Miracle-dz/UniFAR-FTUs huggingface dataset:
British nuclear test veteran family trios for the study of genetic risk

The risk of radiation effects in children of individuals exposed to ionising radiation remains an ongoing concern for aged veterans of the British nuclear testing programme. The genetic and cytogenetic family trio (GCFT) study is the first study to obtain blood samples from a group of British nuclear test veterans and their families for the purposes of identifying genetic alterations in offspring as a consequence of historical paternal exposure to ionising radiation. In this report, we describe the processes for recruitment and sampling, and provide a general description of the study population recruited. In total, blood samples were received from 91 (49 test and 42 control) families representing veteran servicemen from the army, Royal Air Force and Royal Navy. This translated to an overall response rate of 14% (49/353) for test veterans and 4% (42/992) for control veterans (excluding responders known to be ineligible). Due to the lack of dose information available, test veterans were allocated to a three-point exposure rank. Thirty (61%) test veterans were ranked in the lower group. Nineteen (39%) of the 49 test veterans were classified in the mid (5 veterans; 10%)/high (14 veterans; 29%) exposure ranks and included 12 veterans previously identified as belonging to the special groups or listed in health physics documents. An increased number of test veteran families (20%), compared with control families (5%), self-reported offspring with congenital abnormalities (p = 0.03). Whether this observation in this small group is reflective of the entire UK test veteran cohort or whether it is selection bias requires further work. The cohort described here represent an important and unique family trio grouping whose participation is enabling genetic studies, as part of the GCFT study, to be carried out. The outcomes of these studies will be published elsewhere. ISRCTN Registry: 17461668.
Short- and medium-term effect of inhaled corticosteroids on exhaled breath biomarkers in severe asthma

Inhaled corticosteroids (ICS) are the mainstay of therapy in asthma, but benefits vary due to disease heterogeneity. Steroid insensitivity is a particular problem in severe asthma, where patients may require systemic corticosteroids and/or biologics. Biomarkers sensitive to ICS over a short period of time could inform earlier and more personalised treatment choices. To investigate how exhaled breath biomarkers change over two-hours and one-week following monitored ICS dosing in severe asthma patients with evidence of uncontrolled airway inflammation. Patients with severe asthma and elevated fractional exhaled nitric oxide (FeNO) (⩾45 ppb, indicative of active airway inflammation) were recruited. Exhaled breath biomarkers were evaluated using (FeNO), exhaled breath temperature (EBT), particles in exhaled air (PExA) and volatile organic compounds (VOCs). Samples were collected over 2 h following observed inhalation of 1000 mcg fluticasone propionate, and at a second visit 1 week after taking the same dose daily via an inhaler monitoring device that recorded correct actuation and inhalation. Changes in parameters over 2 h were analysed by the Friedman test and 1 week by Wilcoxon’s test (p-value for significance set at 0.05; for VOCs false discovery rate q of 0.1 by Benjamini–Hochberg method applied). 17 participants (9 male) were recruited, but three could not complete PExA and two FeNO testing, as they were unable to comply with the necessary technique; complete datasets were available from 12 (9 male) with median (interquartile range) age 45 (36–59) yrs. EBT (p < 0.05) and levels of six VOCs (q < 0.1) fell over the 2 h after high dose ICS; there were no changes in FeNO or PExA. After one week of using high dose ICS, there were falls in FeNO, EBT and two VOCs (p < 0.05), but no changes in PExA. Reduction in EBT over the short and medium term after high dose ICS may reflect airway vascular changes, and this, together with the observed changes in exhaled VOCs, merits further investigation as potential markers of ICS use and effectiveness.
Neural processing and perception of Schroeder‐phase harmonic tone complexes in the gerbil: Relating single‐unit neurophysiology to behavior

Schroeder‐phase harmonic tone complexes have been used in physiological and psychophysical studies in several species to gain insight into cochlear function. Each pitch period of the Schroeder stimulus contains a linear frequency sweep; the duty cycle, sweep velocity, and direction are controlled by parameters of the phase spectrum. Here, responses to a range of Schroeder‐phase harmonic tone complexes were studied both behaviorally and in neural recordings from the auditory nerve and inferior colliculus of Mongolian gerbils. Gerbils were able to discriminate Schroeder‐phase harmonic tone complexes based on sweep direction, duty cycle, and/or velocity for fundamental frequencies up to 200 Hz. Temporal representation in neural responses based on the van Rossum spike‐distance metric, with time constants of either 1 ms or related to the stimulus' period, was compared with average discharge rates. Neural responses and behavioral performance were both expressed in terms of sensitivity, d', to allow direct comparisons. Our results suggest that in the auditory nerve, stimulus fine structure is represented by spike timing, whereas envelope is represented by rate. In the inferior colliculus, both temporal fine structure and envelope appear to be represented best by rate. However, correlations between neural d' values and behavioral sensitivity for sweep direction were strongest for both temporal metrics, for both auditory nerve and inferior colliculus. Furthermore, the high sensitivity observed in the inferior colliculus neural rate‐based discrimination suggests that these neurons integrate across multiple inputs arising from the auditory periphery.
Esketamine for Unipolar Major Depression With Psychotic Features

Abstract Purposes/Background The aims of the study were to assess subanesthetic esketamine as an antidepressant for major depressive disorder with psychotic features (PMDD) and to compare posttreatment symptoms among those with PMDD to a sample of nonpsychotic depression (major depressive disorder [MDD]). Methods/Procedures This study is a retrospective chart review of patients with major depression and current psychotic symptoms, treated with a single parenteral 0.5-mg/kg dose of esketamine. Depression symptoms were assessed at baseline and 24-hour posttreatment with the Montgomery-Åsberg Depression Rating Scale. Individuals with PMDD were matched in a 1:2 ratio to nonpsychotic MDD patients from a randomized, noninferiority clinical trial of esketamine. Findings/Results A total of 15 individuals with PMDD were included, which had higher baseline depression scores (PMDD = 40.9, MDD = 33.6, P = 0.004). A statistically significant change in depressive symptoms was found for the PMDD sample (β = −16.20 [95% confidence interval, −23.30 to −9.10], P < 0.001), and no difference between PMDD and MDD groups was observed in the matched-sample analysis (β = −2.2 [95% confidence interval, −9.32 to 4.58], P = 0.537). Treatment-induced dissociative symptoms were present for both groups, self-contained to within 2 hours after treatment, and no exacerbation of psychotic symptoms was found in clinical assessments. Implications/Conclusions Results suggest a single 0.5-mg/kg dose of esketamine may benefit individuals with PMDD, and the symptom reduction may be comparable with esketamine's effects for MDD. Furthermore, esketamine may induce an antidepressant response in those with PMDD without complication of psychotic symptoms. Future research with controlled designs is warranted.
Laminin-511 Activates the Human Induced Pluripotent Stem Cell Survival via α6β1 Integrin-Fyn-RhoA-ROCK Signaling

In human induced pluripotent stem cells (hiPSCs), laminin-511/α6β1 integrin interacts with E-cadherin, an intercellular adhesion molecule, to induce the activation of the phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway. The interaction between laminin-511/α6β1 integrin and E-cadherin, an intercellular adhesion molecule, results in protection against apoptosis through the proto-oncogene tyrosine-protein kinase Fyn(Fyn)-RhoA-ROCK signaling pathway and the Ras homolog gene family member A (RhoA)/Rho kinase (ROCK) signaling pathway (the major pathway for cell death). In this article, the impact of laminin-511 on hiPSC on α6β1 integrin-Fyn-RhoA-ROCK signaling is discussed and explored along with validation experiments. PIK3CA mRNA (mean [standard deviation {SD}]: iMatrix-511, 1.00 [0.61]; collagen+MFGE8, 0.023 [0.02]; **P < 0.01; n = 6) and PIK3R1 mRNA (mean [SD]: iMatrix-511, 1.00 [0.79]; collagen+MFGE8, 0.040 [0.06]; *P < 0.05; n = 6) were upregulated by iMatrix-511 resulting from an increased expression of Integrin α6 mRNA (mean [SD]: iMatrix-511, 1.00 [0.42]; collagen+MFGE8, 0.23 [0.05]; **P < 0.01; n = 6). The iMatrix-511 increased the expression of p120-Catenin mRNA (mean [SD]: iMatrix-511, 1.00 [0.71]; collagen+MFGE8, 0.025 [0.03]; **P < 0.01; n = 6) and RAC1 mRNA (mean [SD]: iMatrix-511, 1.00 [0.28]; collagen+MFGE8, 0.39 [0.15]; **P < 0.01; n = 6) by increasing the expression of E-cadherin mRNA (mean [SD]: iMatrix-511, 1.00 [0.38]; collagen+MFGE8, 0.16 [0.11]; **P < 0.01; n = 6). As a result, iMatrix-511 increased the expression of P190 RhoGAP (GTPase-activating proteins) mRNA, such as ARHGAP1 mRNA (mean [SD]: iMatrix-511, 1.00 [0.57]; collagen+MFGE8, 0.032 [0.03]; **P < 0.01; n = 6), ARHGAP4 mRNA (mean [SD]: iMatrix-511, 1.00 [0.56]; collagen+MFGE8, 0.039 [0.049]; **P < 0.01; n = 6), and ARHGAP5 mRNA (mean [SD]: iMatrix-511, 1.00 [0.39]; collagen+MFGE8, 0.063 [0.043]; **P < 0.01; n = 6). Western blotting showed that phospho-Rac1 remained in the cytoplasm and phospho-Fyn showed nuclear transition in iPSCs cultured on iMatrix-511. Proteome analysis showed that PI3K signaling was enhanced and cytoskeletal actin was activated in iPSCs cultured on iMatrix-511. In conclusion, laminin-511 strongly activated the cell survival by promoting α6β1 integrin-Fyn-RhoA-ROCK signaling in hiPSCs.
Systematic overexpression of genes encoded by mycobacteriophage Waterfoul reveals novel inhibitors of mycobacterial growth

Abstract Bacteriophages represent an enormous reservoir of novel genes, many of which are unrelated to existing entries in public databases and cannot be assigned a predicted function. Characterization of these genes can provide important insights into the intricacies of phage–host interactions and may offer new strategies to manipulate bacterial growth and behavior. Overexpression is a useful tool in the study of gene-mediated effects, and we describe here the construction of a plasmid-based overexpression library of a complete set of genes for Waterfoul, a mycobacteriophage closely related to those infecting clinically important strains of Mycobacterium tuberculosis and/or Mycobacterium abscessus. The arrayed Waterfoul gene library was systematically screened in a plate-based cytotoxicity assay, identifying a diverse set of 32 Waterfoul gene products capable of inhibiting the growth of the host Mycobacterium smegmatis and providing a first look at the frequency and distribution of cytotoxic products encoded within a single mycobacteriophage genome. Several of these Waterfoul gene products were observed to confer potent anti-mycobacterial effects, making them interesting candidates for follow-up mechanistic studies.
Cancer‐related cognitive impairment in survivors of adolescent and young adult non‐central nervous system cancer: A scoping review

Cancer‐related cognitive impairments (CRCI) are common after treatment and can have important impacts on the lives of adolescent and young adult (AYA) cancer survivors—those cancer survivors diagnosed between ages 15 and 39. However, most research focuses on survivors diagnosed under age 15 or over age 39 so we know relatively little about CRCI among AYA survivors of non‐central nervous system (CNS) cancers. Here we review the research on CRCI among AYA survivors of non‐CNS cancers to determine prevalence, associated factors, and impact on survivors' lives as well as implications for future research.
Effectiveness of prophylactic application of negative pressure wound therapy in stopping surgical site wound problems for closed incisions in breast cancer surgery: A meta‐analysis

We performed a meta‐analysis to evaluate the effect of prophylactic application of negative pressure wound therapy in stopping surgical site wound problems for closed incisions in breast cancer surgery. A systematic literature search up to April 2022 was performed and 2223 women with closed incisions in breast cancer surgery at the baseline of the studies; 964 of them were using the prophylactic application of negative pressure wound therapy, and 1259 were using standard dressings. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of prophylactic application of negative pressure wound therapy in stopping surgical site wound problems for closed incisions in breast cancer surgery using the dichotomous method with a random or fixed‐effect model. The prophylactic application of negative pressure wound therapy women had a significantly lower total wound problems (OR, 0.62; 95% CI, 0.43‐0.90, P = .01), lower surgical site wound infection (OR, 0.59; 95% CI, 0.36‐0.96, P = .03), lower wound dehiscence (OR, 0.54; 95% CI, 0.39‐0.75, P < .001) and lower wound necrosis (OR, 0.44; 95% CI, 0.27‐0.71, P < .001), in women with closed incisions in breast cancer surgery compared with standard dressings. However, prophylactic application of negative pressure wound therapy did not show any significant difference in wound seroma (OR, 0.73; 95% CI, 0.32‐1.65, P = .45), and hematoma (OR, 0.73; 95% CI, 0.33‐1.59, P = .001) compared with standard dressings in women with closed incisions in breast cancer surgery. The prophylactic application of negative pressure wound therapy women had a significantly lower total wound problems, surgical site wound infection, wound dehiscence, and wound necrosis and no significant difference in wound seroma, and hematoma compared with standard dressings in women with closed incisions in breast cancer surgery. The analysis of outcomes should be with caution because of the low sample size of 5 out of 12 studies in the meta‐analysis and a low number of studies in certain comparisons.
Bio-guided isolation of androsta-1,4-dien-3,16-dione as a vasodilator active principle from the inflorescence of Ravenala madagascariensis Sonn. (Strelitziaceae)

Abstract Androsta-1,4-dien-3,16-dione was isolated for the first time from the plant kingdom of the ethanolic extract of the Ravenala madagascariensis’ inflorescence by the bio-guided method. Its structure was elucidated by NMR and MS spectroscopic data analysis. The vascular effects of ethanol extracts, fractions and androsta-1,4-dien-3,16-dione were assessed on the phenylephrine pre-contracted isolated rat aorta. The isolated compound exerted the most potent vaso-relaxing effect (EC50 = 109.32 ± 15.82 µM) than the ethanol extract and fractions. The pharmacological mechanism of its vaso-relaxing action was analysed on isolated rat aorta using free-endothelial vascular tissue, specific contracting reagents (CaCl2 and KCl), antagonist (propranolol), enzyme inhibitors (L-NAME, methylene blue) and channel blocker (glibenclamide). Its vaso-relaxing activity could be due, at least partly, to the non-specific inhibition of the calcic influx. Graphical Abstract
Associations between physical activity, motor skills, executive functions and early numeracy in preschoolers

ABSTRACT We investigated direct and indirect cross-sectional associations of physical activity, fundamental motor skills, executive functions, and early numeracy in preschoolers. The participants were 214 preschoolers aged three to five years. Time spent in moderate and vigorous physical activity was measured by hip-worn accelerometers and fundamental motor skills using the tasks assessing locomotor, object control, and stability skills. Inhibition/switching and working memory/updating, as components of executive functions, were assessed by computerised tests and a standardised test was used to assess early numeracy. Path analyses were used to examine direct and indirect associations between the constructs. Our results showed that stability skills were indirectly positively associated with early numeracy through inhibition/switching (β = 0.07, p < 0.05, 95% CI [0.02, 0.14]) and locomotor skills through working memory/updating (β = 0.13, p = 0.001, 95% CI [0.06, 0.20]). Vigorous physical activity was positively associated with early numeracy through locomotor skills and working memory/updating (β = 0.04, p = 0.01, 95% CI [0.01, 0.07]) and negatively associated with early numeracy through inhibition/switching (β = −0.06, p < 0.05, 95% CI [−0.11, −0.02]). Highlights Locomotor skills are positively associated with early numeracy through working memory/updating. Stability skills are positively associated with early numeracy through inhibition/switching. Vigorous physical activity is indirectly associated with early numeracy: Positively through locomotor skills and working memory/updating and negatively through inhibition/switching.
“Trying to develop a better workforce”: Stakeholders’ perspectives of a practice-integrated Australian hospital pharmacist foundation residency program

Background Practice-integrated education and professional development programs (also known as residencies), have been available to pharmacists in America and the United Kingdom for many years. In 2016, the Society of Hospital Pharmacists of Australia launched Australia’s novel Foundation Residency Program to support the development of early-career pharmacists, and has been implemented across many hospitals nationally. This model was adopted by the South Australian (SA) public hospital pharmacy statewide service and was granted full accreditation. The study aimed to explore key stakeholders’ expectations and early perceptions of the structure, role and impact of the SA program and in that process, to identify key influencing factors and strategies informing future program planning and design. Methods Purposeful sampling was adopted to recruit participants who oversee preceptors and residents, across all employment levels and pharmacy service sites. Stakeholders participated in individual semi-structured interviews. Each interview was audio-recorded and transcribed verbatim. The transcribed dataset was managed using NVivo softwareTM (version 10) and analysed using reflexive thematic analysis through the lens of the PRECEDE-PROCEED logic model framework. Results Thirty-three staff consented to participate. Participants were de-identified with a randomly assigned code number. Three key themes were identified using reflexive thematic analysis; alignment of program goals and visions, culture shift to prioritising workforce development as core business, program structure supports focused workforce development. Conclusions Participants view the residency as beneficial for development of the residents, preceptors, and the hospital pharmacy workforce. The multisite structure was a strength of the program. Whilst it was acknowledged that the rotations, cross-site rotations, and research project presented challenges, they were deemed worth the investment. Overall, it was felt that incremental increases in program capacity will occur over time, as culture changes, and as investing in workforce development becomes core business. The findings have led to several key recommendations to guide program expansion.
The Drivers of Acceptance of Artificial Intelligence–Powered Care Pathways Among Medical Professionals: Web-Based Survey Study

Background The emergence of Artificial Intelligence (AI) has been proven beneficial in several health care areas. Nevertheless, the uptake of AI in health care delivery remains poor. Despite the fact that the acceptance of AI-based technologies among medical professionals is a key barrier to their implementation, knowledge about what informs such attitudes is scarce. Objective The aim of this study was to identify and examine factors that influence the acceptability of AI-based technologies among medical professionals. Methods A survey was developed based on the Unified Theory of Acceptance and Use of Technology model, which was extended by adding the predictor variables perceived trust, anxiety and innovativeness, and the moderator profession. The web-based survey was completed by 67 medical professionals in the Netherlands. The data were analyzed by performing a multiple linear regression analysis followed by a moderating analysis using the Hayes PROCESS macro (SPSS; version 26.0, IBM Corp). Results Multiple linear regression showed that the model explained 75.4% of the variance in the acceptance of AI-powered care pathways (adjusted R2=0.754; F9,0=22.548; P<.001). The variables medical performance expectancy (β=.465; P<.001), effort expectancy (β=–.215; P=.005), perceived trust (β=.221; P=.007), nonmedical performance expectancy (β=.172; P=.08), facilitating conditions (β=–.160; P=.005), and professional identity (β=.156; P=.06) were identified as significant predictors of acceptance. Social influence of patients (β=.042; P=.63), anxiety (β=.021; P=.84), and innovativeness (β=.078; P=.30) were not identified as significant predictors. A moderating effect by gender was found between the relationship of facilitating conditions and acceptance (β=–.406; P=.09). Conclusions Medical performance expectancy was the most significant predictor of AI-powered care pathway acceptance among medical professionals. Nonmedical performance expectancy, effort expectancy, perceived trust, and professional identity were also found to significantly influence the acceptance of AI-powered care pathways. These factors should be addressed for successful implementation of AI-powered care pathways in health care delivery. The study was limited to medical professionals in the Netherlands, where uptake of AI technologies is still in an early stage. Follow-up multinational studies should further explore the predictors of acceptance of AI-powered care pathways over time, in different geographies, and with bigger samples.
A meta‐analysis of the associations of elements of the fear‐avoidance model of chronic pain with negative affect, depression, anxiety, pain‐related disability and pain intensity

Biopsychosocial conceptualizations of clinical pain conditions recognize the multi‐faceted nature of pain experience and its intersection with mental health. A primary cognitive‐behavioural framework is the Fear‐Avoidance Model, which posits that pain catastrophizing and fear of pain (including avoidance, cognitions and physiological reactivity) are key antecedents to, and drivers of, pain intensity and disability, in addition to pain‐related psychological distress. This study aimed to provide a comprehensive analysis of the magnitude of the cross‐sectional association between the primary components of the Fear‐Avoidance Model (pain catastrophizing, fear of pain, pain vigilance) with negative affect, anxiety, depression, pain intensity and disabilities in studies of clinical pain.