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Abstract Background Informal abortions, commonly known as unsafe abortions, refer to all induced abortions that occur outside of formal healthcare settings conducted without the assistance of a licensed, trained healthcare provider. Despite the legalization of safe induced abortion care services, informal abortions continue to be among the major causes of maternal mortality and morbidity among young women in Rwanda living in rural areas with limited or no access to safe abortion care services. The purpose of this qualitative study was to gain an in-depth understanding of the lived experience of seeking informal abortions from the perspective of young women in rural Rwanda and to identify the underlying factors for these women seeking abortion care services outside of the formal healthcare setting. Methods This qualitative study was guided by a descriptive phenomenology in rural Rwanda, specifically in a selected district located in the Northern Province of Rwanda. Ten young women between 18 and 24 years of age, who had the experience of seeking informal abortion services from informal providers within the last eight years participated in audio-recorded, in-depth, face-to-face interviews. Collected data were analyzed using Colaizzi’s (1978) seven steps of the phenomenological method. Results The study found that young Rwandan women still seek unregulated abortions to end their unintended pregnancies due to limited access to or utilization of sexual reproductive health and rights services. Among the reasons for seeking abortion care services outside of the formal healthcare setting in Rwanda were sociocultural and economic factors and the stigma associated with terminating unintended pregnancies before marriage. Conclusion In light of the findings of this study, the authors recommend the Ministry of Health and its stakeholders to expand access to comprehensive adolescent and youth-friendly reproductive health and reproductive rights while addressing the sociocultural stigma through public awareness and economic factors that play a big role in unregulated abortions rather than safe abortion care services.

Abstract Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes.

Abstract Hypertension is a leading contributor to mortality in low‐middle income countries including Haiti, yet only 13% achieve blood pressure (BP) control. We evaluated the effectiveness of a community‐based hypertension management program delivered by community health workers (CHWs) and physicians among 100 adults with uncontrolled hypertension from the Haiti Cardiovascular Disease Cohort. The 12‐month intervention included: community follow‐up visits with CHWs (1 month if BP uncontrolled ≥140/90, 3 months otherwise) for BP measurement, lifestyle counseling, medication delivery, and dose adjustments. Primary outcome was mean change in systolic BP from enrollment to 12 months. Secondary outcomes were mean change in diastolic BP, BP control, acceptability, feasibility, and adverse events. We compared outcomes to 100 age, sex, and baseline BP matched controls with standard of care: clinic follow‐up visits with physicians every 3 months. We also conducted qualitative interviews with participants and providers. Among 200 adults, median age was 59 years, 59% were female. Baseline mean BP was 154/89 mmHg intervention versus 153/88 mmHg control. At 12 months, the difference in SBP change between groups was −12.8 mmHg (95%CI −6.9, −18.7) and for DBP −7.1 mmHg (95%CI −3.3, −11.0). BP control increased from 0% to 58.1% in intervention, and 28.4% in control group. Four participants reported mild adverse events. In mixed methods analysis, we found community‐based delivery addressed multiple participant barriers to care, and task‐shifting with strong teamwork enhanced medication adherence. Community‐based hypertension management using task‐shifting with CHWs and community‐based care was acceptable, and effective in reducing SBP, DBP, and increasing BP control.

Abstract Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. This therapeutic regimen resulted in deep and durable responses in 19% of patients, with the median duration of response not yet reached. Notwithstanding, a significant proportion of AGC patients exhibited no therapeutic advantage, prompting investigations into mechanisms of inherent resistance. Comprehensive biomarker profiling elucidated that non-responders predominantly exhibited an augmented presence of M2 macrophages within the tumor microenvironment and a marked overexpression of S100A10 by neoplastic cells, a protein previously implicated in macrophage chemotaxis. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.

Abstract Background Poverty is a key social determinant of mental health among forcibly displaced persons. This study aimed to design and pilot test a strategy to integrate existing mental health and economic inclusion interventions for displaced families in Ecuador. Methods We conducted a series of qualitative interviews (n = 30), focus groups (n = 6), and workshops (n = 3) to develop a set of strategies for integrating cross-cutting and focused mental health and psychosocial support (MHPSS) strategies into an existing economic inclusion program for displaced families in Quito. We non-randomly assigned two field offices in Quito to (1) integrate cross-cutting strategies focused on improving economic outcomes or (2) integrate both those cross-cutting strategies plus focused MHPSS strategies into an economic inclusion program. We measured site-level implementation outcomes (adoption, appropriateness, acceptability, feasibility, fidelity, reach, retention, usability) and participant-level psychosocial (wellbeing, depressive symptoms, anxiety symptoms, functioning) and economic inclusion outcomes (financial resources, diet diversity, social capital/networks, self-reliance) over six months. We conducted a mixed-methods analysis to explore the acceptability and feasibility of the integration strategies and the ability to evaluate their effects in a future cluster randomized trial. Results We developed a toolkit that included 10 strategies for integrating MHPSS into economic inclusion interventions. Fifty displaced persons participating in an existing economic inclusion program (25 per study condition) were enrolled and 88% remained in the study through the six-month follow-up. Participants and implementers reported that the integration strategy was appropriate, acceptable, feasible, and usable. Implementers, including people without prior experience in delivering mental health services, were able to deliver the intervention with high fidelity. Integration of focused MHPSS intervention components into an economic inclusion program appeared to improve MHPSS outcomes, the strength of social capital and networks, and engagement in economic and other programs. Conclusions This study provides preliminary evidence of the acceptability and feasibility of integrating MHPSS into economic inclusion programs for displaced people. We found evidence supporting evaluation methods that can be employed in a future study to definitively test the added value of integrated approaches to mental health and economic wellbeing for displaced persons.

Introduction Dengue is one of the most serious and rapidly spreading major mosquito borne diseases in the world. Despite many acute febrile illnesses in Tchad, the burden of illness due to dengue in the country is largely unknown. Hence, the present study aimed to determine the seroprevalence of dengue viral (DENV) infection and its association with hematological parameters. Method A cross sectional study was carried out in Bongor Provincial Hospital. Blood samples were collected from each participant and were used to determine the hematological profile and to diagnose the presence of DENV infection. A total of 130 participants were enrolled in the study. Among these, 114 (87.7%) were diagnosed positive for DENV infection. Results The majority of the positive cases were of the age group 21 to 40 years old. Leukocytosis was the most common hematological parameter affecting 120 (92.3%) of them followed by anemia and thrombocytopenia affecting 69 (53.1%) and 16 (12.3%) of them, respectively, and then lymphocytosis affecting 5 (3.8%) of them. No case of leukopenia was recorded. Discussion The seroprevalence rate among participants suggests that the dengue virus is in circulation in Mayo Kebbi province: south of Tchad. The abnormal hematological parameters may contribute to the severity of the infection like the incidence of bleeding in the case of thrombocytopenia.

Abstract Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

Abstract Background The undergraduate medical training programme is demanding and rigorous. This underlines the importance of a peer mentorship strategy to improve the well-being, self-determination, school connectedness, and performance of struggling medical and nursing students. This study is aimed at identifying struggling medical and nursing students using two cumulative continuous assessment test (CAT) scores, assess their subjective vitality and school engagement and evaluate the impact of the peer mentorship intervention on them. Methods The study will adopt a mixed-methods approach and will be conducted in the medical colleges of Nnamdi Azikiwe University, Awka, Nigeria, and the University of Rwanda. Three instruments will be used: The subjective Vitality Scale (SVS), the University Student Engagement Inventory (USEI), and the academic records of the students before and after the commencement of the intervention programme. The consenting least-performing medical and nursing students identified by their low CAT scores (below 45%) in basic medical sciences will be selected for study in each institution. The outcome measures will include students’ CAT scores, subjective vitality, and school engagement scores. The data will be analysed both quantitatively and qualitatively. Thematic content analysis will be adopted in the analysis of the responses generated from the focus group discussion. The mean ± standard deviation or median and interquartile range statistic will be adopted for the quantitative data. Discussion Given the paucity of data on struggling medical and nursing students in Nigeria and Rwanda, this research was designed to help in exploring evidence-based interventions to improve and prevent poor subjective well-being of struggling students. The study is expected to fill these knowledge gaps. Trial registration: Pan African Clinical Trial registry, PACTR202405546896613, registration date: 27th May, 2024. This proposal has been supported by grant 1R25TW011217 from the US National Institutes of Health (NIH)/Fogarty International Center (FIC) which also includes co-funds from the U.S. Department of State’s Office of the U.S. Global AIDS Coordinator and Health Diplomacy (S/GAC) and the President’s Emergency Plan for AIDS Relief (PEPFAR) to the African Forum for Research and Education in Health (AFREhealth). The Grant Principal Investigators are Profs. Nelson K.Sewankambo (contact PI), Prisca Adejumo, Jean Bisimwa Nachega, Fatima Suleman.

Abstract Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. Nowadays, these two groups present distinct genetic diversity and group-specific variation linked to pathogens. We propose differing hydrology patterns and effectiveness of geographic barriers have modulated the intra-group connectivity and structure of bald and black uakari populations. With this work we have explored the effects of the Amazon rainforest’s dynamism on wild primates’ genetics and increased the representation of platyrrhine genomes, thus opening the door to future research on the complexity and diversity of primate genomics.

Abstract Malaria is one of the major health threats in Africa, and the risk of transmission is projected to be exacerbated by global warming. Rwanda experienced an 11-fold increase in malaria incidence from 2011 to 2015 despite extensive funding and implementation of control measures. Here, we focus on Rwanda as a case study and simulate monthly malaria incidence between 2010 and 2015, employing an ensemble learning method. Next, we project future malaria prevalence using shared socio-economic pathways (SSP2-4.5 and SSP5-8.5). We find that the projected increases in temperature and precipitation may shift malaria transmission risk to the highlands of western and northern Rwanda. These two regions that currently experience low malaria transmission. The seasonal effects of malaria incidence may be less apparent from January to June, and the peak season for malaria transmission in the highlands could occur one month earlier. Our findings highlight the impacts of climate change on malaria epidemics in Rwanda, which have implications for other world regions.

Résumé : La problématique relative à l’existence d’une presse libre au Congo Démocratique suscite encore des questions sans réponses appropriées dans les clubs des hommes de la presse. Allons-nous, dans cet article, essayer de relever les phénomènes qui torpillent toute tentative amorcée dans ce but ? En effet, nul n’ignore le rôle que peuvent jouer les médias dans le développement socioculturel d’un pays. Le système global congolais de l’information et de la communication quant à lui reste par le pouvoir. Certains observateurs le qualifient de courant Sakombiste (ancien ministre du régime Mobutu). Car, au départ, cette effervescence de libéraliser le secteur des médias en République Démocratique du Congo, avait des repères aux premiers pas posés par les idéologies des pères de l’indépendance dont la presse a fait son travail d’éveil patriotique. La vision du feu Mobutu et l’influence diplomatique des étrangers à l’époque a plongé les professionnels des médias dans une situation contraste devant défendre l’éthique et la déontologie de leur métier. Il sied de noter que, le manque de bonne politique de gestion du secteur médiatique après la libéralisation nous pousse d’avoir une idée particulière, d’étaler les qualités d’un journaliste professionnel et celui qui exerce de l’amateurisme organisé, bien que les origines du journalisme font montre que ce métier était tout simplement de colporter les nouvelles parfois qui n’ont pas des sources certaines ajoutent les hommes de lettres de l’époque. Mais avant cela, nous faisons un bref aperçu historique de cet événement afin parler quelques réalités qui ont amené la confusion dans le secteur de média de masse congolais. Mots-clés : journaliste professionnel, mouton noir, journaliste amateur.

Abstract Silicon photonics arises as a viable solution to address the stringent resource demands of emergent technologies, such as neural networks. Within this framework, photonic memories are fundamental building blocks of photonic integrated circuits that have not yet found a standardized solution due to several trade-offs among different metrics such as energy consumption, speed, footprint, or fabrication complexity, to name a few. In particular, a photonic memory exhibiting ultra-high endurance performance (>106 cycles) has been elusive to date. Here, we report an ultra-high endurance silicon photonic volatile memory using vanadium dioxide (VO2) exhibiting a record cyclability of up to 107 cycles without degradation. Moreover, our memory features an ultra-compact footprint below 5 µm with the potential for nanosecond and picojoule programming performance. Our silicon photonic memory could find application in emerging photonic applications demanding a high number of memory updates, such as photonic neural networks with in situ training.

Abstract Mentha arvensis is an herbaceous plant commonly known as peppermint or Japanese mint. This study investigated the toxic potential and repellent efficacy of M. arvensis essential oil (MaEO) at varying concentrations (15.625–250 mg/mL) in Nauphoeta cinerea, along with its impact on biochemical parameters in N. cinerea. The potential of the major compounds as a new analgesic target was investigated using molecular docking. The essential oil was analyzed by gas Chromatography–mass spectrometry (GC–MS) and the toxic potential, repellent property, and changes in lipid peroxidation (LPO) levels were evaluated as markers of oxidative stress. GC–MS results revealed that the main components were oxygenated monoterpenes such as menthol (71.31%), mentone (13.34%) and isomentone (5.35%). MaEO significantly reduced lipid peroxidation (LPO), the levels of non-protein thiols and iron(II) at the concentration of 125 mg/mL in N. cinerea. Furthermore, the major components, l-(−)-Menthol and menthone demonstrated high gastrointestinal absorption and high affinity with the target protein, suggesting possible links that contribute to the analgesic effect of MaEO.

Full-field transmission X-ray microscopy has been recently implemented at the hard X-ray ROCK–SOLEIL quick-EXAFS beamline, adding micrometre spatial resolution to the second time resolution characterizing the beamline. Benefiting from a beam size versatility due to the beamline focusing optics, full-field hyperspectral XANES imaging has been successfully used at the Fe K-edge for monitoring the pressure-induced spin transition of a 150 µm × 150 µm Fe(o-phen)2(NCS)2 single crystal and the charge of millimetre-sized LiFePO4 battery electrodes. Hyperspectral imaging over 2000 eV has been reported for the simultaneous monitoring of Fe and Cu speciation changes during activation of a FeCu bimetallic catalyst along a millimetre-sized catalyst bed. Strategies of data acquisition and post-data analysis using Jupyter notebooks and multivariate data analysis are presented, and the gain obtained using full-field hyperspectral quick-EXAFS imaging for studies of functional materials under process conditions in comparison with macroscopic information obtained by non-spatially resolved quick-EXAFS techniques is discussed.

Objective Carnosine and anserine affect the meat flavor. The contents of carnosine and anserine in meat are affected by genetic and environmental factors. This study aimed to discover the single-nucleotide polymorphisms (SNPs) in the histamine-N-methyl transferase (HNMT) and histamine-N-methyl transferase-like (HNMT-like) genes and to associate them with the content of carnosine and anserine in Korean native chicken-red brown line (KNC-R). Methods This study used a total of 384 birds (males, n = 192; females, n = 192) aged 10 weeks old, for genotyping HNMT and HNMT-like genes. One synonymous SNP (rs29009298C/T) of the HNMT gene was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) methods whereas four missense SNPs (rs734406537G/A; rs736514667A/G; rs15881680G/A and rs316765035T/C) of the HNMT gene, and one missense SNP rs737657949A/C of the HNMT-like gene were genotyped by PCR allele competitive extension (PACE) genotyping technology. Two-way analysis of variance of the R program was used to associate HNMT genotypes with the contents of carnosine and anserine in KNC-R chickens. Results There were significant associations (p

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

Background: Cassia alata or Senna alata, also known as “ringworm bush” because of its very effective fungicidal properties, is commonly used in African traditional medicine to treat fungal infections. Despite extensive phytochemical and pharmacological studies previously reported on C. alata, the antibiofilm activity against pathogenic yeast as well as the related anti-quorum sensing mechanism of some active constituents has not yet been elucidated. The aim of the study was to isolate the bioactive constituents from the methanol extract of the leaves of C. alata (CAExt) using antibiofilm-guided fractionation against yeast fungal pathogens and then to investigate the anti-quorum sensing activity of the active constituents by assessing their ability to inhibit violacein production in Chromobacterium violaceum. Methods: Chromatographic methods were used to isolate the constituents of CAExt, and spectroscopic methods were used to elucidate the chemical structures of the isolated compounds. The broth microdilution assay was used to evaluate the antifungal activity against Candida albicans and C. parapsilosis, while crystal violet staining was used for the inhibition of biofilm formation and the disruption of preformed biofilm. The biosensor strain C. violaceum ATCC 12472 was used to investigate the anti-quorum sensing activity of the most active constituents. Results: The crude extract exhibited biofilm inhibition and eradication activities against the tested pathogenic yeast. The biofilm inhibition percentages ranged from 53.22 % to 75.38 %, while the biofilm eradication percentages ranged from 23.21 % to 64.25 %. The ethyl acetate fraction demonstrated high biofilm inhibition and eradication activities against the tested microorganisms. The biofilm inhibition percentages ranged from 58.19 % to 79.30 %, while the biofilm eradication percentages ranged from 34.105 % to 69.54 %. The purification of subfractions led to the identification of six compounds: stigmasterol (1), sitosterol (2), lupeol (3), emodin (4), kaempferol (5) and stigmasterol glycoside (6), two of which (4 and 5) showed potent biofilm inhibition and eradication activities. Both compounds demonstrated significantly lower MBIC50 values of 70.81 µg/mL and 65.65 µg/mL against Candida albicans and MBEC50 values of 63.65 µg/mL and 82.66, respectively, against C. albicans and C. parapsilosis. The crude extract and compounds (4) and (5) also demonstrated quorum sensing inhibitory activity, as indicated by the MQSIC value of 1024 µg/mL for the crude extract and 128 µg/mL for the two compounds. Moreover, compounds (4) and (5) displayed significant inhibitory effects on violacein production, as indicated by their low IC50 values of 28.08 µg/mL and 26.44 µg/mL, respectively. Conclusions: Data obtained in this study not only support the traditional use of C. alata in the treatment of fungal infections but also reveal C. alata extract, as well as the two isolated bioactive compounds emodin (4) and kaempferol (5), as a potential source for developing antibiofilm alternative agents against biofilm-associated yeast infections. List of compounds studied: stigmasterol (1), sitosterol (2), lupeol (3), emodin (4), kaempferol (5), stigmasterol glycoside (6)

Introduction First-line oxygenation strategy in patients with acute hypoxaemic respiratory failure consists in standard oxygen or high-flow nasal oxygen therapy. Clinical practice guidelines suggest the use of high-flow nasal oxygen rather than standard oxygen. However, findings remain contradictory with a low level of certainty. We hypothesise that compared with standard oxygen, high-flow nasal oxygen may reduce mortality in patients with acute hypoxaemic respiratory failure.Method and analysis The Standard Oxygen versus High-flow nasal Oxygen-trial is an investigator-initiated, multicentre, open-label, randomised controlled trial comparing high-flow nasal oxygen versus standard oxygen in patients admitted to an intensive care unit (ICU) for acute respiratory failure with moderate-to-severe hypoxaemia. 1110 patients will be randomly assigned to one of the two groups with a ratio of 1:1. The primary outcome is the number of patients who died 28 days after randomisation. Secondary outcomes include comfort, dyspnoea and oxygenation 1 hour after treatment initiation, the number of patients intubated at day 28, mortality in ICU, in hospital and until day 90, and complications during ICU stay.Ethics and dissemination The study has been approved by the central Ethics Committee ‘Sud Méditerranée III’ (2020-07-05) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04468126.

The classical BCR::ABL-negative myeloproliferative neoplasms (MPN) include Polycythemia Vera (PV), Essential Thrombocytemia (ET), and Primary Myelofibrosis (PMF). They are acquired clonal disorders of the hematopoietic stem cells (HSC) leading to hyperplasia of one or several myeloid lineages. MPN are caused by three main recurrent mutations, JAK2V617F and mutations in the calreticulin (CALR) and the thrombopoietin receptor (MPL) genes. Here, we review the general diagnosis, the complications, and the management of MPN. Second, we explain the physiopathology of the natural disease development and its regulation, which contributes to MPN heterogeneity. Thirdly, we describe the new paradigm of the MPN development highlighting the early origin of driver mutations decades before the onset of symptoms and the consequence on early detection of MPN cases in the general population for early diagnosis and better medical management. Finally, we present the interferon alpha (IFNα) therapy as a potential early disease-modifying drug after reporting its good hematological and molecular efficacies in ET, PV and early MF in clinical trials as well as its mechanism of action in pre-clinical studies. As a result, we may expect that, in the future, MPN patients will be diagnosed very early during the course of disease and that new selective therapies under development, such as IFNα, JAK2V617F inhibitors and CALRmut monoclonal antibodies, would be able to intercept the mutated clones.

ABSTRACT Agriculture intensification in Southern Brazil’s subtropical regions combined with the frequent occurrence of erosive rainfall has rendered the area a global water erosion hotspot. In this scenario, understanding and regulating erosion processes at the river catchment scale is critical for mitigating soil and water resource degradation. Traditional methods for tracing sediment sources are expensive and time-consuming and justify the development of alternative approaches. Therefore, in this study, we employed diffuse reflectance spectroscopy analyses in the ultraviolet-visible (UV-VIS), near-infrared (NIR), and mid-infrared (MIR) ranges, combined with multivariate models and spectral pre-processing techniques to estimate sediment source contributions in a homogeneous subtropical catchment (Conceição River, 804 km²). Soil samples (n = 181) were collected to characterize the four potential sediment sources, including: cropland (n = 78), stream bank (n = 36), unpaved road (n = 40) and pasture (n = 27). Moreover, 44 sediment samples were collected, including suspended sediment (n = 8), fine sediment deposited on the riverbed (n = 15), and suspended sediment samples collected in the water column during storm events (n = 21). Vector machine (SVM) model outperformed the others, with better accuracy and reliability. While UV-VIS spectra proved less effective due to soil homogeneity across the catchment, NIR and MIR spectra provided valuable information for discriminating sediment sources. Furthermore, reducing the number of potential sources (from four to three or two) improved model predictions, especially when distinguishing between surface sources (cropland and pasture) and subsurface sources (unpaved roads and stream banks). The study’s findings shed light on the power of efficient and cost-effective alternative methods for assessing sediment sources, which are vital for promoting effective erosion control and sustainable land management in similar regions.

Abstract Background Skin prick tests (SPTs), or intraepidermal tests, are often the first diagnostic approach for people with a suspected allergy. Together with the clinical history, SPTs allow doctors to draw conclusions on allergies based on the sensitization pattern. The purpose of this study is to investigate the potential cost consequences that would accrue to a Swiss University hospital after the adoption of computer vision-based SPTs. Methods We conducted a cost-consequence analysis from a hospital’s perspective to evaluate the potential cost consequences of using a computer vision-based system to read SPT results. The patient population consisted of individuals who were referred to the allergology department of one of the five university hospitals in Switzerland, Inselspital, whose allergology department averages 100 SPTs a week. We developed an early cost-consequence model comparing two SPT techniques; computer vision-based SPTs conducted with the aid of Nexkin DSPT and standard fully manual SPTs. Probabilistic sensitivity analysis and additional univariate sensitivity analyses were used to account for uncertainty. Results The difference in average cost between the two alternatives from a hospital’s perspective was estimated to be CHF 7 per SPT, in favour of the computer vison-based SPTs. Monte Carlo probabilistic simulation also indicated that SPTs conducted using the computer vision-based system were cost saving compared to standard fully manual SPTs. Sensitivity analyses additionally demonstrated the robustness of the base case result subject to plausible changes in all the input parameters, with parameters representing the costs associated with both SPT techniques having the largest influence on the incremental cost. However, higher sensitization prevalence rates seemed to favour the more accurate standard fully manual SPTs. Conclusion Against the backdrop of rising healthcare costs especially in Switzerland, using computer-aided or (semi) automated diagnostic systems could play an important role in healthcare cost containment efforts. However, results should be taken with caution because of the uncertainty associated with the early nature of our analysis and the specific Swiss context adopted in this study.

Abstract The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington’s disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, one protoplasmic astrocyte state showed high levels of metallothioneins and was correlated with the selective vulnerability of distinct striatal neuronal populations. When modeled in vitro, this state improved the viability of HD-patient-derived spiny projection neurons. Our findings uncover key roles of astrocytic states in protecting against neurodegeneration in HD.

Objective The analysis of runs of homozygosity (ROH) has been applied to assess the level of inbreeding and identify selection signatures in various livestock species. The objectives of this study were to characterize the ROH pattern, estimate the rate of inbreeding, and identify signatures of selection in the red-brown Korean native chickens. Methods The Illumina 60K single nucleotide polymorphism chip data of 651 chickens was used in the analysis. Runs of homozygosity were analysed using the PLINK v1.9 software. Inbreeding coefficients were estimated using the GCTA software and their correlations were examined. Genomic regions with high levels of ROH were explored to identify selection signatures. Results A total of 32,176 ROH segments were detected in this study. The majority of the ROH segments were shorter than 4 Mb. The average ROH inbreeding coefficients (FROH) varied with the length of ROH segments. The means of inbreeding coefficients calculated from different methods were also variable. The correlations between different inbreeding coefficients were positive and highly variable (r = 0.18–1). Five ROH islands harbouring important quantitative trait loci were identified. Conclusion This study assessed the level of inbreeding and patterns of homozygosity in Red-brown native Korean chickens. The results of this study suggest that the level of recent inbreeding is low which indicates substantial progress in the conservation of red-brown Korean native chickens. Additionally, Candidate genomic regions associated with important production traits were detected in homozygous regions.

Background: A primary barrier to curing HIV is the HIV reservoir. The leading infectious cause of death worldwide for people living with HIV is tuberculosis (TB), but we do not know how TB impacts the HIV reservoir. Methods: Participants in identification and validation cohorts were selected from previously enrolled studies at Groupe Haïtien d’Étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of peripheral blood mononuclear cell (PBMC)-derived CD4+ T cells. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. Results: In the identification cohort, we found that people living with HIV with a history of active pulmonary TB (n=19) had higher levels of intact provirus than people living with HIV without a history of active TB (n=47) (median 762; IQR, 183-1173 vs 117; IQR, 24-279 intact provirus per million CD4, respectively; P=0.0001). This difference also was seen in the validation cohort (n=31), (median 102; IQR, 0-737 vs 0; IQR, 0-24.5 intact provirus per million CD4, P=0.03) for TB vs no-TB history groups, respectively. The frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of interleukin-1 beta (r=0.524, P= 0.0025) and interleukin-2 (r=0.622, P=0.0002). Conclusions: People living with HIV with a history of active pulmonary TB have more HIV provirus in their circulating CD4+ T cells, even years after TB cure. We need to characterize which CD4+ T cells are harboring intact provirus to consider the impact of T cell-targeting HIV cure interventions for people living in TB-endemic areas.

Background: The alarming prevalence of non- or poor adherence to Home-based Exercise Programs (34–79.2 %, HEP) in parents of Children with Cerebral Palsy (C-CP) is a global health concern due to its detrimental effect on treatment outcomes. Objective: To examine whether Perceived Therapist Guidance and Advice (TGA) or social support moderate the effects of PTSD, depression, parenting stress, low self-efficacy, the burden of care, or the effects of perceived family stigma on adherence to HEP. Method: A stratified random sample of 301 mothers of C-CP attending the largest seven physical rehabilitation hospitals or centres in Rwanda participated in this study. Data were collected using validated measures of all investigated constructs. We conducted hierarchical multiple linear regressions, and the nature of moderation was scrutinized using the process macro 4.1 model number 1 within SPSS version 28. Results: The prevalence of adherence to HEP in the present sample was 32.9 %. Mothers' TGA and social support were positively associated with adherence to HEP; whereas mothers' stressors, including PTSD, parenting stress, depression symptoms, low self-efficacy, burden of care, and family stigma were negatively associated with adherence to HEP. In addition, TGA significantly moderated the associations of the different mothers' stressors with adherence to HEP, leading to increased HEP adherence for mothers with high stressor levels. Social support did not moderate any of these associations. Our respondents often reported poor family and friends’ social support due to family stigma-related to caring C-CP. Conclusions: Therapists play a vital role by providing education, support, and counselling to parents, emphasizing the importance of adherence, and addressing any stigma-related concerns, especially for mothers who experience high levels of stress. Therapists should be aware that mothers of C-CP frequently relied solely on their support to improve adherence to HEP.

L’évolution de la taille humaine sur plusieurs décennies permet d’évaluer la qualité de vie des hommes dans leur environnement, leur pays ou leur région de vie. Par conséquent, en proposant des meilleures conditions de vie humaine offrant une meilleure alimentation à une population, alliées à un meilleur accès aux soins, on crée des conditions, non seulement pour que cette population augmente son espérance de vie, mais aussi la taille de ses individus. La croissance de l’enfant, sa taille, sa morphologie traduisent l’état général des bien-être de la population. L’anthropométrie est ainsi utilisée pour apprécier la corpulence, les proportions et la composition du corps humain. Ce texte livre la situation de Mbuji-Mayi.

Precast composite structures are new trend in construction technology in China due to their high sustainability and structural performance. As Chinese construction companies enter Africa continuously, the Chinese developed technologies are increasingly applied in Africa. A novel precast prestressing composite structure, developed in China, is believed to have a good prospect in Africa. In this study, a design method of the novel precast structure based on the African design system was developed to promote the application in Africa. The structural design systems in Africa and China were compared to help designers know the difference between the two design systems and develop a better design method for the new precast prestressed composite frame in Africa. It can be found that the basic theory of the two design systems is similar, but the technical design parameters and equations are different. The structural design method of the novel precast structure was built with African design system. The basic structural design steps based on the limit state method according to Eurocodes were established, and the seismic design process for the novel precast structure was also developed based on equivalent lateral seismic force method. Some important structural details of the novel frame for earthquakes based on African manner were presented. The developed detailed design method of the novel structure was applied by designing a four storey novel building structure expected in Huye City at Southern Province of Rwanda. The design results were validated by comparison with results of the novel four storey building structure constructed in Suzhou, China. It is shown that both design systems provide safe design since all the results are within allowable limit, and the Chinese design method is more economical but the African design method is more conservative.

Background: Homelessness is a global challenge affecting both high-income and lower-income countries. While survival is a priority, when assessing rehousing programs, thriving should be a goal. There is, however, a lack of clarity around the concept of thriving in existing literature, as for example it is used interchangeably across a number of professions. Aim: This paper provides an in-depth concept analysis of thriving, with a specific focus on thriving post-homelessness. Method: Walker and Avant’s (2011) concept analysis method was utilized. Results: As a result of this concept analysis, eight defining attributes were identified, including bio-psycho-social-spiritual improvement, adaptive coping styles, a sense of accomplishment, satisfaction across multiple life domains, functional well-being, improving or achieving a high level of performance, finding meaning in life or life activities, and having the necessities of daily living. It was found that thriving is a multidimensional process with subjective and objective components as well as an outcome, which all contribute to an individual's well-being and satisfaction. As a consequence of thriving, one feels more secure and confident and an enhanced sense of belonging. Conclusion: This concept analysis includes an updated definition of an individual's thriving post-homelessness in order to allow for comprehensive measurement in the context of housing research, including a positive assessment of one's life situation across multiple domains, as well as access to basic necessities such as shelter, food, and clothing. Future research can utilize the results of this concept analysis to explore thriving within the context of housing, especially to establish a well-structured housing program for persons exiting homelessness.

Abstract Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.

Abstract Despite of excellent thermal properties and high sputtering resistance, pure tungsten cannot fully satisfy the requirements for plasma facing materials in future high-duty cycle nuclear fusion reactions due to the coupled extreme environments, including the high thermal loads, plasma exposure, and radiation damage. Here, we demonstrated that tungsten-based composite materials fabricated using spark-plasma sintering (SPS) present promising solutions to these challenges. Through the examination of two model systems, i.e., tungsten-zirconium composite for producing porous tungsten near the surface and dispersoid-strengthened tungsten, we discussed both the strengths and limitations of the SPS-fabricated materials. Our findings point towards the need for future studies aimed at optimizing the SPS process to achieve desired microstructures and effective control of oxygen impurities in the tungsten-based composite materials.

Abstract Background Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. Methods The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. Results 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). Conclusions Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. Trial Registration Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018

While business ethics (BE) courses have increasingly formed part of business school curricula, we still do not know much about how these courses can change students’ capacity to deal with ethical issues. Drawing on a sensemaking perspective, we conducted an action research study with 66 business professionals enrolled in an executive training program at a French university. The aim was to investigate the processes underlying ethical judgment (EJ) change through a BE course. Participants were invited to pick a significant ethical issue they had personally experienced at work. They were then asked to make sense of it, in writing, at the beginning and at the end of the course, 3 months later. In comparing pre-course and post-course judgments, we concluded that the structure and contents of the respondents’ initial judgment had indeed been modified. This change could be accounted for as the outcome of four ‘sense-remaking’ mechanisms, which we theorize as complexifying, reprioritizing, conceptualizing and contextualizing. Our study contributes to the literature on BE education by demonstrating the benefits of a sensemaking approach. It also offers an original process-based model of EJ, specifying the mechanisms at play in EJ change. Finally, it contributes to the field of sensemaking studies by introducing the concept of sense-remaking, shedding new light on the evolutive dimension of sensemaking.

Objective. To assess changes in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) in Haiti from August 2018 to September 2021, before and during the COVID-19 pandemic. Methods. A retrospective study using surveillance data from the Haitian Unique Health Information System, examining two periods: pre- and peri-COVID-19 pandemic. Health indicators at the national level in the two periods were compared using two-sample t-tests for proportions, and average absolute monthly changes were calculated using variance-weighted regression. Results. There was a statistically significant decline in the proportion of most of the indicators assessed from the pre- to the peri-COVID-19 pandemic period. However, the most affected indicators were the proportions of pregnant women with four antenatal care visits, with five antenatal care visits or more, and those who received a second dose of tetanus vaccine, which decreased by over 4 percentage points during the two periods. Likewise, the proportions of children who received diphtheria, tetanus, and pertussis (DTaP), BCG, polio, pentavalent, and rotavirus vaccines also all declined by over 8 percentage points. In contrast, pneumococcal conjugate vaccine increased by over 4 percentage points. A statistically significant decrease was also observed in the average absolute monthly changes of several reproductive and child health indicators assessed. Conclusions. The COVID-19 pandemic may have contributed to the decline observed in several RMNCAH indicators in Haiti. However, the role played by the sociopolitical crisis and control exercised by armed groups over the population in the last three years cannot be ruled out.

Abstract Background The Accum® platform was initially designed to accumulate biomedicines in target cells by inducing endosomal-to-cytosol escape. Interestingly however, the use of unconjugated Accum® was observed to trigger cell death in a variety of cancer cell lines; a property further exploited in the development of Accum®-based anti-cancer therapies. Despite the impressive pro-killing abilities of the parent molecule, some cancer cell lines exhibited resistance. This prompted us to test additional Accum® variants, which led to the identification of the AccuTOX® molecule. Methods A series of flow-cytometry and cell-based assays were used to assess the pro-killing properties of AccuTOX® along with its ability to trigger the production of reactive oxygen species (ROS), endosomal breaks and antigen presentation. RNA-seq was also conducted to pinpoint the most prominent processes modulated by AccuTOX® treatment in EL4 T-cell lymphoma. Finally, the therapeutic potency of intratumorally-injected AccuTOX® was evaluated in three different murine solid tumor models (EL4, E0771 and B16) both as a monotherapy or in combination with three immune-checkpoint inhibitors (ICI). Results In total, 7 Accum® variants were screened for their ability to induce complete cell death in 3 murine (EL4, B16 and E0771) and 3 human (MBA-MD-468, A549, and H460) cancer cell lines of different origins. The selected compound (hereafter refereed to as AccuTOX®) displayed an improved killing efficiency (~ 5.5 fold compared to the parental Accum®), while retaining its ability to trigger immunogenic cell death, ROS production, and endosomal breaks. Moreover, transcriptomic analysis revealed that low dose AccuTOX® enhances H2-Kb cell surface expression as well as antigen presentation in cancer cells. The net outcome culminates in impaired T-cell lymphoma, breast cancer and melanoma growth in vivo especially when combined with anti-CD47, anti-CTLA-4 or anti-PD-1 depending on the animal model. Conclusions AccuTOX® exhibits enhanced cancer killing properties, retains all the innate characteristics displayed by the parental Accum® molecule, and synergizes with various ICI in controlling tumor growth. These observations will certainly pave the path to continue the clinical development of this lead compound against multiple solid tumor indications. Graphical Abstract

Japanese encephalitis virus (JEV) is transmitted by Culex species of mosquitoes. In 2022, JEV belonging to a previously unrecognised lineage of genotype IV (GIV) caused a major outbreak of JE in South-eastern Australia, resulting in human cases and affecting piggeries. Cx. annulirostris has previously been implicated as the major vector of JEV in northern Australia where the virus has circulated since its first detection in 1995. Here, we showed that experimental infection of a laboratory colony of Australian Cx. annulirostris with the isolate JEV NSW/22 resulted in a 100% mosquito infection rate, with 87% of mosquito saliva samples testing positive by RT-qPCR at 14 days post-infection. Immunohistochemistry confirmed the presence of a replicating virus in the mosquito midgut and dissemination throughout the body, including the salivary glands. Our results also showed evidence of transovarial transmission of this virus; however, transstadial transmission from the eggs to the adult stage was not found. Comparison with an Indonesian isolate of GIV JEV and previous Australian isolates belonging to genotypes I and II showed that infection with JEV NSW/22 resulted in higher viral titres in the early stage of infection and higher proportions of mosquitoes with JEV-positive saliva, indicating a greater transmission potential compared to other isolates. This study provides compelling experimental evidence that Australian Cx. annulirostris is a highly efficient vector for the 2022 Australian JEV GIV outbreak strain.

IntroductionCerebral malaria (CM) is a devastating disease and better understanding of etiologies of the resulting neurologic injury is needed. The purpose of this study is to describe the day-to-day (DTD) pulsatility index (PI) change measured by transcranial Doppler ultrasound (TCD), a novel measure of cerebral and vascular changes, in children with CM.MethodsA retrospective analysis of 122 children in sub-Saharan Africa with CM and 3 or more sequential TCD measurements was performed. Variability of DTD PI change was calculated as a measure of changes in vasculature overtime. Neurologic outcome was determined by the Pediatric Cerebral Performance Category (PCPC) score, a measure of neurologic function.ResultsOf the 122 participants, 77.9% had a good neurologic outcome (no neurologic sequelae), and 22.1% had a poor outcome (neurologic sequelae or died). Patients who had a poor neurologic outcome had higher levels of variability of DTD PI change in the right middle cerebral artery (MCA) (0.14 ± 0.21) and left MCA (0.17 ± 0.41) compared to those who had a good neurologic outcome (0.1 ± 0.1 and 0.11 ± 0.19, respectively). A higher variability of both left and right MCA DTD PI change was also associated with higher brain volume assessed through neuroimaging.DiscussionVariability of DTD PI change may provide early prognostic information regarding PCPC outcomes and brain volume changes seen in CM patients. Expanded research on pathophysiologic contributors to variability of DTD PI changes in children with CM is warranted.

Diarrheal disease is the second leading cause of death among children under five in developing communities, despite active interventions to improve access to water, sanitation, and hygiene resources. Even interventions with high fidelity and compliance saw minimal improvements in health outcomes, necessitating a need for looking beyond traditionally targeted exposure pathways. This study focuses on the pathogen exposure a young child may receive while playing in the public spaces of informal settlements, where animal feces, human feces, and garbage are frequently observed. The study utilized 79 soil samples previously collected across ten cluster sites in Corail, Haiti and processed using DelAgua cultural assays and quantitative Polymerase Chain Reaction methods. Molecular assays screened for Aeromonas, Vibrio cholera, and several pathogenic Escherichia coli species. Behavioral observations of young children (

Abstract BackgroundAlthough at the base of the pyramid-shaped organization of the Rwandan health system, community health workers (CHWs) are central to the community-based management of disease outbreaks. ObjectiveThis mixed methods study aimed to explore the feasibility, acceptability, satisfaction, and challenges of a mobile health (mHealth) tool for community-based COVID-19 screening in Rwanda. MethodsTwo urban (Gasabo and Nyarugenge) and 2 rural (Rusizi and Kirehe) districts in Rwanda participated in the project (smartphone app for COVID-19 screening). A mixed methods approach was used to inform the feasibility (awareness and expectation), acceptability (use and perceived benefits), satisfaction, and challenges of the mHealth intervention. At the end of the project, CHWs were asked to complete a quantitative questionnaire on the use of and satisfaction with the app. Then, in-depth interviews and focus group discussions were organized with CHWs. A content analysis was performed on the transcripts. ResultsOverall, 383 CHWs were recruited and trained; 378 CHWs participated in the study. The mean age of CHWs was 36.7 (SD 6.6) to 45.3 (SD 9.9) years and most were women (237/378, 62.7%). More than 7000 people were registered with the use of the app and 20% were referred to a local COVID-19 testing facility. According to CHW reporting, the median number of people screened by each CHW ranged from 152 (IQR 70-276) for Nyarugenge to 24 (IQR 16-90) for Rusizi. COVID-19 positivity rates were higher in urban than rural districts: more than half of the CHWs in Gasabo reported a confirmed positive case versus only 2.4% for Kirehe and 15.4% for Rusizi. Despite the app being a novel tool, CHWs were well aware of the use of such a tool and had appropriate expectations. Acceptability and satisfaction were very high, with differences between urban and rural districts. Satisfaction was higher in Nyarugenge (72.8/100) and Gasabo (80.7/100) than in Kirehe (61.6/100) and Rusizi (64.5/100). More than 80% of the CHWs were willing to continue using the e-ASCov app, with the exception of CHWs in Kirehe (56.7%). The app was perceived as a tool to generate information on COVID-19, inform on the status of the pandemic, and help curb the spread of the pandemic in Rwanda. CHWs were satisfied with the app at all stages of its implementation in their districts. ConclusionsIn this proof-of-concept study, a smartphone app for screening COVID-19 was useful as an mHealth tool to be used by CHWs, with the potential to increase health system efficiency in an epidemic context. The context should be analyzed for generalization on a country-wide scale, both in case of an epidemic and to take into account certain conditions at the community level. Information is needed on the conditions of generalization and transferability of this type of app to other health conditions so that CHWs can be given their full place in a pyramidal health system.

The intermittency in photovoltaic systems (PV) can lead to power quality issues, especially in off-grid applications. In these cases, adding an energy storage element helps to cope with the intermittency to provide adequate power to the local load. In this scenario, combining Li-Ion batteries and supercapacitors as a hybrid energy storage system (HESS) is powerful due to the battery's high energy density and the supercapacitor's high power density. The HESS demands adequate power management to operate adequately. This paper proposes an adaptive frequency-based power management for a Li-Ion battery and supercapacitor HESS applied to an off-grid PV converter. The main idea of this strategy is to guarantee a smoother current in the battery and reduce the power dissipation in the HESS. The smoother battery current transition helps avoid excessive battery stress and improves lifespan. The proposed strategy is compared with two other strategies. The results show that the proposed approach is more efficient in reducing the HESS' power dissipation and providing smooth current variations to the battery.

Phytochemical study of the root barks of Cassia arereh resulted in the isolation of a new phenolic ester, 3′-hydroxy-4′-methoxystyrenyl-(E)-p-coumarate (1) isolated for the first time from natural source, alongside eight known compounds (2–9). Compounds 1, 7 and 8 are depicted for the first time from Cassia genus. The structures of all compounds were established through NMR analysis (1D and 2D), High Resolution Mass Spectrometry (HRMS) and comparison with previously reported data in literature. Antioxidant activity was investigated through DPPH method while the antibacterial activity was done by the disc diffusion method on Escherichia coli and Salmonella typhimurium strains. Results showed that the methanol extract and compound 7 displayed significant (p

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Abstract: The strong increase in global demand for lithium, driven by the ion battery market and the use of this non-metallic mineral in various economic sectors such as mining (as a non-metallic and non-renewable mineral), health, technology, and geopolitical issues, has fueled the development of disruptive innovation, with new products linked to knowledge creation. These developments have included, among other things, the use of new processing techniques, the creation of new high-capacity cathode materials, the investigation of new sources of lithium, and increased recycling of lithium-ion batteries. This article's primary goal is to assess how this knowledge gap is related with innovation issues using the analysis of the scholar as a case study. Additionally, the examination of public policy related to the lithium business will be continued and updated in this publication. This study uses computerized bibliometric analysis based on the R program and Biblioshiny, a web interface for Bibliometrix analysis. One of the earliest studies to examine the discrepancy between lithium production and consumption based on innovation is this one. The research's contribution is to highlight the disparities and gaps in knowledge generation between producer and consumer countries, which creates a great opportunity to develop better public policies that use existing knowledge and promote collaborations between mining and technology companies for the development of a more sustainable, efficient, effective and competitive industry with future societies.

Measuring socioeconomic indices at the scale of regions or countries is required in various contexts, in particular to inform public policies. The use of Deep Learning (DL) and Earth Observation (EO) data is becoming increasingly common to estimate specific variables like societal wealth. This paper presents an end-to-end framework ‘DeepWealth’ that calculates such a wealth index using open-source EO data and DL. We use a multidisciplinary approach incorporating satellite imagery, socio-economic data, and DL models. We demonstrate the effectiveness and generalizability of DeepWealth by training it on 24 African countries and deploying it in Madagascar, Brazil and Japan. Our results show that DeepWealth provides accurate and stable wealth index estimates with an R2 of 0.69. It empowers computer-literate users skilled in Python and R to estimate and visualize well-being-related data. This open-source framework follows FAIR (Findable, Accessible, Interoperable, Reusable) principles, providing data, source code, metadata, and training checkpoints with its source code made available on Zenodo and GitHub. In this manner, we provide a DL framework that is reproducible and replicable.

This paper introduces p5.quadrille.js, an open-source p5.js library and game-based learning tool for creative coding. It enables board game design, creative code applications like photo and video mosaics, and visualizing complex concepts like image convolution. The design of the library ensures students engage with essential skills in functional and object-oriented programming, set and logical operations, geometric transformations, and game design. Illustrative examples demonstrate its main functionalities, and a preliminary evaluation highlights the potential for future quantitative research to assess its impact on learning outcomes.

Abstract Childhood stunting is a serious public health concern in Rwanda. Although stunting causes have been documented, we still lack a more in‐depth understanding of their local factors at a more detailed geographic level. We cross‐sectionally examined 615 height‐for‐age prevalence observations in the Northern Province of Rwanda, linked with their related covariates, to explore the spatial heterogeneity in the low height‐for‐age prevalence by fitting linear and non‐linear spatial regression models and explainable machine learning. Specifically, complemented with generalized additive models, we fitted the ordinary least squares (OLS), a standard geographically weighted regression (GWR), and multiscale geographically weighted regression (MGWR) models to characterize the imbalanced distribution of stunting risk factors and uncover the nonlinear effect of significant predictors, explaining the height‐for‐age variations. The results reveal that 27% of the children measured were stunted, and that likelihood was found to be higher in the districts of Musanze, Gakenke, and Gicumbi. The local MGWR model outperformed the ordinary GWR and OLS, with coefficients of determination of 0.89, 0.84, and 0.25, respectively. At specific ranges, the study shows that height‐for‐age decreases with an increase in the number of days a child was left alone, elevation, and rainfall. In contrast, land surface temperature is positively associated with height‐for‐age. However, variables like the normalized difference vegetation index, slope, soil fertility, and urbanicity exhibited bell‐shaped and U‐shaped non‐linear associations with the height‐for‐age prevalence. Identifying areas with the highest rates of stunting will help determine the most effective measures for reducing the burden of undernutrition.

Este ensayo explora el vínculo entre la educación dialógica (experiencia dialógica) y la educación física (experiencia motriz) como una oportunidad de promoción de una cultura democrática en el territorio escolar. Se examina cómo el diálogo se convierte en un dinamizador del conocimiento colectivo y la participación activa y democrática, con base en las propuestas teóricas de John Dewey, Jürgen Habermas y Paulo Freire, principalmente. Se reflexiona sobre la importancia de la interacción motriz y el diálogo en el desarrollo de una cultura democrática en la educación física, subrayando cómo su integración en el currículo escolar, la perspectiva didáctica disciplinar y el rol del profesorado pueden enriquecer un ambiente de aprendizaje democrático. Sin embargo, se señalan los desafíos que enfrentan las y los educadores al intentar priorizar las experiencias dialógicas en prácticas educativas motrices que aún favorecen el movimiento por sobre el diálogo. A pesar de estas tensiones, se exploran oportunidades como el juego espontáneo y la problematización a través de preguntas reflexivas, que ofrecen vías para fomentar el diálogo como fundamento democratizador en la educación física. En conclusión, se argumenta que la promoción del diálogo en la experiencia motriz es fundamental para cultivar una educación física para una ciudadanía activa y democrática.

BackgroundEosinophilic esophagitis (EoE) is a chronic and progressive type 2 inflammatory disease affecting the esophagus. Its prevalence has increased in recent years due to increased awareness, evolving clinical guidelines, and heightened sensitivity among healthcare professionals managing the condition. The exact causes behind EoE’s development remain unknown, and its clinical presentation varies, often leading to significant diagnostic delays depending on the age at which symptoms manifest. Consequently, achieving long-term disease control through heightened awareness becomes imperative. EoE generates a significant clinical burden, resulting in substantial economic consequences for patients, healthcare systems, and society. This study aimed to assess the economic and social impacts on EoE patients within the Italian context.MethodsA cost-of-illness analysis was conducted from two perspectives: the National Health System (NHS) and the societal perspective. This analysis encompassed direct healthcare, indirect healthcare, and non-healthcare costs. Data were collected and assessed through a survey administered to a panel of expert clinicians and EoE-affected patients.ResultsManaging EoE incurs a significant burden on healthcare systems, amounting to €6,852.28 per patient per year. The primary cost component appears to be direct costs, comprising 60.73% of the total cost per patient for this condition, while indirect costs contribute to 29.68% of the overall management expenses.ConclusionThis analysis underscores a substantial financial burden on both the healthcare system and patients affected by eosinophilic esophagitis. It emphasizes the imperative need for a continuous and combined effort from clinicians, patients, and families to promptly recognize symptoms and adaptive behavior to mitigate diagnostic delays.

IntroductionThe employment landscape for multiply marginalized people with disabilities presents significant challenges, exacerbated by intersecting identities such as race/ethnicity, sexual orientation, gender identity, poverty, and geography. Recent studies highlight the compounded employment disparities faced by this group, including discriminatory hiring practices, inadequate accommodations, and uneven gains in employment during the COVID-19 public health emergency.MethodsOur study employed a three-round Delphi process with 20 diverse experts across 14 states across the United States (U.S.) to formulate recommendations for improving employment experiences for multiply marginalized people with disabilities. The panel's insights were gathered through surveys administered online, with each round designed to refine the collective recommendations. This iterative process aimed to build a consensus on the most effective policy and practice recommendations for improving employment outcomes within this population.ResultsThe Delphi study identified key areas for strategic focus, including emergency preparedness, education and training, transportation, assistive technology, workplace accommodations, and combating discrimination and stigma. Notable recommendations included improving emergency preparedness training, enhancing employment education, increasing funding for accessible transportation and assistive technology, and promoting inclusive hiring practices. The study also emphasized the need for policies supporting telework and simplifying disability-related benefits.DiscussionThe findings highlight the critical role of tailored strategies to address employment challenges faced by people with disabilities from marginalized communities. Meaningfully and fully implementing these recommendations would create a more inclusive environment that improves employment outcomes for multiply marginalized people with disabilities.

Background: Hibiscus sabdariffa var. altissima, which is known for its high-quality fiber, is commonly used in Traditional Chinese Medicine (TCM) for its diuretic, choleretic, analgesic, antitussive, and hypotensive effects. Furthermore, the flowers have been used to treat diabetes, hypertension, atherosclerosis, and obesity. However, there are no studies assessing its neuroprotective effects on cerebral ischemia, unlike the sabdariffa variety known for its neuroprotective effects. Therefore, this study was aimed to investigate the potential efficacy of Hibiscus sabdariffa var. altissima extract (HAS) and its underlying mechanism on oxidative stress and neuroinflammation during cerebral ischemia-reperfusion (I/R) injury. Methods: A model of cerebral ischemia was established in male Wistar rats through middle cerebral artery occlusion (MCAO) and reperfusion. Rats were randomly divided into the sham, IR, IR + HSA100, IR + HSA200, IR + HSA400 and IR + Eda groups and were treated for 14 consecutive days. The neurological deficit score and the cylinder test were performed to assess neurological impairment. Oxidative stress was determined by measuring the levels of malondialdehyde (MDA) and antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured to evaluate antioxidant activities. In addition, the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were also determined. Results: Our results demonstrated that HSA significantly ameliorated neurological impairment and reduced the volume of brain infarct. HSA also decreased the levels of MDA and enhanced the antioxidant activities of GSH, SOD and CAT in brain tissues. Furthermore, HSA decreased the expression of the proinflammatory cytokines TNF-α, IL-1β and IL-6 in the serum. Conclusion: These findings demonstrated that HSA exhibited a potential neuroprotective effect against cerebral I/R injury, possibly by improving oxidative stress and attenuating inflammatory responses. Therefore, HSA could be used as a potential therapeutic option for cerebral ischemic injuries.