Miracle-dz/UniFAR-FTUs huggingface dataset:
The Contribution of Pharmacists and Pharmacy Technicians to Person-Centred Care within a Medicine’s Optimisation in Care Homes Service: A Qualitative Evaluation

Pharmacists and pharmacy technicians seek to improve person-centred care. Improvements to systems for care homes seeks to reduce medicines waste and inefficiency, particularly through supporting care home staff, to enhance safer administration of medicines. A complex evaluation used qualitative design and utilised narrative enquiry, and team members and key stakeholders were interviewed. Framework analysis was used, aligning findings to a person-centred care framework for older people. The Medicines Optimisation in Care Homes (MOCH) team brokered improvement practices across care homes to enhance person-centred care. The framework analysis confirms that the team used ‘authentic attention’ in relation to the residents’ experiences and flexibility in relation to negotiating medication. The importance of transparency of processes and systems in medicines management is highlighted, alongside requirements for person-centred care to make explicit the reason for taking a medication, and the continuous discussion with a range of stakeholders about the continuing need for particular medications. The outcome of the evaluation includes insights into a new area of pharmacy practice in community, based on the skills, knowledge, and experience of pharmacists and pharmacy technicians working in the care home sector. Further study is needed into the efficacy and outcomes of medicines management interventions.
DNA Mismatch Repair and its Role in Huntington’s Disease

DNA mismatch repair (MMR) is a highly conserved genome stabilizing pathway that corrects DNA replication errors, limits chromosomal rearrangements, and mediates the cellular response to many types of DNA damage. Counterintuitively, MMR is also involved in the generation of mutations, as evidenced by its role in causing somatic triplet repeat expansion in Huntington’s disease (HD) and other neurodegenerative disorders. In this review, we discuss the current state of mechanistic knowledge of MMR and review the roles of key enzymes in this pathway. We also present the evidence for mutagenic function of MMR in CAG repeat expansion and consider mechanistic hypotheses that have been proposed. Understanding the role of MMR in CAG expansion may shed light on potential avenues for therapeutic intervention in HD.
Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis

Abstract Background: In osteosarcoma, the lung is the most common metastatic organ. Intensive work has been made to illuminate the pathogeny, but the specific metastatic mechanism remains unclear. Thus, we conducted the study to seek to find the key genes and critical functional pathways associated with progression and treatment in lung metastasis originating from osteosarcoma. Methods: Two independent datasets (GSE14359 and GSE85537) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using DAVID. Meanwhile, the protein-protein interaction (PPI) network constructed by STRING was visualized using Cytoscape. Afterwards, the key module and hub genes were extracted from the PPI network using the MCODE and cytoHubba plugin. Moreover, the raw data obtained from GSE73166 and GSE21257 were applied to verify the expression differences and conduct the survival analyses of hub genes, respectively. Finally, the interaction network of miRNAs and hub genes constructed by ENCORI was visualized using Cytoscape. Results: A total of 364 DEGs were identified, comprising 96 downregulated genes and 268 upregulated genes, which were mainly involved in cancer-associated pathways, adherens junction, ECM-receptor interaction, focal adhesion, MAPK signaling pathway. Subsequently, 10 hub genes were obtained and survival analysis demonstrated SKP2 and ASPM were closely related to poor prognosis of patients with osteosarcoma. Finally, hsa-miR-340-5p, has-miR-495-3p, and hsa-miR-96-5p were found to be most closely associated with these hub genes according to the interaction network of miRNAs and hub genes. Conclusion: The key genes and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of lung metastasis originating from osteosarcoma, and provide potential diagnostic and therapeutic targets.
Deep Learning Techniques for Speech Emotion Recognition, from Databases to Models

The advancements in neural networks and the on-demand need for accurate and near real-time Speech Emotion Recognition (SER) in human–computer interactions make it mandatory to compare available methods and databases in SER to achieve feasible solutions and a firmer understanding of this open-ended problem. The current study reviews deep learning approaches for SER with available datasets, followed by conventional machine learning techniques for speech emotion recognition. Ultimately, we present a multi-aspect comparison between practical neural network approaches in speech emotion recognition. The goal of this study is to provide a survey of the field of discrete speech emotion recognition.
Investigating the representation of uncertainty in neuronal circuits

Skilled behavior often displays signatures of Bayesian inference. In order for the brain to implement the required computations, neuronal activity must carry accurate information about the uncertainty of sensory inputs. Two major approaches have been proposed to study neuronal representations of uncertainty. The first one, the Bayesian decoding approach, aims primarily at decoding the posterior probability distribution of the stimulus from population activity using Bayes' rule, and indirectly yields uncertainty estimates as a by-product. The second one, which we call the correlational approach, searches for specific features of neuronal activity (such as tuning-curve width and maximum firing-rate) which correlate with uncertainty. To compare these two approaches, we derived a new normative model of sound source localization by Interaural Time Difference (ITD), that reproduces a wealth of behavioral and neural observations. We found that several features of neuronal activity correlated with uncertainty on average, but none provided an accurate estimate of uncertainty on a trial-by-trial basis, indicating that the correlational approach may not reliably identify which aspects of neuronal responses represent uncertainty. In contrast, the Bayesian decoding approach reveals that the activity pattern of the entire population was required to reconstruct the trial-to-trial posterior distribution with Bayes' rule. These results suggest that uncertainty is unlikely to be represented in a single feature of neuronal activity, and highlight the importance of using a Bayesian decoding approach when exploring the neural basis of uncertainty.
The Impact of Whole Sesame Seeds on the Expression of Key-Genes Involved in the Innate Immunity of Dairy Goats

Simple Summary This study examined the impact of whole sesame seeds (WSS), rich in both linoleic acid and lignans, on the innate immunity of goats. WSS were incorporated in the concentrates of the control group at 5 and 10% respectively, by partial substitution of both soybean meal and corn grain. The highest supplementation level of WSS resulted in a significant down-regulation in the expression levels of several pro-inflammatory genes in the neutrophils of goats. In conclusion, the dietary supplementation of goats with WSS might be a good nutritional strategy to improve their innate immunity. Abstract Whole sesame seeds (WSS) are rich in both linoleic acid (LA) and lignans. However, their impact on the innate immunity of goats is not well studied. Twenty-four goats were divided into three homogeneous sub-groups; comprise one control (CON) and two treated (WWS5 and WWS10). In the treated groups, WSS were incorporated in the concentrates of the CON at 5 (WSS5) and 10% (WSS10) respectively, by partial substitution of both soybean meal and corn grain. The expression levels of MAPK1, IL6, TRIF, IFNG, TRAF3, and JUND genes in the neutrophils of WSS10 fed goats were reduced significantly compared with the CON. The same was found for the expression levels of IFNG and TRAF3 genes in the neutrophils of WSS5 fed goats. Both treated groups primarily affected the MYD88-independent pathway. The dietary supplementation of goats with WSS might be a good nutritional strategy to improve their innate immunity.
RELATIONSHIP OF THE EATING BEHAVIOR FEATURES WITH ANTHROPOMETRIC INDICATORS AND ENERGY VALUE OF THE DIET IN YOUNG PEOPLE WITH NORMAL WEIGHT AND OVERWEIGHT.

OBJECTIVE The aim: Was to determine the relationship between the characteristics of eating behavior with anthropometric indicators and the energy value of the diet in young people with normal weight and overweight. PATIENTS AND METHODS Materials and methods: We examined 84 subjects of both sexes aged from 18 to 25 years. We determined their body weight, height. According to the body mass index (BMI), we formed the following groups: the control group embraced 22 men and 22 women with a BMI of 18.50-24.99 kg/m2, and the group of overweight subjects included 20 men and 20 women with a BMI of 25.00-29.99 kg/m2. We evaluated the dietary regimen using the Dutch eating behavior questionnaire (DEBQ). The obtained data were processed statistically. RESULTS Results: Changes in eating behavior were observed in 79.55% of subjects with normal weight and 90% of overweight subjects. In people with normal body weight, the restrictive type of eating behavior prevailed, in overweight subjects, the external and emotional types were observed. CONCLUSION Conclusions: The study established the formation of negative relationships of medium and high strength between the restrictive type of eating behavior and anthropometric indicators, as well as positive relationships of medium and high strength between indicators of emotional and external types with anthropometric indicators and energy value of diet in the subjects of both groups.
Biotechnologically-Produced Myconoside and Calceolarioside E Induce Nrf2 Expression in Neutrophils

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that might possess antioxidant or redox activity. This study aimed to analyze the metabolic profile of in vitro cultured H. rhodopensis and to identify molecules that increase Nrf2 expression in bone marrow neutrophils. Fractions B, D, and E containing myconoside, or myconoside and calceolarioside E in ratios 1:0.6 and 0.25:1 were found to be the most active ones. Fraction B (200 µg/mL) improved neutrophil survival and strongly increased the Nrf2 intracellular level, while D and E, as well as, myconoside and calceolarioside E at the same ratios had a superior effect. Calceolarioside E (32 µg/mL) had stronger activity than myconoside, the effect of which was very similar to that of 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), used as a positive control. These data indicate that both molecules, used alone or in combination have stimulatory activity on the endogenous Nrf2 level, indicating their therapeutic potential to regulate the cellular redox homeostasis oxidative stress-associated pathologies.
Total attenuation compensation for backscatter coefficient estimation using full angular spatial compounding in physical phantoms

The backscatter coefficient (BSC) quantifies the frequency-dependent reflectivity of tissues. Accurate estimation of the BSC requires knowledge of the attenuation coefficient slope (ACS) of tissues in the beam path between the transducer and the insonified region of interest, namely, the total attenuation. In this study, the total attenuation is calculated as the cumulative sum of values of a local attenuation map devised using full angular spatial compounding (FASC). The BSC was parameterized through the integrated backscatter coefficient (iBSC) obtaining iBSC maps. Experimental validation of the proposed approach consisted of scanning two cylindrical physical phantoms with off-centered inclusions having different ACS and BSC values than the background. Additional iBSC maps were computed assuming an uniform ACS map of 0.5 dB/cm/MHz (which is a value assumed for soft tissues) instead of the FASC-ACS map. Finally a iBSC map was obtained using an ideal ACS map formed with ground truth ACS values and knowledge of inclusion true position. The results were comparable when using the FASC-ACS map or the ideal ACS map in term of inclusion detectability and estimation accuracy. The use of the uniform ACS map resulted in some cases with very high fractional error (>;9 dB), which highlights the relevance of accurate compensation for total attenuation. These results suggest that BSCs can be reliably estimated using total attenuation compensation from FASC-ACS maps.
SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs

Abstract N 6-Methyladenosine (m6A) is the most abundant modification within diverse RNAs including mRNAs and lncRNAs and is regulated by a reversible process with important biological functions. Human YTH domain family 2 (YTHDF2) selectively recognized m6A-RNAs to regulate degradation. However, the possible regulation of YTHDF2 by protein post-translational modification remains unknown. Here, we show that YTHDF2 is SUMOylated in vivo and in vitro at the major site of K571, which can be induced by hypoxia while reduced by oxidative stress and SUMOylation inhibitors. SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. Moreover, Disease-free survival analysis of patients with lung adenocarcinoma derived from TCGA dataset reveals that higher expression of YTHDF2 together with higher expression of SUMO1 predicts poor prognosis. Our works uncover a new regulatory mechanism for YTHDF2 recognition of m6A-RNAs and highlight the importance of YTHDF2 SUMOylation in post-transcriptional gene expression regulation and cancer progression.
Development of an optimized and scalable method for isolation of umbilical cord blood‐derived small extracellular vesicles for future clinical use

Extracellular vesicles (EV) are a promising therapeutic tool in regenerative medicine. These particles were shown to accelerate wound healing, through delivery of regenerative mediators, such as microRNAs. Herein we describe an optimized and upscalable process for the isolation of EV smaller than 200 nm (sEV), secreted by umbilical cord blood mononuclear cells (UCB‐MNC) under ischemic conditions and propose quality control thresholds for the isolated vesicles, based on the thorough characterization of their protein, lipid and RNA content. Ultrafiltration and size exclusion chromatography (UF/SEC) optimized methodology proved superior to traditional ultracentrifugation (UC), regarding production time, standardization, scalability, and vesicle yield. Using UF/SEC, we were able to recover approximately 400 times more sEV per mL of media than with UC, and upscaling this process further increases EV yield by about 3‐fold. UF/SEC‐isolated sEV display many of the sEV/exosomes classical markers and are enriched in molecules with anti‐inflammatory and regenerative capacity, such as hemopexin and miR‐150. Accordingly, treatment with sEV promotes angiogenesis and extracellular matrix remodeling, in vitro. In vivo, UCB‐MNC‐sEV significantly accelerate skin regeneration in a mouse model of delayed wound healing. The proposed isolation protocol constitutes a significant improvement compared to UC, the gold‐standard in the field. Isolated sEV maintain their regenerative properties, whereas downstream contaminants are minimized. The use of UF/SEC allows for the standardization and upscalability required for mass production of sEV to be used in a clinical setting.
Antibacterial, Molecular Docking, DNA Binding and Photocleavage Studies on Novel Heterocyclic Pyrazoles.

The antibacterial activity, in-silico DNA molecular docking, DNA binding and photo cleavage studies of newly synthesized pyrazole is described. Antibacterial potential of these compounds screened against a wide range of Gram-positive and Gram-negative bacteria showed significant zone of inhibition and MIC with standard drug ciproflaxin is investigated. Among all the orientation of binding, fourth orientation showed significant binding and revealed that the binding and docking energy of 4a was -8.62 and -8.66 and inhibition constant 7.46 X e -6 . The absorption spectra showed the dynamic interaction with CT DNA and as proficient DNA intercalator (Kb = 4.5×10 4 M -1 ). The viscosity measurements and thermal denaturation affords the positive results towards DNA intercalation in both the studies. The light induced DNA damage was pragmatic in the absence of various ‘‘inhibitors’’ shows in photo cleavage activities at 360 nm.
How Did Italian Adolescents with Disability and Parents Deal with the COVID-19 Emergency?

The COVID-19 emergency has imposed distanced education and has interrupted most rehabilitation services. Adolescents with disabilities have been isolated, and the burden on their families has been exacerbated. A cross-sectional survey was administered to adolescents with disability and to parents of disabled children to describe their experience during lockdown and their concerns or expectations about rehabilitation. A sample of 53 adolescents and 239 parents completed the survey. Adolescents were ages 13–18 years old (45.3% female). Most parents were between 35 and 55 years old (84.9% female). While 53.6% of the parents reported no positive effects of the lockdown, 92.5% of the adolescents expressed favorable consequences. The increased time spent with family members was judged positively by 27.2% of parents and by 64.2% of adolescents. Concern for their child’s disability was expressed by 47.3% of parents, while 73.6% of adolescents expressed concerns regarding the ban on meeting friends. In both groups, anxiety symptoms were correlated with the fear of contracting COVID-19 and with financial problems. Parents would have liked even more remote support from school and healthcare professionals, which was available for most participants. Thus, socioeconomic support, assistive technology and telerehabilitation strategies might help families with disabilities during a lockdown.
Health‐related quality of life in adults with osteogenesis imperfecta

Patient‐reported outcome measures (PROMs) are increasingly utilized as endpoints in clinical trials. The Short Form Health Survey‐12 (SF‐12v2) is a generic PROM for adults. We sought to evaluate the validity of SF‐12v2 in adults with osteogenesis imperfecta (OI). Physical and mental health‐related quality of life (HRQoL) were assessed in a large cohort of adults in a multicenter, observational, natural history study. Physical HRQoL scores were correlated with the Gillette Functional Assessment Questionnaire (GFAQ). We calculated sample sizes required in clinical trials with crossover and parallel‐group designs to detect clinically meaningful changes in physical HRQoL. Three hundred and two adults with OI types I, III, and IV were enrolled. Physical HRQoL scores in the study population were lower than population norms. Physical HRQoL scores moderately correlated with GFAQ for OI types I and IV. We found no correlations between mental and physical HRQoL. From a clinical trial readiness perspective, we show that SF‐12v2 reliably measures physical function in adults with OI and can be utilized in crossover trials to detect meaningful physical HRQoL changes with small sample sizes. This study shows that SF‐12v2 can be used to measure changes in physical HRQoL in response to interventions in OI.
Two Expansin Genes, AtEXPA4 and AtEXPB5, Are Redundantly Required for Pollen Tube Growth and AtEXPA4 Is Involved in Primary Root Elongation in Arabidopsis thaliana

The growth of plant cells is inseparable from relaxation and expansion of cell walls. Expansins are a class of cell wall binding proteins, which play important roles in the relaxation of cell walls. Although there are many members in expansin gene family, the functions of most expansin genes in plant growth and development are still poorly understood. In this study, the functions of two expansin genes, AtEXPA4 and AtEXPB5 were characterized in Arabidopsis thaliana. AtEXPA4 and AtEXPB5 displayed consistent expression patterns in mature pollen grains and pollen tubes, but AtEXPA4 also showed a high expression level in primary roots. Two single mutants, atexpa4 and atexpb5, showed normal reproductive development, whereas atexpa4 atexpb5 double mutant was defective in pollen tube growth. Moreover, AtEXPA4 overexpression enhanced primary root elongation, on the contrary, knocking out AtEXPA4 made the growth of primary root slower. Our results indicated that AtEXPA4 and AtEXPB5 were redundantly involved in pollen tube growth and AtEXPA4 was required for primary root elongation.
Surgical Aortic Valve Replacement with Concomitant Aortic Surgery in Patients with Purely Bicuspid Aortic Valve and Associated Aortopathy

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation associated with aortopathy. The current study provides surgical clinical data on the patient characteristics and long-term survival of this less common adult purely BAV population undergoing surgical aortic valve replacement (SAVR) with concomitant aortic surgery. Adult patients with purely BAV who underwent SAVR and concomitant aortic surgery were included. Prevalence, predictors of survival, and outcomes for this patient population were analyzed. A total of 48 patients (mean age 58.7 ± 13.2 years, 33% female) with purely BAV underwent SAVR and concomitant aortic surgery between 1987 and 2016. The majority (62%) of the patients had pure aortic stenosis (AS). A total of 12 patients died. Survival was 92%, 73%, and 69% at 1, 5, and 20 years of follow-up. At 15 years of follow-up, the survival was close to that of the Dutch population, with a relative survival of 77%. Adult patients with a purely bicuspid aortic valve morphology undergoing SAVR and concomitant aortic root and/or ascending aorta present with excellent survival.
A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca2+ Channels

To establish a computer model for evaluating the binding affinity of phenylalkylamines (PAAs) to T-type Ca2+ channels (TCCs), we created new homology models for both TCCs and a L-type calcium channel (LCC). We found that PAAs have a high affinity for domains I and IV of TCCs and a low affinity for domains III and IV of the LCC. Therefore, they should be considered as favorable candidates for TCC blockers. The new homology models were validated with some commonly recognized TCC blockers that are well characterized. Additionally, examples of the TCC blockers created were also evaluated using these models.