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Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Despite initiatives by key actors in the last two decades, Early Childhood Development in Ghana, measured by physical, cognitive, linguistic, and social-emotional development of children up to 8 years of age, remains poor. This study aimed to assess Ghana's Early Childhood Development (ECD) status and determinants by analyzing the Ghana Multiple Indicator Cluster Survey 2017/18 data. Among the 3801 Ghanaian children (35-59 months; 1880 males), 42.7% were developmentally on track in literacy-numeracy, 93.6% in physical, 68.2% in social-emotional, 82.3% in learning, and about 67% in at least 3 of the 4 domains. Multiple logistic regression analyses suggest a positive association between ECD and female sex of children, their age, mothers' attendance in any ECD programs, mothers' educational qualification, and household wealth. On the other hand, evidence of a negative association was observed between ECD and child disability, stunting status of children, maternal disability, the number of days children were left alone for more than an hour, and residence in a rural area. The level of maternal education may be implicated in ECD policies as it affected several ECD domains.

Abstract Background Non-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive tool to explore the microbial landscape underlying NMFI in this vulnerable population ensuring effective management. Methods In this study, we employed shotgun metagenomics to analyse stool samples from HIV-infected children at the Baylor Children’s Clinic Uganda presenting with non-malarial febrile illness. Samples were collected and subjected to DNA extraction at the Molecular and Genomics Laboratory, Makerere University followed by shotgun metagenomics sequencing at the Chan Zuckerberg Biohub San Francisco. Bioinformatics analysis was conducted to identify and characterise the microbial composition and potential pathogenic taxa associated with NMFI using the CZID pipeline. Results Our findings reveal a diverse array of microbial taxa in the stool samples of HIV-infected children with NMFI. Importantly, shotgun metagenomics revealed potentially pathogenic players including Trichomonas vaginalis, Candida albicans, Giardia, and Bacteroides in stool from this patient population. This sheds light on the complexities of microbial interactions that potentially underpin non-malarial febrile illness in this group. Taxonomic profiling identified recognised pathogens and comorbidities and revealed possible new correlations with NMFI, shedding light on the pathophysiology of fever in HIV-infected children. Conclusion Shotgun metagenomics is a valuable method for understanding the gut microbial landscape of NMFI in HIV-infected children, providing a comprehensive approach to pathogen identification and characterisation. By revealing potential pathogenic actors beyond the fever, this work demonstrates how metagenomic sequencing may improve our knowledge of infectious illnesses in vulnerable groups and inspire targeted therapies for better clinical care and outcomes.

Abstract Background The prevalence of hypertension is high in Uganda, which places a significant burden on an already strained healthcare system. The behavioural risk factors, such as unhealthy diet, tobacco use, physical inactivity, and heavy drinking, contribute to hypertension development and complications. This study explored the associations of combined tobacco smoking and heavy alcohol consumption with existing hypertension in a community-based cross-sectional study conducted in two rural districts of Uganda. Methods We analysed data collected between December 2018 and January 2019 from 4,372 adults aged 25–70 from 3,689 random households in the Mukono and Buikwe districts, Uganda. Using logistic regression, crude, and adjusted odds ratios were calculated to describe the associations between participant characteristics, smoking, drinking behaviours, and high blood pressure (HBP). To determine effect modification due to combined tobacco smoking and heavy drinking, the relative excess risk due to interaction (RERI) was computed. All analyses were performed via R programming software version 4.2.3. Results HBP was prevalent in 23% of the participants. Smokers were 1.36 times more likely to have HBP than non-smokers (Crude OR, 1.36; 95% CI, 1.04–1.76). Compared with non-drinkers, moderate alcohol drinkers were 1.45 times more likely to have HBP (AOR, 1.45; 95% CI, 1.18–1.79), and heavy drinkers were 2.53 times more likely to have HBP (AOR, 2.53; 95% CI, 1.92–3.32). The RERI indicated an additive interaction effect between smoking and heavy drinking, with conjoint smokers and heavy drinkers having 45% higher odds of having HBP than the summation of the individual risk due to smoking and heavy drinking. Conclusion Tobacco smoke interacts with heavy alcohol consumption to increase the risk of increased blood pressure (BP) when it cooccurs. Integrated intervention strategies targeting both smoking and heavy drinking are essential for reducing the incidence of hypertension in rural Uganda.

Vitamin D is a conditionally essential fat-soluble vitamin found in foods such as fish; fish oil; egg yolks; animal fats; some mushroom varieties; and fortified foods such as cheese, margarine, milk, infant formula, and some ready-to-eat cereals. Calcium (Ca) is found in milk, cheese, canned fish, ready-to-eat cereals, milk substitutes, dark green leafy vegetables, and sports drinks. There are more than fifty metabolites of vitamin D. Vitamin D participates in immune regulation, apoptosis induction, insulin secretion, inflammation, cell differentiation, calcium balance and regulation, bone mineralization, and phosphorus homeostasis. Ca is an essential macro-mineral involved in bone and teeth matrices, strength, and hardness; muscle and cardiovascular movement; neurological messaging; and in the release of hormones. Peer-reviewed journal articles were accessed from the search engine PubMed. The authors reviewed the references in the peer-reviewed journal articles, websites, and review articles if the authors proposed a new theory or mechanism. Vitamin D and Ca have important relationships; therefore, many factors may impede or interfere with the body’s ability to absorb or utilize vitamin D and or Ca and may result in low or excessive levels of each. Additionally, genetic/medically related absorption issues and low intake may also result in deficiencies. This review discusses the introduction of each, their functions, absorption, somatic transportation, the relationship between vitamin D and Ca, and recommendations and supplementation strategies if available.

Abstract This paper investigates the deployment of solar technology throughout an electric railway system to accommodate tractive power needs. The approach is evaluated from both a technical and financial standpoint to better understand its overall feasibility. A case study is presented using New York City's subway system as the centre of deployment. As a means to both prevent excess voltages, as well as contribute to the city's shift to zero emission, parallel electric bus charging is also studied. It has been demonstrated that the proposed integration allows the subway system to still function without any hindrance to rail operation. The system is able to provide charging power for three to six electric buses per passenger station. In addition, the approach shows long‐term financial growth with average annual electric bill savings of approximately $50,000 per passenger station, each with a relatively short payback period of approximately 4 years.

ObjectiveCo-occurring anti-tripartite motif-containing protein 9 and 67 autoantibodies (TRIM9/67-IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67-IgG detection are not known.MethodsWe performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67-IgG cases by tissue-based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell-based assay (CBA), and immunoblot. Cases in which TRIM9/67-IgG was detected by at least 2 assays were considered TRIM9/67-IgG positive.ResultsAmong these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67-IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases.InterpretationTRIM9/67-IgG is a rare but likely high-risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086-1101.

Studies informed by poststructuralist theories of language have examined the relationship between language teachers' emotion labor, identity, and agency. However, research has not yet explored the relationship between emotion labor and volunteer teaching, which is an important practice in language education. Our research seeks to address this gap, drawing on a 2-year qualitative case study at the community-based Vancouver Bangla School (VBS). With emotion labor and investment as the conceptual underpinnings, our study investigated how the VBS heritage language (HL) program structured the emotion labor of seven volunteer teachers, what the feeling rules associated with the VBS program were, and the extent to which volunteer teachers' investment in HL education helped them manage their emotion labor. Data sources included participant classroom observations, field notes, focus group and interview transcripts, questionnaires, and educational resources, which were analyzed using reflexive thematic analysis. Findings indicate that the emotion labor of volunteer teachers was structured by the following characteristics of the VBS program: lack of funding, poor organizational structure and teacher recognition, challenges of online teaching, insufficient number of teachers, limited parental support, and lack of training. This emotion labor was associated with four feeling rules implicit in the VBS program: (a) be generous and caring, (b) be committed and dedicated, (c) be a good and efficient teacher, and (d) have limited expectations of the community. Findings suggest that teachers' investment in Bangla as a mother tongue in multicultural Canada, and their investment in promoting the children's transcultural identities, was particularly powerful, and enabled the volunteer teachers to navigate and manage their emotion labor. The study suggests that an enhanced understanding of a language teacher's investment in a program, institution, or community might provide insight into the important relationship among desire, agency, and emotion labor.

PURPOSE: Basic science medical educators (BSME) play a vital role in the training of medical students, yet little is known about the factors that shape their professional identities. This multi-institutional qualitative study investigated factors that support and threaten the professional identity formation (PIF) of these medical educators. METHOD: A qualitative descriptive study was conducted with a purposive sample of 58 BSME from 7 allopathic medical schools in the U.S. In-depth semi-structured interviews of individual BSME were conducted between December 2020 and February 2021 to explore the facilitators and barriers shaping the PIF of BSME. Thematic analysis was conducted. RESULTS: Factors shaping PIF were grouped into 3 broad domains: personal, social, and structural. Interrelated themes described a combination of factors that pushed BSME into teaching (early or positive teaching experiences) and kept them there (satisfaction and rewards of teaching, communities of like-minded people), as well as factors that challenged their PIF (misunderstanding from medical students, clinical, and research faculty, lack of formal training programs, and lack of tenure-track educator positions). The structural environment was reported to be crucial for PIF and determined whether BSME felt that they belonged and were valued. CONCLUSIONS: This study shows that although most BSME derive a sense of fulfillment and meaning from their role as medical educators, they face considerable obstacles during their PIF. Structural change and support are needed to increase recognition, value, promotion, and belonging for BSME to improve the satisfaction and retention of this important group of faculty.

Various history books as media to learn the history of Indonesia people are actually quite complete and adequate. However, the interest of younger generation, especially the children, to read the books is quite low. Additionally, the advance of computer technology makes kids and students more interested playing game than reading books. The game trend backgrounds the need for research on the use of computer game application as a medium to learn the history of the building through a game. As the special purpose of this research is to obtain a game application that can be a medium of learning historical buildings. The research is divided into two stages: the first stage is to identify gaming software that can be used as an educational game for historical buildings and to develop the model of 3D gaming applications; the second phase is the application trial and implementation at schools.

Inadequate safe water supply and cholera outbreaks are significant contributors to ill health in displaced populations, exacerbating the vulnerability of refugees fleeing conflicts. In November 2021, the Nakivale Refugee Settlement faced a cholera outbreak and water scarcity, putting displaced persons at risk of ill health. This study aimed to investigate the lessons learned from this incident and identify pathways to prevent future outbreaks, ultimately safeguarding the lives and well-being of vulnerable populations. A descriptive cross-sectional study analysed epidemiological data from the Uganda Ministry of Health, investigating the cholera outbreak among refugees in Nakivale Refugee Settlement, Isingiro district, from November 3rd to December 2nd, 2021. The outbreak affected 173 refugees, primarily in Nyarugugu B and C villages, with consumption of contaminated lake water identified as the likely cause. Inadequate access to clean water and sanitation facilities exacerbated the outbreak, which disproportionately affected individuals aged 10-19 years (30.1%) and females (65%). Promotion of safe water, sanitation, and oral cholera vaccination campaigns effectively controlled the outbreak. This study highlights the critical importance of providing refugees with access to safe water and sanitation infrastructure to prevent cholera outbreaks. Timely implementation of oral cholera vaccination campaigns and enhanced water management systems are crucial to preventing future outbreaks in refugee settlements.

A comprehensive understanding of the genetics of resistance is essential for developing an effective breeding strategy to create germplasm resistant to Fusarium Ear Rot. This study aimed to determine the general combining ability (GCA), specific combining ability (SCA), and heritability of resistance to infection by Fusarium verticillioides in tropical maize. Using the North Carolina II mating design, six inbred lines as females and seven as males were crossed to produce 42 hybrids, which were evaluated across five environments using artificial inoculation. At harvest, the hybrids were scored for Fusarium Ear Rot (FER) infection using a 1-9 severity scale. Significant GCA effects for the parents and SCA effects for the hybrids were observed. The narrow-sense heritability estimate was 0.22, while the broad-sense heritability was 0.73, and the additive genetic effects, as represented by GCA (m+f), were more significant than non-additive effects. The inbred parents JPS25-13, JPS26-125, JPS26-86, JPS25-11, JPS25-5, JPS25-7, and JPS25-9 were identified as the best general combiners for FER resistance. These lines, with favorable general combining ability effects for resistance to Fusarium verticillioides, are strong candidates for breeding resistant varieties.

Este trabajo presenta un estudio exploratorio sobre la implementación del Aprendizaje Basado en Proyectos (ABPr) en cursos de Ciencias Biológicas dirigidos a estudiantes de carreras no STEM. El objetivo del proyecto fue integrar conceptos biológicos con otras disciplinas para fomentar el pensamiento crítico e interdisciplinario. Luego de su ejecución se exploraron las percepciones de los participantes respecto al impacto de una metodología interdisciplinaria basada en proyectos (ABPr) en su aprendizaje. Para ello, se adaptaron cinco etapas simplificadas del ABPr para guiar a 46 estudiantes en el desarrollo de proyectos que vincularon la biología con sus áreas de estudio. La investigación utilizó un diseño metodológico mixto, con un cuestionario y el análisis de producciones estudiantiles como instrumentos de recolección de datos. Los resultados revelaron un aumento significativo en la motivación de los estudiantes, especialmente durante las etapas prácticas de desarrollo del proyecto. Además, el 97.2 % de los participantes percibió mejoras en la integración de conceptos biológicos al relacionarlos con sus propias disciplinas, lo que demuestra la efectividad del ABPr en entornos de enseñanza interdisciplinaria. Se concluye que esta metodología facilita la comprensión de conceptos científicos y promueve el pensamiento crítico e interdisciplinario.

Introduction Patient navigation is recommended by accrediting bodies such as the Commission on Cancer and is a key element in payment reform demonstration projects, due to the established benefits in reducing barriers to healthcare, improving care coordination and reducing healthcare utilisation. However, oncology practices are often resource constrained and lack the capacity to extend navigation services at the desired intensity for their patient population. The American Cancer Society (ACS) developed the ACS Community Access to Resources, Education, and Support (CARES) programme to expand navigation capacity through the training of students from local universities as volunteers to serve as non-clinical navigators to support cancer patients. Although this approach has great potential for scalability, the best approach to early implementation and impact of volunteer navigation remains unclear.Methods and analysis This pragmatic single-arm pre–post study evaluates the implementation and effectiveness of volunteer navigation for patients participating in the 2023–2024 pilot. This study will use data collected during routine care for quantitative implementation and patient outcomes. The Updated Consolidated Framework for Implementation Research will guide evaluation of early programme implementation with three initial pilot sites. This pragmatic evaluation of real-world implementation of volunteer navigation in the oncology setting will support future efforts to scale-up this intervention across US health systems.Ethics and dissemination This study was approved by University of Morehouse School of Medicine Social and Behavioral (IRB), which served as the IRB for record for this project (IRB-2025819–2). No consent required for this study protocol. ACS CARES plans to disseminate this model and include additional sites as participants in future years.

Aim of the studyTuberous sclerosis complex (TSC) is a genetic and multisystemic disorder that affects between 1/6’000 and 1/10’000 of newborns. Clinical criteria and/or genetic analysis establish the diagnosis. The mechanistic target of rapamycin (mTOR) inhibitors everolimus or sirolimus reduce the severity of several TSC-related clinical traits. We report here on the epidemiology and management of TSC patients in a large Swiss canton: the canton of Vaud.MethodWe extracted patient files containing the diagnostic code TSC in 2015 at the Lausanne University hospital (tertiary reference center for a population of about 755’000 people) and in specialized neurological institutions of the same region.ResultsWe identified 52 patients with a diagnosis of TSC. The majority of the patients with a pathologic result in genetic testing were positive for a pathogenic variant in the TSC2 gene, including five cases of contiguous gene deletion syndrome of TSC2 and PKD1 causing both polycystic kidney disease and TSC. The most frequent clinical manifestations encountered were affecting the skin (87% of patients), the brain (83%), the heart (46%) and the kidneys (46%). Neuropsychiatric disorders were described in 56% of cases. At the time of data collection (2015), there were 2 patients using systemic mTOR inhibitors and 16 patients using topical mTOR inhibitors for dermatological features. Next, we compared this data with those of large published cohorts. While we found fewer cases than expected for the screened population, demographic as well as genetic data were overall similar to the literature. However, we observed that some clinical manifestations (renal, lung and neuropsychiatric disorders) were less frequently described in our cohort.ConclusionThis work indicates that TSC and some of its clinical manifestations is under-reported. It raises concern that patients with mild manifestations are often not referred to reference centers with dedicated multidisciplinary group. The follow-up by expert board is instrumental in offering systematic screening of all putatively affected organs and to assess the eligibility for targeted treatment.