Baobab Index

Leukodystrophies are rare inherited neurodegenerative disorders characterized by progressive white matter dysfunction and neurological decline. In low-resource settings, limited access to advanced neuroimaging, biochemical investigations, and genetic testing often delays diagnosis and complicates differentiation from more common infectious, nutritional, and hematological conditions. We describe a 16-month-old boy who presented with lower limb weakness, irritability, feeding difficulties, and skin abnormalities during an acute respiratory infection. Initial evaluation raised differential diagnoses including tuberculosis, lymphoma, and leukemia because of overlapping clinical and laboratory features. Neuroimaging demonstrated bilateral periventricular white matter abnormalities and frontotemporal atrophy suggestive of leukodystrophy, with the clinical and radiologic presentation being compatible with suspected metachromatic leukodystrophy (MLD). Subsequent exome sequencing identified a variant in the fructose-1,6-bisphosphatase 2 (FBP2) gene associated with childhood-onset leukodystrophy. However, definitive biochemical and molecular confirmation for MLD, including ARSA enzyme activity, urinary sulfatide analysis, and ARSA/PSAP sequencing, was not available. The patient showed partial clinical improvement following supportive management, including treatment for intercurrent infection and vitamin D deficiency. This case highlights the diagnostic challenges of suspected leukodystrophies in under-resourced environments, where clinical suspicion often exceeds available diagnostic capacity. Furthermore, it underscores the global disparity in access to specialized metabolic and genetic testing, emphasizing the need for improved multidisciplinary collaboration and expanded diagnostic infrastructure to support timely diagnosis, counseling, and management of rare neurological disorders.

Cancer genomics and precision oncology are increasingly central to cancer care, but many health systems struggle to implement them equitably, effectively, and sustainably. This Commission defines the current global precision oncology landscape and analyses the scientific, structural, and health-system challenges shaping its delivery and impact. Findings indicate that access to cancer genomics and precision oncology remains profoundly unequal across and within countries, leaving millions of patients without guideline-indicated interventions each year. These disparities extend to research, with genomic studies and clinical trials concentrated in high-income settings and among populations of predominantly European ancestry. At the same time, fragmented and poorly integrated data ecosystems restrict evidence generation, knowledge sharing, and clinical impact. Beyond questions of access and implementation, the clinical benefit of precision oncology is highly heterogeneous. The greatest and most consistent gains are confined to a few well validated biomarker-treatment pairings, typically supported by companion diagnostics; broader approaches such as comprehensive genomic profiling and tumour-agnostic strategies, might expand options for selected patients, but only a few patients receiving matched therapy derive meaningful benefit. The Commission also identifies a paradox of success: rapid expansion of precision oncology has increased cognitive, organisational, data, workforce, and financial burdens, while evidence of broad population-level benefit has lagged behind. In response, the Commission offers a comprehensive and context-responsive approach for integrating cancer genomics and precision oncology into health systems effectively, equitably, and sustainably. The Commission developed a value-based resource-stratified implementation framework, a system-readiness assessment tool, a precision oncology workforce competency-based framework, a precision oncology monitoring and evaluation framework, and principles for responsible data sharing and health-system learning. Cancer genomics and precision oncology can improve outcomes and strengthen health systems if scaled equitably, sustainably, and according to evidence, public value, national context, and patient needs. This Commission offers a basis for global consensus on a more equitable, evidence-informed, and sustainable path forward.

Extracellular adenosine 5'-triphosphate (ATP) has been recognized for many years as a prototypical danger signal that promotes inflammation primarily through activation of purinergic receptors, particularly P2X7. This framework has had a massive influence on how immunology, cancer biology, and autoimmunity are now conceived. Nonetheless, increasing experimental and clinical observations do not support the simple, unidimensional model of ATP as a pro-inflammatory mediator; instead, they suggest that, depending on the concentration, timing, receptor context, and cellular status, ATP may have strong immunosuppressive/tolerogenic effects. Prolonged ATP signalling has increasingly been implicated in immune effector fatigue during chronic inflammation, cancer, and sustained infection, which dampens down immune stimulation rather than augmenting it. In this narrative review, we critically examine published evidence supporting the context-dependent effects of extracellular ATP and discuss how receptor expression, ATP concentration, exposure duration, nucleotide metabolism, and cellular state may shape immune responses in cancer and autoimmune disease.

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that couple chromatin acetylation to oncogenic and immune-regulatory gene transcription, making them attractive targets for combination with immune checkpoint inhibitors (ICIs) in precision oncology. This review synthesizes current mechanistic, medicinal-chemistry, and translational evidence on BET-ICI combination strategies. We describe how BET blockade reshapes tumor chromatin architecture, suppresses

Advances in high-throughput DNA sequencing technologies have accelerated research on aquatic microorganisms, their diversity, and ecological functions. This has also significantly advanced research on fungi that shape aquatic ecosystems and food webs. Here, we present the FunAqua dataset, which describes global fungal biodiversity in aquatic ecosystems based on eukaryotic long-read metabarcoding data from 1,076 sediment and 1,299 filtered water samples collected across 1,452 sampling sites in 87 countries. We targeted the internal transcribed spacer (ITS) region. In total, 50,152 fungal OTUs were recorded. The sequencing data is accompanied by comprehensive sample metadata, including physicochemical data of water and sediments. The FunAqua dataset provides a new resource for analysing and better understanding the biodiversity of fungi in different types of aquatic habitats across biogeographical regions. The dataset described in this data paper will be periodically updated with additional metabarcoding data.

Paragonimiasis is a neglected food-borne trematode infection endemic to parts of Africa, Asia, and the Americas acquired by raw/undercooked freshwater crab consumption. Pulmonary manifestations mimic pulmonary tuberculosis (TB). Diagnosis relies on microscopy, with low sensitivity. Development of molecular assays is constrained by an absence of genomic data for African Paragonimus species. Serological testing depends on crude worm antigen, resulting in restricted availability and reproducibility. This study was nested within a prospective cohort of adults with presumed TB in Lambaréné, Gabon. The reference standard for paragonimiasis consisted of sputum and stool microscopy. Molecular index tests included PCRs (ITS2, cox1) on sputum and stool, followed by sequencing. Serological index tests consisted of recombinant ELISAs using GST-tagged Myo-1, MDP, and Egg antigens. Diagnostic accuracy was evaluated using positive control sera (three individuals with confirmed P. westermani infection). Stool, urine and blood were examined for potentially serologically cross-reactive parasites. Among 103 participants (enrolled September 2024-January 2025), no Paragonimus eggs were detected. PCR assays amplified only non-Paragonimus sequences, including other helminths. Control sera (confirmed P. westermani) showed marked reactivity, particularly toward Myo-1 and Egg antigen, background reactivity in participants was generally low. Without confirmed cases of African paragonimiasis, we could only calculate analytical sensitivity for P. westermani-sera. Exploratory cut-offs resulted in tentative diagnostic sensitivity between 17 and 100%. Exploratory cut-offs yielded specificities of 76-100%, assuming that no infections were missed by the reference standard. No relevant cross-reactivity with other infections was observed. In this first real-life application of recombinant antigen-based ELISAs for the serodiagnosis of paragonimiasis, our results showed promise, particularly for Myo-1 and Egg antigen. These results require further validation in larger and diverse populations including cases with African Paragonimus species to better define the epidemiology and burden of paragonimiasis in Gabon and beyond.

Monozygotic (MZ) twins are expected to share nearly identical genomes, yet a substantial proportion is discordant for complex diseases like nonsyndromic orofacial clefts (nsOFC). This suggests a role for postzygotic discordant genetic variations and other developmental mechanisms. In this study, we performed whole genome sequencing of two MZ twin pairs of African ancestry who were discordant for nsOFC to identify genetic variants that may contribute to phenotypic discordance. Following quality control and genotype-level filtering, we identified 37,271 variants that were present exclusively in the affected twins. Of these, 431 variants were predicted by CADD to have deleterious effects. Among these, 66 were in protein-coding regions, including 2 predicted protein-altering missense variants and splice-site variants. The remaining 365 variants were in noncoding regions including putative craniofacial enhancers. Some of these variants are rare (MAF < 0.01) and were predicted to alter transcription factor binding or disrupt local chromatin architecture within putative craniofacial enhancers located near genes with established roles in craniofacial development, including

Actinomycetoma is a neglected tropical disease characterized by large tumorous lesions. It is caused by actinomycetes belonging to the genera Actinomadura, Nocardia and Streptomyces. Despite the differences between these genera and species, all actinomycetoma cases are treated with the same antibiotics. It is currently not known if the actinomycetoma causative agents have similar susceptibility patterns against these antibiotics. We therefore set out to determine the MICs for the most common causative agents against commonly used antibiotics. We used the standard in vitro susceptibility method from the CLSI to assess the antimicrobial susceptibility of 94 actinomycete isolates belonging to the Actinomadura, Nocardia and Streptomyces genera and associated with actinomycetoma against 12 antibiotics. The molecular basis behind the reduced susceptibility was further explored using the genomes of the isolates. All isolates were highly susceptible to linezolid (100%), amikacin (98.9%) and trimethoprim/sulfamethoxazole (87.2%). For amoxicillin/clavulanate and rifampicin, species-dependent susceptibility was noted. We found that 55% of Actinomadura madurae isolates, 61.5% of Nocardia brasiliensis isolates and 100% of Streptomyces somaliensis and Streptomyces sudanensis were susceptible to amoxicillin/clavulanate. All A. madurae, Actinomadura pelletieri and N. brasiliensis isolates were resistant to rifampicin, whereas all S. somaliensis and S. sudanensis isolates were susceptible. This was most likely due to amino acid differences in the RpoB gene. Clear differences in antimicrobial susceptibility patterns were noted for the different actinomycetoma causative agents, indicating that actinomycetoma treatment should be tailored to the causative agent.

Enterococcus species are clinically important opportunistic pathogens capable of acquiring and disseminating antimicrobial resistance (AMR). Although vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci (LRE) are increasingly reported in human medicine, their prevalence and genomic features in companion animals remain poorly characterized. This study investigated the global distribution and genetic traits of acquired vancomycin and linezolid resistance determinants in enterococci from dogs and cats. Among 32,971 genomes analyzed, 34 carried vanA, optrA, poxtA, and/or cfr. VanA-positive strains were predominantly Enterococcus faecium and were identified in Europe, Oceania, Asia, and South America between 1995 and 2021. All harbored the vanHAX cluster, mainly associated with Tn1546-like transposons. Transferable oxazolidinone resistance genes were identified in 25 strains, mostly Enterococcus faecalis, recovered exclusively from China and the United States between 2015 and 2023. The optrA gene (OptrA variants RDK and KLDK, defined by specific amino acid substitutions) and optrA-fexA genetic context predominated, whereas poxtA and cfr were each identified in a single isolate. One E. faecium strain co-harbored optrA and poxtA. VRE and LRE populations displayed high sequence type diversity, including lineages previously reported in human healthcare settings (ST78 and ST80) and livestock (ST27), as well as novel lineages (ST3090, ST3091, and ST2180). Genomic analyses and literature data indicate that VRE and LRE in dogs and cats remain uncommon but are globally distributed and associated with diverse lineages and mobile resistance platforms shared across human, animal, and environmental reservoirs. Enhanced surveillance is needed to better understand the epidemiology and dissemination of these clinically relevant resistance determinants.

Despite the ubiquity of wild boar populations across Eurasia, their origins, routes of dispersal, and phenotypic evolution remain uncertain. Here, using 745 genomes representing populations across Eurasia, we demonstrate that wild boar expanded from South Asia during the Middle Pleistocene. This expansion was preceded by a Pliocene introgression (~3 to 5 million years ago) in South Asia from an archaic Suinae lineage that introduced a ~43 megabase X-chromosomal haplotype into the ancestral wild boar population. This haplotype includes loci associated with increased body size and adaptation to cold climates. During domestication, this region was selected at least three times independently to develop modern large-bodied breeds. Our findings reveal a long-lasting evolutionary legacy of this ancient introgression, which provided genetic material that was later shaped by natural and artificial selection.