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Abstract Blockade of NKG2A/HLA-E interaction is a promising strategy to unleash the anti-tumor response. Yet the role of NKG2A+ CD8 T cells in the anti-tumor response and the regulation of NKG2A expression on human tumor-infiltrating T cells are still poorly understood. Here, by performing CITE-seq on T cells derived from head and neck squamous cell carcinoma and colorectal cancer, we show that NKG2A expression is induced on CD8 T cells differentiating into cytotoxic, CD39+CD103+ double positive (DP) cells, a phenotype associated with tumor-reactive T cells. This developmental trajectory leads to TCR repertoire overlap between the NKG2A– and NKG2A+ DP CD8 T cells, suggesting shared antigen specificities. Mechanistically, IL-12 is essential for the expression of NKG2A on CD8 T cells in a CD40/CD40L- dependent manner, in conjunction with TCR stimulation. Our study thus reveals that NKG2A is induced by IL-12 on human tumor-reactive CD8 T cells exposed to a TGF-β-rich environment, highlighting an underappreciated immuno-regulatory feedback loop dependent on IL-12 stimulation.

Abstract Background Pyrethroid-chlorfenapyr nets have shown significant epidemiological impact over pyrethroid-only and pyrethroid plus piperonyl-butoxide (PBO) in Africa. A non-inferiority evaluation of PermaNet® Dual, a new chlorfenapyr plus deltamethrin net, compared to Interceptor® G2, was conducted in experimental huts in Siaya, Kenya against free-flying pyrethroid-resistant Anopheles funestus. Methods This study was an experimental hut trial, following a 7 by 7 Latin Square design. Seven treatments and seven sleepers were deployed in the experimental huts daily and rotated weekly and daily, respectively. Mosquitoes were collected every morning between 06:30 h and 08:30 h and were assessed for blood feeding and then monitored for immediate knockdown 1-h post collection and delayed mortality after 72 h. Differences in proportional outcomes were analysed using the blocked logistic regression model, while differences in numerical outcomes were analysed using the negative binomial regression model. Non-inferiority determination was performed based on World Health Organization (WHO) protocol. Results Mortality at 72 h was 30.2% for PermaNet 3.0, 44.4% for the Interceptor® G2 and 49.2% for the PermaNet® Dual. Blood feeding was highest with PermaNet® Dual at 15%, and least with PermaNet® 3.0 at 10%. PermaNet® Dual and Interceptor® G2 had no significant differences in mortality (OR = 1.10, 95% CI 1.00–1.20) or blood feeding (OR = 1.18, 95% CI 1.04–1.33) and the lower confidence bounds were within the non-inferiority margins but for blood feeding, non-inferiority was relatively high to the upper 95% confidence bound. PermaNet® Dual was non-inferior to the Interceptor® G2 and superior to the PermaNet® 3.0 nets in causing mortality but inferior to PermaNet ®3.0 in blood feeding inhibition of the vectors. Conclusion PermaNet® Dual met the WHO criteria for non-inferiority to Interceptor® G2 and may be considered for deployment for public health use against pyrethroid-resistant Anopheles vectors of malaria.

Abstract Our study in the Nurses’ Health Study (NHS) and NHS2, a nested case-control study with 1260 cases and 2221 controls, investigated the association between C-peptide levels, mammographic density (MD) parameters, V (a measure of gray scale variation), and breast cancer (BC) risk. We also examined how C-peptide and BC risk vary across quartiles of mammographic features. Linear and logistic regressions were used to study the associations between C-peptide and MD parameters, and breast cancer. C-peptide was inversely associated with percent MD and positively with non-dense area, but no associations were found with dense area and V measure. C-peptide was associated with an increased risk of invasive BC risk (top vs. bottom quartile, odds ratio = 1.46, 95% CI: 1.12–1.91). No multiplicative interactions were found between C-peptide, MD parameters, and BC risk. Our results suggest a positive association between C-peptide and BC risk, and MD parameters do not seem to modify this association.

Abstract Background HIV prevalence among female sex workers (FSW) is significantly higher than among women in the general population. Studies have shown that FSW engage in unprotected sex which provides higher compensation when they face emergency situations. We co-created a savings intervention – Jitegemee (rely on yourself) – with FSW to encourage them to save part of their earnings to withdraw in emergency situations in order to reduce risk. Methods We undertook a five-phase intervention development process between February 2021 and July 2023: 1) qualitative interviews with FSW to identify essential intervention features; 2) pilot trial to assess intervention feasibility; 3) literature review of studies on economic empowerment of FSW; 4) scoring of key components of Phases 1–3 on a scale of 1–5 (1 = definitely exclude, 5 = definitely include), for inclusion in the intervention package; 5) workshops with FSW and other key stakeholders to co-design the intervention. Results In phase 1, nearly all participants (99%) found the intervention acceptable to them and 95% believed it would be acceptable to other FSW. Participants suggested inclusion of financial literacy (75%), savings groups (38%) and goal-setting (24%). In the feasibility assessment, 41% saved, of whom 46% withdrew some savings. Condom use was higher among FSW who withdrew their savings compared to those who did not (χ 2 7.52; p = 0.006). In Phase 3, we identified 14 intervention components. In phase 4, all suggested intervention components scored 4.5 on average. In phase 5, we held 3 workshops with FSW to co-design the intervention, which included instructions for how to save and make withdrawals, financial literacy training, and formation of savings groups. Conclusions A savings intervention for and by FSW was highly acceptable and feasible. Involving end-users in the design process is likely to result in greater economic security among FSW and lower engagement in higher risk transactional sex.

Abstract Background Type 1 diabetes (T1D) management exerts a considerable financial burden on patients, caregivers, and developing nations at large. In Ghana, a key governments effort to attenuate the financial burden of T1D on patients was to fashion safety-net mechanisms through financial risk pooling/sharing known as the National Health Insurance Scheme (NHIS). However, there is limited research on patients and caregivers’ experiences with the cost of managing T1D within the NHIS in Ghana. Objective This study explored the cost of T1D management, and the impact of the NHIS policy on mitigating costs of care. Methods A semi-structured interview guide was developed to collect qualitative data from 28 young people living with T1D (PLWD), 12 caregivers, 6 healthcare providers, and other stakeholders in Western, Central and the Greater Accra regions. Multiple data collection techniques including mystery client and in-depth interviews were used to collect data. Thematic content analysis was performed with QSR NVivo 14. Results Five key domains/themes which are: cost of T1D management supplies; cost of clinical care; cost of transportation; cost of diet; and NHIS were identified. The daily cost of blood glucose testing and insulin injection per day was between GHC 5–7 (US$ 0.6 to 1.0). The NHIS did not cover supplies such as strips, glucometers, HbA1c tests, and periodic medical tests. Even for those cost which were covered by the NHIS (mainly pre-mixed insulin), marked government delays in funds reimbursement to accredited NHIS facilities compelled providers to push the financial obligation onto patients and caregivers. Such cost obligations were fulfilled through out-of-pocket top-up or full payment of insulin of about GHC 15–25 (US$ 2–4), and GHC 25–50 (US$4–8) depending on the region and place of residence. Conclusion The cost of managing T1D was a burden for patients and their caregivers. There was a commodification of life-saving insulin on the Ghanaian market, and the NHIS did not function well to ease the cost-burden of T1D management on patients and caregivers. The findings call for the need to scale up NHIS services to include simple supplies, particularly test strips, and always ensure the availability of life-saving insulin in healthcare facilities.

Abstract Animal morphology is influenced by several factors, including gonadal development and gametogenesis. Although their effects are well documented in male/female differentiation, much less is known about same-sex effects, such as those caused by their mode of reproduction. Here, using geometric morphometric analyses, we compare two groups of all-female triploid hybrid fish Chrosomus eos × eos-neogaeus, that differ only by their sexual and asexual reproductive strategies. We demonstrate that morphological differences arise from factors inherently associated with their mode of reproduction, with results replicated in two distinct lineages and in natural and common garden environments. Such differences provide additional insight about the costs and benefits of both reproductive strategies, which have mostly been of a demographic, population genetic, or genetic nature. In particular, these findings have important implications for the ecology of asexual organisms and contribute to the study of sex evolution by adding complexity to the paradox of sex theory.

Spread of the Anopheles stephensi mosquito, an invasive malaria vector, threatens to put an additional 126 million persons per year in Africa at risk for malaria. To accelerate the early detection and rapid response to this mosquito species, confirming its presence and geographic extent is critical. However, existing molecular species assays require specialized laboratory equipment, interpretation, and sequencing confirmation. We developed and optimized a colorimetric rapid loop-mediated isothermal amplification assay for molecular An. stephensi species identification. The assay requires only a heat source and reagents and can be used with or without DNA extraction, resulting in positive color change in 30–35 minutes. We validated the assay against existing PCR techniques and found 100% specificity and analytical sensitivity down to 0.0003 ng of genomic DNA. The assay can successfully amplify single mosquito legs. Initial testing on samples from Marsabit, Kenya, illustrate its potential as an early vector detection and malaria mitigation tool.

Current watershed-scale, nonpoint source pollution models do not represent the processes and impacts of agricultural best management practices on water quality with sufficient detail. A Water Erosion Prediction Project-Water Quality (WEPP-WQ) model was recently developed which is capable of simulating nonpoint source pollutant transport in nonuniform hillslope conditions such as those with BMPs. However, WEPP-WQ has not been validated for these conditions, and prior validation work only evaluated calibrated performance rather than uncalibrated performance, with the latter being most relevant to model applications. This study evaluated uncalibrated and calibrated model performance in two plot-scale, artificial rainfall studies. 179 observations were compared to corresponding WEPP-WQ simulations of runoff, sediment yield, and soluble and particulate nutrient forms for both nitrogen and phosphorus. Uncalibrated validation results were mixed for the different field conditions, model configurations, and prediction variables. Nash-Sutcliffe Efficiencies for uncalibrated simulations of uniform conditions were generally greater than 0.6 except for soluble nitrogen predictions which were poor. Simulations of nonuniform conditions were generally ‘unsatisfactory’ except for runoff predictions which were quite good (NSE = 0.78). Performance was improved substantially for almost all endpoints with calibration. Some exceptions to this occurred because the objective function for calibration was based on log-space differences so as to more equally-weight calibration of unsaturated conditions that tend to produce lesser runoff volumes and sediment yields. Calibrated results for both uniform and nonuniform conditions were generally ‘satisfactory’ or ‘good’ according to widely accepted model performance criteria.

Having in mind the basic pragmalinguistic principle which argues that traces of the unsaid are always present in our communication and guided by Jacob L. Mey’s assertion that titles can be tricky, this study seeks to explore the elements that influence authors’ choice of titles and the opaque meanings of such titles. This research adopted a pragmatic approach to discourse analysis with the aid of the notions of presuppositions, inferences, argumentative orientations, argumentative scales and the theory of possible worlds. Results indicate that the setting of a literary work, the cultural origin, beliefs and philosophies of its author, the era within which the work is written, and the use of figures of speech, among others, are elements that influence an author’s choice of a title of a literary piece. This study has further revealed that careful consideration of these factors could play a critical role in helping a reader unravel the deeper meaning of the title of a piece of work as well as the entire text. This study is a scholarly contribution to titrology, pragmatics, and discourse analysis.

Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age

ABSTRACT Background Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and a high metastatic potential, presenting significant challenges in clinical oncology. A critical aspect of melanoma biology is its metabolic reprogramming, which supports tumor growth, survival, and therapeutic resistance. Objective This review aims to explore the key molecular mechanisms driving metabolic alterations in melanoma and their implications for developing therapeutic strategies. Methods A Pubmed search was conducted to analyze literature discussing key mechanisms of the Warburg effect, mitochondrial dysfunction, enhanced lipid metabolism, epigenetic modifications, and the tumor microenvironment. Results Metabolic reprogramming supports melanoma growth, proliferation, and survival. Understanding these complex metabolic dynamics provides valuable insights for developing targeted therapeutic strategies. Conclusion Potential therapeutic interventions aimed at disrupting melanoma metabolism highlight the promise of precision medicine in improving treatment outcomes in cutaneous oncology. By targeting metabolic vulnerabilities, novel treatment approaches could significantly enhance the clinical management and prognosis of melanoma.

Monitoring at the subnational level has connotations for the effectiveness of local governance in the developing world. Using a cross-sectional survey underpinned by the project life cycle model, the paper contributes to understanding essential considerations in developing and implementing subnational monitoring in Africa. About 74 of the targeted 275 District Development Officers responded to the online Google form questionnaire. The study employed descriptive statistics to analyze data. Results demonstrate that the monitoring system is excellent in design, but its implementation and reflection stages are weak. It highlights planning for subnational monitoring systems encompassing setting clear objectives, utilizing robust indicators, involving stakeholders, and an elaborate plan for data collection, analysis, communication, and reporting as vital ingredients of a monitoring system. Sufficient resources and capacity-building initiatives, including providing on-the-job training, hiring experienced staff, committing financial resources and logistics, and backstopping support, are necessary to implement monitoring activities effectively. An appropriate policy environment, including manuals and legislation, is critical to anchoring and sustaining subnational monitoring systems. Local government’s monitoring systems should prioritize learning, knowledge sharing, and documentation of lessons learned to facilitate programmatic improvements and replication and devote at least 2.5% of the District Assembly Common Fund to finance monitoring and evaluation actions.

Objective: The isthmus-dependent right atrial flutter is a known arrhythmia, but few studies described the sequence activation of the left atrium. It is well established that the interatrial connection occurs through different pathways: the coronary sinus (CS), the Bachmann's bundle and the fossa ovalis. We describe a case of a cavotricuspid isthmus-dependent right atrial flutter with an unexpected left atrial activation sequence. Case presentation: A 47-year-old female with scleroderma and a history of isolated right ventricular cardiomyopathy had recurrent atrial flutter episodes despite medical therapy. The patient was still symptomatic despite full medical therapy. She presented to the electrophysiology laboratory for mapping and ablation of atrial flutter with 2:1 and 3:1 conduction. A decapolar deflectable CS catheter placed in the coronary sinus showed a distal to proximal CS activation with a flutter cycle length of 240 msec. Then, the cavotricuspid isthmus (CTI) demonstrated a concealed entrainment with a post-pacing interval almost equal to the total cycle length confirming the diagnosis of an isthmus-dependent flutter. The CS activation in sinus rhythm also showed a distal to proximal activation. This confirmed that the CS and the left atrium are being activated most probably through the Bachman bundle anteriorly and superiorly. CTI line was performed under intracardiac echo guidance. Clinical improvement was noticed. A distal to proximal CS activation does not exclude a right atrial arrhythmia. Conclusion: A systemic entrainment mapping of both the right and left atrium is crucial to prevent unneeded transseptal puncture.

Rising traffic congestion and fuel costs pose significant challenges for supply chains with numerous retailers. This paper addresses these challenges by optimizing transportation routes for processed tomatoes within a long-haul and intercity distribution network. We use the heterogeneous capacitated vehicle routing problem framework to create a new quadratically constrained mixed-integer non-linear programming model that aims to meet demand at multiple destinations while minimizing transportation costs. Our model incorporates real-time data and route optimization strategies that consider traffic conditions based on freight time and route diversions for expedited deliveries. It aims to devise an optimal transportation schedule that minimizes fuel, operational, and maintenance costs while ensuring efficient delivery of tomato paste. By applying this model to a real-world case study, we estimate a significant 27.59% reduction in transportation costs, dropping them from GH¢20,270 ($1,638.91) to GH¢14,676 ($1,186.61) on average. This highlights the effectiveness of our strategy in lowering costs while maintaining smooth and efficient deliveries.

African Swine Fever (ASF) is caused by a DNA virus (AFSV) maintained and transmitted by the Argasid ticks. The re-emergence of the disease in Africa coupled with its rapid spread globally is a threat to the pig industry, food security and livelihoods. The ecology and epidemiology of the ASFV sylvatic cycle, especially in the face of changing land use and land cover, further compounds the menace and impacts of this disease in Kenya. The study aimed to determine the occurrence and distribution of ASFV seroprevalence in warthog populations, the tick vectors and extent of tick infestation of warthog burrows, and the genotypes of ASFV in soft ticks in Kenya. Warthogs from different parts of Kenya were captured and venous blood was centrifuged to harvest sera. Warthog burrows were examined for their conditions and to extract ticks. Sera were analyzed for antibodies against ASFV using a commercial ELISA kit coated with p32 ASFV recombinant protein. Ticks were pooled, DNA extracted and the p72 gene of the ASFV was amplified by qPCR and conventional PCR. The overall seroprevalence of ASFV in warthogs was 87.5 %. A total of 228 warthog burrows were examined and 2154 argasid ticks were extracted from the burrows. Tick pools from Kigio Farm and Lewa Wildlife Conservancies were ASFV-positive by qPCR and conventional PCR. ASFV was further confirmed by the Twist Comprehensive Viral Research Panel (TCVRP), which also identified the argasid ticks as Ornithodoros porcinus. The ticks were infected with virus genotype IX, and their occurrence overlaps with regions of previous ASF outbreaks in domestic pigs. Further, Viruses that could be tick endosymbionts/commensals or due to bloodmeal were detected in ticks by TCVRP; Porcine type-C oncovirus; Pandoravirus neocaledonia; Choristoneura fumiferana granulovirus; Enterobacteria phage p7; Leporid herpesvirus 4 isolate; 5; Human Lymphotropic virus; Human herpesvirus 5. In conclusion, our results suggest that infected Ornithodoros spp. seems to have a rich virome, which has not been explored but could be exploited to inform ASF control in Kenya. Further, the ecology of Ornithodoros spp. and burrow-use dynamics are complex and more studies are needed to understand these dynamics, specifically in the spread of ASFV at the interface of wild and domestic pigs. Further, our results provide evidence of genotype IX ASFV sylvatic cycle which through O. porcinus tick transmission has resulted in high exposure of adult common warthogs. Finally, the co-circulation of ASFV genotype IX in the same location with past ASF outbreaks in domestic pigs and presently in ticks brings to focus the role of the interface and ticks on virus transmission to pigs and warthogs.

ObjectiveNorm Balance is an approach under the Theory of Planned Behavior (TPB) where subjective norm is weighted by the relative importance of others and self-identity is weighted by the relative importance of self. The relative importance was measured previously by a trade-off measure. In this study, we developed separate measures for the relative importance. The study objectives were to: 1) assess the construct validity of the separate measures; 2) examine the approach of Norm Balance in predicting pharmacists’ intention to collaborate with physicians to improve medication therapy; and 3) establish a modified TPB.MethodsWe selected a random sample of 750 Iowa pharmacists and conducted two surveys. The first survey was to examine intention prediction, and the second survey was to examine behavior prediction by measuring behavior among respondents to the first survey. The relative importance was measured by both the trade-off measure and the separate measures. Exploratory factor analyses were performed for the relative importance of others (separate measures) and subjective norm, and for the relative importance of self (separate measures) and self-identity. Regressions for intention prediction were conducted for TPB with self-identity and the approach of Norm Balance. The same regressions were also conducted for three subgroups according to the median of the relative importance of others (trade-off measure). Moreover, another regression was conducted for behavior prediction.Results239 practicing pharmacists responded to the first survey, and 188 responded to the second survey. The separate measures had cross factor loadings, whereas the trade-off measure had low correlations with other constructs. Both regressions for intention prediction explained 75% of the variance, with self-efficacy and attitude being strong predictors. Self-identity was not a predictor in the TPB with self-identify, but self-identity weighted by the relative importance of self was a significant predictor in the approach of Norm Balance. Regression coefficients of subjective norm and self-identify varied across subgroups. The regression for behavior prediction explained 30% of the variance, with intention and self-efficacy being two predictors.ConclusionThe trade-off measure was better than separate measures. The approach of Norm Balance appears to be a better model than the TPB with self-identity to examine pharmacist-physician collaboration.

Hairdressers are exposed to awkward posture, prolonged standing, long working hours and chemical hazards capable of causing adverse health effects. The present study aimed to evaluate hairdressers' safety and health risks. The study adopted a descriptive cross-sectional and analytical design. Systematic random sampling was used to select salons and hairdressers. Closed and open-ended questionnaires were distributed to 286 hairdressers who consented to participate in the study. An observation checklist, WISHA caution checklist, thermometer, light meter and noise level meter were used to collect data in the sampled salon. Data were analyzed descriptively and with regression analysis. It was found that the average space for salons was 8.79 m2, and 68.5% of hairdressers work for long hours (11-12 hours). It was established that 5.48% of salons have an adequate amount of light and that 8.22% of salons have high temperatures. Aprons were the most used personal protective equipment by hairdressers. Manual handling of salon equipment and awkward posture cause musculoskeletal disorders among hairdressers. Their odd ratios impacting the health and safety of hairdressers were 2.706 and 2.728, respectively. The study reveals that hairdressing salon designs, space, lighting, and temperatures affect the health and safety of hairdressers. The hours off work and minimal or no breaks also have negative impacts on the health and safety of hairdressers

Abstract Introduction Type 1 diabetes mellitus (T1DM) is mostly diagnosed among young people. Despite the evidence that T1DM is disruptive, and affects individuals’ health and cognitive ability, there is dearth of knowledge on the impact of T1DM on schooling in LMICs including Ghana. In this research, we explored the impact of T1DM on the schooling of young people living with the disease, and discussed the results within health selection, social support, and artefactual perspectives of inequality. Methods Data were extracted from a qualitative project on T1DM lived experiences in southern Ghana. The study participants were young persons living with T1DM (n = 28) and their caregivers (n = 12). They were purposively recruited to participate in the study using maximum variation and snowball sampling techniques and interviewed in their support group centres, homes, or healthcare facilities using semi-structured interview guides. A computer-assisted qualitative data analysis was performed using QSR NVivo 14 software, and the results were categorised into themes. Results Three themes were identified from the transcripts. These themes were school and classroom attendance, choice of school, and school/academic performance. T1DM was a major reason for patients’ limited contact hours with teachers, school drop-out, preference for day schools rather than boarding, opting for vocational training instead of continuation of formal education, limited concentration at school, and delayed educational progression. Conclusion T1DM impacted the schooling of young people living with the disease. The mechanisms of these impacts, and young peoples lived experiences are not artefactual, but rather support discourses on health selection and inadequate social support for young people living with the disease. The results call for the need to develop educational and social interventions to address these barriers. The full implementation of the Inclusive Education Policy (IEP) may contribute to reducing educational and social inequalities caused by ill-health.

Abstract Ebola virus (EBOV) is able to persist and actively replicate in the reproductive tract of male disease survivors months or years after recovery from Ebola virus disease (EVD)1. Persistent EBOV infections are usually asymptomatic and can be transmitted sexually, but the host and viral factors that mediate these infections have not been characterized2,3. We investigated the interaction between host and viral factors during EBOV infection of the blood testis barrier (BTB), with a focus on Sertoli cells as a potential reservoir for viral persistence. We assessed viral replication kinetics and host responses of mouse testicular Leydig cells and Sertoli cells infected with EBOV Makona (i.e. infectious EBOV) and collected samples up to 28 days post-infection. Viral replication was apparent in both cell lines, but intracellular early viral loads were much higher in Leydig cells compared to Sertoli cells. We used RNAseq analysis to characterize transcriptomic responses of Leydig cells and Sertoli cells to EBOV infection over time. Further investigation of early interactions between host cells and EBOV was performed using virus-like particles (EBOV trVLP) and assays of phosphorylation-based cell signaling. Our findings indicate that virus-treated Sertoli cells responded more rapidly and robustly than Leydig cells, and with a particular emphasis on detection of, and response to, external stimuli. We discuss how the roles played by Sertoli cells in immune privilege and spermatogenesis may affect their initial and continued response to EBOV infection in a manner that could facilitate asymptomatic persistence.

Abstract Background Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. Results Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. Conclusions The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract

Abstract Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1β, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors’ use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

Abstract This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.

Abstract Background Vector surveillance is among the World Health Organization global vector control response (2017–2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. Methods Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. Results Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P

Abstract Background Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. Methods Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. Results There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65–1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25–0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400–0700 h for An. gambiae and 0300–0700 h for An. funestus. The study population away from home peaked at 1700–1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600–0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. Conclusion While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction.

Background: Young people (aged 14–24 years) living with Type 1 Diabetes (T1D), especially, those in low-resource settings experiencing having T1D complications, and poor mental health. Yet, little is known about T1D complications, mental health, and their lived experiences among young people and their caregivers in Ghana. Objective: This article sought to understand a) the dynamics of T1D complications, mental health, and lived experiences, and b) drawing on this evidence, develop structural and behavioural pathways of T1D complication occurrence among young people in Ghana. Methods: The study design was interpretivist phenomenology (qualitative). Twenty-eight young people living with T1D (YPLWD), 12 caregivers, and six healthcare providers across three regions in southern Ghana were purposively recruited and interviewed using interview guides. The methods included a photovoice where the YPLWD took photographs to highlight visible complications. Themes were formed from the quotes and photovoice. The analytical technique was thematic - performed with the aid of QSR NVivo 14. Results: Four main themes which were: physical complications, mental health, other adverse health outcomes, and structural pathways of complication occurrence were identified from the analyses. Physical complications discussed included visual impairment, diabetic coma, reproductive ill-health, and kidney disease. We found on the average, eight (8) years of living with T1D (with minimum and maximum years of 2 and 4 respectively). Mental health issues including anxiety and suicidal ideation transcended YPLWD to caregivers. Multiple structural and behavioural risk factors of T1D complications were also found. Conclusion: The YPLWD and caregivers in Ghana experienced multiple T1D complications and poor mental health. Unfortunately, these manifested early in their natural history of T1D, and were influenced by inadequate structural resources, and the adoption of sub-optimal self-care practices. This article underscores the need to improve structural T1D resources, promote optimal blood glucose control, alongside mental/psychosocial support for patients and their caregivers in Ghana.

ABSTRACTDengue is often misclassified and underreported in Africa due to inaccurate differential diagnoses of nonspecific febrile illnesses such as malaria, sparsity of diagnostic testing and poor clinical and genomic surveillance. There are limited reports on the seroprevalence and genetic diversity of dengue virus (DENV) in humans and vectors in Nigeria. In this study, we investigated the epidemiology and genetic diversity of dengue in the rainforest region of Nigeria. We screened 515 febrile patients who tested negative for malaria and typhoid fever in three hospitals in Oyo and Ekiti States in southern Nigeria with a combination of anti-dengue IgG/IgM/NS1 rapid test kits and metagenomic sequencing. We found that approximately 28% of screened patients had previous DENV exposure, with the highest prevalence in persons over sixty. Approximately 8% of the patients showed evidence of recent or current infection, and 2.7% had acute infection. Following sequencing of sixty samples, we assembled twenty DENV-1 genomes (3 complete and 17 partial). We found that all assembled genomes belonged to DENV-1 genotype III. Our phylogenetic analyses showed evidence of prolonged cryptic circulation of divergent DENV lineages in Oyo state. We were unable to resolve the source of DENV in Nigeria owing to limited sequencing data from the region. However, our sequences clustered closely with sequences in Tanzania and sequences reported in Chinese with travel history to Tanzania in 2019. This may reflect the wider unsampled bidirectional transmission of DENV-1 in Africa, which strongly emphasizes the importance of genomic surveillance in monitoring ongoing DENV transmission in Africa.

AimThe aim of this study is to understand the development of windsports and the challenges faced by wind-based leisure activities.MethodsThe socio-historical dynamics behind the development of wind leisure are analysed on the basis of specialised tourism blogs, as well as a field study carried out in the Northeast Region of Brazil, combining ethnographic observations and semi-structured interviews with 6 wind leisure enthusiasts. All the data is processed using the serious leisure perspective tools developed by Stebbins, and the body ecology tools developed by Andrieu et al.ResultsThe results show that wind sports provide a dual continuum. First of all, there are the practitioners, from Neophyte to Devotee Worker. Then there is the junction between land, water and air, where wind practices ensure a dual aesthetic. On the one hand, riders are united by a community of flow, emotion and sensation mediated by their relationship with the wind and the creation of play materials (waves, lagoons, trade winds). On the other hand, the tourist development of these practices serves a political narrative based on postcard aesthetics, enabling wind concessions to be traded for the development of wind farms.Conclusionthis original research calls for a more systematic exploration of wind practices and the hybridisation of natural elements, which seems to illustrate the crisis that modern sport and its institutions are going through today.

Background Febrile convulsion (FC) among children is a common emergency concern received in hospitals and clinics. However, in Ghana, FC is commonly perceived as a non-hospital disease and usually managed at home. There is limited research on the home management of FC. This study, therefore, explored the home management of FC.Methods The study design was a descriptive and interpretive phenomenology. Data sources were triangulated among 42 participants across 5 communities within 2 km distance from regional hospitals in the Cape Coast Metropolis. Participants were purposively selected and interviewed face to face in their homes and treatment centres using semistructured interview guides. Interviews were transcribed and thematically analysed with QSR NVivo V.14.Results Three themes were identified from the inductive analysis. These themes were treatment, prevention and case referral. Subthemes on treatment were tepid sponging with lukewarm water, the use of herbal medicine and spiritual approaches. FC was referred to as ‘asram suro’. The ‘asram’ literally means the moon, and ‘suro’ connotes the skies, indicating possibly that the condition emanates from a god of the moon. Caregivers prevented FC through behavioural approaches, herbal medicine, and mystical approaches including making scarification and tying amulets and beads particularly on the child’s face and wrists respectively. FC cases were referred for clinical attention after home care resulted in undesirable treatment outcomes. A conceptual framework depicting the decision-making and practices towards FC management is presented.Conclusion FC is commonly managed at home independent of orthodox care availability. Caregivers employed herbal and ad hoc treatment regimens, usually unwarranted, visually frightening and spiritual approaches which were not the best home management approaches. These findings call for the need to educate caregivers about the best home management of FC.

IntroductionThe KCNQ2/KCNQ3 genes encode the voltage-gated K channel underlying the neuronal M-current, regulating neuronal excitability. Loss-of-function (LoF) variants cause neonatal epilepsy, treatable with the M-current-opener retigabine, which is no longer marketed due to side effects. Gain-of-function (GoF) variants cause developmental encephalopathy and autism that could be amenable to M-current, but such therapies are not clinically available. In this translational project, we investigated whether donepezil, a cholinergic drug used in Alzheimer’s, suppresses M currents in vitro and improves cognitive symptoms in patients with GoF variants.Methods(1) The effect of 1 μM donepezil on the amplitude of the M-current was measured in excitatory and inhibitory neurons of mouse primary cultured hippocampal cells. M-current was measured using the standard deactivation protocol (holding at 0 mV and deactivation at −60 mV) in the voltage-clamp configuration of the whole-cell patch clamp technique. The impact of donepezil was also examined on the spontaneous firing activity of hippocampal neurons in the current-clamp configuration. (2) Four children with autism, aged 2.5–8 years, with the following GoF variants were enrolled: KCNQ2 (p. Arg144Gln) and KCNQ 3 (p.Arg227Gln, p.Arg230Cys). Patients were treated off-label with donepezil 2.5–5 mg/d for 12 months and assessed with: clinical Global Impression of Change (CGI-c), Childhood Autism Rating Scale 2 (CARS-2), Adaptive Behavior Assessment System-II (ABAS-II), and Child Development Inventory (CDI).Results(1) Application of donepezil for at least 6 min produced a significant inhibition of the M-current with an IC50 of 0.4 μM. At 1 μM, donepezil reduced by 67% the M-current density of excitatory neurons (2.4 ± 0.46 vs. 0.89 ± 0.15 pA/pF, p 0.05). Donepezil (1 μM) potently increased by 2.6-fold the spontaneous firing frequency, which was prevented by the muscarinic receptor antagonist atropine (10 μM). (2) The CARS-2 decreased by 3.8 ± 4.9 points (p > 0.05), but in two patients with KCNQ3 variants, the improvement was over the 4.5 clinically relevant threshold. The global clinical change was also clinically significant in these patients (CGI-c = 1). The CDI increased by 65% (p

Temporary labor migration is a household phenomenon among rural communities in India. This study seeks to understand the subjective experiences influencing the temporariness of labor migration among internal migrants in India by examining various factors such as migration conditions, motivation, migration arrangements, coping and adaptation strategies, and determinants of stay. To achieve this objective, the current qualitative study utilized 14 in-depth interviews and 2 focus group discussions to investigate the temporary nature of labor migration among internal migrants in India. Our findings reveal that migration decisions are rational choices made collectively at the household level, considering socio-economic outcomes. We also find that social networks and contractors facilitate migration arrangements and job connections, and migrants employ various strategies to reduce costs and cope with expenses in urban areas. However, migration destinations often fail to meet migrants’ expectations, exposing them to low-wage employment and precarious working and living conditions, which are detrimental to their health. Limited housing and sanitation facilities further contribute to the challenges faced by migrants. Work conditions, including poor wages and high job demands, also affect their well-being. These findings highlight the need for improved support systems that address accommodation challenges, work conditions, and the overall welfare of labor migrants.

Background Approximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are treatment options for recurrent/metastatic HNSCC; however, less than 20% of patients respond. To increase this response rate, it is fundamental to increase our understanding of the spatial tumor immune microenvironment (TIME).Methods In total, 53 HNSCC specimens were included. Using a seven-color multiplex immunohistochemistry panel we identified tumor cells, CD163+macrophages, B cells, CD8+T cells, CD4+T helper cells and regulatory T cells (Tregs) in treatment-naive surgical resection specimens (n=29) and biopsies (n=18). To further characterize tumor-infiltrating CD8+T cells, we stained surgical resection specimens (n=12) with a five-color tumor-resident panel including CD103, Ki67, CD8 and pan-cytokeratin. Secretome analysis was performed on matched tumor suspensions (n=11) to measure protein levels.Results Based on CD8+T cell infiltrates, we identified four different immunotypes: fully infiltrated, stroma-restricted, immune-excluded, and immune-desert. We found higher cytokine levels in fully infiltrated tumors compared with other immunotypes. While the highest immune infiltrates were observed in the invasive margin for all immune cells, CD163+macrophages and Tregs had the highest tendency to infiltrate the tumor center. Within the tumor center, especially B cells stayed at the tumor stroma, whereas CD163+macrophages, followed by T cells, were more often localized within tumor fields. Also, B cells were found further away from other cells and often formed aggregates while T cells and CD163+macrophages tended to be more closely located to each other. Across resection specimens from various anatomical sites within the head and neck, oral cavity tumors exhibited the highest densities of Tregs. Moreover, the distance from B cells and T cells to tumor cells was shortest in oral cavity squamous cell carcinoma (OCSCC), suggesting more interaction between lymphocytes and tumor cells. Also, the fraction of T cells within 10 µm of CD163+macrophages was lowest in OCSCC, indicating fewer myeloid/T-cell suppressive interactions in OCSCC.Conclusions We comprehensively described the TIME of HNSCC using a unique data set of resection specimens. We discovered that the composition, as well as the relative localization of immune cells in the TIME, differed in distinct anatomical sites of the head and neck.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

The study assessed the physicochemical and biological properties of selected groundwater sources in the Southeastern part of the Western Region, to assess the impact on water quality and health risk. The Piper Trilinear plot was used to categorize the water samples into water types based on the dominant anion and cation concentrations. Statistical analysis (One way ANOVA and two sample t-test) was used to determine the sources of variation in the data at 95% confidence interval. The Water Quality Index (WQI) and Hazard Quotient (HQ) were used to estimate the water quality and health risk respectively. TDS and turbidity were above the acceptable WHO guidelines in 16.7% of the samples with a mildly acidic pH in 83.3% of the water samples. Also, 91.7% of the water samples were contaminated with total coliform (TC) and 25% with e-coli. Generally, the groundwater samples were dominated by Ca2+ and HCO3- ion water types. The variations between parameters were found not significant for all the parameters (p>0.05). Water samples in the North are of good quality with a mean WQI of 96, but of poor quality in the South with a mean WQI of 144.6. HQ values for all the samples were less than 0.1, suggesting less harmful impacts of the heavy metal concentrations on human health. Overall, the results showed the presence of heavy metals in the groundwater sources sampled, however in quantities with low health risks either through oral or dermal channels. Groundwater within the communities is good for domestic purposes but needs treatment for drinking. To improve upon the study, it is recommended that further studies consider a higher number of samples and include other accessible groundwater stations where possible.

The disruption in daily activity performance during COVID-19 lockdowns is widely understood to have impacted health, but a better understanding of how restricted performance of specific activities are associated with health is needed. This cross-sectional study answers the following question: How were changes in the performance of 16 daily activities associated with health during COVID-19 lockdowns? A total of 116 participants completed an online survey rating their health before and during COVID-19 lockdowns and comparing their recollection of the performance of 16 activities before COVID-19 with their performance during lockdowns. Multiple stepwise linear regression analysis was used to estimate the relationship between self-reported changes in activities during lockdowns and concurrent (during-lockdown) health status, while controlling for pre-COVID-19 health status. Only changes in activities that were uniquely and significantly associated with lockdown health status were retained in the final model. Health before COVID-19 accounted for 3.7% (P = 0.039) of the variance in health during COVID-19 lockdowns. After controlling for health before COVID-19, five types of activity were significantly and uniquely predictive of health during lockdowns, together accounting for 48.3% of the variance. These activities and the variances they accounted for were rest and sleep (29.5%, P

IntroductionMotor vehicular trauma, bite wounds, high-rise syndrome, and trauma of unknown origin are common reasons cats present to the emergency service. In small animals, thoracic injuries are often associated with trauma. The objective of this retrospective study was to evaluate limits of agreement (LOA) between thoracic point-of-care ultrasound (thoracic POCUS) and thoracic radiography (TXR), and to correlate thoracic POCUS findings to animal trauma triage (ATT) scores and subscores in a population of cats suffering from recent trauma.MethodsCats that had thoracic POCUS and TXR performed within 24 h of admission for suspected/witnessed trauma were retrospectively included. Thoracic POCUS and TXR findings were assessed as “positive” or “negative” based on the presence or absence of injuries. Cats positive on thoracic POCUS and TXR were assigned 1 to 5 tentative diagnoses: pulmonary contusions/hemorrhage, pneumothorax, pleural effusion, pericardial effusion, and diaphragmatic hernia. When available ATT scores were calculated. To express LOA between the two imaging modalities a kappa coefficient and 95% CI were calculated. Interpretation of kappa was based on Cohen values.ResultsOne hundred and eleven cats were included. 83/111 (74.4%) cats were assessed as positive based on thoracic POCUS and/or TXR. Pulmonary contusion was the most frequent diagnosis. The LOA between thoracic POCUS and TXR were moderate for all combined injuries, moderate for pulmonary contusions/hemorrhage, pneumothorax, diaphragmatic hernia, and fair for pleural effusion. Cats with positive thoracic POCUS had significantly higher median ATT scores and respiratory subscores compared to negative thoracic POCUS cats.DiscussionThe frequency of detecting intrathoracic lesions in cats was similar between thoracic POCUS and TXR with fair to moderate LOA, suggesting thoracic POCUS is useful in cats suffering from trauma. Thoracic POCUS may be more beneficial in cats with higher ATT scores, particularly the respiratory score.

Background During adolescence, behaviours are initiated that will have substantial impacts on the individual’s short-term and long-term health and well-being. However, adolescents rarely have regular contact with health services, and available services are not always appropriate for their needs. We co-developed with adolescents a health and well-being check-up programme (Y-Check). This paper describes the methods to evaluate the feasibility, acceptability, short-term effects and cost-effectiveness of Y-Check in three African cities.Method This is a multi-country prospective intervention study, with a mixed-method process evaluation. The intervention involves screening, on-the-spot care and referral of adolescents through health and well-being check-up visits. In each city, 2000 adolescents will be recruited in schools or community venues. Adolescents will be followed-up at 4 months. The study will assess the effects of Y-Check on knowledge and behaviours, as well as clinical outcomes and costs. Process and economic evaluations will investigate acceptability, feasibility, uptake, fidelity and cost effectiveness.Ethics and dissemination Approval has been received from the WHO (WHO/ERC Protocol ID Number ERC.0003778); Ghana Health Service (Protocol ID Number GHS-ERC: 027/07/22), the United Republic of Tanzania National Institute for Medical Research (Clearance No. NIMR/HQ/R.8a/Vol.IX/4199), the Medical Research Council of Zimbabwe (Approval Number MRCZ/A/2766) and the LSHTM (Approval Numbers 26 395 and 28312). Consent and disclosure are addressed in the paper. Results will be published in three country-specific peer-reviewed journal publications, and one multicountry publication; and disseminated through videos, briefs and webinars. Data will be placed into an open access repository. Data will be deidentified and anonymised.Trial registration number NCT06090006.

A new analysis is presented of the retrograde tracer measurements of connections between anatomical areas of the marmoset cortex. The original normalisation of raw data yields the fractional link weight measure, FLNe. That is re-examined to consider other possible measures that reveal the underlying in link weights. Predictions arising from both are used to examine network modules and hubs. With inclusion of the in weights the InfoMap algorithm identifies eight structural modules in marmoset cortex. In and out hubs and major connector nodes are identified using module assignment and participation coefficients. Time evolving network tracing around the major hubs reveals medium sized clusters in pFC, temporal, auditory and visual areas; the most tightly coupled and significant of which is in the pFC. A complementary viewpoint is provided by examining the highest traffic links in the cortical network, and reveals parallel sensory flows to pFC and via association areas to frontal areas.

The difficulties of girls working in the "Kaya" trade in Ghana's urban markets are the main subject of this policy review paper. It is to demonstrate the ineffectiveness of the family and the government in dealing with "Kayayie" in Ghana. The paper largely adopted a desk study approach, the main sources being scholarly studies, and a review of information from government agencies, with the addition of the authors’ observations and experiences with Kayayie. The argument of the paper is based on Everett Lee's (1960) Push and Pull Model, which describes migration in terms of factors making people move out of their origins. The paper concludes that budget issues hinder the government's ability to address the kayayei phenomenon. The paper suggests that the government prioritize the welfare of "Kayayei" in the national budget and consider a nationwide data-collection exercise to generate accurate data on kayayei for improving programming and policy decisions regarding kayayei. The results also show that some families push their daughters into marriage to profit from it, while some girls are compelled to travel to the South to avoid being forced into marriage. Since families are primarily responsible for meeting their children's needs, there is a need to improve family life education about the importance of being more accountable for the maintenance of children in the sending communities as well as other migration-prone communities.

Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with a ubiquitous distribution in numerous tissues and with various functions in both neuronal and non-neuronal cells. IGF-1 provides trophic support for many neurons of both the central and peripheral nervous systems. In the central nervous system (CNS), IGF-1R signaling regulates brain development, increases neuronal firing and modulates synaptic transmission. IGF-1 and IGF-IR are not only expressed in CNS neurons but also in sensory dorsal root ganglion (DRG) nociceptive neurons that convey pain signals. DRG nociceptive neurons express a variety of receptors and ion channels that are essential players of neuronal excitability, notably the ligand-gated cation channel TRPV1 and the voltage-gated M-type K+ channel, which, respectively, triggers and dampens sensory neuron excitability. Although many lines of evidence suggest that IGF-IR signaling contributes to pain sensitivity, its possible modulation of TRPV1 and M-type K+ channel remains largely unexplored. In this study, we examined the impact of IGF-1R signaling on DRG neuron excitability and its modulation of TRPV1 and M-type K+ channel activities in cultured rat DRG neurons. Acute application of IGF-1 to DRG neurons triggered hyper-excitability by inducing spontaneous firing or by increasing the frequency of spikes evoked by depolarizing current injection. These effects were prevented by the IGF-1R antagonist NVP-AEW541 and by the PI3Kinase blocker wortmannin. Surprisingly, acute exposure to IGF-1 profoundly inhibited both the TRPV1 current and the spike burst evoked by capsaicin. The Src kinase inhibitor PP2 potently depressed the capsaicin-evoked spike burst but did not alter the IGF-1 inhibition of the hyperexcitability triggered by capsaicin. Chronic IGF-1 treatment (24 h) reduced the spike firing evoked by depolarizing current injection and upregulated the M-current density. In contrast, chronic IGF-1 markedly increased the spike burst evoked by capsaicin. In all, our data suggest that IGF-1 exerts complex effects on DRG neuron excitability as revealed by its dual and opposite actions upon acute and chronic exposures.

Summary: Background: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). Methods: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00–11:59 (morning), 12:00–17:59 (afternoon), 18:00–23:59 (evening), or 24:00–05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. Findings: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53–1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22–0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68–1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16–0.91]). Interpretation: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. Funding: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.

Abstract Background The purpose of the study was to explore the views of nurses on the concept of patient- and family-centered care (PFCC) and its practices in a peri-operative context in Northern Ghanaian hospitals. Methods The study, using a qualitative explorative, descriptive, and contextual research design was conducted at six selected hospitals located in the Northern part of Ghana. Purposive sampling was used to recruit participants for individual and focus group interviews. Data were generated between March and May 2022. Data saturation was reached with 27 participants comprising 15 individuals and 12 members from two focus group interviews. All interviews were digitally recorded and transcribed verbatim and the data analyzed using thematic analysis. Results Two themes emerged from the study, namely nurses’ understanding of the concept of PFCC and how they see the benefits of PFCC in a peri-operative context. Subthemes of the nurses’ understanding of PFCC included their perceptions of PFCC, the need for collaboration, supporting the patient’s family for better post-operative and effective communication, and PFCC practices in the peri-operative context. Subthemes for benefits of PFCC in the peri-operative context included nurse-related benefits, patient- and family-related benefits, and healthcare system-related benefits. Conclusions The study revealed that the concept of PFCC is unfamiliar to the Ghanaian peri-operative context despite the positive perceptions exhibited by the nurses in terms of their understanding of PFCC and its related benefits to nurses, patients, and families as well as the healthcare system.

Abstract Background In Low-Middle-Income Countries (LMICs), young people living with Type 1 Diabetes Mellitus (T1DM) face structural barriers which undermine adequate T1DM management and lead to poor health outcomes. However, research on the barriers faced by young people living with T1DM have mostly focused on patient factors, neglecting concerns regarding plausible barriers that may exist at the point of healthcare service delivery. Objective This study sought to explore barriers faced by young people living with T1DM and their caregivers at the point of healthcare service delivery. Methods Data were drawn from a qualitative research in southern Ghana. The research was underpinned by a phenomenological study design. Data were collected from 28 young people living with T1DM, 12 caregivers, and six healthcare providers using semi-structured interview guides. The data were collected at home, hospital, and support group centres via face-to-face interviews, telephone interviews, and videoconferencing. Thematic and framework analyses were done using CAQDAS (QSR NVivo 14). Results Eight key barriers were identified. These were: shortage of insulin and management logistics; healthcare provider knowledge gaps; lack of T1DM care continuity; poor healthcare provider-caregiver interactions; lack of specialists’ care; sharing of physical space with adult patients; long waiting time; and outdated treatment plans. The multiple barriers identified suggest the need for an integrated model of T1DM to improve its care delivery in low-resource settings. We adapted the Chronic Care Model (CCM) to develop an Integrated Healthcare for T1DM management in low-resource settings. Conclusion Young people living with T1DM, and their caregivers encountered multiple healthcare barriers in both in-patient and outpatient healthcare facilities. The results highlight important intervention areas which must be addressed/improved to optimise T1DM care, as well as call for the implementation of a proposed integrated approach to T1DM care in low-resource settings.

Abstract Background Spatial repellents (SR) may complement current vector control tools and provide additional coverage when people are not under their bednets or are outdoors. Here we assessed the efficacy of a metofluthrin-based SR in reducing exposure to pyrethroid-resistant Anopheles funestus in Siaya County, western Kenya. Methods Metofluthrin was vaporized using an emanator configured to a liquid petroleum gas (LPG) canister, placed inside experimental huts (phase 1) or outdoors (phase 2), and evaluated for reductions in human landing rate, density, knockdown and mortality rates of An. funestus, which are present in high density in the area. To demonstrate the mosquito recruiting effect of LPG, a hut with only an LPG cooker but no metofluthrin was added as a comparator and compared with an LPG cooker burning alongside the emanator and a third hut with no LPG cooker as control. Phase 2 evaluated the protective range of the SR product while emanating from the centre of a team of mosquito collectors sitting outdoors in north, south, east and west directions at 5, 10 and 20 feet from the emanating device. Results Combustion of LPG with a cook stove increased the density of An. funestus indoors by 51% over controls with no cook stove. In contrast, huts with metofluthrin vaporized with LPG combustion had lower indoor density of An. funestus (99.3% less than controls), with knockdown and mortality rates of 95.5 and 87.7%, respectively, in the mosquitoes collected in the treated huts. In the outdoor study (phase 2), the outdoor landing rate was significantly lower at 5 and 10 feet than at 20 feet from the emanator. Conclusions Vaporized metofluthrin almost completely prevented An. funestus landing indoors and led to 10 times lower landing rates within 10 feet of the emanator outdoors, the first product to demonstrate such potential. Cooking with LPG inside the house could increase exposure to Anopheles mosquito bites, but the use of the metofluthrin canister eliminates this risk. Graphical abstract

Abstract Purpose The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. Materials and methods An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. Results PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. Conclusion The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

While the impact of the pandemic has varied between and within countries, there are few published data on the relationship between social determinants of health (SDoH) and COVID-19 in Africa. This ecological cross-sectional study examines the relationship between COVID-19 risk and SDoH among 28 African countries. Included were countries with a recent demographic and health survey (years 2010 to 2018). The response variables were COVID-19 case rates and death rates (reported as of 15 August 2020); and the covariates comprised eight broad topics common to multiple SDoH frameworks aggregated to the country level: geography (urban residence), wealth index, education, employment, crowding, and access to information. A negative binomial regression was used to assess the association between aspects of SDoH and COVID-19 outcomes. Our analysis indicated that 1 in 4 (25.1%) households in study countries are without safe and clean water and a space for handwashing. The odds of COVID-19 morbidity and deaths were higher in countries with a high proportion of households without access to safe and clean water. Having a high proportional of educated women (1.003: 95% CI, 1.001–1.005) and living in a less crowded home (0.959: 95% CI, 0.920–1.000) were negatively associated with COVID-19 deaths, while being insured and owning a mobile phone predicted illness. Overall, aspects of SDoH contribute either negatively or positively to COVID-19 outcomes. Thus, addressing economic and environmental SDoH is critical for mitigating the spread of COVID-19 and re-emerging diseases on the African continent.

Presupposition can be said to be an assumption of a speaker prior to making an utterance or an implied claim of an utterance. Using qualitative method, the researchers examined various language structures that give rise to presuppositions. This was pursued by exploring the State of the Nation Address (SONA) delivered by President Akufo-Addo of Ghana on 30th March 2022. The analysis of the SONA, as the data of the study, revealed the utilization of a number of presupposition triggers – such as possessive construction, “one” construction, definite noun phrase, adverbial clause, relative clause, “even” construction, iteratives, change of state verbs, and factive verbs or phrases – under the existential, structural and lexical presuppositions. The article thus opines that the enactment of presuppositions, through the identified forms, affords the President the opportunity to disseminate his message with a higher degree of veracity on the conditions and happenings of the Ghanaian state.

Abstract Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role of Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 in mice yet drives low levels of type-1 IFNs but robust IFNγ. Here we examine the role of ongoing IFNγ responses to pre-established bacterial infection on SARS-CoV-2 disease outcomes in two murine models. We report that IFNγ is required for iv BCG induced reduction in pulmonary viral loads, an outcome dependent on IFNγ receptor expression by non-hematopoietic cells. Importantly, we show that BCG infection prompts pulmonary epithelial cells to upregulate IFN-stimulated genes with reported anti-viral activity in an IFNγ-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirm the anti-viral properties of IFNγ by demonstrating that the recombinant cytokine itself provides strong protection against SARS-CoV-2 challenge when administered intranasally. Together, our data show that a pre-established IFNγ response within the lung is protective against SARS-CoV-2 infection, suggesting that concurrent or recent infections that drive IFNγ may limit the pathogenesis of SARS-CoV-2 and supporting possible prophylactic uses of IFNγ in COVID-19 management.