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To examine speaker role models (SRMs) in second language acquisition (SLA), this study explored the sociolinguistic "English as a lingua franca" (ELF) perspective targeting international intelligibility. Thus, it examined the way ELF learners align with self-selected English speakers and anonymous (audio-recorded) English speakers as potential SRMs. The researchers asked the participants, 57 Iranian English majors, "Who do you want to sound like in English and why?" and analyzed their answers in the context of their SRMs and envisioned selves in imagined communities (ICs). The study's findings revealed that most participants had SRMs with three sets of characteristics--high English language proficiency and intelligibility, likeable personal attributes, and notable professional accomplishments. To explore anonymous English speakers in particular as potential SRMs, the researchers asked participants to rate anonymous speakers' intelligibility and likeability. The findings established that, based on the sound of their voices alone, anonymous audiorecorded speakers were less likely to be selected as SRMs. Further, the study found no significant difference between anonymous native and nonnative speakers, celebrities and others, for whom accent intelligibility and likeability increased but did not determine the likelihood of selecting them as their SRMs. Based on its findings, this study draws implications for language and teacher education and offers classroom applications with specific activities.

Malignant melanoma is among the leading forms of cancer on a global scale, accounting for 1 in 5 skin cancers. Over the past decades, the treatment of melanoma has significantly improved following the development of therapies such as MAPK molecular therapy targeted at BRAF and MEK signaling pathways. We present real-world evidence from clinical practice in Bulgaria on the treatment of malignant melanoma with dabrafenib and trametinib from 2018 to 2022. Treatment outcomes from the real-world data are compared against the pivotal clinical trials, namely COMBI-d and COMBI-v. Outcomes are compared on the basis of metrics, including overall survival, progression-free survival, and clinical benefit. Further, iterational proportional fitting is performed to control for differences in characteristics across the patient cohorts. Results show that real-world overall survival and progression-free survival outperform results from the clinical trials, particularly with respect to COMBI-d.

We have analyzed the following polymorphisms: C677T (rs 1801133) and A1298C (rs 1801131) in the methylenetetrahydrofolate reductase (MTHFR) gene in Bulgarian patients with non-obstructive azoospermia, attending reproductive clinics. We have compared the allele and genotype frequencies of both the MTHFR C677T and A1298C polymorphisms in our population to the European population and to a Bulgarian control group (n = 350). The results of our research have revealed a trend for a significantly higher frequency of the homozygote C/C genotype of MTHFR A1298C polymorphism in comparison to the European and Bulgarian controls (p < 0.08). The prevalence of the C/C homozygotes can be accepted as a risk factor for the development of non-obstructive azoospermia, especially in addition to other external and internal factors—diet, vitamin intake, other genetic polymorphisms or mutations in the genes involved in spermatogenesis.

PURPOSE: This study evaluated the effects of polyphenol-rich Aronia melanocarpafruit juice (AMFJ) on the behavior of rats with metabolic syndrome (MS)induced by high-fat high-fructose diet. METHODS: Fifty rats were allocated into 5 groups (10 rats per group): control, MS, MS + AMFJ2.5, MS + AMFJ5and MS + AMFJ10. During the induction of MS in the course of 10 weeks, the last three groups were treated with AMFJ at doses 2,5 ml/kg, 5 ml/kg and 10 ml kg, respectively. The open field test was usedto examine locomotion, the social interaction test was used to evaluate anxiety, the depression-like state was studied by the forced swimming test and spatial memory was evaluated by the place recognition test. RESULTS: No differences were found in the overall motor activity across the groups. Anxiety and memory impairment were established in MS rats. AMFJ counteracted the development of anxiety, and brought the memory function back to normal. CONCLUSIONS: The improvement of the MS-induced behavioral alterations might be attributed to the rich polyphenolic content of AMFJ, essential for its antioxidant, anti-inflammatory and metabolic actions, and probably underlie also the anxiolytic and memory-enhancing effects observed in the present study.

Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge. To delineate disease-specific cell-cell communications involved in immune cell migration, we conducted a meta-analysis of publicly available single-cell RNA sequencing (scRNA-seq) data across diverse immune diseases and tissues. Our comprehensive analysis spanned multiple immune disorders affecting major organs: atopic dermatitis and psoriasis (skin), chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (lung), ulcerative colitis (colon), IgA nephropathy and lupus nephritis (kidney). By interrogating ligand-receptor (L-R) interactions, alterations in cell proportions, and differential gene expression, we unveiled disease-specific and common cell-cell communications involved in chemotaxis and extravasation to shed light on shared immune responses across tissues and diseases. Further, we performed experimental validation of two understudied cell-cell communications. Insights gleaned from this meta-analysis hold promise for the development of targeted therapeutics aimed at modulating immune cell migration to mitigate inflammation and tissue damage. This nuanced understanding of immune cell dynamics at the single-cell resolution opens avenues for precision medicine in immune disease management.

This study aimed to investigate the transferability of novel artificial intelligence (AI) methods for prediction modelling of diabetes based on real-world data (RWD) between early and late adopters of emerging health technologies from the perspective of developers and health technology assessment (HTA) experts. A two-step approach was used. Developers of the new AI methods within HTx consortium completed a survey about the benefits, usability, barriers associated with implementing the new prediction models in routine HTA practices. Then, HTA experts from Central and Eastern European (CEE) countries participated in a focus group discussion. Developers generally expressed optimism regarding the transferability of the methods, while acknowledging potential disparities across CEE countries. Key benefits that were identified included enhanced understanding of diabetes, improved cost-effectiveness modelling, and refined patient stratification, all of which could contribute to clinical and reimbursement decisions across various jurisdictions. The focus group underscored the value of real-world data for diabetes prediction modelling, serving as a beneficial resource for both clinicians and HTA agencies. However, there was a recognized need to clarify the processes of integrating randomized clinical trial data with real-world data. For the other stakeholders, the advancement of the methodology will improve the diagnosis and therapy during the process of decision making. Experts from CEE countries recognized the potential of artificial intelligence-based methods employing real-world data for diabetes modelling. These methods are seen as instrumental in elucidating the heterogeneous nature of the disease, supporting clinician decision-making and holding promises for HTA purposes.

Metabolic syndrome (MS) is often associated with anxiety and depression. Chaenomeles japonica (Thunb.) Lindl, also known as Chaenomeles maulei or Japanese quince, is a medicinal plant with a long history of use forits health-promoting properties.

Abstract The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

Propyl, octy- and dodecyl gallates are largely used in food, cosmetic and pharmaceutical industry as additives – preservatives. The main source of exposure non-related with food consumption is their use of cosmetic products. Gallates are classified as skin sensitization human health hazard. This research aims to evaluate the prevalence of contact sensitization to gallates and to estimate the possible cross/concomitant sensitization to gallate mix and other cosmetics ingredients among cosmeticians and cosmetology students. Skin patch testing with Gallate mix along with 19 other haptens was performed among 109 participants – 37 cosmetology students, 26 cosmeticians, and 46 controls. The study established high prevalence of contact sensitization to gallates, with higher risk for students (45.9%) and cosmeticians (38.5%). A significantly higher (р = 0.008) prevalence of co-sensitization to decyl glucoside was established for the control group. Proper risk information, with complex programs for prevention of occupational skin diseases should be provided.

Abstract Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p

This article focuses on certain demographic processes in Bulgaria during the Covid-19 pandemic in the period 2019-2021. Emphasis is placed on the mechanical migration on various routes. The unexpected intensive flow since the beginning of 2022, as a result of the military actions in Ukraine, which has also impacted a large part of European countries, including Bulgaria, is also taken into account. The PURPOSE of the analysis is to examine the positive and negative effects of Covid-19 pandemic on the demographic situation in the country. Statistical METHODS, synthesis, and analysis of literary sources are used. Statistical data from NSI for previous years for the period of the pandemic are used as a basis for comparative analysis. Articles, scientific publications, and studies by other authors, who examine and describe the impact of the Covid-19 pandemic on various aspects of human life, are reviewed. The RESULTS show the impact of the pandemic on people's desire for internal migration and its direction. This determines how and to what extent the Covid-19 pandemic has impacted the depopulation of rural areas at the expense of overcrowding in large cities.

Poly[2-(methacryloyloxy)ethyl phosphorylcholine] liposomes (pMPC liposomes) gained attention during the last few years because of their potential use in treating osteoarthritis. pMPC liposomes that serve as boundary lubricants are intended to restore the natural lubrication properties of articular cartilage. For this purpose, it is important that the liposomes remain intact and do not fuse and spread as a lipid film on the cartilage surface. Here, we investigate the stability of the liposomes and their interaction with two types of solid surfaces, gold and carbon, by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). With the aid of a hydrophilic species used as an electroactive probe in the solution, the charge transfer characteristics of the electrode surfaces are obtained. Additionally, from EIS, the capacitance characteristics of the surfaces are derived. No decrease of the peak currents and no displacement of the peak potentials to greater overpotentials are observed in the CV experiments. No decrease in the apparent capacitance and increase in the charge transfer resistance is observed in the EIS experiments. On the contrary, all parameters in both CV and EIS do change in the opposite direction. The obtained results confirm that there is only physical adsorption without fusion and spreading of the pMPC liposomes and without the formation of lipid films on the surfaces of both gold and carbon electrodes.

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control in the ER.

Polyphenols are strong antioxidants of plant origin that exhibit protective role against the development of several chronic degenerative diseases. Quantitative data on the content of polyphenolic antioxidants in Bulgarian medicinal plants are sporadic and unsystematic.

IntroductionMeaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries.MethodsBuilt on previous research findings on potential barriers, a prioritisation survey was conducted online with CEE stakeholders. Recommendations for prioritised barriers were formed through a face-to-face workshop by CEE stakeholders and HTx experts.ResultsA total of 105 stakeholders from 13 CEE countries completed the prioritisation survey and identified 12 of the 22 potential barriers as highly important. The workshop had 36 participants representing 9 CEE countries, and 5 Western European countries coming together to discuss solutions in order to form recommendations based on best practices, real-life experience, and transferability aspects. Stakeholder groups involved in both phases included HTA organisation representatives, payers, patients, caregivers, patient organisation representatives, patient experts, health care providers, academic and non-academic researchers, health care consultants and health technology manufacturers/providers. As a result, 12 recommendations were formed specified to the CEE region’s context, but potentially useful for a broader geographic audience.ConclusionIn this paper, we present 12 recommendations for meaningful, systematic, and sustainable patient involvement in HTA in CEE countries. Our hope is that engaging more than a hundred CEE stakeholders in the study helped to spread awareness of the importance and potential of patient involvement and that the resulting recommendations provide tangible steps for the way forward. Future studies shall focus on country-specific case studies of the implemented recommendations.

Background: Medicinal plants are a rich source of antioxidant polyphenols and in particular flavonoids. Materials and methods: In the present study 5 Bulgarian medical plants and 5 food supplements, present at the Bulgarian market, are analyzed for their Total phenolic, Total flavonoids and selected individual flavonoids content. A HPLC method was developed and validated for simultaneous determination of (+)-catechin, (-)-epicatechin and rutin in plant and supplements, using PDA detection. Results: The results show that polyphenols in the selected food supplements are lower than those of the medical plants analyzed. Mentha piperita and Melissa officinalis have the highest polyphenols content (67.38 and 65.17 mg GAE/g; 54.59 and 57.76 mg RE/g respectively). Rutin was detected in all samples analyzed, reaching highest levels in Mentha piperita (7332.5 µg/g), followed by fruits of Sambucus nigra (2818.7 µg/g). Conclusion: The results of the study are a practical contribution to a more complete characterization of the polyphenolic composition in Bulgarian medicinal plants.