational intervention based on Pender’s HPM to improve PA and nutrition behaviours from August 2016 to October 2016. R version 3.0. 2 and SPSS version 16 were used to conduct multiple statistical analyses. Setting: Ten public healthcare centres in Bojnourd, Iran were randomly divided into intervention and control groups. The experimental group received the full intervention programme, which included nine 4-h training sessions and consulting support via phone contact and social media group. The control group did not receive any intervention. Participants: Women aged 4–6 years (n 202) were randomised to intervention (n 102) and control conditions (n 100) and completed baseline and 3-month follow-up. Results: In the experimental group, the intervention programme had a significant effect (P < 0·05) on all construct of Pender’s HPM and behaviour outcome, and the estimates for prior behaviours, self-efficacy, interpersonal influences, feeling, perceived benefits and barriers, commitment and behaviour outcomes in the intervention group were 0·72 (95 % CI 0·31, 0·98), 0·54 (95 % CI 0·27, 0·71), 0·74 (95 % CI 0·27, 0·91), 0·52 (95 % CI 0·19, 0·75), 0·62 (95 % CI 0·22, 0·91), 0·63 (95 % CI 0·30, 0·86) and 0·56 (95 % CI 0·37, 0·85), respectively. Conclusions: Educational intervention based on Pender’s HPM was feasible and highly acceptable to modify PA and nutrition behaviours in the women population.
Phosphorous acid functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment for one-pot C–C and C–N bond formation reactions

The preparation and application of fiber catalysts have attracted much attention. However, research on the effect of the micro-environment of fiber catalysts on the catalytic activities though of special importance is limited. In this work, a novel strategy for the synthesis of phosphoric acid-functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment by hydrophobic groups for one-pot C–C and C–N bond formation reactions is reported. The special hydrophobic surface micro-environment of the fiber catalysts is proven to promote the catalytic activities impressively in cyclocondensation of β-ketoesters with 2-aminobenzamides, the Knoevenagel condensation as well as the multi-component Biginelli reactions in green solvents. Both the surface synergy of the catalytic sites and hydrophobic auxiliary groups (benzyl or n-butyl) in the surface of fiber catalysts and interface acceleration in reaction medium play an important role in the highly efficient promotion of catalytic activity. Thereby a surface synergistic mechanism is proposed to explain the micro-environment effect. In addition, the fiber catalysts could be simply separated from the reaction system using tweezers and directly used in the next cycle without further treatment. Importantly, even after 10 reaction cycles in water or ethanol, there is no significant loss in their catalytic activity. The results indicate that the phosphoric acid functionalized fibers show green and sustainable potential for industrial production.
Molecular modeling and dynamics simulation of alcohol dehydrogenase enzyme from high efficacy cellulosic ethanol-producing yeast mutant strain Pichia kudriavzevii BGY1-γm

Abstract One of the major constraints limiting the use of abundantly available lignocellulosic biomass as potential feedstock for alcohol industry is the lack of C6/C5 co-sugar fermenting yeast. The present study explores a mutant yeast Pichia kudriavzevii BGY1-γm as a potential strain for bioconversion of glucose/xylose sugars of green biomass into ethanol under batch fermentation. The mutant strain having higher alcohol dehydrogenase activity (11.31%) showed significantly higher ethanol concentration during co-fermentation of glucose/xylose sugars (14.2%) as compared to the native strain. Based on 99% sequence similarity of ADH encoding gene from the mutant with the gene sequences from other yeast strains, the ADH enzyme was identified as ADH-1 type. The study reveals first three-dimensional model of ADH-1 utilizing glucose/xylose sugars from P. kudriavzevii BGY1-γm (PkADH mutant). The refined and validated model of PkADH mutant was used for molecular docking against the substrate (acetaldehyde) and product (ethanol). Molecular docking results showed that substrate and product exhibited a binding affinity of −4.55 and −4.5 kcal/mol with PkADH mutant. Acetaldehyde and ethanol interacted at the active site of PkADH mutant via hydrogen bonds (Ser42, His69 and Asp163) and hydrophobic interactions (Cys40, Ser42, His69, Cys95, Trp123 and Asp163) to form the stable protein–ligand complex. Molecular dynamics analysis revealed that PkADH-mutant acetaldehyde and PkADH-mutant ethanol complexes were more stable than PkADH mutant. MMPBSA binding energy confirmed that binding of substrate and product results in the formation of a lower energy stable protein–ligand complex. Communicated by Ramaswamy H. Sarma
Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization–Recommended Weight Band Doses and Formulations

Abstract Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.
Mixed-ligand complexes of N-vinylpyrrolidone/N-vinylformamide/N-vinyl iminodiacedic acid copolymers and diethyldithiocarbamate as a co-ligand with indium/indium-111

ABSTRACT Mixed-ligand metal-polymer complexes (MPC) of N-vinylpyrrolidone-N-vinylformamide-N-vinyl iminodiacedic acid (VP-VFA-VIDA) copolymers and diethyldithiocarbamate (DEDTC) as a co-ligand with indium were synthesized under mild conditions and pH close to physiological values. Isolated MPC were characterized by UV, IR, 1H NMR, atomic absorption spectrophotometry, and HPLC. The obtained data implied that the MPC contain 8–10 wt% of (IDA)In(DEDTC) fragments. The optimal conditions for radiochemical synthesis of VP-VFA-VIDA-111In-(DEDTC) metal-polymer complex with mixed ligands were defined. The closest coordination environment of 111In was studied by perturbed angular correlation technique. The obtained data are in good agreement with the information about weight amounts of the corresponding indium MPC.
Stretchable and Highly Permeable Nanofibrous Sensors for Detecting Complex Human Body Motion

Wearable strain sensors have been attracting special attention in the detection of human posture and activity, as well as for the assessment of physical rehabilitation and kinematics. However, it is a challenge to fabricate stretchable and comfortable‐to‐wear permeable strain sensors that can provide highly accurate and continuous motion recording while exerting minimal constraints and maintaining low interference with the body. Herein, covalently grafting nanofibrous polyaniline (PANI) onto stretchable elastomer nanomeshes is reported to obtain a freestanding ultrathin (varying from 300 to 10 000 nm) strain sensor that has high gas permeability (10–33 mg h–1). The sensor demonstrates a low weight and can be directly laminated onto the dynamic human skin for long periods of time. The sensor, which produces an intimate connection with solid or living objects, has a stable performance with excellent sustainability, linearity, durability, and low hysteresis. It exibits excellent performance for continuous interrogation of complex movements, mimicking muscle activities, and resembling brain activity. This includes a very precise discrimination of bending and twisting stimuli at different angles (1–180°) and speeds (3–18 rpm) and very low exertion of counter‐interference. These results imply the utility of this appraoch for advanced developments of robotic e‐skins or e‐muscles.
Frameworks for selecting appropriate rural sanitation technology options in low- and middle-income countries: a critical review

ABSTRACT Several rural technology options exist on the sanitation market with different characteristics, yet project failures in some developing countries were attributable to inappropriate technology choices. Frameworks that are used to select sanitation technology options (hard copy, computer programmes) were developed by researchers and project implementers. They vary in design and application as there is no standard format. This appears to create a gap between science and practice. Frameworks should have some key elements needed to select appropriate sanitation technologies. We evaluated 12 available frameworks (2000–2019) used to select sanitation technologies in rural communities of low- and middle-income countries against 22 assessment criteria derived from literature. Criteria that were not fully addressed by some of the reviewed frameworks (scores of 8–50%) included equity, sanitation demand, sanitation behaviour change, ongoing contact, replicability, framework limitations, personnel selection and flexibility. Addressing such limitations may assist in future framework development.
Characterization of comprehensive dynamic epigenetic changes during human primary Sjögren’s syndrome progression

Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by reduced exocrine gland (principally the salivary and lacrimal glands) activity caused by chronic lymphocytic infiltration. Although pSS has been closely associated with an increased risk of mucosa-associated lymphoid tissue (MALT) lymphoma, the dynamic epigenetic changes in the gland cells that accompany the pathogenesis are not entirely understood. Methods In this study, we harvested tissue samples from the labial gland with (LG_pSS) or without pSS (LG_NC) before MALT development, as well as the parotid gland with tumor tissues (PG_MALT) and paracancerous tissues (PG_NC) of two pSS patients with MALT lymphoma, and conducted RNA-seq and ChIP-seq for tri-methylated histone 3 lysine 4, 9, 27, 36, and 79 (H3K4/9/27/36/79me3). Results Transcriptome landscapes indicated two outcomes of pSS progression with or without MALT lymphoma represented by distinct populations of differentially expressed genes and their functions. Furthermore, the epigenetic atlas of genome-wide H3K4/9/27/36/79me3 was in different stages for various samples, indicating that the variance of H3K4me3 was the earliest event, followed by selective alterations of H3K9/27/36/79me3. These four epigenetic modifications determine the final outcome of pSS progression. Conclusions Our results not only advance the understanding of the dynamics of pSS progression and highlight the importance of epigenetic alterations in regulating transcription during this pathological process, but also identify potential therapeutic targets for pSS treatment and lymphoma intervention.
Common infectious morbidity and white blood cell count in middle childhood predict behavior problems in adolescence

Abstract We examined the associations of middle childhood infectious morbidity and inflammatory biomarkers with adolescent internalizing and externalizing behavior problems. We recruited 1018 Colombian schoolchildren aged 5–12 years into a cohort. We quantified white blood cell (WBC) counts and C-reactive protein at enrollment and prospectively recorded incidence of gastrointestinal, respiratory, and fever-associated morbidity during the first follow-up year. After a median 6 years, we assessed adolescent internalizing and externalizing behavior problems using child behavior checklist (CBCL) and youth self-report (YSR) questionnaires. Behavior problem scores were compared over biomarker and morbidity categories using mean differences and 95% confidence intervals (CI) from multivariable linear regression. Compared with children without symptoms, CBCL internalizing problem scores were an adjusted 2.5 (95% CI: 0.1, 4.9; p = .04) and 3.1 (95% CI: 1.1, 5.2; p = .003) units higher among children with moderate diarrhea with vomiting and high cough with fever rates, respectively. High cough with fever and high fever rates were associated with increased CBCL somatic complaints and anxious/depressed scores, respectively. WBC >10,000/mm3 was associated with both internalizing problem and YSR withdrawn/depressed scores. There were no associations with externalizing behavior problems. Whether or not decreasing the burden of common infections results in improved neurobehavioral outcomes warrants further investigation.
Close - but not distant - conditioned flanker emotion affects crowding

Crowding is affected by conditioned stimulus emotion. This effect is clearly observed for conditioned flankers, but only marginally pronounced for conditioned targets. Studies on the processing of emotional stimuli suggest that the magnitude of the emotional effect depends on the presentation depth in that effects of emotion increase with decreasing distance to the observer in depth. Based on respective findings, we investigate crowding with stimuli of conditioned negative and neutral emotion across real depth; that is, stimuli were either presented closer, at or farther away than the fixation depth. Conditioned emotion of flankers affected crowding when flankers were presented closer than or at fixation depth, which is also the distance the target was presented at. Farther away than the fixation depth, flanker emotion did not alter crowding (Experiment 1a). Conditioned target emotion, however, did only show weak effects on crowding; neither when flankers (Experiment 1b) nor when targets were varied in depth (Experiment 2) there was a clear effect of target emotion, replicating findings in two-dimensional settings. Taken together, the results suggest that flanker's emotional associations can become important for crowding, although, it depends on the special processing characteristics of stimulus emotion in depth. The conditioned emotion of targets scarcely affected crowding.
Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis‐free survival (MFS) in WHO‐defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3–4.9), male sex (2.1, 1.2–3.9), palpable splenomegaly (2.1, 1.2–3.9), CALR 1/1‐like or MPL mutation (3.4, 1.9–6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6–10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: “high molecular risk” category included patients with JAK2V617F VAF >35%, CALR type 1/1‐like or MPL mutations; all other driver mutation profiles were assigned to “low molecular risk” category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2–11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6–4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3–5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.
Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial

Abstract Aims The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (HFrEF). A risk model incorporating biomarkers and clinical variables has not been validated in contemporary heart failure (HF) trials. Methods and results In EMPEROR-Reduced, 33 candidate variables were pre-selected. Multivariable Cox regression models were developed using stepwise selection for: (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, and (iii) cardiovascular mortality. A total of 3730 patients were followed up for a median of 16 months, 823 (22%) patients had a primary outcome and 515 (14%) patients died, of whom 389 (10%) died from a cardiovascular cause. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last HF hospitalization, longer time since HF diagnosis, lower systolic blood pressure, New York Heart Association (NYHA) Class III or IV, higher heart rate and peripheral oedema were key predictors (eight variables in total, all P < 0.001). The primary outcome risk score discriminated well (c-statistic = 0.73), with patients in the top 10th of risk having an event rate >9 times higher than those in the bottom 10th. Empagliflozin benefitted patients across risk levels for the primary outcome. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality, followed by NYHA Class III or IV and ischaemic aetiology (four variables in total, all P < 0.001). The mortality risk model presented good event discrimination for all-cause and cardiovascular mortality (c-statistic = 0.69 for both). These simple models were externally validated in the BIOSTAT-CHF study, achieving similar c-statistics. Conclusions The combination of NT-proBNP and hs-cTnT with a small number of readily available clinical variables provides prognostic assessment for patients with HFrEF. This predictive tool kit can be easily implemented for routine clinical use.