Smoother: on-the-fly processing of interactome data using prefix sums.

Nucleic acid interactome data, such as chromosome conformation capture data and RNA-DNA interactome data, are currently analyzed via pipelines that must be rerun for each new parameter set. A more dynamic approach is desirable since the optimal parameter set is commonly unknown ahead of time and rerunning pipelines is a time-consuming process. We have developed an approach fast enough to process interactome data on-the-fly using a sparse prefix sum index. With this index, we created Smoother, a flexible, multifeatured visualization and analysis tool that allows interactive filtering, e.g. by mapping quality, almost instant comparisons between different normalization approaches, e.g. iterative correction, and ploidy correction. Further, Smoother can overlay other sequencing data or genomic annotations, compare different samples, and perform virtual 4C analysis. Smoother permits a novel way to interact with and explore interactome data, fostering comprehensive, high-quality data analysis. Smoother is available at https://github.com/Siegel-Lab/BioSmoother under the MIT license.

High carrier frequency of CYP21A2 gene mutations in Southern India - underscoring the need for genetic testing in Congenital Adrenal Hyperplasia.

PURPOSE: Congenital Adrenal Hyperplasia (CAH) is one of the highly prevalent autosomal recessive endocrine disorders. The majority of CAH cases result from mutations in the CYP21A2 gene, leading to 21-hydroxylase deficiency. However, with the pseudogene-associated challenges in CYP21A2 gene analysis, routine genetic diagnostics and carrier screening in CAH are not a part of the first-tier investigations in a clinical setting. Furthermore, there is a lack of data on the carrier frequency for 21-OH deficiency. Therefore, this study is aimed at investigating the carrier frequency of common pseudogene derived CYP21A2 mutations in Southern India. METHODS: Recently, a cost-effective Allele-specific PCR based genotyping for CYP21A2 hotspot mutations has been demonstrated to be a highly specific and sensitive assay at the authors' center. Leveraging this approach, a total of 1034 healthy individuals from South India underwent screening to identify the carrier frequency of nine hotspot mutations in the CYP21A2 gene. RESULTS: In this study, it was observed that 9.76% of the subjects were carriers for one or more of the nine different CYP21A2 mutations. Among the carriers, the most common was the large 30 kb deletion, followed by II72N, E6 CLUS, and I2G mutations. CONCLUSION: We have identified a high prevalence of CYP21A2 mutation carriers in Southern India. These findings emphasize the importance of implementing and expanding cost-effective genetic diagnostics and carrier screening throughout India. Such initiatives would play a crucial role in managing the disease burden, enabling early intervention, and establishing guidelines for CAH newborn genetic screening in the country. This study represents the first carrier screening data on CYP21A2 hotspot mutations from India and is the largest study conducted till date in this context.

Acute Encephalitis Syndrome in Children and Adolescents: A Five-Year Descriptive Study From South India.

OBJECTIVE: Acute encephalitis syndrome (AES) in children results in significant neurocognitive deficits or mortality. It is pertinent to study the AES patterns periodically to identify the changes in the etiological trends and outcomes. Our objective was to find the etiological agents of AES, mode of diagnosis, treatment given, and outcomes. METHODS: We reviewed the electronic records of children aged 1 month to 15 years who were admitted with AES in our centre from January 2015 to December 2019. We analyzed the the clinical, laboratory, and radiological profile of these children and adolescents in relation to their outcome. Poor outcome was defined as death, discharge against medical advice with neurological deficits, or Glasgow Outcome Score Extended (GOS-E) d≤ 5 at the time of discharge. RESULTS: Among 250 patients admitted with AES during the study period, a definitive etiological diagnosis was established in 56.4% of children (30.4% viral, 22% bacterial). Scrub typhus (11.2%) and dengue (9%) were the two most common underlying illnesses. Serology helped in clinching the diagnosis in 30% of children. A surge in AES cases in the post-monsoon season was observed in our cohort. Third-generation cephalosporin drugs (85.7%) and acyclovir (77.7%) were the most commonly used empiric antimicrobial drugs. About one-third of children (n = 80) had a poor outcome. GCS ≤ 8 at presentation and requirement for invasive ventilation were found to be significant predictors of poor outcome. CONCLUSION: A definitive diagnosis was obtained in about half of the children with AES. Viral (30.4%) and rickettsial infections (22%) were the common etiologies identified. Poor outcome was observed in 32% of patients.

Carcinoma Cuniculatum, a Rare Variant of Oral Squamous Cell Carcinoma: Presentation of Five Clinical Cases and Review of the Literature.

Background: Oral carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma. It exhibits a locally aggressive behaviour, and its histopathology poses a diagnostic challenge, as it can be mistaken for other conditions. We present five cases of oral CC treated at our institution and conduct a comprehensive review of the current literature. Case Series: Five patients (two women and three men) were treated in our institution with a final diagnosis of oral CC. Ages ranged from 9 to 85 years at the time of diagnosis. Four patients had mandibular involvement requiring mandibulectomy and reconstruction using an osseous free flap. The diagnosis of oral CC was straightforward in the most recent cases. However, for the first two cases, the diagnosis of oral CC was established after thorough discussions between the surgeons and the pathologist regarding the similarities with recent cases. Consequently, the pathological specimens had to be retrospectively re-evaluated to confirm these diagnoses. Conclusions: Oral CC is a locally aggressive tumour that can present a challenge for pathologists, often leading to misdiagnosis. According to the existing literature, surgical resection with clear margins is the preferred treatment approach.

RNA polymerase III is involved in regulating Plasmodium falciparum virulence.

While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity have been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here, we present evidence that RNA polymerase III (RNA Pol III) transcription in Plasmodium falciparum is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between P. falciparum cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified P. falciparum Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and for responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of P. falciparum virulence. Furthermore, they establish a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.