Extended sequences for 13 HLA alleles were found which had limited coverage previously.

Cases of imported malaria are reported each year in several malaria non-endemic countries, including Kuwait. PCR testing is the ideal method for identification of the infecting Plasmodium spp. The present study documented the epidemiologic characteristics of molecularly confirmed cases of imported malaria in Kuwait during the first year of COVID-19 pandemic. Malaria diagnosis was made by microscopy of blood-stained smears and confirmed by a multiplex real-time PCR assay. Samples with discordant species identification results were sequenced. A total of 27 cases (27%) [P. falciparum, 14; P. vivax, 11; P. ovale, 1; mixed P. falciparum and P. malariae, 1] were detected, of whom 12 came to Kuwait for the first time and 15 were returning after visiting their home countries. Most of the returning travelers (12 out of 15 cases, 80%) had not received malaria chemoprophylaxis. Most cases of falciparum malaria (13/15) were Africans while most of the vivax cases (9/11) were Asians. Malaria was more common among subjects entering Kuwait for the first time (OR = 4.025, CI 1.07,15.1) and illiterates (OR = 13.8, CI 1.8,101.4). In conclusion, imported malaria caused mainly by P. falciparum and P. vivax was an ongoing problem during the COVID-19 pandemic. Travel history and education level were significant predictors of malaria among suspected cases.

The study analyzed the outcomes of comprehensive genetic testing in patients at a multidisciplinary inherited heart disease clinic in India from August 2017 to October 2023. It included 77 subjects (48 probands, 29 relatives) with an average age of 43 years, 68% male, and 44% symptomatic, spanning various conditions such as hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, peripartum cardiomyopathy, congenital long QT syndrome, Brugada syndrome, and Marfan Syndrome. Next-generation sequencing (NGS) was employed, with a 31% diagnostic yield, 54% identifying variants of uncertain significance (VUS), and 15% being genotype-negative. Genetic testing guided follow-up and treatment, with periodic monitoring recommended for genotype-positive and high-risk VUS carriers, while others were discharged from further surveillance. The study highlights the importance of genetic testing in specialized clinics for effective management and family screening in inherited heart diseases.

Recombinant antibodies (rAbs) offer solutions for improving antigen specificity, enhancing immunogenic potential, and enabling versatile functionalization for disease treatment. Single-chain variable fragments (scFvs) have advanced cancer and viral infection therapies due to their favorable pharmacokinetics and human compatibility. However, experimental antibody selection often requires iterative optimization, prompting a shift toward in silico methods. To streamline this process, rAbDesFlow, an open-source computational workflow, was developed. It integrates antigen selection, antibody library generation, structure modeling, interaction analysis, and consensus ranking to identify optimal rAb candidates for experimental validation. Demonstrated in designing rAbs for ovarian cancer antigen Mucin-16 (CA-125), this workflow provides a blueprint for targeting various disease-specific biomarkers.

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.

This study describes the clinical and histopathological characteristics of genetically confirmed congenital myopathies (CMs) in India, aiming to establish phenotype-genotype correlations. A retrospective chart review of patients from January 2016 to December 2020 was conducted, involving 31 unrelated patients (14 males, 17 females) with a median age at onset of 2.0 years and illness duration of 6.0 years. Clinical features included proximodistal weakness (54.8%), facial weakness (64.5%), myopathic facies (54.8%), ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology, available for 38.7%, most frequently showed centronuclear myopathy. Pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%), with novel mutations in 30.3% of the cohort. Follow-up data for 77.4% showed a median duration of 4.5 years and age of 13 years at last follow-up, with most patients ambulant with minimal assistance. Mortality was 8.3%, mainly due to respiratory failure in centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON).

Catalogs of pathogenic mutations in hypertrophic cardiomyopathy (HCM) are limited for the South Asian population despite their higher heart disease risk. This study sequenced 200 HCM patients, finding a 40% yield for pathogenic or likely pathogenic (P/LP) variants, primarily in MYBPC3 and MYH7 genes. Key predictors of positive genetic tests included younger age at diagnosis, family history, specific echocardiographic patterns, and absence of hypertension. MYBPC3 variants were linked to severe outcomes like ventricular tachycardia, while MYH7 variants were associated with specific cardiac dimensions. The study underscores the enrichment of rare P/LP variants and variants of uncertain significance (VUSs) in HCM cases, enhancing targeted genetic testing for this population.

In this study, the authors present an interpretable machine learning model that can classify 13 cancer types and non-cancer tissue samples using only DNA methylome data, achieving 98.2% accuracy. The features identified by this model are utilized to develop EMethylNET, a robust framework consisting of an XGBoost model that informs a deep neural network, capable of generalizing to independent data sets. The authors also demonstrate that the methylation-associated genomic loci detected by the classifier are linked to genes, pathways, and networks involved in cancer, providing insights into the epigenomic regulation of carcinogenesis.

There are limitations with morphology and a felt need for a diagnostic test with a short turn-around time for rapid diagnosis of acute promyelocytic leukemia (APL). To identify a unique protein biomarker in APL, we did a quantitative proteomic analysis on five acute myeloid leukemia (AML), APL and acute lymphoblastic leukemia (ALL) bone marrow mononuclear cells (MNCs) collected at diagnosis in comparison with peripheral blood mononuclear cells from healthy control (HC).

Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. We report a 41% pathogenic/likely pathogenic (P/LP) variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.