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OBJECTIVE: Internally displaced persons (IDPs) can have limited access to HIV and hepatitis C Virus (HCV) treatment and prevention. IDPs comprise > 7% of Georgian population but prevalence and levels of HIV and HCV knowledge in this population remain unknown. We tested 100 IDPs in Georgia for HIV and HCV, many of whom had drug injecting experience, and interviewed them about their migration experience, sexual and drug injecting practices, and HIV/HCV transmission knowledge. RESULTS: The average age of participants was 37.5 years (range 18-63); 31% were women. Almost half (N = 48) of participants reported ever injecting drugs; 17% of those (N = 8) started injecting drugs within the last year. Anti-HCV and HIV prevalence was 11% and 0%, respectively. Fewer people without drug use experience compared to people who inject drugs correctly answered all questions on the HIV knowledge test (13% vs. 35%, p = 0.015) or knew where to get tested for HIV (67% vs 98%, p

This study aimed to investigate the impact of eccentric-vision training on population receptive field (pRF) estimates to provide insights into brain plasticity processes driven by practice. Fifteen participants underwent functional magnetic resonance imaging (fMRI) measurements before and after behavioral training on a visual crowding task, where the relative orientation of the opening (gap position: up/down, left/right) in a Landolt C optotype had to be discriminated in the presence of flanking ring stimuli. Drifting checkerboard bar stimuli were used for pRF size estimation in multiple regions of interest (ROIs): dorsal-V1 (dV1), dorsal-V2 (dV2), ventral-V1 (vV1), and ventral-V2 (vV2), including the visual cortex region corresponding to the trained retinal location. pRF estimates in V1 and V2 were obtained along eccentricities from 0.5° to 9°. Statistical analyses revealed a significant decrease of the crowding anisotropy index (p = 0.009) after training, indicating improvement on crowding task performance following training. Notably, pRF sizes at and near the trained location decreased significantly (p = 0.005). Dorsal and ventral V2 exhibited significant pRF size reductions, especially at eccentricities where the training stimuli were presented (p < 0.001). In contrast, no significant changes in pRF estimates were found in either vV1 (p = 0.181) or dV1 (p = 0.055) voxels. These findings suggest that practice on a crowding task can lead to a reduction of pRF sizes in trained visual cortex, particularly in V2, highlighting the plasticity and adaptability of the adult visual system induced by prolonged training.

Abstract Objective Internally displaced persons (IDPs) can have limited access to HIV and hepatitis C Virus (HCV) treatment and prevention. IDPs comprise > 7% of Georgian population but prevalence and levels of HIV and HCV knowledge in this population remain unknown. We tested 100 IDPs in Georgia for HIV and HCV, many of whom had drug injecting experience, and interviewed them about their migration experience, sexual and drug injecting practices, and HIV/HCV transmission knowledge. Results The average age of participants was 37.5 years (range 18–63); 31% were women. Almost half (N = 48) of participants reported ever injecting drugs; 17% of those (N = 8) started injecting drugs within the last year. Anti-HCV and HIV prevalence was 11% and 0%, respectively. Fewer people without drug use experience compared to people who inject drugs correctly answered all questions on the HIV knowledge test (13% vs. 35%, p = 0.015) or knew where to get tested for HIV (67% vs 98%, p

Abstract Background Global policy and guidelines for low back pain (LBP) management promote physical activity and self-management yet adherence is poor and a decline in outcomes is common following discharge from treatment. Health coaching is effective at improving exercise adherence, self-efficacy, and social support in individuals with chronic conditions, and may be an acceptable, cost-effective way to support people in the community following discharge from treatment for LBP. Aim This qualitative study aimed to understand which aspects of a community over-the-phone health-coaching program, were liked and disliked by patients as well as their perceived outcomes of the service after being discharged from LBP treatment. Methods A purposive sampling approach was used to recruit 12 participants with chronic LBP, from a large randomised controlled trial, who were randomly allocated to receive a health coaching program from the Get Healthy Service® in Australia. Semi-structured interviews were conducted, and a general inductive thematic analysis approach was taken. Results The main themes uncovered regarding the intervention included the positive and negative aspects of the health coaching service and the relationship between the participant and health coach. Specifically, the participants spoke of the importance of the health coach, the value of goal setting, the quality of the advice received, the benefits of feeling supported, the format of the coaching service, and LBP-specific knowledge. They also reported the health coach and the coaching relationship to be the primary factors influencing the program outcomes and the qualities of the coaching relationship they valued most were connection, communication, care, and competence. The sub-themes uncovered regarding the outcomes of the intervention included positive impacts (a greater capacity to cope, increased confidence, increased motivation and increased satisfaction) and negative impacts (receiving no personal benefit). Clinical implications In an environment where self-management and self-care are becoming increasingly important, understanding the patient’s experience as part of a coaching program is likely to lead to improved quality of health coaching care, more tailored service delivery and potentially more effective and cost-effective community-based care for individuals with chronic LBP in the community after being discharged from treatment. Trial Registration The GBTH trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000889954) on 10/9/2020. Ethical approval was prospectively granted by the Western Sydney Local Health District Human Research and Ethics Committee (2020/ETH00115). Written informed consent was obtained from all participants. The relevant sponsor has reviewed the study protocol and consent form.

Abstract Aim The current study emphasizes the impact of adverse drug reactions (ADRs) and Drug-Related Problems (DRPs) caused by supportive care medications administered with chemotherapy. Method This is a longitudinal observational study carried out at the Ramaiah Medical College Hospital in Bengaluru, Karnataka, India, at the Department of Oncology. The data was recorded using a specifically created data collecting form. Based on the PCNE (Pharmaceutical Care Network Europe), DRPs are identified. The WHO probability scale, Modified Hartwig and Siegel for ADR severity assessment, Naranjo's algorithm for causality assessment, Rawlins and Thompson for predictability assessment, and Modified Shumock and Thornton for preventability assessment were all utilized. The OncPal guideline was considered in terms of the precision of supportive care medications regarding the reduction of ADRs in cancer patients. Result We enrolled 302 patients,166 (55%) female and 136 (45%) male (SD 14.378) (mean 49.97), patients with one comorbidity 59(19.6%) and multimorbidity (two or more) 45(14.9%), the DRPs identified were found to be 153 (50.6%); only P2 (safeties of drug therapy PCNE) were considered in this study. ADRs which are identified 175(57.9%) contributed/caused by the supportive care medications. WHO probability scale: 97 (32.1%) possible and 60 (19.9%) unlikely; Naranjo’s algorithm: 97 (32.1%) unlikely and 69 (22.8%) possible; ADR severity assessment scale (Modified Hartwig and Siegel): 95 (31.5%) mild and 63 (20.9%) moderates; Rawlins and Thompson for determining predictability of an ADR: 33 (10.9%) predictable and 137 (45.5%) non-predictable; and Modified Shumock and Thornton for determining preventability of an ADR: 81 (26.8%) probably preventable and 90 (29.8%) non-preventable. The statistical comparison through preforming t-test and measuring Chi-Square between group with ADRs and without ADRs shows in some variables, significantly (Alcohol consumption status, P = .019) and Easter Cooperative Oncology Group (ECOG) performance status P

Abstract Background Hereditary cancer is estimated to account for up to 10% of the worldwide cancer burden; 5% of all thyroid cancers are thought to be genetic. Inheritance of a deleterious mutation in genes associated with a high lifetime risk of developing cancer. Cancer-predisposing genes can promote the initiation and progression of thyroid cancer by enhancing the activation of major signaling pathways through oxidative stress mechanisms. Aim Identification of the possible link between familial susceptibility to cancer and the level of oxidative stress in thyroid cancer patients. Methods Patients with thyroid cancer (with and without genetic predisposition) were investigated. Study participants were treated in Limited Liability Company (LLC) “Oncology Scientific Research Center” (Tbilisi, Georgia). The study group was collected between 2020 and 2021. In patients’ blood, the thyroid hormones content (free Triiodothyronine (fFT3), free Thyroxine (fFT4), bound Triiodothyronine (FT3), bound Thyroxine (FT4), Thyroid-stimulating hormone (TSH)), and oxidative stress intensity (total activity of non-enzymatic antioxidant system (TAA) and the lipid peroxidation product, malondialdehyde (MDA), content) were investigated. Results The difference in free and bound forms of T3 and T4 levels in the blood serum between patients with thyroid cancer (Group 2 and Group 3) and the control group (Group 1) was not statistically significant (F 1,2 =0.5, p 1,2 =0.8, F 1,3 =2.31, p 1,3 =0.16). In patients with thyroid cancer the TSH level significantly increased compared to the control group (Group 1) (TSH (mean ± Std error): Group 1– 1.21 ± 0.12, Group 2–2.45 ± 0.11 (F 1,2 =107, p 1,2

The article focuses on the application of mathematical methods in economics, in particular discussing economic problems that are easily solved using definite integral. The purpose of the article is to show students the way and opportunity to use mathematical methods to solve economic problems. To this end, the article discusses and analyzes several economic tasks in detail, which will be interesting and easy for students to master

Located at the intersection of Asia and Europe, Georgia’s tourism industry encounters unique challenges amidst regional geopolitical tensions, notably the ongoing Russian-Ukrainian confl ict and the subsequent Russian migration. This article employs both qualitative and quantitative research methods to explore the impacts of these political realities on Georgia’s tourism sector and advocates for a strategic reorientation towards European integration as a means of promoting sustainable development. Drawing insights from qualitative interviews with key stakeholders and quantitative surveys with international tourists, the study unfolds the complex relationship between politics and tourism. Despite the predominantly negative perception of the infl ux of refugees, concerns about rising prices, perceived changes in service quality, and the expanding presence of Russian-owned businesses, the resilience and appeal of Georgia’s tourism realm remain evident. Specifi cally, all respondents recommended Georgia as a tourist destination and reported feeling safe during their stay. The study also presents a comparative perspective, evaluating the potential effects of further European integration on Georgia’s tourism landscape, and underscores key mitigation strategies, including policy development, diversifi cation of tourism offerings, strategic communication, digital platform advancement and utilization, and in general, the adoption of European best practices in sustainable tourism. These findings emphasize the need for nuanced, proactive, and inclusive policymaking and industry regulation in line with Georgia’s European aspirations. This comprehensive exploration provides invaluable insights for stakeholders in the tourism sphere and contributes to the broader understanding of the intricate relationship between geopolitical realities and tourism.

Background: Transforming growth factor β-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer. Methods: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens. Expression levels of cytoplasmic TAK1 by QuPath digital quantification and punctate TAK1 staining was scored using a manual point scoring technique and correlated with clinicopathological features, immune checkpoint expression and cancer-specific survival. Bulk RNA sequencing was performed in specimens to determine mutational profiles and differentially expressed genes. Results: A cohort of 875 patients who had undergone colorectal cancer resection were assessed for TAK1 expression. Higher levels of cytoplasmic TAK1 expression correlated with elevated PD1 and PD-L1 expression (p < 0.010). High punctate TAK1 expression was more commonly identified in poorly differentiated colorectal cancers (p = 0.036), had dysregulated mutational and transcriptional profiles with decreased insulin-like growth factor 2(IGF2) expression (p < 0.010), and independently predicted poor cancer-specific survival (HR 2.690, 95% CI 1.419–5.100, p = 0.002). The association of punctate TAK1 expression and recurrence remained after subgroup analysis for microsatellite-stable colorectal cancer (p = 0.028). Discussion: Punctate TAK1 expression is associated with worse cancer specific survival. TAK1 signalling may be an important pathway to investigate underlying mechanisms for recurrence in microsatellite-stable colorectal cancer.

Summary: Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples. AIMMeR shows an area under the receiver-operator curve (AUROC) of 0.98, and specificity of ≥75% at 98% sensitivity against pathologist ground truth in stage II/III in two trial cohorts, with positive predictive value of ≥98% for the commonest pattern of somatic MMRd. Lower agreement with microsatellite instability (MSI) testing (AUROC 0.86) reflects discordance between MMR and MSI PCR rather than AIMMeR misclassification. Analysis of the SCOT trial confirms MMRd prognostic value in oxaliplatin-treated patients; while MMRd does not predict differential benefit of chemotherapy duration, it correlates with difference in relapse by regimen (PInteraction = 0.04). AIMMeR may help reduce pathologist workload and streamline diagnostics in CRC.

Global warming is an environmental issue that threatens life on Earth. A significant rise in global temperature at the end of the century is estimated to be 2.4 °C, which necessitates action. The growth of energy needs urges scholars/researchers to think about developing suitable solutions. The key goal is to achieve zero-net emissions by 2050 in accordance with the goals outlined in the Paris Agreement (Climate Accords). To accomplish this, it is vital to have a strong strategy that initially includes high emissions reduction goals and addresses the challenges of global warming on our planet. Therefore, by 2050, the global energy strategy aims to eliminate emissions from the energy industry to zero. It is worth noting that most energy of the energy consumed comes from transport, power generation, industry, and buildings. The use of renewable technology is a method that is widely recommended to eliminate such challenges. Solar energy has two main technologies: solar photovoltaic (PV) and concentrating solar power (CSP), which have great potential in fulfilling energy needs. This work provides insight into solar energy technology’s role in global decarbonisation and towards net-zero emissions by 2050 through wide deployment and energy yield. The perspectives of solar energy technologies can save the environment by reducing emissions and energy supply, lowering energy bills, and creating job opportunities. Hence, investment in solar energy and other clean energy technologies will substantially achieve sustainable development in the coming decades; as forecasted, solar energy will have great installation capacity worldwide.

Abstract Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes. In this study we investigated the use of JAK inhibitors for anti-cancer activity in CRC cell lines, mouse model organoids and patient-derived organoids. Immunohistochemical staining of the TransSCOT clinical trial cohort, and 2 independent large retrospective CRC patient cohorts was performed to assess the prognostic value of JAK/STAT3 expression. We performed mutational profiling, bulk RNASeq and NanoString GeoMx® spatial transcriptomics to unravel the underlying biology of aberrant signaling. Inhibition of signal transduction with JAK1/2 but not JAK2/3 inhibitors reduced cell viability in CRC cell lines, mouse, and patient derived organoids (PDOs). In PDOs, reduced Ki67 expression was observed post-treatment. A highly significant association between high JAK/STAT3 expression within tumor cells and reduced cancer-specific survival in patients with high stromal invasion (TSPhigh) was identified across 3 independent CRC patient cohorts, including the TrasnSCOT clinical trial cohort. Patients with high phosphorylated STAT3 (pSTAT3) within the TSPhigh group had higher influx of CD66b + cells and higher tumoral expression of PDL1. Bulk RNAseq of full section tumors showed enrichment of NFκB signaling and hypoxia in these cases. Spatial deconvolution through GeoMx® demonstrated higher expression of checkpoint and hypoxia-associated genes in the tumor (pan-cytokeratin positive) regions, and reduced lymphocyte receptor signaling in the TME (pan-cytokeratin- and αSMA-) and αSMA (pan-cytokeratin- and αSMA +) areas. Non-classical fibroblast signatures were detected across αSMA + regions in cases with high pSTAT3. Therefore, in this study we have shown that inhibition of JAK/STAT3 represents a promising therapeutic strategy for patients with stromal-rich CRC tumors. High expression of JAK/STAT3 proteins within both tumor and stromal cells predicts poor outcomes in CRC, and aberrant signaling is associated with distinct spatially-dependant differential gene expression.

The presence of pathogenic micro-organisms in drinking water is responsible for certain public health diseases. The use of plant extracts is an alternative to commonly used chemical and physical treatments. The aim of this study is to evaluate the hydroethanolic extracts of Lantana camara stems and leaves on the cultivability of planktonic bacteria Escherichia coli and Staphylococcus aureus in an aquatic microcosm, to determine the effect of extract concentration (0,5 g/L, 1 g/L, 1,5 g/L and 2 g /L), incubation temperature (7 and 37 °C) and incubation time (3, 6 and 9 hours) on the cultivability of bacterial cells and also to evaluate the effect of some bioactive compounds isolated from these bacteria. The bioactive compounds identified are Stigmasterol (sterol), lantanilic acid and lantic acid (triterpenes) isolated in the leaf extract of L. camara and β-sistosterol (sterol) and oleanolic acid (triterpenes) isolated in the stem extract of L. camara. The cultivability of two bacterial strains studied is influenced by the presence of Lantana camara extract solution. A reduction in cell density was observed in the presence of the plant extract in question. With Lantana camara leaf extract, at an incubation temperature of 37 °C, the percentage of inhibition ranged from 3–100% for E. coli with the highest value observed after 6 hours at extract concentrations of 1.5 g/L and 2 g/L. In general, the extract has both a bactericidal and bacteriostatic effect on each bacterium, depending on the type of organ, whereas the effect of the bleach is specific to each bacterium. It should be noted that in the presence of E. coli, the MICs were 0.00048 mg/mL with the leaf extract and 0.0078 mg/mL with the stem extract. For this bacterium, the MBCs were 0.0039 mg/mL and 0.0312 mg/mL with the leaf and stem extracts respectively. For S. aureus, the MICs were 0.0156 mg/mL with the leaf extract and 0.0078 mg/mL with the stem extract and the MBCs were 0.0019 mg/mL and 0.0156 mg/mL (leaf and stem, respectively). The CMB/MIC ratio shows a bactericidal effect at the level of β-sistosterol in E. coli. On the other hand, in S. aureus, this report shows a bacteriostatic effect and tolerance with the two isolated chemical compounds. The Kruskal-Wallis test shows that the abundance of cultivable cells of each bacterial species differed significantly from one incubation temperature to another at each extract concentration and at each incubation temperature for each part of the plant (P

Abstract Colorectal cancer remains a leading cause of mortality worldwide. Significant variation in response to treatment and survival is evident among patients with similar stage disease. Molecular profiling has highlighted the heterogeneity of colorectal cancer but has had limited impact in daily clinical practice. Biomarkers with robust prognostic and therapeutic relevance are urgently required. Ideally, biomarkers would be derived from H&E sections used for routine pathological staging, have reliable sensitivity and specificity, and require minimal additional training. The biomarker targets would capture key pathological features with proven additive prognostic and clinical utility, such as the local inflammatory response and tumour microenvironment. The Glasgow Microenvironment Score (GMS), first described in 2014, combines assessment of peritumoural inflammation at the invasive margin with quantification of tumour stromal content. Using H&E sections, the Klintrup–Mäkinen (KM) grade is determined by qualitative morphological assessment of the peritumoural lymphocytic infiltrate at the invasive margin and tumour stroma percentage (TSP) calculated in a semi‐quantitative manner as a percentage of stroma within the visible field. The resulting three prognostic categories have direct clinical relevance: GMS 0 denotes a tumour with a dense inflammatory infiltrate/high KM grade at the invasive margin and improved survival; GMS 1 represents weak inflammatory response and low TSP associated with intermediate survival; and GMS 2 tumours are typified by a weak inflammatory response, high TSP, and inferior survival. The prognostic capacity of the GMS has been widely validated while its potential to guide chemotherapy has been demonstrated in a large phase 3 trial cohort. Here, we detail its journey from conception through validation to clinical translation and outline the future for this promising and practical biomarker.

Objective: There is emerging evidence suggesting that pregnancy loss (induced or natural) is associated with an increased risk of cardiovascular diseases (CVD). This prospective longitudinal study investigates the effect of prior pregnancy losses on CVD risk during the first six months following a first live birth. Methods: Medicaid claims of 1,002,556 low-income women were examined to identify history of pregnancy losses, CVD, diabetes, and hyperlipidemia prior to first live birth. The study population was categorized into five groups: A: women with no pregnancy loss or CVD history prior to first live birth; B: women with pregnancy loss and no CVD prior to first live birth. C: women with a first CVD diagnosis after a first pregnancy ending in a loss and before their first live birth. D: women with CVD prior to first live birth and no history of pregnancy loss. E: women with both CVD and pregnancy loss prior to their first live birth. Results: After controlling for age, race, state of residence, and history of diabetes and hyperlipidemia, the risk of CVD in the six-month period following a first live birth were 15%, 214%, 79% and 129% more common for Groups B, C, D and E, respectively, compared to Group A. Conclusions: Pregnancy loss is an independent risk factor for CVD risk following a first live birth, both for women with and without a prior history of CVD. The risk is highest when CVD is first diagnosed after a pregnancy loss and prior to a first live birth.

Abstract Background Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. Main body Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. Conclusion Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

A coronavirus disease (COVID)-related educational emergency is believed to have changed some of the aspects of the educational landscape. Sudden changes to traditional structures that are schools are undoubtedly an interesting issue to explore: complex phenomena such as assessment methods are highly related to many different factors such as normative base, the use of technological tools, etc. This article reports on the reorganization of assessment methods in the context of a rapid and forced transition to remote teaching mode, based on the results of a survey of Italian teachers. Findings indicate that pandemic-related educational emergency and the push toward the use of tools in teaching and learning practices, and the corresponding relaxation of certain established frames of operation, have created grounds for alternative forms of assessment. Results show that when entertaining different options and enjoying some level of autonomy, teachers can explore alternative forms of assessment. Assessment methods also change according to school subjects; while assessment changes are discipline specific, there is a clear trend toward product-based assessment.

A coronavirus disease (COVID)-related educational emergency is believed to have changed some of the aspects of the educational landscape. Sudden changes to traditional structures that are schools are undoubtedly an interesting issue to explore: complex phenomena such as assessment methods are highly related to many different factors such as normative base, the use of technological tools, etc. This article reports on the reorganization of assessment methods in the context of a rapid and forced transition to remote teaching mode, based on the results of a survey of Italian teachers. Findings indicate that pandemic-related educational emergency and the push toward the use of tools in teaching and learning practices, and the corresponding relaxation of certain established frames of operation, have created grounds for alternative forms of assessment. Results show that when entertaining different options and enjoying some level of autonomy, teachers can explore alternative forms of assessment. Assessment methods also change according to school subjects; while assessment changes are discipline specific, there is a clear trend toward product-based assessment.

The present-day rate of development of the society and technologies in any sphere requires from the employee constant raising of qualification and gaining new knowledge and skills--continuous professional development. Life-long learning, continuing education is equally important compared with initial degree education. This leads to the necessity of ensuring continuing education in especially significant areas for the country in which the country's leading universities have to be actively involved. Provision of continuing education for local self-government public servants in recent years in the context of the self-government reform gained special actuality in Georgia. The aim of the article is to underline the significant role of universities of Georgia in developing and providing continuing education courses to public servants of local self-government and identifying those measures which will promote active involvement of universities in this process.

Abstract Colorectal cancer (CRC) is a heterogenous malignancy and research is focused on identifying novel ways to subtype patients. In this study, a novel classification system, tumour microenvironment score (TMS), was devised based on Klintrup–Mäkinen grade (KMG), tumour stroma percentage (TSP), and tumour budding. TMS was performed using a haematoxylin and eosin (H&E)‐stained section from retrospective CRC discovery and validation cohorts (n = 1,030, n = 787). TMS0 patients had high KMG, TMS1 were low for KMG, TSP, and budding, TMS2 were high for budding, or TSP and TMS3 were high for TSP and budding. Scores were assessed for association with survival and clinicopathological characteristics. Mutational landscaping and Templated Oligo‐Sequencing (TempO‐Seq) profiling were performed to establish differences in the underlying biology of TMS. TMS was independently prognostic in both cohorts (p

Objectives To elicit the Aboriginal community’s cultural and healthcare needs and views about six prominent and emerging models of care, to inform the development of a new hospital.Design Cross-sectional qualitative study co-designed and co-implemented by Aboriginal team members.Setting Western Sydney, New South Wales, Australia.Participants Aboriginal and Torres Strait Islander healthcare providers (n=2) and community members (n=18) aged between 21 and 60+ years participated in yarning circles (20 participants; 14 female, 6 male).Results Handwritten notes from yarning circles were inductively analysed to synthesise the cultural and healthcare needs of providers and community members in relation to a new hospital and six models of care. Three primary themes emerged in relation to future hospitals. These were ‘culturally responsive spaces’, ‘culturally responsive systems’ and ‘culturally responsive models of care’. Strengths (eg, comfort, reduced waiting time, holistic care), barriers (eg, logistics, accessibility, literacy) and enablers (eg, patient navigator role, communication pathways, streamlined processes) were identified for each of the six models of care.Conclusions Aboriginal and Torres Strait Islander community members and providers are invested in the co-creation of an innovative, well-integrated hospital that meets the needs of the community. Common themes of respect and recognition, relationships and partnering, and capacity building emerged as important consumer and provider considerations when developing and evaluating care services. Participants supported a range of models citing concerns about accessibility and choice when discussing evidence-based models of care.

Abstract Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre‐analytical heterogeneity. This study reports an analytical approach to the largest multi‐parameter immunoprofiling study of clinical trial samples to date. We analysed 12,592 tissue microarray (TMA) spots from 3,545 colorectal cancers sourced from more than 240 institutions in two clinical trials (QUASAR 2 and SCOT) stained for CD4, CD8, CD20, CD68, FoxP3, pan‐cytokeratin, and DAPI by mIF. TMA slides were multi‐spectrally imaged and analysed by cell‐based and pixel‐based marker analysis. We developed an adaptive thresholding method to account for inter‐ and intra‐slide intensity variation in TMA analysis. Applying this method effectively ameliorated inter‐ and intra‐slide intensity variation improving the image analysis results compared with methods using a single global threshold. Correlation of CD8 data derived by our mIF analysis approach with single‐plex chromogenic immunohistochemistry CD8 data derived from subsequent sections indicates the validity of our method (Spearman's rank correlation coefficients ρ between 0.63 and 0.66, p ≪ 0.01) as compared with the current gold standard analysis approach. Evaluation of correlation between cell‐based and pixel‐based analysis results confirms equivalency (ρ > 0.8, p ≪ 0.01, except for CD20 in the epithelial region) of both analytical approaches. These data suggest that our adaptive thresholding approach can enable analysis of mIF‐stained clinical trial TMA datasets by digital pathology at scale for precision immunoprofiling.

Green hydrogen technologies are crucial for decarbonization purposes, while cogeneration offers efficient heat and power generation. Integrating green hydrogen and cogeneration brings numerous benefits, optimizing energy utilization, reducing emissions, and supporting the transition to a sustainable future. While there are numerous studies examining the integration of combined heat and power with Power to Gas, certain aspects still requires a more detailed analysis, especially for internal combustion engines fuelled by natural gas, due to their widespread adoption as one of the primary technologies in use. Therefore, this paper presents a comprehensive numerical 0-D dynamic simulation model, implemented within the TRNSYS environment, considering internal combustion engines fuelled by natural gas. Specifically, the study focuses on capturing CO2 from exhaust gases and producing green hydrogen from electrolysis. Based on these considerations, two configurations are proposed: the first involves the methanation reaction, while the second entails the production of a hydromethane mixture. The aim is to evaluate the technical and economic feasibility of these configurations and compare their performance within the Power to Gas framework. Self-sufficiency from the national electricity grid has been almost achieved for the two configurations, considering an industrial case. The production of hydromethane allows smaller photovoltaic plant (81 kWp) compared to the production of synthetic methane (670 kWp) where a high quantity of hydrogen is required, especially if all the carbon dioxide captured is used in the methanation process. Encouraging economic results with payback times below ten years have been obtained with the use of hydromethane. Moreover, hydromethane shows potential residential applications, with small required photovoltaic sizes.

Background. Class IC antiarrhythmic drugs (IC-AADs) are recommended as first-line therapy in treatment of lone paroxysmal atrial fibrillation (AF) along with catheter ablation of pulmonary veins. Despite previous attempts to identify predictors of IC-AADs` efficacy, the choice between IC-AADs agents is still most often carried out using empirical approach. Aim. To determine the predictors of IC-AADs ` efficacy in patients with paroxysmal AF in the absence of structural heart disease. Materials and methods. Seventy four patients (22 men, 52 women, average age 65 [57; 70] years) were treated with IC-AADs: 26 patients were prescribed lappaconitine hydrobromide (Al) (allapinin at a dosage of 75 mg/day or allaforte 50–100 mg/day), 25 patients were prescribed propafenone (P) 450–600 mg/day, 23 patients – diethylaminopropionylethoxycarbonylaminophenothiazine hydrochloride (ethacizine, E) 150 mg/day. The average frequency of AF paroxysms was 2 [0.4; 6.25] per month. Patients were divided into 2 groups depending on the effect of AADs. Results. Over a 12 months follow-up IC-AADs therapy was effective in 28 (37.8%) patients (Eff+ group), in the remaining 46 (62.2%) patients AF recurrences or side effects demanding AADs withdrawal were registered (Eff-group). A DC value greater or equal to 5 ms predicted the effectiveness of IC-AADs therapy with 79% sensitivity and 77% specificity (OR 12, 95% CI 3.07–49.5, p0.0001). In the Al group the deceleration capacity (DC) value greater or equal to 5.25 ms allowed predicting therapy effectiveness with 86% sensitivity and 100% specificity (OR 7, 95% CI 1.14; 43; p=0.002). In the E group, the DC index was characterized by high sensitivity (80%) and specificity (85%) for a threshold value of 5.9 ms. In case of DC above this value, the probability of E therapy efficacy increased by 22-times (OR 22, 95% CI 1.5; 314; p=0.009). In group P, the DC medians in the Eff+ and Eff- groups did not differ significantly (p=0.821). However, at low DC values (less than 4 ms) P turned out to be the most effective compared to other two IC-AADs: its effectiveness was 50%, which was significantly higher compared to E (0%) and Al (0%) (p=0.046). Conclusion. Estimation of the DC level before starting IC-AADs can make it easier to choose a specific drug from this group and improve treatment results: at DC above 5.2 ms, it is advisable to use Al, at DC≥6 ms – Al or E, at DC less than 4 ms – P.

Learning Design, as a field of research, provides practitioners with guidelines towards more effective teaching and learning. In parallel, observational methods (manual or automated) have been used in the classroom to reflect on and refine teaching and learning, often in combination with other data sources (such as surveys and interviews). Despite the fact that both Learning Design and classroom observation aim to support teaching and learning practices (respectively a priori or a posteriori), they are not often aligned. To better understand the potential synergies between these two strategies, this paper reports on a systematic literature review based on 24 works that connect learning design and classroom observations. The review analyses the purposes of the studies, the stakeholders involved, the methodological aspects of the studies, and how design and observations are connected. This review reveals the need for computer-interpretable documented designs; the lack of reported systematic approaches and technological support to connect the (multimodal) observations with the corresponding learning designs; and, the predominance of human-mediated observations of the physical space, whose applicability and scalability are limited by the human resources available. The adoption of ICT tools to support the design process would contribute to extracting the context of the observations and the pedagogical framework for the analysis. Moreover, extending the traditional manual observations with Multimodal Learning Analytic techniques, would not only reduce the observation burden but also support the systematic data collection, integration, and analysis, especially in semi-structured and structured studies.

Abstract Background A broad-based international shift to virtual care models over recent years has accelerated following COVID-19. Although there are increasing numbers of studies and reviews, less is known about clinicians’ and consumers’ perspectives concerning virtual modes in contrast to inpatient modes of delivery. Methods We conducted a mixed-methods study in late 2021 examining consumers’ and providers’ expectations of and perspectives on virtual care in the context of a new facility planned for the north-western suburbs of Sydney, Australia. Data were collected via a series of workshops, and a demographic survey. Recorded qualitative text data were analysed thematically, and surveys were analysed using SPSS v22. Results Across 12 workshops, 33 consumers and 49 providers from varied backgrounds, ethnicities, language groups, age ranges and professions participated. Four advantages, strengths or benefits of virtual care reported were: patient factors and wellbeing, accessibility, better care and health outcomes, and additional health system benefits, while four disadvantages, weaknesses or risks of virtual care were: patient factors and wellbeing, accessibility, resources and infrastructure, and quality and safety of care. Conclusions Virtual care was widely supported but the model is not suitable for all patients. Health and digital literacy and appropriate patient selection were key success criteria, as was patient choice. Key concerns included technology failures or limitations and that virtual models may be no more efficient than inpatient care models. Considering consumer and provider views and expectations prior to introducing virtual models of care may facilitate greater acceptance and uptake.

BackgroundSpecialist care units cater to targeted cohorts of patients, applying evidence-based practice to people with a specific condition (e.g., dementia) or meeting other specific criteria (e.g., children). This paper aimed to collate perceptions of local consumers and health providers around specialist care units, as a model of care that may be considered for a new local healthcare facility.MethodsThis was a qualitative study using two-hour workshops and interviews to collect data. Participants were consumers and health providers in the planned facility's catchment: 49 suburbs in metropolitan Australia. Consumers and health providers were recruited through advertisements and emails. An initial survey collected demographic details. Consumers and health providers participated in separate two-hour workshops in which a scenario around the specialist unit model was presented and discussion on benefits, barriers and enablers of the model was led by researchers. Detailed notes were taken for analysis.ResultsFive consumer workshops (n = 22 participants) and five health provider workshops (n = 42) were conducted. Participants were representative of this culturally diverse region. Factors identified by participants as relevant to the specialist unit model of care included: accessibility; a perceived narrow scope of practice; coordination with other services; resources and infrastructure; and awareness and expectations of the units. Some factors identified as risks or barriers when absent were identified as strengths and enablers when present by both groups of participants.ConclusionsPositive views of the model centred on the higher perceived quality of care received in the units. Negative views centred on a perceived narrow scope of care and lack of flexibility. Consumers hinted, and providers stated explicitly, that the model needed to be complemented by an integrated model of care model to enable continuity of care and easy transfer of patients into and out of the specialist unit.

Georgia signed an Association Agreement with the European Union in 2014, and this launched a process of approximation and harmonization with EU law. Energy law is one of the most important areas, which has to be developed and modified in accordance with the EU directives, regulations and rules of the Energy Community. Georgia took responsibility for establishing the energy exchange system and reorganizing the Georgian electricity market on a new model. In fact, these issues have not been studied, as they require, on the one hand, a very in-depth, practical knowledge of the issue and, on the other hand, erudition in the issues of legal approximation and information about the obligations assumed by the association agreement. The purpose of the article is to review the legislative regulations on the Georgian electricity market, the legal framework that defines the main principles of the market, the basis of operation, and sociopolitical and legal mechanisms of market stability. In the article, special attention will be paid to the status of the energy exchange in Georgia, its concept, its legal basis, problematic issues related to its implementation, and the future perspective. As a result of the analysis of the issues, based on the evaluation of the existing problems, the necessary legal ways of the development of energy law and the mechanisms promoting harmonization with the laws of the European Union are determined.

Medical imaging serves as an indispensable tool for the diagnosis and continuous monitoring of a diverse array of health conditions. A recent and exciting development in this field is the integration of Swarm Intelligence (SI) algorithms, which draw inspiration from the collective behaviors observed in social insects. This collaborative effort between nature and technology is progressively transforming medical image analysis, elevating both its quality and efficiency. In this book chapter we have presented various SI optimization algorithms like ACO, BCO, FA, FSA and WOA in detail. By exploring these algorithms, we aim to provide an in-depth understanding of their respective benefits and limitations when applied to medical image analysis. This knowledge empowers practitioners to choose the most appropriate algorithm for specific tasks, ensuring optimal outcomes. Furthermore, we shed light on SI-Based Segmentation methodologies, elucidating the advantages and constraints associated with these approaches. The ability of SI algorithms to innovate in the realms of image segmentation, feature extraction, and classification is emphasized, with a focus on their potential to enhance diagnostic accuracy and elevate the quality of patient care. One of the most exciting prospects on the horizon is the amalgamation of SI with cutting-edge technologies like deep learning and big data analytics. This union has the potential to revolutionize medical imaging by providing solutions that are not only more accurate and efficient but also highly clinically relevant. As these developments continue to unfold, the synergy between SI and emerging technologies promises to reshape the medical imaging landscape, ultimately enhancing patient care and improving healthcare outcomes in unprecedented ways

Burns in epileptic patients are not uncommon, but it is difficult to manage in remote areas of third-world countries. Despite the reduction in burn injuries secondary to a seizure, such injuries still lead to significant morbidity and mortality. In Darfur, Sudan, we managed such an epileptic patient having a full-thickness burn endangering the limb and life. Since these patients should adhere to a specific medication, controlling it remains to be difficult. The patient was managed with serial debridement, dressings, antibiotics, anti-epileptics and a protein diet. Therefore, preparation for preventive strategies consists of lifestyle modification and patient education that is further warranted.

BackgroundOnline health information seeking is changing the way people engage with health care and the health system. Recent changes in practices related to seeking, accessing, and disseminating scientific research, and in particular health information, have enabled a high level of user engagement. ObjectiveThis study aims to examine an innovative model of research translation, The Huberman Lab Podcast (HLP), developed by Andrew Huberman, Professor of Neurobiology and Ophthalmology at the Stanford School of Medicine. The HLP leverages social media to deliver health information translated into specific, actionable practices and health strategies directly to the general public. This research characterizes the HLP as an Active Model of Research Translation and assesses its potential as a framework for replicability and wider adoption. MethodsWe applied conventional content analysis of the YouTube transcript data and directed content analysis of viewers’ YouTube comments to 23 HLP episodes released from January to October 2021, reflecting the time of data analysis. We selected 7 episodes and a welcome video, to describe and identify key characteristics of the HLP model. We analyzed viewer comments for 18 episodes to determine whether viewers found the HLP content valuable, accessible, and easy to implement. ResultsThe key HLP features are direct-to-the-consumer, zero-cost, bilingual, and actionable content. We identified 3 main organizing categories and 10 subcategories as the key elements of the HLP: (1) Why: Educate and Empower and Bring Zero Cost to Consumer Information to the General Public; (2) What: Tools and Protocols; Underlying Mechanisms; and Grounded in Science; (3) How: Linear and Iterative Knowledge Building Process; Lecture-Style Sessions; Interactive and Consumer Informed; Easily Accessible; and Building the Community. Analysis of viewers’ comments found strong consumer support for the key HLP model elements. ConclusionsThis Active Model of Research Translation offers a way to synthesize scientific evidence and deliver it directly to end users in the form of actionable tools and education. Timely evidence translation using effective consumer engagement and education techniques appears to improve access and confidence related to health information use and reduces challenges to understanding and applying health information received from health providers. Framing complex content in an approachable manner, engaging the target audience, encouraging participation, and ensuring open access to the content meet current recommendations on innovative practices for leveraging social media or other digital platforms for disseminating science and research findings to the general public, and are likely key contributors to HLP impact and potential for success. The model offers a replicable framework for translating and disseminating scientific evidence. Similar active models of research translation can have implications for accessing health information and implementing health strategies for improved outcomes. Areas for further investigation are specific and measurable impacts on health, usability, and relevance of the model for reaching marginalized and high-risk populations.

Objective: This study aimed to evaluate epidemiological aspects of fatal injuries in Georgia.Methods: This was a retrospective, descriptive study that included all traumatic injury deaths in Georgiafrom January 1 to December 31, 2018. The National Center for Disease Control and Public Health of Georgia’sThe Electronic Death Register database was utilized in this research.Results: Of the study fatal injuries, 74% (n=1489) were males. 74% (n=1480) of all fatal injuries were causedby unintentional injuries. Road traffic accidents (25%, n=511) and falls (16%, n=322) were the primary causesof mortality. During the research year, the number of Years of life lost (YLL) was associated with injuries andwas increased to 58172 for both sexes (rate per 1000 population: 15.6). Most of the years were lost in the agegroup of 25-29 years (7515.37). Road traffic deaths accounted for 30% (17613.50) of YLL.Conclusion: Injuries are still a major public health problem in Georgia. In 2018, 2012 individuals died frominjuries across the country. However, mortality and YLL rates of injury varied by age and cause of injury. Toprevent injury-related mortality, it is crucial to conduct ongoing research on high-risk populations.