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Global health initiatives are multistakeholder partnerships that mobilize and disburse resources to address global health challenges, often by supporting implementation of health programmes in low-and middle-income countries. (1) These initiatives [...]

The year 2024 marks the 50th anniversary of the World Health Organization (WHO) Expanded Program on Immunization (EPI) [...]

Abstract Background Mixed phenotype acute leukemia (MPAL), a rare subgroup of leukemia characterized by blast cells with myeloid and lymphoid lineage features, is difficult to diagnose and treat. A better characterization of MPAL is essential to understand the subtype heterogeneity and how it compares with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Therefore, we performed single-cell RNA sequencing (scRNAseq) on pediatric MPAL bone marrow (BM) samples to develop a granular map of the MPAL blasts and microenvironment landscape. Methods We analyzed over 40,000 cells from nine pediatric MPAL BM samples to generate a single-cell transcriptomic landscape of B/myeloid (B/My) and T/myeloid (T/My) MPAL. Cells were clustered using unsupervised single-cell methods, and malignant blast and immune clusters were annotated. Differential expression analysis was performed to identify B/My and T/My MPAL blast-specific signatures by comparing transcriptome profiles of MPAL with normal BM, AML, and ALL. Gene set enrichment analysis (GSEA) was performed, and significantly enriched pathways were compared in MPAL subtypes. Results B/My and T/My MPAL blasts displayed distinct blast signatures. Transcriptomic analysis revealed that B/My MPAL profile overlaps with B-ALL and AML samples. Similarly, T/My MPAL exhibited overlap with T-ALL and AML samples. Genes overexpressed in both MPAL subtypes’ blast cells compared to AML, ALL, and healthy BM included MAP2K2 and CD81. Subtype-specific genes included HBEGF for B/My and PTEN for T/My. These marker sets segregated bulk RNA-seq AML, ALL, and MPAL samples based on expression profiles. Analysis comparing T/My MPAL to ETP, near-ETP, and non-ETP T-ALL, showed that T/My MPAL had greater overlap with ETP-ALL cases. Comparisons among MPAL subtypes between adult and pediatric samples showed analogous transcriptomic landscapes of corresponding subtypes. Transcriptomic differences were observed in the MPAL samples based on response to induction chemotherapy, including selective upregulation of the IL-16 pathway in relapsed samples. Conclusions We have for the first time described the single-cell transcriptomic landscape of pediatric MPAL and demonstrated that B/My and T/My MPAL have distinct scRNAseq profiles from each other, AML, and ALL. Differences in transcriptomic profiles were seen based on response to therapy, but larger studies will be needed to validate these findings.

Abstract Background Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which can arise upon viral integration into the host genome and concurrent loss of viral regulatory gene E2. Gene‐based delivery approaches show that E2 reintroduction reduces proliferative capacity and promotes apoptosis in vitro. Aims This work explored if our calcium‐dependent protein‐based delivery system, TAT‐CaM, could deliver functional E2 protein directly into cervical cancer cells to limit proliferative capacity and induce cell death. Materials and Results TAT‐CaM and the HPV16 E2 protein containing a CaM‐binding sequence (CBS‐E2) were expressed and purified from Escherichia coli. Calcium‐dependent binding kinetics were verified by biolayer interferometry. Equimolar TAT‐CaM:CBS‐E2 constructs were delivered into the HPV16+ SiHa cell line and uptake verified by confocal microscopy. Proliferative capacity was measured by MTS assay and cell death was measured by release of lactate dehydrogenase. As a control, human microvascular cells (HMECs) were used. As expected, TAT‐CaM bound CBS‐E2 with high affinity in the presence of calcium and rapidly disassociated upon its removal. After introduction by TAT‐CaM, fluorescently labeled CBS‐E2 was detected in cellular interiors by orthogonal projections taken at the depth of the nucleus. In dividing cells, E2 relocalized to regions associated with the mitotic spindle. Cells receiving a daily dose of CBS‐E2 for 4 days showed a significant reduction in metabolic activity at low doses and increased cell death at high doses compared to controls. This phenotype was retained for 7 days with no further treatments. When subcultured on day 12, treated cells regained their proliferative capacity. Conclusions Using the TAT‐CaM platform, bioactive E2 protein was delivered into living cervical cancer cells, inducing senescence and cell death in a time‐ and dose‐dependent manner. These results suggest that this nucleic acid and virus‐free delivery method could be harnessed to develop novel, effective protein therapeutics.

This document is a list of contributions to a special issue on immunization inequalities and the need for equity in vaccine access. The contributions include analyses of factors such as wealth inequality, gender barriers, the impact of the COVID-19 pandemic, subnational coverage, childhood immunization coverage, data triangulation, global economic benefits, geospatial analyses, timeliness of vaccinations, factors associated with vaccine uptake, parental hesitancy, and sociodemographic trends. The document emphasizes the importance of addressing structural factors and refining analytical approaches to achieve immunization equity. The Special Issue was funded in part by Gavi, The Vaccine Alliance, but the funder had no role in the writing of the Editorial. The authors declare no conflicts of interest. [Extracted from the article]

Diabetic foot ulcers (DFUs) remain a complication of diabetes that are difficult to heal and lead to disability. Here the authors use single-cell RNA-sequencing and spatial transcriptomics to characterize the DFU cellular landscape and identify a population of fibroblasts that is associated with successful wound closure.

Immunization, hailed as one of the most successful public health interventions in the world, has contributed to major advancements in health as well as social and economic development [...]

Community health workers (CHWs) are increasingly addressing health disparities in primary care settings; however, there is little information about how primary care practitioners (PCPs) interact with CHWs or perceive CHW roles. We examined PCP engagement with CHWs in adult primary care settings. Overall, 55% of 1504 PCPs reported working with CHWs; involvement with CHWs differed by some PCP demographic and practice-related factors. While PCPs perceived CHWs as engaging in most nationally endorsed CHW roles, they identified several barriers to integrating CHWs into care teams. Findings can inform ongoing efforts to advance health equity through integrating CHWs into primary care practices. [ABSTRACT FROM AUTHOR]

South Africa attained its constitutional democracy in 1994 from a contemporary political order that has been shaped by the country's history of colonialism, segregation, less or no service delivery to black communities, and apartheid. Since the inception of the second decade of democracy, the country has experienced numerous service delivery protests, raises brings doubt about whether or not democracy exists in South Africa. The current study was carried out in Hlanganani Cluster in Collins Chabane Local Municipality. A qualitative research methodology that utilised a phenomenological research design was used to investigate democracy, democratisation and governance in the Hlanganani Cluster. A sample of 15 respondents from the area participated in the study. The results of the study revealed that the broader definition of democracy is not familiar in the area, yet the political rhetoric one more widely embraces the concept of democracy. Hence, the challenges of poor service delivery, lack of accountability of public officials' lack of transparency, and corruption are key obstacles hindering the full realisation of democracy in the area. It is recommended that the government enhance the participation of local communities in decision making, encourage the youth, and create a democratic space for civic society to maintain checks and balances. The results of the study are also useful for crafting strategies for creating an enabling environment for democracy, democratisation, and good governance to thrive. [ABSTRACT FROM AUTHOR]

Purpose: Data use cultures in schools determine data use practices. Such cultures can be muted by powerful macro accountability and organizational learning cultures. Further, strong equity-oriented data use cultures are challenging to establish. The purpose of this paper is to engage these cultural tensions. Design/methodology/approach: The data discourse and decisions of four grade-level teams in two elementary schools in one district were studied through observation of 62 grade-level meetings over the course of a year. The observations focused on "data talk," defined as the structure and content of team conversations about interim student performance data. Findings: Distinct macro cultures of accountability and organizational learning existed in the two schools. The teams' own data use cultures partly explained the absence of a focus on equity, and none of the teams used student performance data to make instructional decisions in support of the district's equity aims. Leadership missed opportunities to cultivate an equity-focused data use culture. Practical implications: School leaders who advocate that equity importantly guides data use routines, and can anticipate how cultures of accountability or organizational learning "show up" in data use conversations, will be better prepared to redirect teachers' interpretations of data and clarify expectations of equity reform initiatives. Originality/value: This study is novel in its concept of "data talk," which provided a holistic but nuanced account of data use practices in grade-level meetings.

Summary: Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We find eight EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudotime reveal that ECs are highly heterogeneous and plastic. D-flow induces a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory cells, mesenchymal (EndMT) cells, hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 as an s-flow-sensitive transcription factor binding site, we also find those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to proatherogenic phenotypes, including EndMT and potentially EndICLT.

A biological life support system for spaceflight would capture carbon dioxide waste produced by living and working in space to generate useful organic compounds. Photosynthesis is the primary mechanism to fix carbon into organic molecules. Microalgae are highly efficient at converting light, water, and carbon dioxide into biomass, particularly under limiting, artificial light conditions that are a necessity in space photosynthetic production. Although there is great promise in developing algae for chemical or food production in space, most spaceflight algae growth studies have been conducted on solid agar-media to avoid handling liquids in microgravity. Here we report that breathable plastic tissue culture bags can support robust growth of Chlamydomonas reinhardtii in the Veggie plant growth chamber, which is used on the International Space Station (ISS) to grow terrestrial plants. Live cultures can be stored for at least 1 month in the bags at room temperature. The gene set required for growth in these photobioreactors was tested using a competitive growth assay with mutations induced by short-wave ultraviolet light (UVC) mutagenesis in either wild-type (CC-5082) or cw15 mutant (CC-1883) strains at the start of the assay. Genome sequencing identified UVC-induced mutations, which were enriched for transversions and non-synonymous mutations relative to natural variants among laboratory strains. Genes with mutations indicating positive selection were enriched for information processing genes related to DNA repair, RNA processing, translation, cytoskeletal motors, kinases, and ABC transporters. These data suggest that modification of DNA repair, signal transduction, and metabolite transport may be needed to improve growth rates in this spaceflight production system.

Quantum interactions going hybrid: ferromagnetically mediated coupling Hybrid architectures that combine materials and devices with widely different properties promise to be at the forefront of scalable quantum systems by unlocking access to more than the simple sum of their parts. A team led by David Awschalom at the University of Chicago has now revealed the possibility of using collective spin oscillations in a ferromagnet to mediate long-range, coherent interactions between a microwave source and spin qubits confined in diamond nanoparticles. The strong surface confinement of the ferromagnet excitations and their slow decay result in an effective amplification of the source field over hundreds of micrometers at ambient conditions. This effect can extend the capabilities of solid state qubits for quantum information and nanoscale quantum sensing applications.

Background: Environmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI). Methods: Participants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996–1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models. Results: The highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI

Context: Educators often engage with student performance data to make important instructional decisions, yet limited research has analyzed how educators make sense of student performance data. In addition, scholars suggest that teachers recognize a relationship between their instruction and student performance data, but this is a relatively untested assumption. Focus of Study: We investigated if and how teachers referenced instruction as a contributing factor for why students performed in particular ways on assessments. We also studied other explanations that teachers offered for student performance data. Research Design: Our research team conducted a qualitative case study of six grade-level teams of teachers who met biweekly to make meaning of student performance data. Using data collected from 44 hours of observation of teacher team meetings, 16 individual interviews, and six group interviews with participating teachers, we analyzed the ways in which and the extent to which teachers referenced instruction as a contributing factor to student performance data.?Findings: Teachers connected student performance data to their instruction approximately 15% of the time. Teachers more frequently connected student performance data to student characteristics. Notably, student behavior accounted for 32% of all teacher explanations for student performance. We offer five distinct categories of teachers' explanations of student performance and the extent to which teachers invoked each category. Conclusions: The findings in this study build on research on teachers' attributions for assessment data. In contrast to other studies, our findings suggest that teachers invoked student characteristics in distinct ways when explaining student performance. At times, teachers were knowledgeable about student characteristics, which offered verifiable insights into the "problem" of low achievement. At other times, teachers voiced negative viewpoints of students that served to blame students for their poor performance. We suggest that the practice of data-driven decision making offers an opportunity to bolster educators' informed judgment and undermine negative, unverifiable claims about children.

Background: An estimated 23 million infants are still not being benefitted from routine immunization services. We assessed how many children failed to be fully immunized even though they or their mothers were in contact with health services to receive other interventions. Design: Fourteen countries with Demographic and Health Surveys and Multiple Indicator Cluster Surveys carried out after 2000 and with coverage for DPT (Diphtheria-tetanus-pertussis) vaccine below 70% were selected. We defined full immunization coverage (FIC) as having received one dose of BCG (bacille Calmette-Guérin), one dose of measles, three doses of polio, and three doses of DPT vaccines. We tabulated FIC against: antenatal care (ANC), skilled birth attendance (SBA), postnatal care for the mother (PNC), vitamin A supplementation (VitA) for the child, and sleeping under an insecticide-treated bed-net (ITN). Missed opportunities were defined as the percentage of children who failed to be fully immunized among those receiving one or more other interventions. Results: Children who received other health interventions were also more likely to be fully immunized. In nearly all countries, FIC was lowest among children born to mothers who failed to attend ANC, and highest when the mother had four or more ANC visits Côte d'Ivoire presented the largest difference in FIC: 54 percentage points (pp) between having four or more ANC visits and lack of ANC. SBA was also related with higher FIC. For instance, the coverage in children without SBA was 36 pp lower than for those with SBA in Nigeria. The largest absolute difference on FIC in relation to PNC was observed for Ethiopia: 31 pp between those without and with PNC. FIC was also positively related with having received VitA. The largest absolute difference was observed in DR Congo: 41 pp. The differences in FIC among whether or not children slept under ITN were much smaller than for other interventions. Haiti presented the largest absolute difference: 16 pp. Conclusions: Our results show the need to develop and implement strategies to vaccinate all children who contact health services in order to receive other interventions.