Molecular surveillance of Plasmodium falciparum histidine-rich protein 2/3 gene deletions in Mozambique, 2023.

Background: Rapid diagnostic tests (RDTs) based on the detection of Plasmodium falciparum histidine rich protein 2 (PfHRP2) are widely used for the diagnostic of P. falciparum in Africa. However, deletions of the pfhrp2 and pfhrp3 genes can lead to false negative test results and compromise appropriate case management.

Association of Low Protein-to-Carbohydrate Energy Ratio with Cognitive Impairment in Elderly Type 2 Diabetes Patients.

Background/objectives: The relationship between macronutrient intake and cognitive decline in older adults with type 2 diabetes mellitus (T2DM) remains underexplored.

Methods: This cross-sectional study aimed to evaluate the association between the protein-to-carbohydrate energy ratio (%E:P) and cognitive impairment among 192 elderly T2DM patients. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Self-Administered Gerocognitive Exam (SAGE), while dietary intake data, including (%E:P), was gathered using a validated semi-quantitative food frequency questionnaire.

molecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol.

Introduction: Malaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023-2030) for malaria control and elimination.

Methods And Analyses: This prospective genomic surveillance study aims to generate genetic data to monitor diagnostic failures due to deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination).

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

An and efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs.

Adrenomyeloneuropathy is a progressive neurodegenerative disease caused by pathogenic variants in the gene, resulting in very-long-chain fatty acid (VLCFA) accumulation that leads to dying-back axonopathy. Our candidate gene therapy, SBT101 (AAV9-human [h]), aims to ameliorate pathology by delivering functional copies of h to the spinal cord. Transduced cells produce functional ABCD1 protein, thereby repairing the underlying biochemical defect.

Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.

Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families.

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age.

Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique.

Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes.

Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.

Objective: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD.

Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma.

Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils × monocytes × platelets)/lymphocytes, has been proposed as a prognostic biomarker in different tumour models. The aim of this study is to analyse the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Retrospective study of 1187 patients with HNSCC treated at our centre between 2000-2017.

External validation of the GETTEC algorithm for elective neck dissection in patients candidates for salvage total laryngectomy.

Objective: To perform an external validation of the algorithm for elective treatment of the lymph node areas proposed by GETTEC for patients candidates to salvage total laryngectomy after radiotherapy. This algorithm is based on the initial lymph node status, local extension of the recurrence and time to recurrence.

Material And Methods: Retrospective study performed in 151 patients treated with salvage total laryngectomy without clinical or radiological evidence of regional involvement at the time of diagnosis of recurrence (rcN0).