Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Delayed-Release and Extended-Release Methylphenidate on Caregiver Strain and Validation of Psychometric Properties of the Caregiver Strain Questionnaire: Results from a Phase 3 Trial in Children with Attention-Deficit/Hyperactivity Disorder

Objectives: Inadequately controlled symptoms and associated impaired functioning have a significant negative impact on caregivers of children with attention-deficit/hyperactivity disorder (ADHD). This study aimed to assess the impact of evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) treatment on caregiver strain, measured by the Caregiver Strain Questionnaire (CGSQ), and present post hoc psychometric analyses assessing the reliability and validity of the CGSQ, its ability to detect change (responsiveness), and to derive responder definitions. Methods: The CGSQ was an exploratory efficacy endpoint in a phase 3, 3-week, randomized, double-blind, multicenter, placebo-controlled, forced-dose titration trial of DR/ER-MPH in children aged 6–12 years with ADHD (NCT02520388). Psychometric properties of the CGSQ evaluated post hoc included internal consistency using Cronbach's alpha; test/retest reliability using intraclass correlation coefficients (ICCs); construct validity (known groups and convergent/divergent validity); responsiveness to changes in assessments of ADHD severity (ADHD Rating Scale-IV [ADHD-RS-IV], Conners' Global Index–Parent [CGI-P], and Clinical Global Impression—Severity [CGI-S]/CGI—Improvement [CGI-I]); and meaningful change threshold (MCT) using receiver operating characteristic curves, which were used to compare response between DR/ER-MPH and placebo groups. Results: Randomized DR/ER-MPH (54.5) and placebo (54.9) groups had similar mean CGSQ scores at screening. Caregivers of children on DR/ER-MPH reported significant reductions in CGSQ scores after 3 weeks of DR/ER-MPH treatment versus placebo (least-squares mean: 41.2 vs. 49.1; p < 0.001). The CGSQ demonstrated strong internal consistency (Cronbach's alpha = 0.93) and good test/retest reliability (ICC = 0.72). Known groups, convergent/divergent validity, and responsiveness were demonstrated from relationships between the CGSQ and the CGI-S, ADHD-RS-IV, and CGI-P. The mean anchor-based MCT for CGSQ total score was estimated as −9.0 (DR/ER-MPH vs. placebo: 53.2% vs. 29.9% p = 0.003). Conclusions: CGSQ scores significantly decreased after 3 weeks of DR/ER-MPH treatment versus placebo, and the CGSQ was found to be a valid and reliable measure of strain in caregivers of children with ADHD. Clinical trial registration identification number: NCT02520388.
Fibrin Biopolymer Incorporated with Antimicrobial Agents: A Proposal for Coating Denture Bases

The characteristics of the denture base surface, in combination with the oral environment, promote the colonization and development of Candida albicans biofilm, which is the main cause of denture stomatitis. This study evaluated the effectiveness of fibrin biopolymer with digluconate chlorhexidine or Punica granatum alcoholic extract to prevent C. albicans biofilm. Conventional heat polymerized and pre-polymerized poly(methyl methacrylate) (PMMA) circular specimens (10 × 2 mm) were fabricated (n = 504) and randomly divided into groups: no treatment (control—CT), fibrin biopolymer coating (FB), fibrin biopolymer with P. granatum (FBPg), or digluconate of chlorhexidine (FBCh) coating. The specimens were inoculated with C. albicans SC5314 (1 × 107 cells/mL) and incubated for 24, 48, and 72 h. Crystal violet and colony-forming unit assays were used to quantify the total biofilm biomass and biofilm-living cells. A qualitative analysis was performed using confocal laser scanning microscopy. Data obtained are expressed as means and standard deviations and were statistically analyzed using a three-way analysis of variance (α = 0.05). The FBPg and FBCh groups inhibited the growth of C. albicans biofilm in both PMMA materials analyzed, with FBCh performing better in all periods evaluated (p < 0.0001). The colony forming unit (CFU) assay showed that the FB group favored the C. albicans biofilm growth at 24 h and 48 h (p < 0.0001), with no differences with CT group at 72 h (p = 0.790). All groups showed an enhancement in biofilm development up to 72 h (p < 0.0001), except the FBCh group (p = 0.100). No statistical differences were found between the PMMA base materials (p > 0.050), except in the FB group (p < 0.0001). Fibrin biopolymer, albeit a scaffold for the growth of C. albicans, when combined with chlorhexidine digluconate or P. granatum, demonstrated excellent performance as a drug delivery system, preventing and controlling the formation of denture biofilm.
From Traditional Breeding to Genome Editing for Boosting Productivity of the Ancient Grain Tef [Eragrostis tef (Zucc.) Trotter]

Tef (Eragrostis tef (Zucc.) Trotter) is a staple food crop for 70% of the Ethiopian population and is currently cultivated in several countries for grain and forage production. It is one of the most nutritious grains, and is also more resilient to marginal soil and climate conditions than major cereals such as maize, wheat and rice. However, tef is an extremely low-yielding crop, mainly due to lodging, which is when stalks fall on the ground irreversibly, and prolonged drought during the growing season. Climate change is triggering several biotic and abiotic stresses which are expected to cause severe food shortages in the foreseeable future. This has necessitated an alternative and robust approach in order to improve resilience to diverse types of stresses and increase crop yields. Traditional breeding has been extensively implemented to develop crop varieties with traits of interest, although the technique has several limitations. Currently, genome editing technologies are receiving increased interest among plant biologists as a means of improving key agronomic traits. In this review, the potential application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR-Cas) technology in improving stress resilience in tef is discussed. Several putative abiotic stress-resilient genes of the related monocot plant species have been discussed and proposed as target genes for editing in tef through the CRISPR-Cas system. This is expected to improve stress resilience and boost productivity, thereby ensuring food and nutrition security in the region where it is needed the most.
How Bacterial Redox Sensors Transmit Redox Signals via Structural Changes

Bacteria, like humans, face diverse kinds of stress during life. Oxidative stress, which is produced by cellular metabolism and environmental factors, can significantly damage cellular macromolecules, ultimately negatively affecting the normal growth of the cell. Therefore, bacteria have evolved a number of protective strategies to defend themselves and respond to imposed stress by changing the expression pattern of genes whose products are required to convert harmful oxidants into harmless products. Structural biology combined with biochemical studies has revealed the mechanisms by which various bacterial redox sensor proteins recognize the cellular redox state and transform chemical information into structural signals to regulate downstream signaling pathways.
Radiomic Model Predicts Lymph Node Response to Induction Chemotherapy in Locally Advanced Head and Neck Cancer

This study developed a pretreatment CT-based radiomic model of lymph node response to induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. This was a single-center retrospective study of patients with locally advanced HPV+ HNSCC. Forty-one enlarged lymph nodes were found from 27 patients on pretreatment CT and were split into 3:1 training and testing cohorts. Ninety-three radiomic features were extracted. A radiomic model and a combined radiomic-clinical model predicting lymph node response to induction chemotherapy were developed using multivariable logistic regression. Median age was 57 years old, and 93% of patients were male. Post-treatment evaluation was 32 days after treatment, with a median reduction in lymph node volume of 66%. A three-feature radiomic model (minimum, skewness, and low gray level run emphasis) and a combined radiomic-clinical model were developed. The combined model performed the best, with AUC = 0.85 on the training cohort and AUC = 0.75 on the testing cohort. A pretreatment CT-based lymph node radiomic signature combined with clinical parameters was able to predict nodal response to induction chemotherapy for patients with locally advanced HNSCC.
The Use of Laminates of Commercially Available Fabrics for Anti-Stab Body-Armor

Modern personal protective armor has been generally based on the Kevlar fabrics, with the main goal to offer defense against bullets. In addition to the high cost and poor processability, Kevlar has the disadvantage of limited stab-proofing capability. On the other hand, a large number of crimes involving deadly injures represent knife attacks. Our goal in this work was to investigate composites based on traditional commercially available fabrics of linen and silk, using different adhesives-polymers for forming laminates. The silk composites also contained different amounts of in-woven polyester. Three different water-based adhesives of polyurethane, urea formaldehyde and polyvinyl alcohol were considered. It was found, that besides the strength of the fabrics themselves, the adhesives polymers played a crucial role in the obtained performance of the laminates. The laminates were characterized in their mechanical properties, as well as with scanning electron microscopy and FTIR spectroscopy.
Effect of social structure and introduction history on genetic diversity and differentiation

Invasive species are a global threat to biodiversity, and understanding their history and biology is a major goal of invasion biology. Population‐genetic approaches allow insights into these features, as population structure is shaped by factors such as invasion history (number, origin and age of introductions) and life‐history traits (e.g., mating system, dispersal capability). We compared the relative importance of these factors by investigating two closely related ants, Tetramorium immigrans and Tetramorium tsushimae, that differ in their social structure and invasion history in North America. We used mitochondrial DNA sequences and microsatellite alleles to estimate the source and number of introduction events of the two species, and compared genetic structure among native and introduced populations. Genetic diversity of both species was strongly reduced in introduced populations, which also differed genetically from native populations. Genetic differentiation between ranges and the reduction in microsatellite diversity were more severe in the more recently introduced and supercolonial T. tsushimae. However, the loss of mitochondrial haplotype diversity was more pronounced in T. immigrans, which has single‐queen colonies and was introduced earlier. Tetramorium immigrans was introduced at least twice from Western Europe to North America and once independently to South America. Its monogyny might have limited genetic diversity per introduction, but new mutations and successive introductions over a long time may have added to the gene pool in the introduced range. Polygyny in T. tsushimae probably facilitated the simultaneous introduction of several queens from a Japanese population to St. Louis, USA. In addition to identifying introduction pathways, our results reveal how social structure can influence the population‐genetic consequences of founder events.
Toyoncin, a Novel Leaderless Bacteriocin That Is Produced by Bacillus toyonensis XIN-YC13 and Specifically Targets B. cereus and Listeria monocytogenes

We identified a novel leaderless bacteriocin, toyoncin, produced by B. toyonensis XIN-YC13. Toyoncin shows good pH and heat stability, and it has specific antimicrobial activity against B. cereus and L. monocytogenes (two important foodborne pathogens), likely by destroying their cell membrane integrity. ABSTRACT Bacteriocins have attracted increasing interest because of their potential as natural preservatives. Recent studies showed that the Bacillus cereus group is a prominent producer of bacteriocins. Using a laboratory-based screening strategy, we identified a strain in the B. cereus group, Bacillus toyonensis XIN-YC13, with antimicrobial activity against B. cereus. A novel, 70-amino-acid-long leaderless bacteriocin, toyoncin, was purified from the culture supernatant of strain XIN-YC13, and its molecular mass was found to be 7,817.1012 Da. Toyoncin shares no similarity with any other known bacteriocins, and its N-terminal amino acid is formylmethionine rather than methionine. Toyoncin shows good pH and heat stability and exhibits specific antimicrobial activity against two important foodborne pathogens, B. cereus and Listeria monocytogenes. Additionally, toyoncin exerts bactericidal activity and induces cell membrane damage. Toyoncin can also inhibit the outgrowth of B. cereus spores. Preservation assays showed that toyoncin effectively suppressed or eradicated B. cereus and L. monocytogenes in pasteurized skim milk. These results suggest that toyoncin can be used as a new biopreservative against B. cereus and L. monocytogenes in the food industry. IMPORTANCE We identified a novel leaderless bacteriocin, toyoncin, produced by B. toyonensis XIN-YC13. Toyoncin shows good pH and heat stability, and it has specific antimicrobial activity against B. cereus and L. monocytogenes (two important foodborne pathogens), likely by destroying their cell membrane integrity. Toyoncin inhibited the outgrowth of B. cereus spores and effectively inhibited or eliminated B. cereus and L. monocytogenes in a milk model system. These results indicate the potential of toyoncin as a food preservative.
Comparison of Innovative and Traditional Cardiometabolic Indices in Estimating Atherosclerotic Cardiovascular Disease Risk in Adults

This study aimed to investigate the performance of innovative and traditional cardiometabolic indices, including body mass index (BMI), waist circumference (WC), Chinese visceral adiposity index (CVAI), visceral adiposity index, lipid accumulation product, a body shape index (ABSI), body roundness index, conicity index (CI), triglyceride-glucose (TyG) index, TyG-BMI, and TyG-WC, in estimating atherosclerotic cardiovascular disease (ASCVD) risk in 3143 Taiwanese adults aged 20–79 years. Elevated 10-year ASCVD risk was defined as ≥7.5% using the Pooled Cohort Equations. The performance of different indices in estimating elevated ASCVD risk was assessed by receiver operating characteristic (ROC) curves. In multivariate-adjusted logistic regression analyses, all cardiometabolic indices (p-value < 0.001) were significantly associated with elevated ASCVD risk in both genders, except for ABSI and CI in women. In particular, CVAI had the largest area under the curve (AUC) in men (0.721) and women (0.883) in the ROC analyses. BMI had the lowest AUC in men (0.617), while ABSI had the lowest AUC in women (0.613). The optimal cut-off value for CVAI was 83.7 in men and 70.8 in women. CVAI performed best among various cardiometabolic indices in estimating elevated ASCVD risk. CVAI may be a reliable index for identifying people at increased risk of ASCVD.
Serum Levels of Fibroblast Growth Factor 21 Are Positively Associated with Aortic Stiffness in Patients with Type 2 Diabetes Mellitus

Aortic stiffness (AS), assessed using carotid–femoral pulse wave velocity (cfPWV), is associated with cardiovascular disease in type 2 diabetes mellitus (T2DM). The relationship between serum fibroblast growth factor 21 (FGF-21) and AS in T2DM patients was evaluated. Fasting serum FGF-21 levels of 130 T2DM patients were measured using an enzyme immunoassay kit. A validated tonometry system was used to measure cfPWV (>10 m/s indicated AS). Of these T2DM patients, 34.6% were defined as the AS group. T2DM patients with AS were older; exhibited higher systolic blood pressure, diastolic blood pressure, and body fat mass; higher triglyceride, fasting glucose, glycosylated hemoglobin, and creatinine levels; higher urine albumin-to-creatinine ratios and serum FGF-21 levels; and lower estimated glomerular filtration rates. The FGF-21 level (odds ratio = 1.005, 95% confidence interval: 1.002–1.009, p = 0.002) as well as systolic blood pressure was an independent predictor of AS and positively correlated to cfPWV values (β = 0.369, p < 0.001) in T2DM patients. For T2DM patients, serum FGF-21 level could be a predictor for AS.
Reduced RECK levels accelerate skeletal muscle differentiation, improve muscle regeneration, and decrease fibrosis

The muscle regeneration process requires a properly assembled extracellular matrix (ECM). Its homeostasis depends on the activity of different matrix‐metalloproteinases (MMPs). The reversion‐inducing‐cysteine‐rich protein with kazal motifs (RECK) is a membrane‐anchored protein that negatively regulates the activity of different MMPs. However, the role of RECK in the process of skeletal muscle differentiation, regeneration, and fibrosis has not been elucidated. Here, we show that during skeletal muscle differentiation of C2C12 myoblasts and in satellite cells on isolated muscle fibers, RECK is transiently up regulated. C2C12 myoblasts with reduced RECK levels are more prone to enter the differentiation program, showing an accelerated differentiation process. Notch‐1 signaling was reduced, while p38 and AKT signaling were augmented in myoblasts with decreased RECK levels. Overexpression of RECK restores the normal differentiation process but diminished the ability to form myotubes. Transient up‐regulation of RECK occurs during skeletal muscle regeneration, which was accelerated in RECK‐deficient mice (Reck±). RECK, MMPs and ECM proteins augmented in chronically damaged WT muscle, a model of muscle fibrosis. In this model, RECK ± mice showed diminished fibrosis compared to WT. These results strongly suggest that RECK is acting as a potential myogenic repressor during muscle formation and regeneration, emerging as a new player in these processes, and as a potential target to treat individuals with the muscle‐wasting disease.
Towards an Earlier Diagnosis of Acromegaly and Gigantism

Acromegaly is a rare disease and the clinical features of acromegaly develop insidiously; its diagnosis is often significantly delayed. Therefore, earlier diagnosis will improve the quality of life of the patient and reduce the need for other therapies to control the initial and ongoing damage that acromegaly presents. In this chapter, we describe the view of the patient and the clinician on the importance of earlier diagnosis, as well as on what can be done to speed up this process. Earlier diagnosis will not only improve quality of life and the burden of disease in acromegaly patients, but it will also have a positive impact in the economic burden of this rare disease.
"This is not life, this is just vegetation"-Lived experiences of long-term care in Europe's largest psychiatric home: An interpretative phenomenological analysis.

PURPOSE Understanding the experiences of long-term care (LTC) may help to improve care by assisting mental health professionals and allowing mental health policies to be customized more effectively. DESIGN AND METHODS: Semistructured interviews were analyzed using interpretative phenomenological analysis (IPA). FINDINGS Three main themes emerged as a result: 1. Perception of selves, 2. Experience and representation of the institution, 3. Maintenance of safe spaces. PRACTICE IMPLICATIONS: Communication with patients, investigation of their identity processes, and relationship toward their past and present self during LTC might aid in well-being and sense of congruency in their identities. Nurses should encourage patients to keep connected with their memories and past selves through different activities.
PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.
Shared Injection Experiences: Interpersonal Involvement in Injection Drug Practices among Women

Background Many women who inject drugs are aware of the associated risks, however social influences play a part in their behavioral decisions. Incorporation of others in drug use behaviors may be common practice among women who use drugs. The aim of this study was to gain an in-depth understanding of women's injection drug use experiences with a focus on interpersonal involvement. Methods Venue-based recruitment was conducted in collaboration with a harm reduction program. A group of 30 women, ages 18 and older, who reported injecting drugs within the past 30 days took part in a demographic survey and semi-structured interview to gain an understanding of their injection practices. In vivo coding and thematic analysis were conducted. Results Three main themes that relate to incorporating others into injection drug behaviors surfaced, including: (1) injection practices described as we and not I, (2) partnered purchase and drug preparation, and (3) assisted injection. This group of women most often incorporated sexual and/or romantic partners (same and other-gender), friends, or family members into their injection drug use behaviors. Some women described a lack of ability to inject themselves and require assistance every time they use. Women also reported helping other women during drug use behaviors. Conclusions Our primary themes indicate that a variety of relationship partners are important conceptual links in theoretical frameworks explaining drug use behaviors among women. Findings suggest same gender assistance during drug use behaviors, including injection, that may reduce harm. The interpersonal nature of injection drug use among women may indicate the expansion of treatment options designed for couples or other relationship partners, such as family, together.