Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling-Based Decision Support System for Radical Prostatectomy Versus External Beam Radiotherapy for Prostate Cancer Incorporating an In Silico Clinical Trial and a Cost–Utility Study

Simple Summary Low–intermediate prostate cancer has a number of viable treatment options, such as radical prostatectomy and radiotherapy, with similar survival outcomes but different treatment-related side effects. The aim of this study is to facilitate patient-specific treatment selection by developing a decision support system (DSS) that incorporates predictive models for cancer-free survival and treatment-related side effects. We challenged this DSS by validating it against randomized clinical trials and assessing the benefit through a cost–utility analysis. We aim to expand upon the applications of this DSS by using it as the basis for an in silico clinical trial for an underrepresented patient group. This modeling study shows that DSS-based treatment decisions will result in a clinically relevant increase in the patients’ quality of life and can be used for in silico trials. Abstract The aim of this study is to build a decision support system (DSS) to select radical prostatectomy (RP) or external beam radiotherapy (EBRT) for low- to intermediate-risk prostate cancer patients. We used an individual state-transition model based on predictive models for estimating tumor control and toxicity probabilities. We performed analyses on a synthetically generated dataset of 1000 patients with realistic clinical parameters, externally validated by comparison to randomized clinical trials, and set up an in silico clinical trial for elderly patients. We assessed the cost-effectiveness (CE) of the DSS for treatment selection by comparing it to randomized treatment allotment. Using the DSS, 47.8% of synthetic patients were selected for RP and 52.2% for EBRT. During validation, differences with the simulations of late toxicity and biochemical failure never exceeded 2%. The in silico trial showed that for elderly patients, toxicity has more influence on the decision than TCP, and the predicted QoL depends on the initial erectile function. The DSS is estimated to result in cost savings (EUR 323 (95% CI: EUR 213–433)) and more quality-adjusted life years (QALYs; 0.11 years, 95% CI: 0.00–0.22) than randomized treatment selection.
Modulatory Effects of Bacillus subtilis on the Performance, Morphology, Cecal Microbiota and Gut Barrier Function of Laying Hens

Simple Summary The excessive or improper use of antibiotics in chicken feed has led to the emergence of antibiotic-resistant bacteria, drug residues in the tissue, and other relevant issues, and this situation is severe in China. From 31 December 2020, antibiotics were banned for use as supplemental growth promoters in animal feed in China; therefore, antibiotic substitutes are urgently needed in China. People are searching for ideal antibiotic alternatives, and probiotics have proven their potential use for this. Our current trial aims to evaluate the effects of the Bacillus subtilis (B. subtilis) YW1 strain on laying hens, including the effects on performance, morphology, cecal microbiota, and intestinal barrier function. Our study showed that orally administering laying hens with probiotic B. subtilis cannot significantly improve their overall egg production, can induce a healthier microbiota composition characterized by a higher ratio of beneficial bacteria, and strengthens the physical barrier function of the intestine by inducing a higher expression of the tight junction protein. This makes it a valid probiotic alternative to antibiotics, and also a reference strain for clinical application in the poultry industry. Abstract We investigated the efficacy of a single bacterium strain, Bacillus subtilis (B. subtilis) YW1, on the performance, morphology, cecal microbiota, and intestinal barrier function of laying hens. A total of 216 28-week-old Hy-line Brown laying hens were divided into three dietary treatment groups, with six replicates of 12 birds each for 4 weeks. The control group (Ctr) was fed a basal diet and the treatment groups, T1 and T2, were fed a basal diet supplemented with B. subtilis at a dose rate of 5 × 108 CFU/kg and 2.5 × 109 CFU/kg, respectively. Dietary supplementation with B. subtilis did not significantly affect overall egg production in both groups, with no obvious changes in average egg weight and intestine morphology. B. subtilis administration also improved the physical barrier function of the intestine by inducing significantly greater expression levels of the tight junction protein occludin in T1 (p = 0.07) and T2 (p < 0.05). Further, supplementation with B. subtilis effectively modulated the cecal microbiota, increasing the relative level of beneficial bacteria at the genus level (e.g., Bifidobacterium p < 0.05, Lactobacillus p = 0.298, Bacillus p = 0.550) and decreasing the level of potential pathogens (e.g., Fusobacterium p < 0.05, Staphylococcus p < 0.05, Campylobacter p = 0.298). Overall, B. subtilis YW1 supplementation cannot significantly improve the egg production; however, it modulated the cecal microbiota towards a healthier pattern and promoted the mRNA expression of the tight junction protein occludin in laying hens, making B. subtilis YW1 a good probiotic candidate for application in the poultry industry, and further expanding the resources of strains of animal probiotics.
Validation of laser‐induced thermal acoustics for chemically reacting H2/air free jets

The scramjet engine is a promising propulsion concept for future space transportation systems. To enhance the engine efficiency, a strong understanding of combustion mechanisms is essential. Laser-induced thermal acoustics (LITA) – a seedless, non-intrusive measurement technique – is an auspicious technique for the investigation of supersonic combustion. Here, we present two validation cases and first LITA measurements in a chemically reacting hydrogen/air free jet. The first validation case is the investigation of premixed methane/air and hydrogen/air flames, produced with a commercially available flat flame burner. The comparison with coherent anti-Stokes Raman spectroscopy measurements resulted in a deviation between the two measurement techniques smaller than the uncertainty of the techniques. The second validation case is the investigation of hot, supersonic air/air free jets at total temperatures of Tt = 1050 K and Tt = 1300 K. The comparison with computational fluid dynamics predictions shows a reasonable agreement with a maximum deviation of 13.9% for the free jet with a temperature of Tt = 1300 K and a good agreement with a maximum deviation of 4.4% for the free jet with a temperature of Tt = 1050 K. The LITA measurements in a chemically reacting hydrogen/air free jet showed a good reproduction of the flame position determined from an OH∗ image. For the presented investigations, we used a homodyne, resonant LITA setup with a pulsed interrogation beam. Copyright © 2016 John Wiley & Sons, Ltd.
The Effects of Technological Interventions on Social Participation of Community-Dwelling Older Adults with and without Dementia: A Systematic Review

Social isolation in community-dwelling older adults with dementia is a growing health issue that can negatively affect health and well-being. To date, little attention has been paid to the role of technology in improving their social participation. This systematic review aims to provide a systematic overview of the effects of technological interventions that target social participation in community-dwelling older adults with and without dementia. The scientific databases Medline (PubMed), PsycINFO, CINAHL, Web of Science, and the Cochrane Library were systematically searched and independently screened by two reviewers. Results were synthesized narratively. The methodological quality of included studies was independently assessed by two reviewers. In total, 36 studies of varying methodological quality were identified. Most studies evaluated social networking technology and ICT training programs. Three studies focused on people with dementia. Quantitative findings showed limited effects on loneliness, social isolation, and social support. Nevertheless, several benefits related to social participation were reported qualitatively. Social interaction, face-to-face contact, and intergenerational engagement were suggested to be successful elements of technological interventions in improving the social participation of community-dwelling older adults. Rigorous studies with larger sample sizes are highly needed to evaluate the long-term effects of technology on the multidimensional concept of social participation.
Effect of sex chromosomes versus hormones in neonatal lung injury

The main mechanisms underlying sexually dimorphic outcomes in neonatal lung injury are unknown. We tested the hypothesis that hormone- or sex chromosome–mediated mechanisms interact with hyperoxia exposure to impact injury and repair in the neonatal lung. To distinguish sex differences caused by gonadal hormones versus sex chromosome complement (XX versus XY), we used the Four Core Genotypes (FCG) mice and exposed them to hyperoxia (95% FiO2, P1–P4: saccular stage) or room air. This model generates XX and XY mice that each have either testes (with Sry, XXM, or XYM) or ovaries (without Sry, XXF, or XYF). Lung alveolarization and vascular development were more severely impacted in XYM and XYF compared with XXF and XXM mice. Cell cycle–related pathways were enriched in the gonadal or chromosomal females, while muscle-related pathways were enriched in the gonadal males, and immune-response–related pathways were enriched in chromosomal males. Female gene signatures showed a negative correlation with human patients who developed bronchopulmonary dysplasia (BPD) or needed oxygen therapy at 28 days. These results demonstrate that chromosomal sex — and not gonadal sex — impacted the response to neonatal hyperoxia exposure. The female sex chromosomal complement was protective and could mediate sex-specific differences in the neonatal lung injury.
Brazilian version of the Clinical COPD Questionnaire, administered by interview: reliability and validity measurement properties

ABSTRACT Objective: To test the reliability, validity, and interpretability of the Brazilian version of the Clinical COPD Questionnaire (CCQ) in patients with COPD. Methods: Fifty patients with COPD completed the CCQ by interview on two occasions. At the first visit, the CCQ was administered twice, by two different raters, approximately 10 min apart; the patients also underwent spirometry and were administered the COPD Assessment Test, the modified Medical Research Council scale, and Saint George’s Respiratory Questionnaire (SGRQ). At the second visit (1-2 weeks later), the CCQ was readministered. We tested the hypothesis that the CCQ total score would correlate positively with the total and domain SGRQ scores (r ≥ 0.5). Results: Of the 50 patients, 30 (60%) were male. The mean age was 66 ± 8 years, and the mean FEV1 was 44.7 ± 17.9% of the predicted value. For all CCQ items, Cronbach’s alpha coefficient (95% CI) was 0.93 (0.91-0.96). To analyze the interrater reliability and test-retest reliability of the CCQ, we calculated the two-way mixed effects model/single measure type intraclass correlation coefficient (0.97 [95% CI: 0.95-0.98] and 0.92 [95% CI: 0.86-0.95], respectively); the agreement standard error of measurement (0.65 for both); the smallest detectable change at the individual level (1.81 and 1.80, respectively) and group level (0.26 and 0.25, respectively); and the limits of agreement (−0.58 to 0.82 and −1.14 to 1.33, respectively). The CCQ total score correlated positively with all SGRQ scores (r ≥ 0.70 for all). Conclusions: The Brazilian version of the CCQ showed an indeterminate measurement error, as well as satisfactory interrater/test-retest reliability and construct validity.
Quantitative Multiplex Immunofluorescence Evaluation of the Tumor Microenvironment in Pretreatment Tumors of Patients with Metastatic Breast Cancer and Serous Ovarian Carcinoma Treated with Liposomal Eribulin

Abstract Eribulin inhibits microtubule polymerization and suppresses epithelial-mesenchymal transition. Conventional pathology approaches have not identified a precise predictive biomarker for Eribulin. We performed qmIF on pre-treatment tissue from 11 patients (6 TNBC, 5 HGSOC) treated with Eribulin-LF. T-lymphocytes were the dominant immune-subset in TME, with higher levels detected in stroma vs tumor (9% vs 2%). Greater density of CD3+ (p = 0.01) and CD3 + CD8+ (p = 0.03) cells and closer proximity between CD3 + CD8+ and tumor cells was observed in the patients with disease control (PR + SD) vs. progressive disease. QmIF identified an association between TIL infiltration and Eribulin-LF sensitivity, which should be evaluated further in prospective studies.
RETRACTED: Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment

Raloxifene hydrochloride (RLX), an antiosteoporotic agent, has been utilized for guarding against breast cancer and recently, for the disease management owing to its estrogen antagonist activity. Nevertheless, RLX exhibits poor bioavailability that could be attributed to reduced water solubility and first pass metabolism. To overcome these challenges, this study aimed at formulating and optimizing RLX emulsomes (RLX-EMLs) to enhance the drug antitumor activity. A 4131 factorial design was employed for assessing the effect of lipoid: solid lipid ratio and solid lipid type on the emulsomes characteristics. The anticancer potential of the optimized formulation and apoptotic parameters were assessed. Vesicle size, entrapment, and release efficiency were significantly influenced by both variables, while zeta potential was influenced by lipoid: solid lipid at p < 0.05. The optimal formulation exhibited vesicle size of 236 ± 8.6 nm, zeta potential of −18.6 ± 0.7 mV, drug entrapment of 98.9 ± 4.9%, and release efficiency of 42.7 ± 1.8%. MTT assay showed concentration-dependent inhibition of MCF-7 cells viability. In addition, cells treated with RLX-EMLs showed significant arrest at G2/M phase associated with significant increase in apoptotic and necrotic cells. The enhanced cytotoxic and anti-proliferative effect of RLX-EMLs relative to raw drug was authenticated through increased Bax/Bcl-2 ratio, caspase-9 activation and depletion of mitochondrial membrane potential.
Test‐dose pharmacokinetics guided melphalan dose adjustment in reduced intensity conditioning allogeneic transplant for non‐malignant disorders

We studied melphalan pharmacokinetics (PK) and feasibility of melphalan full‐dose adjustment based on test‐dose PK in children and young adults with non‐malignant disorders (NMD) undergoing allogeneic hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) containing alemtuzumab, fludarabine and melphalan.
Modelling covalent linkages in CCP4

The mechanism for modelling covalent linkages in CCP4 is reviewed and the method of link-dictionary generation used by AceDRG is described. An overview of the various protocols available for the modelling and application of covalent linkages within the CCP4 suite is presented, providing instructive guidelines with a focus on practical application.
An investigation on microfluidic droplet formation, reagent addition and mixing.

Significant efforts have been targeted towards developing a droplet-based microfluidic system and understanding the droplet formation process and the physics behind it and yet the underlying physics of the droplet formation in terms of evolution of pressures in both the continuous phase and dispersed phase has received less attention over the years and is not understood clearly. A numerical investigation on the mechanism of droplet formation in a microfluidic T-junction has been conducted and validated against the experimental flow visualisation. From the computational results it is shown that the pressure profile of the dispersed phase and the continuous phase in the squeezing regime changes as the droplet break-up process proceeds. New insights on the droplet break-up process such as the minimum pressure difference between the continuous phase and the dispersed phase happens at the last moment of the the droplet break-up and not during the second and third stage of the droplet formation mechanism in the squeezing regime have been identified. As a next step in the analysis, reagent addition to microfluidic droplets is a fundamental operation in high-throughput screenings. Adding precise amount of reagents to droplets poses difficulties and many of the available designs use complicated structures and fabrication methods. A design that reliably adds reagents into droplets by exploiting the physics of fluid flow at an expanded section right after the T-junction which enhances merging of a stream with a droplet, eliminates the drawbacks such as extra droplet formation and long mixing time is demonstrated. Experimental results show that the expanded section minimizes the tendency to form extra droplets; the reactants are in axial arrangement inside the droplets which leads to faster mixing; reliable addition of reagent to the droplets happens for the combination of flow rates in a broad range of both substrate and reagent streams. To understand the physics behind the reliable operation of reagent addition, a numerical investigation using VOF model has been conducted. The flow field and the pressure measurements show that
Common pediatric infestations: update on diagnosis and treatment of scabies, head lice, and bed bugs

Purpose of the review This review will update pediatric providers on the recent data regarding the epidemiology, diagnosis, and treatment of common skin infestations affecting children and adolescents. Recent findings Standard superficial skin biopsy for scabies and the vacuum method for head lice can increase diagnostic accuracy and efficiency. There is growing resistance to some of the traditional treatments for scabies and head lice, and progress has been made in finding newer and potentially more effective treatments, such as oral moxidectin for scabies and abametapir for head lice. Recent studies have established the safety of traditional treatments, such as permethrin and oral ivermectin in infants and small children. Summary Permethrin and ivermectin are both considered safe and effective for children and adolescents with scabies. Permethrin is generally considered safe in infants less than two months of age. Proper application of permethrin is critical, and providers should emphasize proper application technique. Treatment of head lice should only be initiated with active infestations. Resistance to permethrin continues to increase and other options are now available, including an over-the-counter topical ivermectin formulation. Identification and eradication of bed bug infestations are crucial in preventing bedbug bites.
Overconfidence in news judgments is associated with false news susceptibility

Significance Although Americans believe the confusion caused by false news is extensive, relatively few indicate having seen or shared it—a discrepancy suggesting that members of the public may not only have a hard time identifying false news but fail to recognize their own deficiencies at doing so. If people incorrectly see themselves as highly skilled at identifying false news, they may unwittingly participate in its circulation. In this large-scale study, we show that not only is overconfidence extensive, but it is also linked to both self-reported and behavioral measures of false news website visits, engagement, and belief. Our results suggest that overconfidence may be a crucial factor for explaining how false and low-quality information spreads via social media. We examine the role of overconfidence in news judgment using two large nationally representative survey samples. First, we show that three in four Americans overestimate their relative ability to distinguish between legitimate and false news headlines; respondents place themselves 22 percentiles higher than warranted on average. This overconfidence is, in turn, correlated with consequential differences in real-world beliefs and behavior. We show that overconfident individuals are more likely to visit untrustworthy websites in behavioral data; to fail to successfully distinguish between true and false claims about current events in survey questions; and to report greater willingness to like or share false content on social media, especially when it is politically congenial. In all, these results paint a worrying picture: The individuals who are least equipped to identify false news content are also the least aware of their own limitations and, therefore, more susceptible to believing it and spreading it further.
An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgshΔex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgshΔex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgshΔex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgshΔex5−6 mutant larvae in a context-dependent manner. We expect the sgshΔex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.
Invasive Fungal Infections in Persons Living with HIV in an Amazonian Context: French Guiana, 2009–2019

Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view integrating all invasive fungal infections diagnosed over a decade in French Guiana. All patients hospitalized at Cayenne hospital from 1 January 2009 to 31 December 2018 with a proven diagnosis of invasive fungal infection were included (n = 227). Histoplasmosis was the most common (48.2%), followed by Cryptococcus infection (26.3%), and pneumocystosis (12.5%). For cryptococcal infection, there was a discordance between the actual diagnosis of cryptococcal meningitis n = (26) and the isolated presence of antigen in the serum (n = 46). Among the latter when the information was available (n = 34), 21(65.6%) were treated with antifungals but not coded as cryptococcocosis. Most fungal infections were simultaneous to the discovery of HIV (38%) and were the AIDS-defining event (66%). The proportion of major invasive fungal infections appeared to remain stable over the course of the study, with a clear predominance of documented H. capsulatum infections. Until now, the focus of attention has been histoplasmosis, but such attention should not overshadow other less-studied invasive fungal infections.