Publications by authors named "Ram Mani"

Article Synopsis
  • PAX2 is identified as an endometrial tumor suppressor frequently inactivated through a unique epigenetic mechanism, rather than promoter hypermethylation.
  • In 80% of endometrial cancers, the loss of PAX2 is linked to transcriptional silencing, which alters chromatin features, contributing to cancer development.
  • The research highlights new pathways for understanding endometrial cancer origins, potentially influencing future diagnosis and treatment approaches.
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Objective: There is conflicting evidence whether decreased clerkship duration is associated with reduced NBME shelf examination performance. We hypothesized that scores would remain stable for students in a shortened 2-week flipped classroom-based virtual rotation as compared to the traditional 4-week Neurology clerkship.

Background: There is conflicting evidence whether decreased clerkship duration is associated with reduced NBME shelf examination performance.

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Background: Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes.

Purpose: This work aimed to ensure brain availability of nalbuphine via the nasal route.

Method: Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised.

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Objective: In recent years, an overwhelming association between Pediatric Type 1 Diabetes Mellitus (T1DM) and autoimmune diseases has been largely reported. The current study was designed to determine a possible association between autoimmune thyroiditis (AIT), celiac disease (CD) - associated autoantibodies, and Parvovirus B19 infection among pediatric T1DM cases in the southwestern region of Saudi Arabia.

Patients And Methods: Blood samples from age groups 1-18 years attending the Diabetic Clinic were collected over a period of 12 months.

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CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear.

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The three-dimensional genome organization influences diverse nuclear processes. Here we present Chromatin Interaction Predictor (ChIPr), a suite of regression models based on deep neural networks, random forest, and gradient boosting to predict cohesin-mediated chromatin interaction strength between any two loci in the genome. The predictions of ChIPr correlate well with ChIA-PET data in four cell lines.

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The dehydration of ethanol into diethyl ether over a SO/SiO catalyst was investigated. The SO/SiO catalysts were prepared by the sulfation method using 1, 2, and 3 M of sulfuric acid (SS1, SS2, and SS3) via hydrothermal treatment. This study is focused on the synthesis of a SO/SiO catalyst with high total acidity that can be subsequently utilized to convert ethanol into diethyl ether.

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Colorectal cancer (CRC) at advanced stages is rarely curable, underscoring the importance of exploring the mechanism of CRC progression and invasion. NOD-like receptor family member NLRP12 was shown to suppress colorectal tumorigenesis, but the precise mechanism was unknown. Here, we demonstrate that invasive adenocarcinoma development in Nlrp12-deficient mice is associated with elevated expression of genes involved in proliferation, matrix degradation, and epithelial-mesenchymal transition.

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CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. loss-of-function alterations confer acquired resistance to CDK4/6i, but the optimal therapy for these patients is unclear.

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Therapy resistance to second-generation androgen receptor (AR) antagonists, such as enzalutamide, is common in patients with advanced prostate cancer (PCa). To understand the metabolic alterations involved in enzalutamide resistance, we performed metabolomic, transcriptomic, and cistromic analyses of enzalutamide-sensitive and -resistant PCa cells, xenografts, patient-derived organoids, patient-derived explants, and tumors. We noted dramatically higher basal and inducible levels of reactive oxygen species (ROS) in enzalutamide-resistant PCa and castration-resistant PCa (CRPC), in comparison to enzalutamide-sensitive PCa cells or primary therapy-naive tumors respectively.

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Targeted therapies, such as endocrine therapies (ET), can exert selective pressure on cancer cells and promote adaptations that confer treatment resistance. In this study, we show that ET resistance in breast cancer drives radiation resistance through reprogramming of DNA repair pathways. We also show that pharmacological bromodomain and extraterminal domain inhibition reverses pathological DNA repair reprogramming in ET-resistant breast tumors and overcomes resistance to radiation therapy.

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Objective: Excessive daytime sleepiness (EDS) is common in patients with epilepsy (PWE). The Epworth Sleepiness Scale (ESS) is a self-reported measure of sleepiness in widespread use. The purpose of this study was to identify contributors to the ESS score in PWE and to identify variables associated with a high score indicative of EDS.

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Prostate cancer is the most commonly diagnosed and frequently occurred cancer in the males globally. The current treatment strategies available to treat prostate cancer are not much effective and express various adverse effects. Hence, there is an urgent need to identify novel treatment that can improve patient outcome.

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Unlabelled: Prostate cancer is one of the most heritable human cancers. Genome-wide association studies have identified at least 185 prostate cancer germline risk alleles, most noncoding. We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors.

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Transcription-coupled cellular stress is associated with several physiological and pathological features, including membraneless biomolecular condensates. In the study by Yasuhara et al., the authors have described specific nuclear condensates in multiple cell types upon inhibition of RNA polymerase II transcription, discovered their main constituent proteins, and elucidated their functions.

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Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is associated with development of resistance to most endocrine therapies used to treat breast cancer. Employing a high-throughput screen of nearly 1,200 Federal Drug Administration-approved (FDA-approved) drugs, we show that OTX015, a bromodomain and extraterminal domain (BET) inhibitor, is one of the top suppressors of ESR1 mutant cell growth.

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FOXA2 encodes a transcription factor mutated in 10% of endometrial cancers (ECs), with a higher mutation rate in aggressive variants. FOXA2 has essential roles in embryonic and uterine development. However, FOXA2's role in EC is incompletely understood.

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The bromodomain and extraterminal (BET) family of chromatin reader proteins bind to acetylated histones and regulate gene expression. The development of BET inhibitors (BETi) has expanded our knowledge of BET protein function beyond transcriptional regulation and has ushered several prostate cancer (PCa) clinical trials. However, BETi as a single agent is not associated with antitumor activity in patients with castration-resistant prostate cancer (CRPC).

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Objective: We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)-resistant vs ASM-responsive outcome for patients with idiopathic generalized epilepsy (IGE).

Methods: This was a case-control study of ASM-resistant cases and ASM-responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient.

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Prostate cancer is a major cause of cancer morbidity and mortality. Intra-prostatic inflammation is a risk factor for prostate carcinogenesis, with diet, chemical injury and an altered microbiome being causally implicated. Intra-prostatic inflammatory cell recruitment and expansion can ultimately promote DNA double-strand breaks and androgen receptor activation in prostate epithelial cells.

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Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019.

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Objective: Obstructive sleep apnea (OSA) is common in patients with epilepsy (PWE), and treatment may improve seizure control. However, OSA is often undiagnosed in PWE, and understanding of the risk profile for OSA is important. In this study, we sought to determine if OSA risk is similar in patients with generalized versus focal epilepsy.

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Article Synopsis
  • Transcriptional dysregulation is a key feature of prostate cancer, involving altered chromatin interactions between various genomic elements.
  • The research identified how structural proteins and master transcription factors, such as the androgen receptor, enhance or alter the regulation of important PCa genes.
  • The findings suggest that changes in genome organization significantly contribute to abnormal transcription regulation, particularly in the context of specific genetic risk factors and gene fusions in PCa.
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Studies employing whole genome and exome sequencing have revealed two remarkable features of prostate cancer (PCa)-the overall low mutation rates, and high rates of genomic rearrangements resulting in recurrent gene fusions. Genomic rearrangements involving the ETS transcription factor family genes are early driver events in PCa. These rearrangements typically involve the fusion of androgen-regulated transcriptionally active genes with the ETS genes (ERG, ETV1, ETV4 and ETV5), resulting in over-expression of fusion genes.

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