Baobab Index

Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by upper limb and congenital heart anomalies, with an estimated incidence of 1 in 100,000 live births. An 18-year-old Ethiopian male with a history of congenital heart disease presented with progressive dyspnea and limb deformities. Imaging confirmed a membranous ventricular septal defect, severe pulmonary hypertension, mitral and tricuspid regurgitation, and skeletal anomalies, including thumb hypoplasia and absent distal radial bone. This case underscores the importance of early diagnosis and multidisciplinary management of HOS, especially in resource-limited settings where genetic testing is unavailable. Increased awareness can facilitate timely intervention and improve patient outcomes.

Molecular surveillance is essential to detect emerging artemisinin partial resistance (ART-R) and partner drug resistance in Sub-Saharan Africa. To describe the prevalence of Plasmodium falciparum resistance markers in two high-burden countries using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL): the Democratic Republic of the Congo (DRC) and Tanzania. A total of 1254 day-0 P. falciparum-positive samples were analysed: 837 from four sentinel sites of a therapeutic efficacy study (TES) in the DRC (2017) and 417 from an intermittent preventive treatment in schoolchildren (IPTsc) trial in Handeni and Kilindi districts, Tanga Region, Tanzania (2020-2021). Pfkelch13, Pfcrt and Pfmdr1 were analysed by Illumina MiSeq amplicon sequencing. Reliable sequences were obtained for 1193 isolates. The Pfkelch13 wild-type allele predominated (98.4%); none of the four non-synonymous mutations detected (N489Y, K568T, A578S, V589I) are classified as validated, candidate or potential ART-R markers, and the validated markers R561H, P441L and C469Y reported elsewhere in East Africa were absent. Pfcrt K76T was found in 23.3% of Tanzanian and 26.3% of DRC isolates, with substantial between-site variation in the DRC (4.3% to 93.6% at Rutshuru). Pfmdr1 haplotype profiles differed between countries: NFSND predominated in Tanzania (71.5%) while NYSND remained the most frequent in the DRC (60.9%); 86Y was twice as frequent in the DRC (11.1%) as in Tanzania (6.2%). No validated ART-R marker was detected, but partner-drug haplotype distributions reflected the first-line ACTs used in each country. Continued molecular surveillance is needed to track these signatures alongside the recent emergence of ART-R.

Precision medicine requires computational methods that can integrate genomic, transcriptomic, proteomic, metabolomic, epigenomic, single-cell and spatial measurements into decisions about individual patients, and artificial intelligence has become the enabling technology for doing so. This review argues that the binding constraint is no longer modelling capability but validation, calibration and governance. We compare seventeen multi-omics integration algorithms on the sample sizes they actually require and on whether independent groups have reproduced them; we set classical machine learning against deep learning by omics task and sample-size regime, and find that penalised regression and tree ensembles remain competitive wherever the number of samples is small relative to the number of features. We then examine seven documented failures of deployed clinical artificial intelligence, trace each to its root cause, and derive an eighteen-item appraisal checklist adapting existing reporting and risk-of-bias instruments to the failure modes of molecular data. Calibration, uncertainty quantification, batch effects and information leakage are treated as first-class problems rather than caveats. To show what leakage costs, we analysed 696 breast tumours with matched transcriptomic and copy-number profiles under randomly permuted labels, where the only honest result is chance. A pipeline that selects features before splitting the data reports an area under the receiver operating characteristic curve of 0.95 in cohorts of forty and 0.65 on the full cohort; the corresponding leak-free pipeline returns 0.50 at every size. What limits clinical adoption is the evidence a model can be held to, not the sophistication of the model.

Tuberculosis (TB) remains the deadliest infectious disease in humans; however, a robust immune response can either protect against or control the infection. Household contacts of TB patients can remain uninfected for decades, while a quarter of the world's population that is latently infected can remain healthy for years. Characterization of the effectors of such an immune response would help in developing novel host-directed tools to better treat and/or prevent TB. IL-6 is a crucial cytokine that plays a central role in orchestrating a protective TB immune response; however, a delicate balance between its beneficial and detrimental effects must be maintained to effectively control the infection. Here, we aimed to characterize the cellular effectors that regulate IL-6 expression in mycobacteria-infected cells. We used PI3K and AKT inhibitors, as well as FOXO3-specific siRNA, to modulate FOXO3 activity in BCG-infected macrophages and assessed the effect on IL-6 expression. Reporter gene assays were performed using four IL-6 promoter constructs (-600 bp, -900 bp, -1.5 kb, and -2 kb). The PI3K/AKT/FOXO3 axis regulates IL-6 expression in human macrophages: FOXO3 activation (via PI3K or AKT inhibition) induced IL-6 expression, while FOXO3 silencing reduced IL-6 production in BCG-infected macrophages. FOXO3 positively regulated IL-6 promoter activity across all cloned fragments, with the strongest effect at -1.5 kb; extension to -2 kb modulated this FOXO3-mediated induction. We report for the first time that FOXO3 exerts both positive and negative regulation of IL-6 transcription, fine-tuning its expression in mycobacteria-infected macrophages. Together with our previous report on FOXO3-mediated suppression of IL-10, these results highlight the crucial role of FOXO3 in the TB immune response and support targeting the PI3K/Akt/FOXO3 axis as a host-directed approach to improve TB treatment and prevention.

A wide range of behavioral phenotypes has been described in PWS patients including autism spectrum disorder (ASD). The prevalence of behavioral disorders was studied in 292 participants over 3 years with genetically confirmed PWS (N = 164 females and N = 128 males) with deletion (N = 182) and mUPD (maternal uniparental disomy) (N = 99). The prevalence of ASD, and other behavioral disorders was tested for association with gender, genetic subtypes, and growth hormone (GH) treatment. The prevalence of ASD in PWS individuals was 19.5%, in concordance with previous studies at 25%. The frequency of ADHD was 10.7%. The mean age at diagnosis for ASD, ADHD, and disruptive behavior was 14.9 ± 10.5, 9.3 ± 5.9, and 19.6 ± 14 years, respectively. There was no statistically significant difference in the prevalence of ASD and ADHD between deletion and UPD subjects, and between GH-treated and non-treated subjects. Patients with mUPD had higher frequencies of anxiety than those with deletions (p = 0.001). GH-treated participants had a lower frequency of depression and a higher frequency of anxiety than non-treated participants (p = 0.04, p = 0.02, respectively). This is the largest study to evaluate an association between genetically confirmed PWS and ASD. We found no significant differences in the frequency of ASD and other behavioral disorders across the genetic groups and GH treatment.

The olive oil industry produces large volumes of by-products which, if not properly managed, can negatively impact water resources, aquatic ecosystems, soil quality, and the atmosphere. The extraction process generates several by-products that have previously been regarded as waste. Utilizing these residues as alternative feed ingredients aligns with the principles of a circular economy, making the agri-food system more sustainable, conserving natural resources, and reducing the environmental footprint of livestock production. Therefore, the proper use of industrial by-products is of great importance and requires continuous attention. Olive pomace, a major by-product of olive oil extraction, can be used in animal feed as an inexpensive yet nutritious residue. It consists mainly of pasty pulp, kernel, skin, and vegetation water. Once dried, it becomes a stable by-product suitable for feed use. Olive by-products can be incorporated into animal diets in several forms, such as fresh, ensiled, or dried material, or as components of concentrate pellets and multi-nutrient feed blocks. Among these, dried olive pomace is considered one of the most practical and stable options. Olive pomace, as a by-product of the olive oil industry, is rich in phenolic compounds and beneficial fatty acids that play significant roles in animal health and productivity. Hence, it is crucial to evaluate its potential as a feed ingredient; however, current understanding of its specific effects on livestock production remains limited. This review focuses on the influence of olive pomace inclusion in animal diets on milk production, growth performance, nutrient digestibility, feed efficiency, and overall health status. In general, dietary olive pomace has shown satisfactory results, serving as a low-cost nutrient source that can enhance both the productivity and the quality of animal-derived products.

Cholera outbreaks remain a major public-health challenge in sub-Saharan Africa, where diagnostic capacity is limited and clinical case definitions are non-specific and re ly heavily on syndromic diagnosis. Rapid identification of Vibrio cholerae is critical, yet cholera-suspected diarrhoea can have multiple infectious causes not captured by targeted diagnostics. We evaluated a mobile, culture-independent metagenomic sequencing workflow for on-site detection of gastrointestinal pathogens directly from faecal samples in Burundi. The offline workflow combined long-read Oxford Nanopore Technologies (ONT) sequencing with rapid, laptop-based taxonomic and antimicrobial resistance (AMR) screening and was deployed across a health centre, a district hospital, and a refugee transit camp. The frontline and real-time results were verified using both conventional culturing and in-depth bioinformatic analyses. V. cholerae signals were only detected in a subset of suspected cholera cases, while many samples were dominated by alternative bacterial taxa, most frequently Escherichia coli. V. cholerae abundance correlated strongly with detection of the C holera T oxin P hage CTXφ, supporting differentiation between toxigenic signal and background exposure. AMR genes were detected across samples, providing early situational insight into resistance determinants among gastrointestinal bacteria. Mobile, offline metagenomic sequencing enables rapid frontline characterization of gastrointestinal disease, especially cholera-suspected, in resource-limited settings and complements existing diagnostics by improving etiological resolution and outbreak response.

Rice is facing attacks from emerging diseases caused by fungi of the

A significant proportion of individuals with suspected genetic developmental and epileptic encephalopathies (DEEs) remain unsolved following whole genome sequencing (WGS). Here we describe biallelic RNU2-2 variants causing a recently reported, severe, recessive DEE. We screened individuals who have received WGS analyses at the Genomic Medicine Centre Karolinska for Rare Diseases for biallelic RNU2-2 variants. Deep phenotyping was performed through reviewing entire medical histories and phenotypic traits were transcribed to their corresponding Human Phenotype Ontology (HPO) term. HPO terms were used to generate pairwise phenotypic similarity scores and assess for significantly shared phenotype enrichment in the RNU2-2 sub-cohort. RNA sequencing analyses were performed in fibroblast and blood tissues to compare splicing events between RNU2-2 individuals and two independent control groups. We identified 14 individuals from nine families with 12 ultra-rare biallelic RNU2-2 variants clustering in the conserved 5' domains. Genotype data from 13 of 14 individuals has been reported previously as part of a larger cohort. All individuals presented with a highly concordant, severe DEE, characterized by severe to profound intellectual disability, inability to walk or communicate, hyperkinesia, and refractory seizures. Infantile spasms and tonic seizures were the predominant seizure types and a Lennox-Gastaut syndrome-like phenotype was common. These individuals had a significantly similar phenotypic signature when compared with 703 individuals with complex pediatric epilepsies (two-sided Monte Carlo permutation test, p = .005). RNA sequencing analyses showed aberrant splicing, with the most pronounced effects in fibroblast tissues in mutually exclusive exon and alternate 3' splice-site events, which were not detectable in blood. We present deep phenotyping data and transcriptomic analyses that provide support for rare, 5' clustering biallelic RNU2-2 variants causing this novel, severe DEE. We propose an RNA sequencing methodology on fibroblast tissue for future validation of RNU2-2 variants.