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Abstract Diminished mitochondrial function underlies many rare inborn errors of energy metabolism and contributes to more common age-associated metabolic and neurodegenerative disorders. Thus, boosting mitochondrial biogenesis has been proposed as a potential therapeutic approach for these diseases; however, currently we have a limited arsenal of compounds that can stimulate mitochondrial function. In this study, we designed molybdenum disulfide (MoS2) nanoflowers with predefined atomic vacancies that are fabricated by self-assembly of individual two-dimensional MoS2 nanosheets. Treatment of mammalian cells with MoS2 nanoflowers increased mitochondrial biogenesis by induction of PGC-1α and TFAM, which resulted in increased mitochondrial DNA copy number, enhanced expression of nuclear and mitochondrial-DNA encoded genes, and increased levels of mitochondrial respiratory chain proteins. Consistent with increased mitochondrial biogenesis, treatment with MoS2 nanoflowers enhanced mitochondrial respiratory capacity and adenosine triphosphate production in multiple mammalian cell types. Taken together, this study reveals that predefined atomic vacancies in MoS2 nanoflowers stimulate mitochondrial function by upregulating the expression of genes required for mitochondrial biogenesis.

Russia’s open aggression against Ukraine has resulted in significant changes across all sectors of the Ukrainian economy and its financial sphere, including financial security. The paper aims to identify the impact of the primary macroeconomic determinants, i.e., military defense spending, non-performing bank loans, exchange rate, foreign debt, and state (total) reserves, on the financial security of Ukraine under martial law. The canonical correlation analysis is employed to assess the strength of the relationship between the above macroeconomic indicators and the level of the state’s financial security. It was found that the reduction of the state’s financial security level in 2022 was 63.9%, explained exactly by the changes in the above macroeconomic determinants after the start of a full-scale invasion. The study determined the degree of influence of each indicator on Ukraine’s financial security level. An increase in the level of military defense spending, non-performing bank loans, hryvnia’s devaluation, and external debt growth had a direct negative impact on Ukraine’s financial security. At the same time, an upsurge in total reserves had an indirect negative impact (through the external debt growth). The research findings confirm the necessity for effective monitoring and management of the macroeconomic indicators to maintain both Ukraine’s financial security and macro-financial stability in order to ensure its’ sustainable economic development during the postwar recovery period. AcknowledgmentThis research is financially supported by the NATO SPS Program “Security of territorial communities: evidence from the Eastern European countries”.

There has been a rise in popularity of “stimulant-free” or caffeine-free fat loss supplements, but it is not well understood whether those fat loss supplements are effective at enhancing thermogenesis without caffeine’s influence. The purpose of this study was to examine the effects of a caffeinated and non-caffeinated commercially available fat loss supplement on resting energy expenditure (REE), hunger, and hemodynamic variables in healthy adults. Twenty-five healthy male and female participants completed three separate laboratory visits after overnight fasts. Baseline assessments of REE, subjective hunger, heart rate (HR), and blood pressure (BP) were followed by ingestion of a caffeinated (Phoenix, Legion®; CAF), non-caffeinated (Phoenix Caffeine-Free, Legion®; NCAF), or placebo (PL) fat loss supplement. REE, hunger, HR, and BP assessments were repeated at 60-, 120-, and 180-min post-ingestion. CAF, but not NCAF, significantly elevated REE greater than PL at all time points (p < 0.05). NCAF significantly reduced hunger compared to CAF and PL at the 120-min time point (p = 0.006). CAF significantly increased diastolic BP 60-min post-ingestion and significantly increased systolic BP 120- and 180-min post-ingestion compared to NCAF and PL. Further research is warranted with respect to investigating non-caffeinated ingredients and their effects on REE.

Introduction: Even if antibody titers wane over time, T-cells demonstrate longevity and remain unaffected by viral variants. This study was done with the rationale of examining the virus-destroying cells post-vaccination, specifically focusing on their ability to produce the vital antiviral cytokine Interferon gamma (IFNγ) upon potential reinfection and investigates the impact of the Covishield vaccine on T-cell response, which is a largely unexplored domain due to the novelty of the disease. Aim: To study T-cell response by doing IFN γ release assay by employing Enzyme Linked Immunosorbent Spot (ELISpot) method. Materials and Methods: This was a cross-sectional study conducted from March 2021 to May 2023 at Sree Balaji Medical College and Hospital in Chennai, Tamil Nadu, India. The study included participants from all categories who were staff members of the College and Hospital. It is part of an extensive study done by the authors on immunological changes following Covishield vaccination. As part of this study, T-cell response was also separately studied by collecting an additional 2 mL of blood from 90 individuals one year after initiating the vaccination, specifically after administering the Covishield vaccine at 0 and 3 months. For T-cell response analysis, 2 mL of blood was collected and processed to separate Peripheral Blood Mononuclear Cells (PBMC). The Interferon Gamma Release assay (IGRA) was performed using ELISpot method, utilising a 96-well plate. The spots appearing in the sample wells {Spot Forming Cells (SFC) = T-cells} were quantified using an automated ELISpot reader. Sample wells demonstrating more than 12 spots were considered positive. The results were analysed using various statistical tests, including Chi-square test, One-way Analysis of Variance (ANOVA), Kruskal-Wallis Test, Karl Pearson correlation coefficient, t-test, and Mann-Whitney U-test. Results: The number of spots in the wells containing blood samples from volunteers ranged from a minimum of 2 to a maximum of 631. Importantly, all participants had detectable spots in their sample wells. Out of 90 participants, 84 (93.4%) had more than 12 SFC, while 6 (6.6%) had less than 12 SFCs. High Immunoglobulin G (IgG) levels were positively correlated with good T-cell responses (SFC). Participants under 60 years of age and females exhibited superior responses. Individuals with co-morbidities had lower levels of T-cell response compared to the healthy/normal participants. Conclusion: The volunteers in this study exhibited robust humoral and cellular immunity, with females showing a significantly better response. The T-cell response remained strong even nine months after the second dose of the vaccine

This perspective paper introduces a novel framework for container orchestration called CODECO. The CODECO orchestration framework relies on a data-network-computing approach to define the best infrastructure that can support the operation of next-generation Internet applications across a mobile, heterogeneous Edge-Cloud continuum. The selection of such an infrastructure is aligned with target performance profiles defined by the user, such as resilience or greenness. CODECO proposes to rely on decentralized Artificial Intelligence approaches to provide the most suitable infrastructure to an application deployment, considering infrastructural challenges, such as intermittent connectivity and node failure. This paper explains the current CODECO framework and gives insight into operational use-cases where CODECO is being deployed, as relevant examples of application for such a framework. Recent developments in the creation of the open-source CODECO framework are described and explained, allowing the use of the framework by the research community. The paper then provides a thorough analysis of CODECO’s features in comparison with existing orchestration frameworks, explaining the benefits introduced with this dynamic orchestration approach.

Abstract Background A reduction in right ventricular (RV) function during recovery from prolonged endurance exercise has been documented alongside RV dilatation. A relative elevation in pulmonary artery pressure and therefore RV afterload during exercise has been implicated in this post-exercise dysfunction but has not yet been demonstrated. The current study aimed to assess RV structure and function and pulmonary artery pressure before, during and after a 6-h cycling exercise bout. Methods Eight ultra-endurance athletes were recruited for this study. Participants were assessed prior to exercise supine and seated, during exercise at 2, 4 and 6 h whilst cycling seated at 75% maximum heart rate, and post-exercise in the supine position. Standard 2D, Doppler and speckle tracking echocardiography were used to determine indices of RV size, systolic and diastolic function. Results Heart rate and RV functional parameters increased from baseline during exercise, however RV structural parameters and indices of RV systolic and diastolic function were unchanged between in-exercise assessment points. Neither pulmonary artery pressures (26 ± 9 mmHg vs 17 ± 10 mmHg, P > 0.05) nor RV wall stress (7.1 ± 3.0 vs 6.2 ± 2.4, P > 0.05) were significantly elevated during exercise. Despite this, post-exercise measurements revealed RV dilation (increased RVD1 and 3), and reduced RV global strain (− 21.2 ± 3.5 vs − 23.8 ± 2.3, P = 0.0168) and diastolic tissue velocity (13.8 ± 2.5 vs 17.1 ± 3.4, P = 0.019) vs pre-exercise values. Conclusion A 6 h cycling exercise bout at 75% maximum heart rate did not alter RV structure, systolic or diastolic function assessments during exercise. Pulmonary artery pressures are not elevated beyond normal limits and therefore RV afterload is unchanged throughout exercise. Despite this, there is some evidence of RV dilation and altered function in post-exercise measurements.

Abstract Background Multi-omics research has the potential to holistically capture intra-tumor variability, thereby improving therapeutic decisions by incorporating the key principles of precision medicine. The purpose of this study is to identify a robust method of integrating features from different sources, such as imaging, transcriptomics, and clinical data, to predict the survival and therapy response of non-small cell lung cancer patients. Methods 2996 radiomics, 5268 transcriptomics, and 8 clinical features were extracted from the NSCLC Radiogenomics dataset. Radiomics and deep features were calculated based on the volume of interest in pre-treatment, routine CT examinations, and then combined with RNA-seq and clinical data. Several machine learning classifiers were used to perform survival analysis and assess the patient’s response to adjuvant chemotherapy. The proposed analysis was evaluated on an unseen testing set in a k-fold cross-validation scheme. Score- and concatenation-based multi-omics were used as feature integration techniques. Results Six radiomics (elongation, cluster shade, entropy, variance, gray-level non-uniformity, and maximal correlation coefficient), six deep features (NasNet-based activations), and three transcriptomics (OTUD3, SUCGL2, and RQCD1) were found to be significant for therapy response. The examined score-based multi-omic improved the AUC up to 0.10 on the unseen testing set (0.74 ± 0.06) and the balance between sensitivity and specificity for predicting therapy response for 106 patients, resulting in less biased models and improving upon the either highly sensitive or highly specific single-source models. Six radiomics (kurtosis, GLRLM- and GLSZM-based non-uniformity from images with no filtering, biorthogonal, and daubechies wavelets), seven deep features (ResNet-based activations), and seven transcriptomics (ELP3, ZZZ3, PGRMC2, TRAK1, ATIC, USP7, and PNPLA2) were found to be significant for the survival analysis. Accordingly, the survival analysis for 115 patients was also enhanced up to 0.20 by the proposed score-based multi-omics in terms of the C-index (0.79 ± 0.03). Conclusions Compared to single-source models, multi-omics integration has the potential to improve prediction performance, increase model stability, and reduce bias for both treatment response and survival analysis.

Intestinal dysbiosis is a major contributor to colorectal cancer (CRC) development, leading to bacterial translocation into the bloodstream. This study aimed to evaluate the presence of circulated bacterial DNA (cbDNA) in CRC patients (n = 75) and healthy individuals (n = 25). DNA extracted from peripheral blood was analyzed using PCR, with specific primers targeting 16S rRNA, Escherichia coli (E. coli), and Fusobacterium nucleatum (F. nucleatum). High 16S rRNA and E. coli detections were observed in all patients and controls. Only the detection of F. nucleatum was significantly higher in metastatic non-excised CRC, compared to controls (p < 0.001), non-metastatic excised CRC (p = 0.023), and metastatic excised CRC (p = 0.023). This effect was mainly attributed to the presence of the primary tumor (p = 0.006) but not the presence of distant metastases (p = 0.217). The association of cbDNA with other clinical parameters or co-morbidities was also evaluated, revealing a higher detection of E. coli in CRC patients with diabetes (p = 0.004). These results highlighted the importance of bacterial translocation in CRC patients and the potential role of F. nucleatum as an intratumoral oncomicrobe in CRC.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Abstract Mosquitoes have profoundly affected human history and continue to threaten human health through the transmission of a diverse array of pathogens. The phylogeny of mosquitoes has remained poorly characterized due to difficulty in taxonomic sampling and limited availability of genomic data beyond the most important vector species. Here, we used phylogenomic analysis of 709 single copy ortholog groups from 256 mosquito species to produce a strongly supported phylogeny that resolves the position of the major disease vector species and the major mosquito lineages. Our analyses support an origin of mosquitoes in the early Triassic (217 MYA [highest posterior density region: 188–250 MYA]), considerably older than previous estimates. Moreover, we utilize an extensive database of host associations for mosquitoes to show that mosquitoes have shifted to feeding upon the blood of mammals numerous times, and that mosquito diversification and host-use patterns within major lineages appear to coincide in earth history both with major continental drift events and with the diversification of vertebrate classes.

Background: COVID-19 infection causes the persistence of respiratory symptoms and functional impairment, which require prolonged follow-up care. Identification of individuals at risk for respiratory sequelae helps in optimal follow-up and early identification of complications. Aims and Objectives: The present study aims to find the clinical profile, predictors of respiratory symptom persistence, and functional impairment in post-COVID patients. Materials and Methods: Prospective observational study was done on patients who attended the post-COVID clinic in the pulmonary medicine outpatient department (OPD) in a tertiary care center in central Kerala from June 2021 to August 2021 with persisting respiratory symptoms after becoming COVID-19 negative and evaluated with a proforma regarding clinical history and symptoms. Patients were followed up at one and 3 months. Clinical, functional, and radiological factors were assessed. They were reassessed at 3 months. Spirometry was done in those with persistent symptoms at 3 months. High-resolution computed tomography (CT) was performed in those with significant desaturation on 6-min walk test (6MWT). Results: Of 348 patients, 6 died, 4 lost follow-up, 12 patients had alternative diagnoses during the study period. About 29.4% were symptomatic at 3 months. CT severity score improved over 3 months and the proportion of patients with exercise-induced desaturation in 6MWT decreased over 3 months. All patients showed a restrictive abnormality except two. A significant association was found between the persistence of symptoms at 3 months and type 2 diabetes mellitus, severe illness during the initial phase, persistent elevation of inflammatory markers, and increased radiological involvement. Alternative diagnosis and treatment-related complication was seen in 12 patients, which included infections such as tuberculosis, nocardia and fungal infection, malignancy, CTEPH, and post-intubation tracheal stenosis. Conclusion: A minor group of severe COVID-19 pneumonia survivors have delayed resolution of symptoms with functional impairment. Improvement in spirometry lags behind clinical and radiological improvement.

Neglected Tropical Diseases (NTDs) are a group of chronic infectious diseases of poverty affecting over one billion people globally. Intersections of NTDs, disability, and mental ill-health are increasingly evidenced but are rarely studied from a mixed-methods perspective. Here, we advance syndemic understandings by further assessing and contextualising the syndemic relationship between NTDs (particularly their associated disability) and mental distress in Liberia. Participatory qualitative methods, including body mapping (56 participants), social mapping (28 participants), and in-depth interviews (12) provided space for persons affected by NTDs to narrate their experiences. Simultaneously, 201 surveys explored experiences of common mental health conditions among persons affected by skin NTDs. An intersectionality approach was applied within the analysis for both qualitative and quantitative methods informed by Meyer’s minority stress model, adapted for NTDs. Qualitative data was analysed thematically and gender-disaggregated, univariable and multivariable analyses were applied to survey data for the outcome measures depression (PHQ-9) and anxiety (GAD-7). Disability was associated with higher levels of depression and anxiety (p < 0.001). An interaction between disability and being a women increased incidence risk ratio of depression (p < 0.001). In alignment with qualitative findings, persons affected experienced additional generalised (financial concerns), external (experience of stigma) and internal (experience of pain and physical symptoms) minority stressors, to varying degrees, which contributed towards their mental distress, and mental health conditions. These findings were used to co-develop a syndemic-informed person-centred health system response to address the suffering associated with NTDs and mental distress, including a focus on strengthening relationships between formal and informal community health actors and the broader health system.

The magnitude and azimuth of horizontal ice flow at Camp Century, Greenland have been measured several times since 1963. Here, we provide a further two independent measurements over the 2017–21 period. Our consensus estimate of horizontal ice flow from four independent satellite-positioning solutions is 3.65 ± 0.13 m a−1 at an azimuth of 236 ± 2°. A portion of the small, but significant, differences in ice velocity and azimuth reported between studies likely results from spatial gradients in ice flow. This highlights the importance of restricting inter-study comparisons of ice flow estimates to measurements surveyed within a horizontal distance of one ice thickness from each other. We suggest that ice flow at Camp Century is stable on seasonal to multi-decadal timescales. The airborne and satellite laser altimetry record indicates an ice thickening trend of 1.1 ± 0.3 cm a−1 since 1994. This thickening trend is qualitatively consistent with previously inferred ongoing millennial-scale ice thickening at Camp Century. The ice flow divide immediately north of Camp Century may now be migrating southward, although the reasons for this divide migration are poorly understood. The Camp Century flowlines presently terminate in the vicinity of Innaqqissorsuup Oqquani Sermeq (Gade Gletsjer) on the Melville Bay coast.

Abstract Background In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. Methods This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. Results The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9–10 times more patients were diagnosed and treated. Conclusions The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

The Kyrenia Ship, found off the north coast of Cyprus, is a key vessel in the history of scientific underwater excavations and in the history of Greek shipbuilding. The first volume of the site's final publication appeared in 2023 and provides detailed archaeological information tightly constraining the dating of the ship. A very specific date range is proposed: ca. 294-290 BCE, but is based on a less than certain reading of one coin recovered from the ship. While there is clear benefit to finding high-precision dates for the Kyrenia Ship and its rich assemblage using independent scientific dating (combined with Bayesian chronological modeling), efforts to do so proved more challenging and complex than initially anticipated. Strikingly, extensive radiocarbon dating on both wooden materials from the ship and on short-lived contents from the final use of the ship fail to offer dates using the IntCal20 calibration curve-the current Northern Hemisphere radiocarbon calibration curve at the time of writing-that correspond with the archaeological constraints. The issue rests with a segment of IntCal20 ca. 350-250 BCE reliant on legacy pre-AMS radiocarbon data. We therefore measured new known-age tree-ring samples 350-250 BCE, and, integrating another series of new known-age tree-ring data, we obtained a redefined and more accurate calibration record for the period 433-250 BCE. These new data permit a satisfactory dating solution for the ship and may even indicate a date that is a (very) few years more recent than current estimations. These new data in addition confirm and only very slightly modify the dating recently published for the Mazotos ship, another Greek merchant ship from the southern coast of Cyprus. Our work further investigated whether ship wood samples impregnated with a common preservative, polyethylene glycol (PEG), can be cleaned successfully, including a known-age test.

Nowadays public policymakers are offered with opportunities to take data-driven evidence-based decisions by analyzing the very large volumes of policy-related data that are generated through different channels (e.g., e-services, mobile apps, social media). Machine learning (ML) and artificial intelligence (AI) tehcnologies ease and automate the analysis of large policy-related datasets, which helps policymakers to realize a shift toward data-driven decisions. Nevertheless, the deployment and use of AI tools for public policy development is also associated with significant technical, political, and operation challenges. For instance, AI-based policy development solutions must be transparent and explainable to policymakers, while at the same time adhering to the mandates of emerging regulations such as the AI Act of the European Union. This paper introduces some of the main technical, operational, regulatory compliance challenges of AI-based policymaking. Accordingly, it introduces technological solutions for overcoming them, including: (i) a reference architecture for AI-based policy development, (ii) a virtualized cloud-based tool for the specification and implementation of ML-based data-driven policies, (iii) a ML framework that enables the development of transparent and explainable ML models for policymaking, and (iv) a set of guidelines for using the introduced technical solutions to achieve regulatory compliance. The paper ends up illustrating the validation and use of the introduced solutions in real-life public policymaking cases for various local governments.

Financial sentiment analysis plays a crucial role in decoding market trends and guiding strategic trading decisions. Despite the deployment of advanced deep learning techniques and language models to refine sentiment analysis in finance, this study breaks new ground by investigating the potential of large language models, particularly ChatGPT 3.5, in financial sentiment analysis, with a strong emphasis on the foreign exchange market (forex). Employing a zero-shot prompting approach, we examine multiple ChatGPT prompts on a meticulously curated dataset of forex-related news headlines, measuring performance using metrics such as precision, recall, f1-score, and Mean Absolute Error (MAE) of the sentiment class. Additionally, we probe the correlation between predicted sentiment and market returns as an addition evaluation approach. ChatGPT, compared to FinBERT, a well-established sentiment analysis model for financial texts, exhibited approximately 35% enhanced performance in sentiment classification and a 36% higher correlation with market returns. By underlining the significance of prompt engineering, particularly in zero-shot contexts, this study spotlights ChatGPT’s potential to substantially boost sentiment analysis in financial applications. By sharing the utilized dataset, our intention is to stimulate further research and advancements in the field of financial services.

Jaboticaba is healthy and delicious berries rich in phenolic compounds, particularly flavonoids, anthocyanins and ellagitannins. The natural occurring polyphenols have been getting interested by food and pharmaceutical industries, mainly due to their remarkable pharmacological actions. Therefore, this study was focused on the extraction of water soluble phenolics from jaboticaba berries using maceration technique with and without ultrasonic pretreatment. A short period of ultrasonic treatment (30 min) prior to maceration could improve the extraction to recover total phenolic and anthocyanin content, especially from its thick fruit peel for 75% and 61%, respectively. About 4.5% - 8.5% and 8.6% - 9.4% of the total phenolics was flavonoids and anthocyanins, respectively. The phenolics were statistically correlated to different colorimetric antioxidant assays to postulate the plausible antioxidant pathway. Hierarchical clustering revealed that phenolics in jaboticaba extracts were the dominant scavengers against free, cationic and peroxyl radicals, specifically flavonoids and anthocyanins were likely to be reducing agents. Jaboticaba extracts were also found to have higher scavenging capacity against peroxyl radicals, and higher reducing power than that of Trolox. Mass screening by UPLC-MS/MS detected many phenolics including glycosylated cyanidins and delphinidins, as well as galloylated flavonoids, ellagitannins and phospholipids in the peel extract.

Abstract We examine key aspects of the theory of the Bardeen–Cooper–Schrieffer (BCS) to Bose–Einstein condensation (BEC) crossover, focusing on the temperature dependence of the chemical potential, μ. We identify an accurate method of determining the change of μ in the cuprate high temperature superconductors from angle-resolved-photoemission data (along the ‘nodal’ direction), and show that μ varies by less than a few percent of the Fermi energy over a range of temperatures from far below to several times above the superconducting transition temperature, T c . This shows, unambiguously, that not only are these materials always on the BCS side of the crossover (which is a phase transition in the d-wave case), but are nowhere near the point of the crossover (where the chemical potential approaches the band bottom).

Abstract This paper details the investigation of a discrete coating observed on a group of Egyptian panel paintings, six mummy portraits and one funerary panel, dating from first-third century CE. Six mummy portraits in this group are encaustic, and the funerary panel is tempera using an animal glue binder. An accretion or coating has been observed on the surface and recesses of the paint layers on these panels. Examination of the portraits using ultraviolet radiation revealed an irregular visible fluorescence on the surface. On the mummy portraits, the fluorescence often extends only as far as where the linen wrappings would have secured the portrait to its mummy. Under magnification, the coating appears as a crizzled encrustation. Material exhibiting these characteristics was sampled from the surface of all seven panels. Initial analysis of samples from four panels by gas chromatography mass spectrometry (GC/MS) and enzyme-linked immunoassay (ELISA) revealed the presence of egg. Subsequent analysis of the coating from all seven portraits by peptide mass fingerprinting (PMF) and liquid chromatography with tandem mass spectrometry (LCMSMS) confirmed egg and further characterized the coating as highly deamidated, whole hen egg, or hen egg white in one instance. Importantly, the 14C date of the coating from two portraits indicates the time of application as approximately 2000 years ago, implying that the coating, at least in those cases, is not a modern addition. This report summarizes the examination and analytical characterization of this unusual coating. Possibly applied as an aesthetic or protective layer, or a symbolic and ritual unguent, the principal function of this coating remains unknown.

Background: Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. Methods: Stage I–III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. Results: In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for “hospital survival” and “no unplanned stoma” (96.9% and 97.7%), while the lowest rates were for “no major complications” and “no prolonged hospital stay” (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). Conclusions: Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

The recent rise in the applications of advanced technologies in the sustainable design and construction of transportation infrastructure demands an appropriate medium for their integration and utilization. The relatively new concept of Civil Integrated Management (CIM) is such a medium; it enhances the development of digital twins for infrastructure and also embodies various practices and tools, including the collection, organization, and data-management techniques of digital data for transportation infrastructure projects. This paper presents a comprehensive analysis of advanced CIM tools and technologies and categorizes its findings into the following research topics: application of advanced surveying methods (Advanced Surveying); geospatial analysis tools for project planning (Geospatial Analysis); multidimensional virtual design models (nD Modeling); Integrated Geospatial and Building Information Modeling (GeoBIM); and transportation infrastructure maintenance and rehabilitation planning (Asset Management). Despite challenges such as modeling complexity, technology investment, and data security, the integration of GIS, BIM, and artificial intelligence within asset-management systems hold the potential to improve infrastructure’s structural integrity and long-term performance through automated monitoring, analysis, and predictive maintenance during its lifetime.

Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

This research utilizes the Long-Term Pavement Performance database, focusing on devel-oping a predictive model for flexible pavement performance in the Southern United States. Analyzing 367 pavement sections, this study investigates crucial factors influencing asphaltic concrete (AC) pavement deterioration, such as structural and material components, air voids, compaction density, temperature at laydown, traffic load, precipitation, and freeze–thaw cycles. The objective of this study is to develop a predictive machine learning model for AC pavement wheel path cracking (WpCrAr) and the age at which cracking initiates (WpCrAr) as performance indicators. This study thoroughly investigated three ensemble machine learning models, including random forest, extremely randomized trees (ETR), and extreme gradient boosting (XGBoost). It was observed that XGBoost, optimized using Bayesian methods, emerged as the most effective among the evaluated models, demonstrating good predictive accuracy, with an R2 of 0.79 for WpCrAr and 0.92 for AgeCrack and mean absolute errors of 1.07 and 0.74, respectively. The most important features influencing crack initiation and progression were identified, including equivalent single axle load (ESAL), pavement age, number of layers, precipitation, and freeze–thaw cycles. This paper also showed the impact of pavement material combinations for base and subgrade layers on the delay of crack initiation.

The United States along with the rest of the world has experienced an unprecedented disruption in daily life due to the COVID-19 pandemic. Almost everyone has experienced some sort of stay at home order resulting in an economic catastrophe greater than the Great Recession of 2008 and on par with the Great Depression almost a century ago. Educational institutions at both the K-12 and post-secondary levels have not been immune from the shutdown, with many schools closed from mid-March through the end of the 2020 school year. Many schools moved classes to remote, distance delivery platforms. Career and Technical Education (CTE) teachers were tasked with creative engaging learning activities online for curricula which is taught in a hands-on contextual learning environment. This paper will present preliminary results from research conducted by a collaborative group of nine researchers from across the United States with collectively over 200 years of career and technical education experience. The conceptual framework used for this study was Danielson's Framework for Teaching and Enhancing Professional Practice and Foundations of Career and Technical Education including Constructivism. 3,267 participants representing all 50 states responded to the 37-item survey. The research objectives included description of participants and identified challenges to planning and delivery of CTE content when schools were closed, and instruction was moved to remote/distance/online platforms. Participants ranked their challenges as instructors and their perceptions of challenges that were experienced by their students. CTE teachers ranked replicating classroom or lab environments online and lack of experience teaching online as their biggest challenges. The perceptions of the participants concerning challenges for their students included motivation to guide and manage their own learning and students' access to reliable internet connection. The emergence and prevalence of the COVID-19 pandemic added a layer of complexity to educational practice that was not foreseen and for which no intentional preparation had occurred. Understanding how CTE teachers and instructors responded to this call, and the challenges they and their students encountered, is important to efforts to improve practice in the future and to be in a better position should another crisis occur that forces learning to be delivered in alternative formats from that of the traditional face-to-face classroom. [Note: The page range (177-194) shown on the PDF is incorrect. The correct page range is 177-193.]

"Marinyo" is a culture left by the Portuguese around the 15th century in Maluku. The purpose of this study was to find out to what extent students' misconceptions about the concept of sound in the "Marinyo" case in the Kepuluan Tanimbar Regency. The method used was a qualitative study in ethnography in ten villages in two sub-districts. In addition, they conducted a survey in the form of a diagnostic test in the form of questions related to the "Marinyo" case on 300 elementary school students. The findings in the field show that students experience relatively high misconceptions. It was because teachers did not accustom students to learn from natural phenomena around them and were given scientific questions to seek, find and provide answers and solutions related to these natural phenomena. The teacher was more pursuing the conditions and problems of physics in textbooks and less exploring contextual matters. Future researchers are suggested to develop physics or science teaching materials based on regional local advantages that are oriented towards understanding concepts, mental models, critical thinking, problem-solving, creativity and innovative thinking so that teachers and students can learn well so that knowledge of science becomes better.

This study aims to assess and examine secondary school teachers' perceptions of school climate and job satisfaction in five diverse countries: Japan, Korea, Finland, the United States of America (USA), and Australia. It explores the impact of school climate on teachers' job satisfaction, a pivotal factor influencing teacher retention, mobility, and professional development. In order to improve teachers' skills and abilities in the classroom, improving teachers' job satisfaction and understanding the factors that influence it is highly critical. Utilizing secondary data from the Teaching and Learning International Survey (TALIS) 2018, this study provides valuable insights. The findings reveal that teachers in all five countries generally hold positive perceptions of school climates and report high job satisfaction. However, teachers in Japan and Korea express comparatively lower job satisfaction levels when contrasted with their counterparts in Finland, the USA, and Australia. Furthermore, their perceptions of school climate also rank lower. Consequently, this study concludes that a positive correlation exists between favorable perceptions of school climate and elevated job satisfaction. This assertion is supported by regression analyses, individual country data, and aggregate data from all five countries.

Idiomatics--the scientific study of idiomatic language and figurative language--is a pervasive theme in global literature, yet its precise terminology often lacks clear definition. This article addresses this challenge directly by delving into the etymology, significance, and universality of idiomatics. It emphasizes the pivotal role of idiomatics in understanding human behavior and language development, stressing its interdisciplinary relevance. Advocating for idiomatics to gain recognition as a distinct academic discipline, the article calls for the establishment of clear boundaries and methodologies within academia. It concludes with a compelling appeal for collective action, urging idiomatists worldwide to unite under the imperative "Make it happen!" To this end, it presents ten strategic priorities that transcend geographical and linguistic divides, uniting researchers and language professionals in a common mission to advance idiomatics. These priorities underscore the urgency of addressing the current state of idiomatics and shaping its future trajectory, emphasizing the need for decisive action and collaboration. Through concerted efforts, the article seeks to propel idiomatics into new heights of understanding and application across diverse linguistic and cultural contexts, one priority at a time.

G-quadruplex stabilizers, including CX-5461, exhibit synthetic lethality with loss of BRCA1/2 in preclinical models. Here the authors report the results of a phase I study of CX-5461 in patients with solid tumors enriched for DNA-repair deficiencies.

Abstract Introduction Neglected tropical diseases (NTDs) are an important global health challenge, however, little is known about how to effectively finance NTD related services. Integrated management in particular, is put forward as an efficient and effective treatment modality. This is a background study to a broader health economic evaluation, seeking to document the costs of integrated case management of NTDs versus standard care in Liberia. In the current study, we document barriers and facilitators to NTD care from a health financing perspective. Methods We carried out key informant interviews with 86 health professionals and 16 national health system policymakers. 46 participants were active in counties implementing integrated case management and 40 participants were active in counties implementing standard care. We also interviewed 16 patients and community members. All interviews were transcribed and analysed using the thematic framework approach. Findings We found that decentralization for NTD financing is not yet achieved – financing and reporting for NTDs is still centralized and largely donor-driven as a vertical programme; government involvement in NTD financing is still minimal, focused mainly on staffing, but non-governmental organisations (NGOs) or international agencies are supporting supply and procurement of medications. Donor support and involvement in NTDs are largely coordinated around the integrated case management. Quantification for goods and budget estimations are specific challenges, given the high donor dependence, particularly for NTD related costs and the government’s limited financial role at present. These challenges contribute to stockouts of medications and supplies at clinic level, while delays in payments of salaries from the government compromise staff attendance and retention. For patients, the main challenges are high transportation costs, with inflated charges due to fear and stigma amongst motorbike taxi riders, and out-of-pocket payments for medication during stockouts and food/toiletries (for in-patients). Conclusion Our findings contribute to the limited work on financing of SSSD services in West African settings and provide insight on challenges and opportunities for financing and large costs in accessing care by households, which is also being exacerbated by stigma.

COVID-19 vaccine coverage in most countries in Africa remains low. Determinants of uptake need to be better understood to improve vaccination campaigns. Few studies from Africa have identified correlates of COVID-19 vaccination in the general population. We surveyed adults at 32 healthcare facilities across Malawi, purposively sampled to ensure balanced representation of adults with and without HIV. The survey, informed by the World Health Organization’s Behavioural and Social Drivers of Vaccination Framework, asked about people’s thoughts and feelings about the vaccine, social processes, motivation to vaccinate, and access issues. We classified respondents’ COVID-19 vaccination status and willingness to vaccinate, and used multivariable logistic regression to assess correlates of these. Among 837 surveyed individuals (median age was 39 years (IQR 30–49) and 56% were female), 33% were up-to-date on COVID-19 vaccination, 61% were unvaccinated, and 6% were overdue for a second dose. Those up-to-date were more likely to know someone who had died from COVID-19, feel the vaccine is important and safe, and perceive pro-vaccination social norms. Despite prevalent concerns about vaccine side effects, 54% of unvaccinated respondents were willing to vaccinate. Access issues were reported by 28% of unvaccinated but willing respondents. Up-to-date COVID-19 vaccination status was associated with positive attitudes about the vaccine and with perceiving pro-vaccination social norms. Over half of unvaccinated respondents were willing to get vaccinated. Disseminating vaccine safety messages from trusted sources and ensuring local vaccine availability may ultimately increase vaccine uptake.

Introduction: Many low- and middle-income countries have introduced the human papillomavirus (HPV) vaccine, but uptake remains extremely low. Malawi has the second-highest incidence of cervical cancer globally, and launched a national HPV vaccination program in 2019. We sought to understand attitudes about, and experiences with, the HPV vaccine among caregivers of eligible girls in Malawi. Methods: We conducted qualitative interviews with 40 caregivers (parents or guardians) of preadolescent girls in Malawi to understand their experiences with HPV vaccination. We coded the data informed by the Behavioural and Social Drivers of vaccine uptake model and recommendations from WHO’s Strategic Advisory Group of Experts Working Group on Vaccine Hesitancy. Results: In this sample, 37% of age-eligible daughters had not received any HPV vaccine doses, 35% had received 1 dose, 19% had received 2 doses, and 10% had an unknown vaccination status. Caregivers were aware of the dangers of cervical cancer, and understood that HPV vaccine is an effective prevention tool. However, many caregivers had heard rumors about the vaccine, particularly its alleged harmful effect on girls’ future fertility. Many caregivers, especially mothers, felt that school-based vaccination was efficient; but some caregivers expressed disappointment that they had not been more engaged in the school-based delivery of HPV vaccine. Caregivers also reported that the COVID-19 pandemic has been disruptive to vaccination. Conclusions: There are complex and intersecting factors that affect caregivers’ motivation to vaccinate their daughters against HPV, and the practical challenges that caregivers may encounter. We identify areas for future research and intervention that could contribute to cervical cancer elimination: better communicating about vaccine safety (particularly to address concerns about loss of fertility), leveraging the unique advantages of school-based vaccination while ensuring parental engagement, and understanding the complex effects of the COVID-19 pandemic (and vaccination program).

Recent data protection regulatory frameworks, such as the Protection of Personal Information Act (POPI Act) in South Africa and the General Data Protection Regulation (GDPR) in the European Union, impose governance requirements for research involving high-risk and vulnerable groups such as children and adolescents. Our paper's objective is to unpack what constitutes adequate safeguards to protect the personal information of vulnerable populations such as children and adolescents. We suggest strategies to adhere meaningfully to the principal aims of data protection regulations. Navigating this within established research projects raises questions about how to interpret regulatory frameworks to build on existing mechanisms already used by researchers. Therefore, we will explore a series of best practices in safeguarding the personal information of children, adolescents and young people (0-24 years old), who represent more than half of sub-Saharan Africa's population. We discuss the actions taken by the research group to ensure regulations such as GDPR and POPIA effectively build on existing data protection mechanisms for research projects at all stages, focusing on promoting regulatory alignment throughout the data lifecycle. Our goal is to stimulate a broader conversation on improving the protection of sensitive personal information of children, adolescents and young people in sub-Saharan Africa. We join this discussion as a research group generating evidence influencing social and health policy and programming for young people in sub-Saharan Africa. Our contribution draws on our work adhering to multiple transnational governance frameworks imposed by national legislation, such as data protection regulations, funders, and academic institutions.

Objective: to assess the outcome of health education on the knowledge of iso-immunization among pregnant women in selected government hospitals in Lagos state. Method: This was a quasi-experimental study where a semi-structured questionnaire was used to obtain data from 162 pregnant women who were selected by multi-stage Sampling in 3 selected government hospitals in Lagos state. Data collected were analyzed using SPSS version 24 and results were analyzed using frequency tables. An Independent t-test was used to test the mean difference between the two hypotheses. The level of statistical significance was set at a p-value of

Propolis, especially meliponini propolis is getting more popular in the functional food market, mainly due to its pharmacological importance. The quality of propolis is largely dependent upon the extraction technology and its solvent system. The present study investigated the performance of propolis extraction from maceration with and without ultrasonic pretreatment (30 min) in both water and 20% ethanol systems. Maceration was chosen to avoid degradation of heat sensitive compounds. Ultrasonic pretreatment was introduced to enhance propolis extraction from recalcitrant raw material. The yield of propolis was 4.0-5.5%. The results found that maceration with ultrasonic pretreatment, especially in aqueous ethanol increased the phenolics (17.043 mg GA/g), tannins (5.411 mg GA/g) and flavonoids (0.83 mg Q/g) content, as well as antioxidant capacity of propolis (80% at 1 mg/mL). Mass spectral based principal component analysis revealed that solvent system had higher effect (> 30%) on the variance of propolis quality rather than extraction technology. The variance of chemical composition had also led to the difference of antioxidant capacity among propolis samples. Alcohol precipitation would remove polymeric substance from propolis which was then characterised by thermogravimetric analysis coupled with Fourier transform infrared spectrometer (TGA-FTIR) after acid hydrolysis. The substance was putatively identified as hygroscopic lignocelluloses (14.4% moisture, 36.6% hemicelluloses and celluloses, 40% lignins), and started to decompose at 203°C, involving 4 steps of degradation mechanism at the highest derivative weight of 12.09%/min.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were