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Improving food safety is crucial in the context of a "One Health" approach. To guarantee product quality and safety, the food industry, which has a very high turnover rate, needs short time-to-result analyses. Therefore, user-friendly systems at the point-of-need are necessary, presenting relevant analytical information and fulfilling the current regulations. To answer these challenges, a microfluidic platform integrating sample preparation and subsequent multiplex qPCR detection has been developed for on-site testing. The system consists of a fully automated instrument driving a microfluidic cartridge dedicated to the detection of multiple allergens in complex food matrices. The first part of the microfluidic cartridge contains pumps, reservoirs, valves and a filter to achieve DNA extraction, concentration and purification. Multiplex qPCR detection is carried out in the second part of the cartridge including a negative control chamber and five chambers for target analyte detection. The in-house developed instrument contains all functions to autonomously drive the microfluidic cartridge: pneumatic control for fluid actuation, thermal control for qPCR amplification and an optical system using three fluorescent wavelengths for multiplex detection of the target analytes and controls. We demonstrate the simultaneous detection of four different allergens - gluten, sesame, soy and hazelnut - from various complex food matrices. The turn-around-time from sample to result is close to two hours and controls in place validate the obtained results. For gluten, a direct comparison with ELISA shows that the regulatory threshold of 20 ppm is comfortably fulfilled. Moreover, all results are in agreement with external laboratory analyses performed in parallel on the same samples. Our findings confirm that the system can be used safely on-site without the risk of cross contamination between the various samples being analysed. In conclusion, our microfluidic platform offers a robust method for on-site allergen management.

Forests face an escalating threat from the increasing frequency of extreme drought events driven by climate change. To address this challenge, it is crucial to understand how widely distributed species of economic or ecological importance may respond to drought stress. In this study, we examined the transcriptome of white spruce (Picea glauca (Moench) Voss) to identify key genes and metabolic pathways involved in the species' response to water stress. We assembled a de novo transcriptome, performed differential gene expression analyses at four time points over 22 days during a controlled drought stress experiment involving 2-year-old plants and three genetically distinct clones, and conducted gene enrichment analyses. The transcriptome assembly and gene expression analysis identified a total of 33,287 transcripts corresponding to 18,934 annotated unique genes, including 4,425 genes that are uniquely responsive to drought. Many transcripts that had predicted functions associated with photosynthesis, cell wall organization, and water transport were down-regulated under drought conditions, while transcripts linked to abscisic acid response and defense response were up-regulated. Our study highlights a previously uncharacterized effect of drought stress on lipid metabolism genes in conifers and significant changes in the expression of several transcription factors, suggesting a regulatory response potentially linked to drought response or acclimation. Our research represents a fundamental step in unraveling the molecular mechanisms underlying short-term drought responses in white spruce seedlings. In addition, it provides a valuable source of new genetic data that could contribute to genetic selection strategies aimed at enhancing the drought resistance and resilience of white spruce to changing climates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ribeyre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An incursion and outbreak of Japanese encephalitis virus (JEV) was reported in Australia in 2021 and 2022, respectively. There was speculation that JEV may have been circulating in Australia unknowingly prior to the detection. In this study, we determined sero-prevalence and transmission of West Nile virus (WNV), Murray Valley encephalitis virus (MVEV) and JEV, prior to and post JEV incursion in a sentinel equine population in south-east Queensland (SEQ), Australia, using blocking ELISAs (screening test) and virus neutralisation test (confirmatory). Serum samples collected between 2018 and 2020 (prior to JEV incursion; n  = 607) from horses residing in SEQ revealed that sero-prevalence to pathogenic orthoflaviviruses was low, specifically WNV (1.3 %; 8/607), MVEV (1.2 %; 7/607), and JEV (4.9 %; 30/607). The significantly higher prevalence of JEV ( P  < 0.05) was skewed by the high proportion of horses previously enrolled in one or more JEV vaccine studies (17/30; 56.7 %) and the unknown JEV vaccination history due to international travel (6/30; 20 %). Thirty-two foals were enrolled as sentinels to monitor for arbovirus transmissions in SEQ between 2020 and 2023. Results showed that JEV seroconversion was first detected in April 2022 ( n  = 4), with seven more seroconversions detected in the following months until November 2022. This study (i) confirms that it is highly unlikely that JEV incursion in SEQ occurred prior to February 2022; (ii) circulation of WNV in SEQ remains very low; and (iii) highlights the complexity in the interpretation of orthoflavivirus serological results. The authors propose that horses should be included as sentinels for arbovirus transmission monitoring in Australia., Competing Interests: H.B.O. is the proprietor of the consultancy firm BIOHMPATHOLOGY. Data included in this publication are based on a patent (WO/2018/176075), on which H.B.O and J.J.H are inventors. All other authors declare no conflict of interest., (© 2024 The Authors.)

Objectives: To compare fatigue in a large multinational systemic sclerosis (SSc) cohort to general population data and identify associated sociodemographic, lifestyle and SSc disease factors., Methods: Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System-29 v2.0 fatigue domain. T-scores were compared with the USA general population (mean = 50; SD = 10). Multivariable linear regression was used to assess associations with sociodemographic, lifestyle, and disease-related variables., Results: Among 2,385 participants (mean age 54.9 (SD = 12.6) years, 87% female, 38% diffuse SSc), mean fatigue T-score was 54.6 (SD = 11.0); 438 (18%) reported mild fatigue, 641 (27%) moderate, and 180 (8%) severe fatigue. Fatigue was independently associated with sociodemographic factors age (-0.10 points per year, [95% CI -0.14;-0.07]), male sex (-1.67 points, [-2.96;-0.37]), non-married status (0.97 points [0.04; 1.89]), and country (reference USA; France -2.35 points [-3.48;-1.21] and UK 2.38 points [0.80; 3.97]), and lifestyle factors smoking (4.16 points [2.52; 5.80]), alcohol consumption (-0.18 points per drink per week [-0.28;-0.07]), and body-mass index (0.34 points per unit [0.27; 0.42]). Fatigue was associated with disease-related factors gastrointestinal involvement (4.21 points [2.99; 5.43]), digital ulcers (1.51 points, [0.25; 2.77]), moderate small joints contractures (1.41 points [0.13; 2.69]), rheumatoid arthritis (4.34 points [2.37-6.31]) and Sjögren's syndrome (1.89 points [0.23; 3.55]). When pain was included in the model, its association was large (2.19 points [2.03; 2.34]) and interstitial lung disease was also associated (1.21 points [0.42; 2.00])., Conclusions: In people with SSc, fatigue scores were substantially higher than the general population and associated with multiple disease factors including gastrointestinal involvement, several painful disease manifestations, and lung involvement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Mutations in the TP53 tumor suppressor gene are well-established drivers of colorectal cancer (CRC) development. However, data on the prevalence of TP53 variants and their association with consensus molecular subtype (CMS) classification in patients with CRC from Rwanda are currently lacking. This study addressed this knowledge gap by investigating TP53 mutation status concerning CMS classification in a CRC cohort from Rwanda., Methods: Formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained from 51 patients with CRC at the University Teaching Hospital of Kigali, Rwanda. Exons 4 to 11 and their flanking intron-exon boundaries in the TP53 gene were sequenced using Sanger sequencing to identify potential variants. The recently established immunohistochemistry-based classifier was employed to determine the CMS of each tumor., Results: Sequencing analysis of cancerous tissue DNA revealed TP53 pathogenic variants in 23 of 51 (45.1%) patients from Rwanda. These variants were predominantly missense types (18/23, 78.3%). The most frequent were c.455dup (p.P153Afs*28), c.524G > A (p.R175H), and c.733G > A (p.G245S), each identified in three tumors. Trinucleotide sequence context analysis of the 23 mutations (20 of which were single-base substitutions) revealed a predominance of the [C > N] pattern among single-base substitutions (SBSs) (18/20; 90.0%), with C[C > T]G being the most frequent mutation (5/18, 27.8%). Furthermore, pyrimidine bases (C and T) were preferentially found at the 5' flanking position of the mutated cytosine (13/18; 72.2%). Analysis of CMS subtypes revealed the following distribution: CMS1 (microsatellite instability-immune) (6/51, 11.8%), CMS2 (canonical) (28/51, 54.9%), CMS3 (metabolic) (9/51, 17.6%), and CMS4 (mesenchymal) (8/51, 15.7%). Interestingly, the majority of TP53 variants were in the CMS2 subgroup (14/23; 60.1%)., Conclusion: Our findings indicate a high frequency of TP53 variants in CRC patients from Rwanda. Importantly, these variants are enriched in the CMS2 subtype. This study, representing the second investigation into molecular alterations in patients with CRC from Rwanda and the first to explore TP53 mutations and CMS classification, provides valuable insights into the molecular landscape of CRC in this understudied population., (© 2024. The Author(s).)

Objectives: To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors., Methods: Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrolment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables., Results: Among 2385 participants, the mean physical function T-score (43.7, SD = 8.9) was ∼2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in the multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45-1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77), pulmonary arterial hypertension (-3.72, -4.91 to -2.52), rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56)., Conclusion: Physical function is impaired for many individuals with SSc and is associated with multiple disease factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction/objective: We investigated (1) work status changes during COVID-19, (2) financial resource adequacy, (3) preferences for work requirements (e.g. remote, workplace, mixed) and (4) work requirements versus preferences, among people with systemic sclerosis., Methods: This was a cross-sectional study of participants in the Scleroderma Patient-centered Intervention Network COVID-19 Cohort, which enrolled participants from the ongoing Scleroderma Patient-centered Intervention Network Cohort and externally in April 2020. In August 2022, participants completed questions on work status, financial well-being using the Consumer Financial Protection Bureau Financial Well-Being Scale, work requirements and work requirement preferences., Results: A total of 298 participants with systemic sclerosis were included. Mean age was 58.6 years (SD = 11.4). There were 101 (34%) participants working at the start of the pandemic and still working in August 2022, 179 (60%) not working at the start of the pandemic and still not working, 10 (3%) who stopped working after April 2020 and 8 (3%) who started working. Mean financial well-being did not change from April 2020 to August 2022 (difference: 0.2 points; 95% confidence interval: -1.1 to 0.7). Working participants (N = 109) preferred flexible work requirements (N = 34, 31%) or working entirely remotely (N = 32, 29%), but most were required to work entirely at a workplace (N = 35, 32%) or combined workplace and remotely with a fixed schedule (N = 31, 28%)., Conclusion: Work status and financial well-being did not change substantively among people with systemic sclerosis during the pandemic. Flexible work policies may support people with systemic sclerosis to work., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Background: Type 2 diabetes, cardiovascular disease, and related cardiometabolic disturbances are increasing rapidly in the Asia-Pacific region. We investigated the contribution of excess adiposity, a key determinant of type 2 diabetes and cardiovascular risk, to unfavourable cardiometabolic profiles among Asian ethnic subgroups., Methods: The Health for Life in Singapore (HELIOS) Study is a population-based cohort comprising multiethnic Asian men and women living in Singapore, aged 30-84 years. We performed a cross-sectional analysis of data from individuals who had assessment of body composition by dual-energy x-ray absorptiometry and metabolic characterisation. In a subset of participants on no medication for type 2 diabetes, hypertension, and hypercholesterolaemia, we tested the relationship of BMI and visceral fat mass index (vFMI) with cardiometabolic phenotypes (glycaemic indices, lipid levels, and blood pressure), disease outcomes (type 2 diabetes, hypercholesterolaemia, and hypertension), and metabolic syndrome score with multivariable regression analyses., Findings: Between April 2, 2018, and Jan 28, 2022, 10 004 individuals consented to be part of the HELIOS cohort, of whom 9067 were included in the study (5404 [59·6%] female, 3663 [40·4%] male; 6224 [68·6%] Chinese, 1169 [12·9%] Malay, 1674 [18·5%] Indian; mean age 52·8 years [SD 11·8]). The prevalence of type 2 diabetes, hypercholesterolaemia, and hypertension was 8·2% (n=744), 27·2% (n=2469), and 18·0% (n=1630), respectively. Malay and Indian participants had 3-4-times higher odds of obesity and type 2 diabetes, and showed adverse metabolic and adiposity profiles, compared with Chinese participants. Excess adiposity was associated with adverse cardiometabolic health indices including type 2 diabetes (p<0·0001). However, while vFMI explained the differences in triglycerides and blood pressure between the Asian ethnic groups, increased vFMI did not explain higher glucose levels, reduced insulin sensitivity, and increased risk of type 2 diabetes among Indian participants., Interpretation: Visceral adiposity is an independent risk factor for metabolic disease in Asian populations, and accounts for a large fraction of type 2 diabetes cases in each of the ethnic groups studied. However, the variation in insulin resistance and type 2 diabetes risk between Asian subgroups is not consistently explained by adiposity, indicating an important role for additional mechanisms underlying the susceptibility to cardiometabolic disease in Asian populations., Funding: Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, and National Medical Research Council, Singapore., Competing Interests: Declaration of interests JC receives support for attending meetings and travel from Lee Kong Chian School of Medicine Strategic Academic Initiative and National Medical Research Council Singapore Translational Research Investigator Award and President's Chair in Cardiovascular Epidemiology. JC is Programme Director for Population and Global Health Programme at Lee Kong Chian School of Medicine, and Chief Scientific Officer at Precision Health Research, Singapore. JN receives research funding from Astra Zeneca. JL participates in the advisory board of Boehringer Ingelheim and is a council member of National Council Against Drug Abuse, Singapore. BLCC receives honorarium for obesity-related presentations and participates in the advisory boards of Novo Nordisk, Abbott Nutrition, and DKSH, and all honoraria were paid to Khoo Teck Puat Hospital, Singapore. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum., Methods: People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0-10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation., Findings: Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6-8·1), which occurred at -25°C. Severity scores decreased minimally from -15°C to 5°C (0·05-0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37-0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5-2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0-4·1) at 35°C and 5·6 points (4·5-6·8) at 40°C. Results were similar for feels like temperature., Interpretation: Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns., Funding: Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University., Competing Interests: Declaration of interests JDP has received speaker honoraria or consultancy fees from Astra Zeneca, Boehringer Ingelheim, IsoMab, Janssen, Permeatus, and Sojournix Pharma. MDM has received research grants or contracts from Prometheus Biosciences, Mitsubishi Tanabe, Boehringer Ingelheim, EICOS, Corbus, and Horizon Pharma; consulting fees from Cabaletta Pharma; an honorarium from GSK Pharma; and was a member of a data safety monitoring board or advisory board with Mitsubishi Tanabe, Boehringer Ingelheim, and EICOS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: E-LN, M-EC, LK, RSH, SH, SP, SJB, LM, SBP, JV, AB, and BDT conceptualised and designed the study. E-LN, M-EC, LK, RSH, and BDT acquired data. E-LN, GV-G, and MG directly accessed and verified the data and did the statistical analysis. E-LN and BDT drafted the manuscript. All authors revised the manuscript, approved the final version, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 patient advisors were Catherine Fortuné, Amy Gietzen, Geneviève Guillot, Nancy Lewis, Michelle Richard, Maureen Sauvé, and Joep Welling. De-identified individual participant data with a data dictionary and analysis codes will be made available upon request to the corresponding author and presentation of a methodologically sound proposal that is approved by the SPIN Data Access and Publications Committee. Data will be available after publication. Data requesters will need to sign a data transfer agreement. Additional, related documents (eg, study protocol or informed consent form) can be made available on request to the corresponding author. This study was funded by the Canadian Institutes of Health Research (CIHR; VR4–172745, GA4–177764), the McGill Interdisciplinary Initiative in Infection and Immunity Emergency COVID-19 Research Fund, Scleroderma Canada via an educational grant from Boehringer Ingelheim, the Scleroderma Society of Ontario, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, Scleroderma Queensland, the Scleroderma Association of Saskatchewan (Scleroderma SASK), the Scleroderma Association of BC, and Sclérodermie Québec. E-LN was supported by a Fonds de recherche du Québec—Santé (FRQS) Doctoral Research Award, a Canadian Behavioural Interventions Trials Network Platform, and a CIHR Doctoral Studentship. RSH was supported by a CIHR Postdoctoral Fellowship. SP was supported by a FRQS Masters Research Award. BDT was supported by a tier 1 Canada Research Chair. All other authors declare no competing interests.

&lt;b&gt;Background and Objective:&lt;/b&gt; Biological exploration of male infertility is important for its treatment. Seminal plasma, by its composition, presents numerous molecules that can be exploited in the investigation of new sperm biomarkers. The evaluation of new biomarkers of azoosperm seminal plasma aims to identify vitamins A, D and E which can serve as discriminating biochemical markers in the exploration of azoospermia. &lt;b&gt;Materials and Methods:&lt;/b&gt; Thirty normozoospermic and 30 azoospermic sperm samples were collected by masturbation after three days of sexual abstinence from consulting patients at the Pasteur Institute of Côte d'Ivoire. After centrifugation of the sperm, the seminal plasma was collected and were analyzed for vitamin A, D and E. After extracting the vitamins from the seminal plasma, they were quantified using high-performance liquid chromatography. &lt;b&gt;Results:&lt;/b&gt; The concentration of vitamin A in seminal plasma from normal samples was 1.66±1.81 and 0.28±0.52 mg/L in pathological samples. The average vitamin D concentration in seminal plasma of normospermia was 0.27±0.40 and 0.08±0.12 mg/L in seminal plasma of azoospermia. For vitamin E, the results obtained show an average concentration of 2.56±3.58 mg/L in normal ejaculate and 0.33±0.51 mg/L in pathological ejaculate. Only vitamins A and E showed a significant difference in the two categories of sperms. &lt;b&gt;Conclusion:&lt;/b&gt; The determination of the concentration of vitamins A, D and E in seminal plasma showed that only vitamins A and E can serve as a biomarker for the differentiation of normozoospermic and azoospermic sperm.

This is the first report on a unique hybrid molecule made of estradiol and testosterone (TS). This distinctive hybrid molecule (1) was designed to interact with both the estrogen receptor (ER) and the androgen receptor (AR) found in hormone-dependent female and male cancer cells, and was synthesized using ethynylestradiol (17EE) as the estrogenic component and 7α-(4-azido-but-2-enyl)-4-androsten-17β-ol-3-one as the androgenic counterpart in a seven-step reaction with ∼ 26 % overall yield. We reasoned that the dual receptor binding ability could allow 1 to act as an antihormone. This was tested on hormone-dependent and hormone-independent breast cancer (BCa) and prostate cancer (PCa) cells. The antiproliferative activity was also assessed on colon and skin cancer cells. We found that 1 was active against MCF7 (ER + ) BCa cells (IC 50 of 4.9 μM), had lower inhibitory potency on LNCaP (AR + ) PCa cells (IC 50  > 5 μM) and no effect on PC3 and DU145 (AR-) PCa cells. This suggests that the estrogenic component of 1 can interact with the ER on MCF7 cells more effectively than the androgenic component with the AR on LNCaP PCa cells, possibly due to a suboptimal spacer or linkage site(s). Nonetheless, the hybrid 1 was active against colon (HT-29) and melanoma (M21) cancer cells (IC 50 of 3.5 μM and 2.3 μM, respectively), and had low cross-reactivity with the drug- and androgen-metabolizing cytochrome P450 3A4 (CYP3A4, IC 50 ≫ 5 µM). These findings demonstrate the anticancer potential of 1 and warrant further explorations on this new type of hybrids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obituary for Dieter Schwarzenbach.

Objective: Symptoms of anxiety increased early in the COVID-19 pandemic among people with systemic sclerosis (SSc) then returned to pre-pandemic levels, but this was an aggregate finding and did not evaluate whether vaccination may have contributed to reduced anxiety symptom levels. We investigated whether being vaccinated for COVID-19 was associated with reduced anxiety symptoms among people with SSc., Methods: The longitudinal Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 Cohort was launched in April 2020 and included participants from the ongoing SPIN Cohort and external enrollees. Participants completed measures bi-weekly through July 2020, then every 4 weeks afterwards through August 2022 (32 assessments). We used linear mixed models to evaluate longitudinal trends of PROMIS Anxiety 4a v1.0 anxiety domain scores and their association with vaccination., Results: Among 517 participants included in analyses, 489 (95%) were vaccinated by September 2021, and no participants were vaccinated subsequently. Except for briefly at the beginning, when few had received a vaccine, and end, when only 28 participants remained unvaccinated, anxiety symptom trajectories were largely overlapping. Participants who were never vaccinated had higher anxiety symptoms by August 2022, but there were no other differences, and receiving a vaccination did not appear to change anxiety symptom trajectories meaningfully., Conclusion: Vaccination did not appear to influence changes in anxiety symptoms among vulnerable people with SSc during the COVID-19 pandemic. This may be due to people restricting their behavior when they were unvaccinated and returning to more normal social engagement once vaccinated to maintain a steady level of anxiety symptoms., Competing Interests: Declaration of competing interest The authors have competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Myasthenia gravis is a rare disease that can lead to a serious condition known as myasthenic crisis (MC). The diagnosis of MC is clinical and relies on the presence of typical symptoms that can be absent, emphasizing the importance of attracting the attention of emergency physicians to this rare cause of respiratory failure. We present the case of a 66-year-old woman presenting to the emergency department with a history of recent muscle fatigue and dehydration who developed acute respiratory failure requiring mechanical ventilation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ntawuruhunga et al.)

In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak of disease in pigs and humans in Australia. As no veterinary vaccines against JEV are approved in Australia and all current approved human and veterinary vaccines are derived from genotype (G) III JEV strains, we used the recently described insect-specific Binjari virus (BinJV) chimeric flavivirus vaccine technology to produce a JEV GIV vaccine candidate. Herein we describe the production of a chimeric virus displaying the structural prM and E proteins of a JEV GIV isolate obtained from a stillborn piglet (JEV NSW/22 ) in the genomic backbone of BinJV (BinJ/JEV NSW/22- prME). BinJ/JEV NSW/22- prME was shown to be antigenically indistinguishable from the JEV NSW/22 parental virus by K D analysis and a panel of JEV-reactive monoclonal antibodies in ELISA. BinJ/JEV NSW/22- prME replicated efficiently in C6/36 cells, reaching titres of >10 7 infectious units/mL - an important attribute for vaccine manufacture. As expected, BinJ/JEV NSW/22- prME failed to replicate in a variety of vertebrate cells lines. When used to immunise mice, the vaccine induced a potent virus neutralising response against JEV NSW/22 and to GII and GIII JEV strains. The BinJ/JEV NSW/22- prME vaccine provided complete protection against lethal challenge with JEV NSW/22 , whilst also providing partial protection against viraemia and disease for the related Murray Valley encephalitis virus. Our results demonstrate that BinJ/JEV NSW/22- prME is a promising vaccine candidate against JEV., (© 2024. The Author(s).)

Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological activities. This literature survey on chemical and pharmacological studies of steroids from the Meliaceae plants indicates that 157 distinct steroids classified into six subclasses including (in decreasing number): pregnane-, stigmastane-, ergostane-, cholestane-, androstane- and ecdysterone-type steroids have been reported from a total of 49 plant species. This review aims to provide a reference document compiling information about the occurrence, chemistry and biological activities of meliaceous steroids for the period from 1988 to July 2023. In particular, generalities about the chemistry of steroids with unusual skeletons and underlying biosynthetic pathways are highlighted. In addition, some structural relationships between different compound types and their biological activities are presented. The information used during the writing of this paper was collected from the online libraries PubMed, Google Scholar and Scifinder using the keywords steroids and Meliaceae with no language restriction. This review points out new avenues for further investigations of steroids from plants of the Meliaceae family., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: A previous study using Scleroderma Patient-centered Intervention Network (SPIN) Cohort data identified five classes of people with systemic sclerosis (also known as scleroderma) based on patient-reported somatic (fatigue, pain, sleep) and mental health (anxiety, depression) symptoms and compared indicators of disease severity between classes. Across four classes ("low", "normal", "high", "very high"), there were progressively worse somatic and mental health outcomes and greater disease severity. The fifth ("high/low") class, however, was characterized by high disease severity, fatigue, pain, and sleep but low mental health symptoms. We evaluated resilience across classes and compared resilience between classes., Methods: Cross-sectional study. SPIN Cohort participants completed the 10-item Connor-Davidson-Resilience Scale (CD-RISC) and PROMIS v2.0 domains between August 2022 and January 2023. We used latent profile modeling to identify five classes as in the previous study and multiple linear regression to compare resilience levels across classes, controlling for sociodemographic and disease variables., Results: Mean CD-RISC score (N = 1054 participants) was 27.7 (standard deviation = 7.3). Resilience decreased progressively across "low" to "normal" to "high" to "very high" classes (mean 4.7 points per step). Based on multiple regression, the "high/low" class exhibited higher resilience scores than the "high" class (6.0 points, 95% confidence interval [CI] 4.9 to 7.1 points; standardized mean difference = 0.83, 95% CI 0.67 to 0.98)., Conclusions: People with worse disease severity and patient-reported outcomes reported substantially lower resilience, except a class of people with high disease severity, fatigue, pain, and sleep disturbance but positive mental health and high resilience., Competing Interests: Declaration of competing interest The authors have no competing interests to report., (Copyright © 2023. Published by Elsevier Inc.)

Background: Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer., Results: Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon-intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459&#95;477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed., Conclusions: Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda., (© 2024. The Author(s).)

Objective: The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities., Methods: Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors., Results: Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (-1.13, 95% CI -2.18 to -0.08); living in Canada (-1.33, 95% CI -2.40 to -0.26 (reference USA)) or the UK (-2.49, 95% CI -3.92 to -1.06); body mass index (-1.08 per SD, 95% CI -1.47 to -0.69); gastrointestinal involvement (-3.16, 95% CI -4.27 to -2.05); digital ulcers (-1.90, 95% CI -3.05 to -0.76); moderate (-1.62, 95% CI -2.78 to -0.45) or severe (-2.26, 95% CI -3.99 to -0.52) small joint contractures; interstitial lung disease (-1.11, 95% CI -1.97 to -0.25); pulmonary arterial hypertension (-2.69, 95% CI -4.08 to -1.30); rheumatoid arthritis (-2.51, 95% CI -4.28 to -0.73); and Sjogren's syndrome (-2.42, 95% CI -3.96 to -0.88)., Conclusion: Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: With the containment of the COVID-19 pandemic in Côte d'Ivoire, efforts were made to seamlessly integrate COVID-19 vaccination into the national immunization program. A collaborative initiative involving UNICEF, WHO, GAVI, and partner organizations resulted in the creation of the COVID-19 Vaccine Integration Mapping Tool. This paper presents a case study documenting the field testing of the integration mapping tool and assessing the integration of COVID-19 vaccination within primary healthcare and routine immunization in Côte d'Ivoire. The study aims to describe the pilot process, gather feedback on tool usefulness and challenges, and establish integration priorities through roadmap development., Methods: Under the guidance of the Ministry of Health and Universal Coverage Cabinet, a workshop was conducted with participants from major health programs to field test the tool. Data analysis was performed using Excel, and the results were presented through tables, heat maps, and line graphs., Results: The first-of-its-kind field test of the integration mapping tool in Côte d'Ivoire showcased its potential to bring key partners together to discuss the current state of integration, improve transparency about resource allocation, and enhance data management for the incorporation of COVID-19 vaccination into existing immunization systems. The integration of COVID-19 vaccines in Côte d'Ivoire showed a moderate level of progress, with improvement needed in resource allocation, payment systems, targeting of highest-risk groups and vaccine administration. Support should be increased for target population identification, distribution points, quality of care mechanisms, and health personnel training. Health information systems and access to essential medicines were relatively satisfactory. Integration into existing programs, intersectoral collaboration, national health strategy, communication strategy, community participation, and data utilization require improvement. The post-workshop satisfaction survey gave the tool a score of 7 out of 10. Early lessons from Côte d'Ivoire provide guidance on enhancing integration, focusing on data-driven decision-making, collaboration, stakeholder engagement, and effective leadership., Conclusions: The field test of the integration mapping tool (IMT) in Côte d'Ivoire is groundbreaking as it exemplifies the transformative potential of innovative tools in immunization practices. Application of the IMT sets a precedent for seamless COVID-19 vaccination integration worldwide, emphasizing data-driven decision-making, collaboration, timing, and leadership. The success of the pilot exercise in Côte d'Ivoire was attributed to political commitment, well-facilitated workshops, assessments, and the fact that the team in the country had previously developed an initial integration plan.

The importance of the inert environment in the transmission of pathogens has been reassessed in recent years. To reduce cross-contamination, new biocidal materials used in high touch surfaces (e.g., stair railings, door handles) have been developed. However, their impact on skin remains poorly described. The present study aimed to evaluate the antibacterial properties and the risk of skin irritation of two materials based on hard-anodized aluminum (AA) impregnated with quaternary ammonium compound solutions (QAC#1 or QAC#2). The QAC#1 or QAC#2 solutions vary in composition, QAC#2 being free of dioctyl dimethyl ammonium chloride (Dio-DAC) and octyl decyl dimethyl ammonium chloride (ODDAC). Unlike AA used as a control, both AA-QAC#1 and AA-QAC#2 had excellent and rapid antibacterial efficacy, killing 99.9 % of Staphylococcus aureus and Escherichia coli bacteria, in 15 s and 1 min, respectively. The impregnation solutions (QAC#1 and QAC#2) did not show any skin sensitizing effect on transformed human keratinocytes. Nevertheless, these solutions as well as the materials (AA-QAC#1, AA-QAC#2), and the liquid extracts derived from them, induced a very rapid cytotoxicity on L929 murine fibroblasts (>70 % after 1 h of contact) as shown by LDH, MTS and neutral red assays. This cytotoxicity can be explained by the fast QACs release occurring when AA-QAC#1 and AA-QAC#2 were immersed in aqueous medium. To overcome the limitation of assays based on liquid condition, an in vitro skin irritation assay on reconstructed human epidermis (RHE) was developed. The effect of the materials upon their direct contact with the epidermis grown at the liquid-air interface was determined by evaluating tissue viability and quantifying interleukin-1 alpha (IL-1α) which is released in skin during injury or infection. AA-QAC#1 induced a significant decrease in RHE viability, close to OECD and ISO 10993-10 acceptability thresholds and enhanced the pro-inflammatory IL-1α secretion compared with AA-QAC#2. Finally, these results were corroborated by in vivo assays on mice using erythema and edema visual scores, histological observations, and epidermal thickness measurement. AA had no effect on the skin, while a stronger irritation was induced by AA-QAC#1 compared with AA-QAC#2. Hence, these materials were classified as moderate and slight irritants, respectively. In summary, this study revealed that AA-QAC#2 without Dio-DAC and ODDAC could be a great candidate for high touch surface applications, showing an extremely effective and rapid bactericidal activity, without inducing adverse effects for skin tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests. MAG (A3Surfaces) provided the materials that were tested independently by JJ under the supervision of LCF and NF as described above. The authors declare that they have no personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2023. Published by Elsevier B.V.)

West Nile virus (WNV) causes skin lesions in farmed crocodiles leading to the depreciation of the value of their hides and significant economic losses. However, there is no commercially available vaccine designed for use in crocodilians against WNV. We tested chimeric virus vaccines composed of the non-structural genes of the insect-specific flavivirus Binjari virus (BinJV) and genes encoding the structural proteins of WNV. The BinJV/WNV chimera, is antigenically similar to wild-type WNV but replication-defective in vertebrates. Intramuscular injection of two doses of BinJV/WNV in hatchling saltwater crocodiles (Crocodylus porosus) elicited a robust neutralising antibody response and conferred protection against viremia and skin lesions after challenge with WNV. In contrast, mock-vaccinated crocodiles became viraemic and 22.2% exhibited WNV-induced lesions. This suggests that the BinJV/WNV chimera is a safe and efficacious vaccine for preventing WNV-induced skin lesions in farmed crocodilians., (© 2023. The Author(s).)

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC) , Kirsten rat sarcoma ( KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC , including 3 novel mutations (c.4310&#95;4319delAAACACCTCC, c.4463&#95;4470delinsA, and c.4506&#95;4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13 . For KRAS , we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

Background: Previous reports showed limited efficacy of immune checkpoint inhibitors as single-agent treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of immune checkpoint inhibitor combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup., Methods: We conducted a French national open-label multicentre non-randomised non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine kinase inhibitor and no prior chemotherapy. Patients received platinum, pemetrexed, atezolizumab, bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary end-point was the objective response rate (RECIST v1.1) after 12 weeks, evaluated by blind independent central review., Results: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, objective response rate was 58.2% (90% confidence interval [CI], 47.4-68.4) in PPAB cohort and 46.5% (90% CI, 36.3-56.9) in PPA cohort. Median progression-free survival and overall survival were 7.3 (95% CI 6.9-9.0) months and 17.2 (95% CI 13.7-NA) months in PPAB cohort and 7.2 (95% CI 5.7-9.2) months and 16.8 (95% CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related adverse events occurred in 27.9% and 15.3%, respectively., Conclusion: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after tyrosine kinase inhibitor failure, with acceptable safety profile., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: O.B reports adviser and consultant for BMS, AstraZeneca, Roche, MSD, Takeda; P.T reports adviser and consultant for Roche, AstraZeneca, BMS, Amgen, Takeda, Janssen-Cillag and Novartis; F.G reports research support from Takeda and Pfizer, adviser and consultant for Amgen, BMS, AstraZeneca, Roche, MSD, Pfizer and Takeda; C.R reports research support from AstraZeneca, reports adviser and consultant for BMS, AstraZeneca and Takeda; L.B-G reports adviser and consultant for AstraZeneca, MSD, BMS, Amgen, Takeda, Viatris, Ipsen and Pfizer; M.G reports research support from BMS and Roche, adviser and consultant for BMS, AstraZeneca, Pfizer and Sanofi; C.C reports adviser and consultant for AstraZeneca, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer and Amgen; C.Da. reports adviser and consultant for AstraZeneca, BMS and Novartis; A.S. reports adviser and consultant for Roche and Lilly; A-C.T reports adviser and consultant for AstraZeneca, Roche, MSD, BMS, Leo Pharma, Amgen, Nutrician, Pfizer; H.D. reports research support from MSD and Pfizer, adviser and consultant BMS, Amgen, Leo Pharma, Novartis, Roche; C.De. reports adviser and consultant for AstraZeneca, Roche, Sanofi, Janssen-Cilag, Takeda, BMS, Sandoz, Novartis, Lilly and Pfizer; L.G. reports research support from Abbvie, AstraZeneca, BMS, MSD, Novartis, Pfizer, PharmaMar, Roche, Sanofi and Takeda, adviser and consultant for Abbvie, AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda. All other authors have declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The synthesis of a 17α-linked C2-symmetric testosterone dimer and its dihydrotestosterone analog is reported. The dimers were synthesized using a short five-step reaction sequence with 28% and 38% overall yield for the testosterone and dihydrotestosterone dimer, respectively. The dimerization reaction was achieved by an olefin metathesis reaction with 2nd generation Hoveyda-Grubbs catalyst. The dimers and their corresponding 17α-allyl precursors were tested for the antiproliferative activity on androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cell lines. The effects on cells were compared with that of the antiandrogen cyproterone acetate (CPA). The results showed that the dimers were active on both cell lines, with an increased activity towards androgen-dependent LNCaP cells. However, the testosterone dimer (11) was fivefold more active than the dihydrotestosterone dimer (15), with an IC 50 of 11.7 μM vs. 60.9 μM against LNCaP cells, respectively, and more than threefold more active than the reference drug CPA (IC 50 of 40.7 μM). Likewise, studies on the interaction of new compounds with drug-metabolizing cytochrome P450 3A4 (CYP3A4) showed that 11 was a fourfold stronger inhibitor than 15 (IC 50 of 3 μM and 12 μM, respectively). This suggests that changes in the chemical structure of sterol moieties and the manner of their linkage could largely affect both the antiproliferative activity of androgen dimers and their crossreactivity with CYP3A4., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Emerald ash borer (Agrilus planipennis; EAB) is an Asian insect species that has been invasive to North America for 20 years. During this time, the emerald ash borer has killed tens of millions of American ash (Fraxinus spp) trees. Understanding the inherent defenses of susceptible American ash trees will provide information to breed new resistant varieties of ash trees., Results: We have performed RNA-seq on naturally infested green ash (F. pennsylvanica) trees at low, medium and high levels of increasing EAB infestation and proteomics on low and high levels of EAB infestation. Most significant transcript changes we detected occurred between the comparison of medium and high levels of EAB infestation, indicating that the tree is not responding to EAB until it is highly infested. Our integrative analysis of the RNA-Seq and proteomics data identified 14 proteins and 4 transcripts that contribute most to the difference between highly infested and low infested trees., Conclusions: The putative functions of these transcripts and proteins suggests roles of phenylpropanoid biosynthesis and oxidation, chitinase activity, pectinesterase activity, strigolactone signaling, and protein turnover., (© 2023. Crown.)

Background: The Infants and Young Children Dietary Diversity Score (IYC-DDS-7) has been validated to assess dietary quality in children. However, its applicability to predict the adequacy of micronutrient intake remains a challenge in all contexts., Design and Methods: A 24-hour dietary recall assessment was conducted on a sample of 628 children aged 6 to 23 months in the plenty season (PS) as well as in the lean season (LS). The IYC-DDS-7 was calculated based on 7 food groups, whereas the mean micronutrient density adequacy (MMDA) for 11 micronutrients. The β regression models were used to assess the relationship between IYC-DDS and MMDA and differences in nutrient intake between the 2 seasons. A receiver-operating characteristic curve analysis was also performed to determine IYC-DDS-7 cutoff levels that maximized sensitivity and specificity in assessing dietary quality and predicting MMDA below- or above-selected cutoff levels., Results: Participating children's MMDA was 56.9% ± 12.8% versus 61.9% ± 8.6% and IYC-DDS-7 was 3.43 ± 1.5 versus 3.77 ± 1.0 in the PS and LS. The IYC-DDS-7 had a positive correlation with MMDA, irrespective of the season. For a 1-unit increase in IYC-DDS-7, MMDA increased by a mean of 10.7% (CI, 8.3%-13.1%; P < .001). The minimum threshold of the 4 food groups corresponded to a sensitivity of 76% and 61% and a specificity of 75% and 70% for the prediction of inadequate diet in the PS and LS, respectively., Conclusions: The IYC-DDS-7 predicted MMDA, regardless of seasons for infants and young children. The IYC-DDS-7 cutoff of 4 groups performed well in classifying children with low-diet quality.

Background: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study., Methods: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30-84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ' g ' was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ' g ' using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ' g ', using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition., Findings: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ' g ' at P < 0.05. In multivariable analyses, reduced ' g ' was consistently associated with increased visceral fat mass index and lower HDL cholesterol (P < 0.001), but not with blood pressure, triglycerides, or glycemic indices. The reduction in ' g ' associated with 1SD higher visceral fat, or 1SD lower HDL cholesterol, was equivalent to a 0.7 and 0.9-year increase in chronological age respectively (P < 0.001). Inverse variance MR analyses showed that reduced ' g ' is associated with genetically determined elevation of VAT, BMI and WHR (all P < 0.001). In contrast, MR did not support a causal role for blood pressure, lipid, or glycemic indices on cognition., Interpretation: We show an independent relationship between adiposity and cognition in a multi-ethnic Asian population. MR analyses suggest that both visceral adiposity and raised BMI are likely to be causally linked to cognition. Our findings have important implications for preservation of cognitive health, including further motivation for action to reverse the rising burden of obesity in the Asia-Pacific region., Funding: The Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, National Medical Research Council, Ministry of Education, Singapore., Competing Interests: J.C receives support for attending meetings and travel from Lee Kong Chian School of Medicine Strategic Academic Initiative and/or National Medical Research Council Singapore Translational Research Investigator Award and/or President's Chair in Cardiovascular Epidemiology. J.C. is Programme Director for Population and Global Health Programme at Lee Kong Chian School of Medicine, and Chief Scientific Officer at Precision Health Research, Singapore. J.N. receives research and educational grant from Astra Zeneca for cancer research unrelated to this work. All other authors declare no conflict of interest., (© 2023 The Author(s).)

Phytochemical investigation of the methanolic extract of the trunk bark of Caloncoba welwitschii (Oliv.) Gilg (Achariaceae) led to the isolation of four new compounds, including three new 30-norfriedelane triterpenes, welwitschiilactones D-F ( 1 - 3 ), one new friedelane triterpene, welwitschioic acid ( 4 ) as well as ten known compounds: stigmastane-3,6-dione (7), a mixture of β -sitosterol and stigmasterol ( 6a and 6b ), a mixture of β -sitosterol and stigmasterol glucoside ( 11a and 11b ), (2 S ,3 S ,4 R ,5 R )- N -(1,3,4,5-tetrahydroxyndecan-2-yl)tetradecanamide ( 10 ), 1- O - β - D- glucopyranosyl-(2 S ,3 R ,8 E )-2-[(2' R )-2-hydroxylpalmitoylamino]-8-octadecene-1,3-diol (12), 3 β ,21 β -dihydroxy-27-oxo-30-nor-(D:A)-friedo-olean-20(29))en-27,19α-lactone ( 8 ), 21 β- hydroxy-3,27-dioxo-30-nor-(D:A)-friedo-olean-20(29)-en-27,19α-lactone ( 9 ) and 2 β ,21 β -dihydroxy-27-oxo-30-nor-(D:A)-friedo-olean-20(29)-en-27,19 α -lactone ( 5 ). The structures of all the isolated compounds were determined by extensive spectroscopic analyses (1D and 2D NMR as well as ESI-MS). The relative configuration of the 20-oxymethine in 1 as well as that of 19-oxymethine in 2 and 3 has been established using the NOESY spectrum. In an experiment, a sample of welwitschiilactone C ( 5 ) was chemically modified through reduction reaction to give a new hemi-synthetic derivative namely 2 β ,3 β ,21 β -trihydroxy-30-nor-(D:A)-friedo-olean-20(29)-en-27,19α-lactone ( 5a) .

In developing countries, 15.6% of pregnant women and 19.8% after childbirth experience a mental disorder. In the absence of data on the situation in Cameroon, we carried out a study to determine the prevalence of perinatal mental illness in this hospital and its risk factors among women in perinatal period and the relationship between both at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, a reference mother and child hospital. We conducted a hospital-based, cross sectional, observational study. Data was collected using structured and semi-structured interviews. There were six sub-themes covered: participants' socio-demographic profile, clinical profile, perinatal history, psychopathology aspects with the Mini International Psychiatric Interview, the Edinburgh Postnatal Depression Scale, the State Trait Anxiety Inventory and the perinatal mental illness risk factors. Data entry was done using Microsoft Excel 2010 and transferred to Statistical Package for the Social Sciences version 23.0 for analysis. Among 194 women who participated in the study, the general prevalence for perinatal mental disorders was 53.6% (104/194), 25.8% among pregnant women and 27.8% among postnatal women. Comorbidities were present in 17.5% of our study population. We observed that 45.8% suffered from depression, 17% had a risk of suicide, 10.3% suffered from perinatal anxiety, 3.1% presented with post-traumatic stress disorder, 3.6% acute stress disorder, 7.7% had adjustment disorder. Concerning risk factors, we found a significant link between depression and severe anxiety before delivery ( p  < 0.05) and the absence of social support ( p  = 0.005). We found that women with at least four risk factors were 1.6 times more likely to present with a perinatal mental disorder. The prevalence of perinatal mental disorders at this Hospital is very high. This highlights the need for institutional screening and management of perinatal mental disorders, which suggests that we explore the situation in others and other health facilities in Cameroon., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Djatche Miafo, Woks, Nzebou, Tchaptchet, Delene, Kegha Tchidje, Ndzodo, Siewe Kamga and Assumpta.)

This study examines the relative contributions to dietary diversity of the diversity of plant and domesticated animal species which rural households produce or collect, i.e., nonmarket food sources, versus the diversity of foods purchased in markets. Although opinions differ in the literature as to their relative importance, clarifying how different sources of food contribute to the dietary diversity of rural households in the developing world is important to inform policies and interventions to improve their food security and dietary quality. This case study was carried out among a random sample of 654 rural households in southern Benin during two seasons: when food is plentiful after harvest; and when food is scarcer between harvests. We collected data on crops, wild plants, and domesticated animals utilized by households, the number of markets they visited, and the diet of a mother in the household, with a structured 24-hour food frequency questionnaire. We hypothesize that the number of markets visited is an indicator of the diversity of foods available in the markets they have access to, and thus shows the contribution of markets as food sources. Results support this hypothesis and show that households that produced more plant and domesticated animal species and those that visited more markets had more diversified diets. Obtaining diverse foods from multiple sources provides households with more options to achieve better diets. These results suggest a need for a more holistic approach that recognizes the complementarities between market and nonmarket sources of foods. This approach should build on the diversity of species rural households already utilize, and on the ways they interact with markets., Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-022-01320-w., Competing Interests: Conflict of interestThe authors declared that they have no conflict of interest., (© The Author(s) 2022.)

Background: Available data suggest that women with disabilities have an increased risk of sexual violence, but little is known about the situation of those women living in resource-limited settings., Objectives: To assess the burden and examine the drivers of sexual violence among women with disabilities., Methods: This is a pooled analysis of two population-based surveys conducted in Cameroon and Burundi. Adults with and without disabilities were randomly recruited from the general population. Structured interviews were conducted at both sites to collect data on participants' functional limitations, life-course history of sexual violence, education, employment, and resources. Only women with disabilities whose impairments started before the age of 10 years (n = 359) and women without disabilities (n = 720) are included in this analysis. The age-adjusted prevalence of violence was computed, and risk factors were assessed using a discrete survival regression and mediation analysis., Results: At both sites, the participants with disabilities had a lower education level and had an increased risk of food insecurity. The pooled age-adjusted prevalence of lifetime sexual violence was 19.8% (95%CI:15.3-24.3) among women with disabilities and 11.7% (95%CI:9.3-14.1) among those without disabilities (OR ap : 2.0, 95%CI:1.4-2.8). Women with cognitive limitations and those with visual impairments had the highest risk of sexual violence (OR ap : 3.5 (95%CI:2.0-6.3) and 2.7 (95%CI:1.4-5.0), respectively). Over the life course, the risk of sexual violence was especially high among women with disabilities who had lived with an intimate partner before the age of 25 years ( p < 0.001). Education level mediated approximately one-third of the total association between disability and sexual violence ( p = 0.001). There was no evidence of an indirect effect through food insecurity., Conclusion: This study provides evidence of the high burden of sexual violence among women with disabilities who live in urban African contexts. The social environment and access to education may be key contributors to this vulnerability.

Objectives: We examined the construct validity of 2 self-reported frailty questionnaires, the Frailty Phenotype Questionnaire (FPQ) and FRAIL, against the Cardiovascular Health Study frailty phenotype (CHS-FP)., Design: Cross-sectional data analysis of longitudinal prospective cohort study., Settings and Participants: We included data from 230 older adults (mean age: 67.2 ± 7.4 years) from the "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and Osteosarcopenic Obesity in predicting frailty and functional decline in community-dwelling Asian older adults Study" (GeriLABS 2) recruited between December 2017 and March 2019., Methods: We compared area under receiver operating characteristic curves (AUC), agreement, correlation, and predictive validity against outcome measures [Short Physical Performance Battery, 5 times repeat chair stand (RCS-5), Frenchay activities index, International Physical Activity Questionnaire, life-space assessment, Social Functioning Scale 8 (SFS-8), EuroQol-5 dimensions (utility value)] using logistic regression adjusted for age, gender, and vascular risk factors. We examined concurrent validity across robust versus prefrail/frail for inflammatory blood biomarkers [tumor necrosis factor receptor 1 and C-reactive protein (CRP)] and dual-energy x-ray absorptiometry body composition [bone mineral density (BMD); appendicular lean mass index (ALMI), and fat mass index (FMI)]., Results: Prevalence of prefrail/frail was 25.7%, 14.8%, and 48.3% for FPQ, FRAIL, and CHS-FP, respectively. Compared with FRAIL, FPQ had better diagnostic performance (AUC = 0.617 vs 0.531, P = .002; sensitivity = 37.8% vs 18.0%; specificity = 85.6% vs 88.2%) and agreement (AC1-Stat = 0.303 vs 0.197). FPQ showed good predictive validity [RCS-5: odds ratio (OR) 2.38; 95% CI: 1.17-4.86; International Physical Activity Questionnaire: OR 3.62; 95% CI:1.78-7.34; SFS-8: OR 2.11; 95% CI: 1.64-5.89 vs FRAIL: all P &gt; .05]. Only FRAIL showed concurrent validity for CRP, compared with both FPQ and FRAIL for TNF-R1. FRAIL showed better concurrent validity for BMD, FMI, and possibly ALMI, unlike FPQ (all P &gt; .05)., Conclusions and Implications: Our results support complementary validity of FPQ and FRAIL in independent community-dwelling older adults. FPQ has increased case detection sensitivity with good predictive validity, whereas FRAIL demonstrates concurrent validity for inflammation and body composition. With better diagnostic performance and validity for blood biomarkers and clinical outcomes, FPQ has utility for early frailty detection in the community setting., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

This scoping review provides overview on the historical and major developments, current status, quantitative magnetic resonance (MR) studies and the role of medical physics bodies in MR imaging in Africa. The study analyzed MRI availability in 32 (59 %) of the 54 African countries. South Africa and Egypt have the most dominant MR systems. Number of MR systems in the 4 northern countries (Egypt, Morocco, Algeria and Libya) alone constitute 53 % of the total number of machines in the studied countries. Less than one-third of the countries have 1 MR system serving less than a million population. Libya recorded the most MR systems per million population. The studied countries altogether have an average of 1 machine per million population. The private sector far dominates number of installed MR systems across the region, making up two-thirds of the distribution. A major challenge was revealed where less than 3 % of Medical Physicists in the studied countries are engaged in MRI facilities. Review of MRI published studies in the last 5 years indicates dominance of literature on brain studies and most of such published works coming from Nigeria. Only 7 out of 27 published studies reviewed were quantitative. The African region has no dedicated MRI physics societies; however, the regional medical physics body and national associations have big roles to play in developing MRI through education, research, training and leveraging on awareness creation. Thisreview is the first of such wide scale study on MRI availability and quantitative studies in the African region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The conjugation of chitosan 15 and 100 KD with anticancer drugs cis- and trans-Pt (NH 3 ) 2 Cl 2 (abbreviated cis-Pt and trans-Pt) were studied at pH 5-6. Using multiple spectroscopic methods and thermodynamic analysis to characterize the nature of drug-chitosan interactions and the potential application of chitosan nanoparticles in drug delivery. Analysis showed that both hydrophobic and hydrophilic contacts are involved in drug-polymer interactions, while chitosan size and charge play a major role in the stability of drug-polymer complexes. The overall binding constants are K ch-15-cis-Pt = 1.44 (±0.6) × 10 5 M -1 , K ch-100-cis-Pt = 1.89 (±0.9) × 10 5 M -1 and K ch-15-trans-Pt = 9.84 (±0.5) × 10 4 M -1 , and K ch-100-trans-Pt = 1.15 (±0.6) × 10 5 M -1 . More stable complexes were formed with cis-Pt than with trans-Pt-chitosan adducts, while stronger binding was observed for chitosan 100 in comparison to chitosan 15 KD. This study indicates that polymer chitosan 100 is a stronger drug carrier than chitosan 15 KD in vitro.