Baobab Index

Megakaryocyte polyploidization is a specialized process essential for platelet production, orchestrated by tightly regulated transcriptional programs, cell-cycle control, and signaling pathways. Disruption of this process - characterized by incomplete endomitosis, low ploidy, and maturation arrest - contributes to leukemic transformation, particularly in acute megakaryoblastic leukemia and related myeloid malignancies. Aberrant polyploidization arises from transcription factor dysregulation, cell-cycle abnormalities, hyperactive proliferative signaling, microenvironmental alterations, and genomic instability. These defects collectively promote proliferation, differentiation arrest, and malignant expansion of megakaryocytic progenitors. Therapeutic strategies targeting these pathways, including modulation of transcription factors, restoration of endomitotic progression, inhibition of JAK-STAT and RAS/MAPK signaling, epigenetic reprogramming, and niche-directed interventions, offer promising avenues to suppress leukemic growth and restore normal maturation. Understanding aberrant polyploidization as a driver of leukemogenesis provides a framework for developing precision therapies in megakaryocytic leukemia.

Breast cancer is characterized by diverse cytogenetic alterations that play a pivotal role in tumor initiation, progression, and therapeutic resistance. These chromosomal abnormalities, including gains, losses, and structural rearrangements, contribute to genomic instability and influence cellular behavior in ways that extend beyond tumor growth. One significant but often overlooked consequence of these cytogenetic changes is their impact on the coagulation system, leading to a hypercoagulable state and increasing the risk of thrombosis in breast cancer patients. Emerging evidence links specific cytogenetic aberrations to the dysregulation of coagulation pathways through molecular mechanisms such as upregulation of tissue factor expression, enhanced release of procoagulant microparticles, and modulation of platelet and endothelial cell activation. These processes collectively foster a prothrombotic environment, exacerbating complications like venous thromboembolism and disseminated intravascular coagulation, which significantly affect patient morbidity and mortality. Moreover, the interplay between chromosomal instability and coagulation dysregulation may also influence tumor progression and metastasis.

Conservation translocations have become important assets in saving African wild dogs (Lycaon pictus) from local extinction, which have declined drastically due to anthropogenic pressures. In South Africa, wild dogs were eradicated except for a small, isolated population remaining in Kruger National Park. Due to reintroductions into private reserves, the country now holds a viable metapopulation of over 150 individuals that is used as a donor to repopulate other countries in southern Africa. This Range Expansion Project allows a unique opportunity to quantify the genomic effect of founder events, population isolation and conservation translocations. For this purpose, we harvested 30 whole genomes of wild dogs from Kruger, private reserves and outside protected areas. Demographic reconstructions indicate that populations were historically large (10,000-40,000 individuals) but began declining gradually ~500-100 kya, coinciding with Mid-Pleistocene climate shifts, followed by a sharp collapse ~2-0.8 kya. The Kruger population showed a substantially higher genetic load and a greater extent of runs of homozygosity (ROHs), indicating that its reduced genetic variation is driven primarily by inbreeding rather than demographic history. In contrast, reintroduced populations in private reserves exhibited the highest genetic diversity and the lowest genetic load. The short ROHs and close genetic affinity to an individual from Kenya support the view that wild dogs historically functioned as a largely panmictic species, and that reconnecting isolated populations can restore evolutionary potential. The absence of drift and relaxed selection implies that genetic resilience can be restored through population admixture, providing valuable guidance for managing threatened species.

Antimicrobial resistance (AMR) is a growing threat to child health in low- and middle-income countries (LMICs), where inadequate antibiotic access frequently causes morbidity and mortality. We sought to identify effective interventions to optimize antibiotic use in children with suspected infections in LMIC ambulatory healthcare settings. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Infectious Disease Group Specialized Register, Web of Science, PsycInfo, WHO library database (WHOLIS) and regional databases (inception until 16 December 2024) were searched to identify studies of interventions to optimize antibiotic use in children in LMIC peripheral healthcare settings. Our search identified 7154 articles post de-duplication; 23 studies met the inclusion and Integrated quality Criteria for the Review of Multiple Study designs (ICROMS) assessment criteria. Seventeen were randomized trials, conducted in five LMICs, four upper-middle income countries (UMICs) and two low-income countries (LICs). Single-intervention studies investigated electronic algorithms ( Initial evidence suggests that algorithmic decision-support tools combined with point-of-care diagnostics and provider education can reduce antibiotic prescribing in children attending ambulatory healthcare settings in LMICs, with most studies demonstrating no compromise of clinical outcomes. However, few studies assessed prescription appropriateness or microbiological outcomes, limiting conclusions about long-term impact. Future interventions should prioritize context-adaptable strategies that incorporate rapid diagnostics, evaluate clinical and appropriateness outcomes, and consider implementation feasibility across diverse LMIC settings.

Syphilis diagnosis in resource-limited settings relies on syndromic management and treponemal-based antibody screening tests that cannot distinguish active infection from past-treated infection, both of which can lead to overtreatment. Point-of-care (POC) tests that detect active infection could reduce unnecessary treatment. We developed an agent-based model of co-transmitting syphilis and human immunodeficiency virus, calibrated to Zimbabwe using population-based survey data (ZIMPHIA) and UNAIDS estimates. We modeled five scenarios involving two hypothetical new POC diagnostic products introduced from 2027: (1) a test detecting Treponema pallidum DNA in genital ulcer specimens, and (2) a non-treponemal test identifying active infection following a treponemal-positive result, applied across antenatal care, key population, and human immunodeficiency virus care settings. We also conducted a threshold-based cost analysis to assess whether reductions in unnecessary treatment alone could be cost-saving. Under the current standard of care, approximately 112,000 adult syphilis treatments are administered annually across all modeled detection and screening use cases, of which approximately 80% are unnecessary (i.e., administered to individuals who do not have an active syphilis infection). Combining both diagnostics reduces overtreatment to 24% (a 3.4-fold reduction). Across use cases, each test avoids approximately 0.4 to 0.8 unnecessary treatments, implying cost savings whenever the test price is less than 40% to 80% of the treatment cost. Even under the conservative assumption that current syndromic management and screening practices achieve high syphilis treatment rates among care-seeking individuals, introducing POC diagnostics for active syphilis could substantially reduce overtreatment while maintaining treatment of individuals with active infection. Reductions in unnecessary treatment alone may be cost-saving at low test prices, even without accounting for downstream health outcomes. This analysis does not model the impact of improved diagnostics on transmission dynamics, congenital syphilis burden, or other health outcomes; studies that quantify these additional benefits are needed to inform a full economic evaluation.

Genomic pathogen surveillance is a powerful tool for public health and research, but is costly and unachievable in low-resource settings. Most sub-genomic typing methods sacrifice resolution whilst remaining costly. We developed "Phylo-Plex", a novel approach that identifies information-rich genomic regions to maximise phylogenetic information whilst minimising the number of regions. Applied to Treponema pallidum and Neisseria gonorrhoeae, we designed a high-resolution multiplex PCR sequencing scheme for lineage tracking pathogens with different extremes of genome variation. For Treponema pallidum, we also designed and evaluated the Phylo-Plex scheme in the laboratory and field settings by sequencing 72 clinical samples using MinION Flongle cells. Our T. pallidum scheme comprising 59 multiplex amplicons achieved high discrimination of fine-scale sublineages comparable to those defined using whole genomes, and demonstrating a qPCR detection limit ≤Ct 32. Variant calls from MinION amplicon sequencing were highly correlated with Illumina whole genome sequencing. We successfully deployed the method in a low-resource laboratory in Zimbabwe, costed at <£300/24 samples (£12.47/sample). Phylo-Plex enables low-cost tracking of priority pathogenic lineages in low resource settings and at scale.

Wastewater antimicrobial resistance (AMR) surveillance is limited in many low- and middle-income countries where wastewater infrastructure is absent or inadequate. Surface water may provide an alternative for AMR surveillance in such settings. We investigated the resistome, virulome, and phylogenetic relationships of ESBL-producing Escherichia coli (ESBL-Ec) from surface water (SW), healthy residents (HR), and a clinical facility (CL) to determine whether SW isolates reflect human-associated AMR. During an eight-month longitudinal study in South Africa, 95 ESBL-Ec isolates (SW = 32, HR = 32, CL = 31) underwent whole-genome sequencing. Bioinformatics was used to characterise antimicrobial resistance genes (ARGs), virulence genes, sequence types (STs), phylogroups, and phylogenetic relationships. Seven phylogroups and 21 STs were identified. Phylogroups A, B1, and D and STs 10 and 38 occurred across all sources. Several clinically important lineages, including ST131, were shared between SW and HR isolates; no ST was unique to clinical isolates. Phylogenetic analysis revealed predominantly ST-driven clustering, with SW isolates showing greater similarity to HR isolates than to clinical isolates. Forty-five ARGs were detected, including 12 β-lactamase genes. bla

Sorghum is an important crop in sub-Saharan Africa sustaining many livelihoods. However, despite its importance, sorghum continues to have limited research attention and priority and is categorized as one of the Neglected and Underutilised Species. The paucity of current information on genetic diversity and structure of sorghum accessions being cultivated, improved, introduced, and or conserved across east and southern Africa remains limited. Ex situ genetic diversity and population structure for 177 sorghum accessions from diverse sources was studied using high throughput Diversity Array Technology markers. A total of 15,220 DArTseq SNP markers were generated with over 90% call rate and 95% reproducibility. DArTseq SNP markers had an average polymorphic information content of 0.21 indicating the discriminatory power of DArTSeq markers. Genetic relationships estimated using discriminant analysis of principal components and ancestry coefficients revealed eight populations. Observed heterozygosity was lower than the expected heterozygosity across populations with a mean inbreeding coefficient (F

Despite a significant decline in the incidence of neonatal sepsis, the clinical imperative to avoid missing life-threatening infection continues to drive widespread antibiotic overprescription. Antimicrobial stewardship is universally recognized and explicitly mandated within the UK 2024-2029 National Action Plan on Antimicrobial Resistance as a critical mechanism to combat resistance and prevent iatrogenic harms related to infant dysbiosis. However, a major misalignment exists within the current evidence base: most of the neonatal stewardship research is conducted in highly resourced, tertiary Neonatal Intensive Care Units (Level 3), even though most postnatal inpatient care occurs in Special Care Baby Units (Level 1) and Local Neonatal Units (Level 2). This Viewpoint explores the operational and structural barriers that limit the transferability of intensive-care stewardship models to lower-acuity settings, identifies key research gaps around baseline prescribing practices and multidisciplinary collaboration, and argues for the inclusion of Level 1 and 2 populations in future validation studies of emerging diagnostic tools for neonatal sepsis.

Coffee is a major export earner for Uganda, raking in over USD 2 billion in 2025. The global price of coffee is tagged to the perceived quality in the cup which in turn is affected by the chemical composition of the green bean. Breeding for market-preferred Arabica coffee varieties is a major objective of coffee breeding programs. Determination of coffee bean chemical constituents is routinely done through expensive, slow and tedious laboratory procedures, making it unsustainable of resource-limited public sector coffee breeding programs. Here, we demonstrate the use of near-infrared spectroscopy (NIRS) and the machine learning algorithms partial least squares (PLS), random forest (RF) and support vector machine (SVM) for the prediction of caffeine, protein and trigonelline in Arabica coffee. NIRS provides a fast, accurate and reliable method of simultaneously predicting multiple sample constituents. Ripe coffee cherries were picked from 172 farmers' fields, air dried in the laboratory at room temperature and processed to green beans. NIRS spectra were taken on the milled green bean at 400-2500 nm, with a 0.5 nanometer (nm) step. Reference data for caffeine, protein and trigonelline were collected on the same sample scanned with NIRS. A set of 12 spectral pretreatments were applied prior to making calibrations with the PLS, RF and SVM algorithms and 70% of the data as a training set and 30% as a test set. Caffeine content of reference samples ranged from 1.94-3.0 g/100 g, protein content ranged from 11.16-15.94% while trigonelline ranged from 0.94-1.23 g/100 g. The best calibrations for all algorithms and analytes were obtained using raw (untreated) spectra, which gave the same results as the Savitzky-Golay (SG) pretreatment. For caffeine, the best model (R