Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers and facilitators in the delivery of a proportionate universal parenting program model (E-SEE Steps) in community family services

Background A proportionate universal (PU) approach to early years’ service provision has been advocated to improve children’s health and development and to reduce health inequality, by ensuring that services provide timely and high-quality parenting support commensurate with need. Process-oriented research is critical to examine the factors that contribute to, or hinder, the effective delivery/implementation of such a model in community-based family services. This study aimed to assess the delivery, acceptability and feasibility of a new PU parenting intervention model (called E-SEE Steps), using the Incredible Years® (IY) parent program, when delivered by trained health/family service staff in three “steps”—one universal step (the IY Babies Book), and two targeted steps (group-based IY Infant and Toddler programs). Methods An embedded mixed-methods process evaluation within a pragmatic parallel two-arm, assessor blinded, randomized controlled trial was conducted in community services in four local authorities in England. The process evaluation used qualitative data gathered via interviews and focus groups with intervention arm parents who were offered the targeted steps (n = 29), practitioners (n = 50), service managers (n = 7) and IY program mentors (n = 3). This was supplemented by quantitative data collected using group leader pre-training (n = 50) and post-delivery (n = 39) questionnaires, and research notes of service design decisions. Results The E-SEE Steps model was acceptable to most parents, particularly when it was accompanied by engagement strategies that supported attendance, such as providing childcare. Practitioners also highlighted the positive development opportunities provided by the IY training and supervision. However, participant views did not support the provision of the IY Babies book as a standalone universal component, and there were barriers to eligible parents—particularly those with low mood—taking up the targeted programs. Service providers struggled to align the PU model with their commissioned service contracts and with their staff capacity to engage appropriate parents, including tackling common barriers to attendance. Conclusions Despite general enthusiasm and support for delivering high-quality parenting programs in community services in the England, several barriers exist to successfully delivering IY in a proportionate universal model within current services/systems.
The onset of PI3K‐related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib

Low‐flow vascular malformations are congenital overgrowths composed of abnormal blood vessels potentially causing pain, bleeding and obstruction of different organs. These diseases are caused by oncogenic mutations in the endothelium, which result in overactivation of the PI3K/AKT pathway. Lack of robust in vivo preclinical data has prevented the development and translation into clinical trials of specific molecular therapies for these diseases. Here, we demonstrate that the Pik3caH1047R activating mutation in endothelial cells triggers a transcriptome rewiring that leads to enhanced cell proliferation. We describe a new reproducible preclinical in vivo model of PI3K‐driven vascular malformations using the postnatal mouse retina. We show that active angiogenesis is required for the pathogenesis of vascular malformations caused by activating Pik3ca mutations. Using this model, we demonstrate that the AKT inhibitor miransertib both prevents and induces the regression of PI3K‐driven vascular malformations. We confirmed the efficacy of miransertib in isolated human endothelial cells with genotypes spanning most of human low‐flow vascular malformations.
Disease spreading modeling and analysis: a survey

MOTIVATION The control of the diffusion of diseases is a critical subject of a broad research area, which involves both clinical and political aspects. It makes wide use of computational tools, such as ordinary differential equations, stochastic simulation frameworks and graph theory, and interaction data, from molecular to social granularity levels, to model the ways diseases arise and spread. The coronavirus disease 2019 (COVID-19) is a perfect testbench example to show how these models may help avoid severe lockdown by suggesting, for instance, the best strategies of vaccine prioritization. RESULTS Here, we focus on and discuss some graph-based epidemiological models and show how their use may significantly improve the disease spreading control. We offer some examples related to the recent COVID-19 pandemic and discuss how to generalize them to other diseases.
Strategies and Lessons Learned from a Home Delivery Food Prescription Program for Older Adults

Abstract Food insecurity (FI) is a growing health problem, worsening during the COVID-19 pandemic. Fresh food prescription programs (FFRx) have been shown to increase healthy eating and decrease FI, but few FFRx are community-informed, or theory based. Our FFRx was a delivery program developed to alleviate FI for older adults. It was implemented in an academic medical center and guided by the Capabilities, Opportunities, Motivations, and Behaviors and Theoretical Domains Framework. We tested impacts of the program on FI, Fruit and Vegetable (FV) intake, depression, and loneliness at six-month intervals. During the FFRx, 31 people completed surveys every six months. FI decreased by an average of 2.03 points (p = <.001) while FV intake increased from a mean of 2.8 servings per day to 2.9 servings per day (p = .53). Depression and loneliness scores stayed stable. Preliminary data from this FFRx program, a partnership between an academic medical center and community partners, had positive impacts on FI.
Functional genomics screening identifies aspartyl‐tRNA synthetase as a novel prognostic marker and a therapeutic target for gastric cancers

Efficient molecular targeting therapies for most gastric cancers (GCs) are currently lacking, despite GC being one of the most frequent and often devastating malignancies worldwide. Thus, identification of novel therapeutic targets for GC is in high demand. Recent advancements of high‐throughput nucleic acid synthesis methods combined with next‐generation sequencing (NGS) platforms have made it feasible to conduct functional genomics screening using large‐scale pooled lentiviral libraries aimed at discovering novel cancer therapeutic targets. In this study, we performed NGS‐based functional genomics screening for human GC cell lines using an originally constructed 6,399 shRNA library targeting all 2,096 human metabolism genes. Our screening identified aspartyl‐tRNA synthetase (DARS) as a possible candidate for a therapeutic target for GC. In‐house tissue microarrays containing 346 cases of GC combined with public datasets showed that patients with high expression levels of DARS protein exhibited more advanced clinicopathologic parameters and a worse prognosis, specifically among diffuse‐type GC patients. Both in vitro and in vivo experiments concretely evidenced that DARS inhibition achieved robust growth suppression of GC cells. Moreover, RNA sequencing of GC cell lines under shRNA‐mediated DARS knockdown suggested that DARS inhibition exerts its effect through the inactivation of multiple p‐ERK pathways. This MAPK‐related growth suppression by DARS inhibition would also be applicable to other cancers; thus, it is warranted to investigate the expression and clinical significance of DARS in a wide spectrum of malignancies. Taken together, NGS‐based high‐throughput pooled lentiviral screening showed DARS as a novel prognostic marker and a promising therapeutic target for GC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Ethosomes as dermal/transdermal drug delivery systems: applications, preparation and characterization

Abstract Transdermal drug delivery systems (TDDSs) have gained substantial attention during the last decade. TDDS are versatile delivery systems in which active components are delivered to skin for local effects or systemic delivery of active pharmaceutical through the skin. Overcoming stratum corneum is the most challenging step of delivering drugs through the skin. Lipid-based vesicular delivery systems due to the capability of the delivery of both hydrophilic and hydrophobic drugs are becoming more popular during the recent years. Ethosomes are innovative, biocompatible, biodegradable and non-toxic form of lipid-based vesicles that efficiently enable to entrap drugs of various physicochemical properties. These are other forms of liposome which contain high amounts of ethanol in their structure that enabling ethosomes to efficiently penetrate through deeper layers of skin. Ethosomes have various compositions based on their type but are mainly composed of phospholipids, ethanol, water and the active components. Ethosomes are easily manufactured and they are superior compared to liposomes in terms of different aspects due to the presence of ethanol. The purpose of this review is to thoroughly focus on various aspects of ethosomes, including mechanism of penetration, advantages and disadvantages, characterisation and applications.
Órfãos de terapia medicamentosa: a administração de medicamentos por via intravenosa em crianças hospitalizadas

Estudo descritivo, realizado em um hospital universitario, que verificou quantidade e tipo de medicamentos administrados por via intravenosa em criancas, alem da adequacao da apresentacao farmacologica para uso em pediatria e custo estimado de administracao de algumas drogas. Em trinta dias, foram administradas 8.245 doses de medicamentos, com media diaria de 274,83 doses, e projecao anual de 98.940. Os principais medicamentos utilizados foram metilpredinosolona, vancomicina, furosemida, ranitidina, penicilina, amicacina, midazolan, fentanil, ceftriaxone e cefalotina. Nenhum dos 41 medicamentos identificados possuia apresentacao pediatrica, acarretando, em alguns casos, maior manipulacao durante o preparo, risco de contaminacao e perda da estabilidade. Observou-se que a falta de apresentacao pediatrica gerou aumento dos custos de atendimento; na prescricao de uma crianca em pos-operatorio, com tempo de internacao estimado de cinco dias, a terapia administrada diaria foi de US$ 6.71, e US$ 39.52 de medicamentos tiveram que ser desprezados, por excederem as necessidades terapeuticas da crianca.
“Everything looks the same”: wayfinding behaviour and experiences of stroke inpatients in rehabilitation clinics

ABSTRACT Purpose To examine stroke inpatients’ real-life wayfinding behaviour and how the built environment of rehabilitation clinics might influence their behaviour and experiences. Methods Stroke inpatients in seven rehabilitation clinics were observed (n = 70), each over the course of 12 consecutive hours. Their paths through the clinic and the locations of encountered wayfinding-related events were mapped on the floor plans and described in the written notes. The observations were supplemented by a survey asking patients about their wayfinding experiences. Results For a third of observed patients, at least one wayfinding-related event was observed on the observation day, and 50% of patients reported getting lost in their clinic at least once. Most wayfinding-related events occurred between patient rooms and therapy rooms, and patients frequently relied on backtracking or the help of the staff to find their way. Clinics’ layout organization was found to play a role in the wayfinding behaviour of patients. Conclusions Wayfinding is a common challenge that stroke inpatients encounter in rehabilitation clinics. Avoiding multiple decision nodes on the paths between patient rooms and therapy rooms and creating distinct identities for corridor segments in the decision nodes and the areas in front of elevators would likely improve wayfinding performance.
Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease

We studied small vessel disease (SVD) pathology in Familial Alzheimer's disease (FAD) subjects carrying the presenilin 1 (PSEN1) p.Glu280Ala mutation in comparison to those with sporadic Alzheimer's disease (SAD) as a positive control for Alzheimer's pathology and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) bearing different NOTCH3 mutations, as positive controls for SVD pathology. Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. In post‐mortem studies, total SVD pathology in cortical areas and basal ganglia was similar in PSEN1 FAD and CADASIL subjects, except for the feature of arteriosclerosis which was higher in CADASIL subjects than in PSEN1 FAD subjects. Further only a few SAD subjects showed a similar degree of SVD pathology as observed in CADASIL. Furthermore, we found significantly enlarged perivascular spaces in vessels devoid of cerebral amyloid angiopathy in FAD compared with SAD and CADASIL subjects. As expected, there was greater fibrinogen‐positive perivascular reactivity in CADASIL but similar reactivity in PSEN1 FAD and SAD groups. Fibrinogen immunoreactivity correlated with onset age in the PSEN1 FAD cases, suggesting increased vascular permeability may contribute to cognitive decline. Additionally, we found reduced perivascular expression of PDGFRβ AQP4 in microvessels with enlarged PVS in PSEN1 FAD cases. We demonstrate that there is Aβ‐independent SVD pathology in PSEN1 FAD, that was marginally lower than that in CADASIL subjects although not evident by MRI. These observations suggest presence of covert SVD even in PSEN1, contributing to disease progression. As is the case in SAD, these consequences may be preventable by early recognition and actively controlling vascular disease risk, even in familial forms of dementia.
Pro-, pre- and synbiotics for the prevention of incidental ventilator-associated pneumonia among critically ill patients: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Objectives This study investigated the preventive effects of pro-, pre- and synbiotics on ventilator-associated pneumonia (VAP) among critically ill patients. Methods The PubMed, Web of Science, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before 19 February 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of pro-, pre- and synbiotics with placebos or standard treatments for the prevention of incidental VAP were included. Results A total of 15 RCTs were included. Patients receiving pro-, pre- and synbiotics had a lower risk than the control group of contracting VAP (risk ratio [RR], 0.70; 95% CI, 0.57–0.85; I 2 = 67%). The duration of mechanical ventilation was significantly shorter in the study group than in the control group (mean difference [MD], −1.61 days; 95% CI, −2.72 to −0.50; I 2 = 86%), and the study group had a shorter duration of stay in the intensive care unit than the control group did (MD, −1.72 days; 95% CI, −3.22 to −0.23; I 2 = 87%). Conclusions Pro-, pre- and synbiotics can prevent VAP and the use of probiotics for patients who are critically ill should be supported.
Psychological Morbidity in the Farming Community: A Literature Review

ABSTRACT The mental health of the farming community across industrialised nations has long been a major concern. Using an adapted procedure for a systematic literature review of observational epidemiological studies reporting prevalence (informed by the Joanna Briggs Institute method), this paper reviews peer-reviewed literature that explicitly compares farmer and non-farmer mental health (n = 48). In doing so, it provides a central and accessible evidence base for researchers and practitioners, and simultaneously reveals a stark lack of consensus; specifically, 54.0% of measures deployed to assess farmer mental health determined it to be the same as or even better than non-farming populations. This ambiguity sits in sharp contrast to the unequivocally worrisome farmer suicide statistics. Informed by the literature, the paper discusses potential reasons for this mismatch, including (i) farmers’ progression through a different “pathway” to suicide that is not always preceded by mental illness, and (ii) a failure of current methods to accurately gauge the mental health status of farmers. The paper concludes by recommending more research into farmers’ “pathway” to suicide, and highlights the need for a dedicated and multi-disciplinary programme of methods research that will afford a more culturally appropriate and effective means of understanding mental health in the farming community.
Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity

Abstract Objectives. Endothelial dysfunction caused by oxidative stress plays an important role in the development of vasospastic angina pectoris (VSAP). Glutamate causes endothelial dysfunction by generating oxidative stress, and it inhibits cystine import into endothelial cells via the cystine/glutamate antiporter (XC –), which leads to depletion of antioxidant glutathione. However, whether glutamate and cystine are implicated in the pathogenesis of VSAP remains unclear. We investigated plasma glutamate and cystine levels, oxidative stress markers and antioxidant capacity in non-smoker patients with VSAP to determine whether glutamate and cystine are associated with the development of VSAP. We assessed 49 non-smokers assigned to groups with (n = 27) and without (n = 22) VSAP, and also measured plasma glutamate, cystine, nitrotyrosine, reactive oxygen metabolites and biological antioxidant potential. Results. Plasma glutamate and cystine values were significantly higher in the group with, than without VSAP (59.8 ± 25.7 vs. 43.5 ± 18.7 µmol/L, p = .016 and 35.3 ± 14.2 vs. 25.2 ± 9.1 µmol/L, p = .0056, respectively). Plasma glutamate and cystine values were significantly and positively associated (r = 0.32, p = .027). Levels of the oxidative stress markers nitrotyrosine and reactive oxygen metabolites, and biological antioxidant potential of as a measure of antioxidant capacity, did not significantly differ between the two groups. However, glutamate and biological antioxidant potential values were significantly and negatively associated (r = −0.3, p = .036). Conclusion. Plasma glutamate levels were increased in patients with VSAP who did not smoke, and they were positively associated with plasma cystine and negatively associated with the biological antioxidant potential levels.
Fungal communities in European alpine soils are not affected by short-term in situ simulated warming than bacterial communities.

The impact of global warming on biological communities colonizing European alpine ecosystems was recently studied. Hexagonal open top chambers (OTCs) were used for simulating a short-term in situ warming (estimated around 1°C) in some alpine soils to predict the impact of ongoing climate change on resident microbial communities. Total microbial DNA was extracted from soils collected either inside or outside the OTCs over 3 years of study. Bacterial and fungal rRNA copies were quantified by qPCR. Metabarcoding sequencing of taxonomy target genes was performed (Illumina MiSeq) and processed by bioinformatic tools. Alpha- and beta-diversity were used to evaluate the structure of bacterial and fungal communities. qPCR suggests that, although fluctuations have been observed between soils collected either inside and outside the OTCs, the simulated warming induced a significant (p < 0.05) shift only for bacterial abundance. Likewise, significant (p < 0.05) changes in bacterial community structure were detected in soils collected inside the OTCs, with a clear increase of oligotrophic taxa. On the contrary, fungal diversity of soils collected either inside and outside the OTCs did not exhibit significant (p < 0.05) differences, suggesting that the temperature increase in OTCs compared to ambient conditions was not sufficient to change fungal communities.
Differential regulatory roles of microRNAs during intramuscular adipogenesis in Chinese Guizhou Congjiang Xiang pigs

ABSTRACT Intramuscular fat development is regulated by a series of complicated processes, with non-coding RNA (ncRNA) such as microRNA (miRNA) having a critical role during intramuscular preadipocyte proliferation and differentiation in pigs. In the present study, the miRNA expression profiles of intramuscular preadipocytes from the longissimus dorsi muscle of Chinese Guizhou Congjiang Xiang pigs were detected by RNA-seq during various differentiation stages, namely, day 0 (D0), day 4 (D4), and day 8 (D8). A total of 67, 95, and 16 differentially expressed (DE) miRNAs were detected between D4 and D0, D8 and D0, and D8 and D4, respectively. According to gene ontology and Kyoto Encyclopedia of Genes analysis, target genes of DE miRNAs were enriched in categories and pathways related to lipid metabolic process, lipid biosynthetic process, as well as the PI3K-Akt, AMPK, and MAPK signalling pathways. Notably, miR-148a-3p was differentially expressed, with highest expressed abundance in D0, D4, and D8. Overexpression of miR-148a-3p in intramuscular preadipocytes increased cell proliferation and differentiation, and decreased apoptosis, in comparison to the knockdown of miR-148a-3p in intramuscular preadipocytes. Luciferase activity assays, quantitative polymerase-chain reaction, and western blot analysis confirmed that miR-148a-3p regulated adipogenesis by repressing PPARGC1A expression. Accordingly, the effect of miR-148a-3p mimic was attenuated by overexpression of PPARGC1A intramuscular preadipocytes. Furthermore, miR-148a-3p promoted intramuscular preadipocyte differentiation by inhibiting the AMPK/ACC/CPT1C signalling pathway. Taken together, we identified expression profiles of miRNAs in intramuscular preadipocytes and determined that miR-148a-3p acted as a promoter of adipogenesis.