Publications by authors named "Shukla N"

The nucleotides play multiple fundamental roles that are essential in biochemical enzymatic reactions and signaling pathways. Many diseases are closely associated with their dysregulation. Therefore, reliable and sensitive optical probes to discriminate various nucleotides are essential in biochemistry, drug discovery, and disease diagnosis.

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Herein we present a series of luminescent Tb(III)-probes ([Tb-Ltrp], [Tb-Ltyr], and [Tb-Lphe]) for sensing and discriminating purine nucleoside polyphosphates (NPP) based on a modified DTTA chelator appended to aromatic amino acids (Laa). The optically most effective luminescent [Tb-Ltrp] probe preferentially discriminates the guanine-NPPs over the adenine-NPPs PeT-based modulation of Tb(III) luminescence within the biological concentration range.

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Background: Isolation with cotton rolls does not always provide as complete isolation as rubber dam, especially in procedures where absolute moisture control is critical. Therefore, this review aims to summarize and analyze previous studies evaluating the retention and marginal integrity of pit & fissure sealant using rubber dam and cotton roll isolation techniques during dental treatment in children.

Material And Methods: In accordance with PRISMA guidelines, search yielded 1361 articles, with seven RCTs and one non-RCT design meeting the inclusion criteria.

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Objective: This systematic review and meta-analysis aimed to assess the association between the dental caries and the level of salivary alpha amylase activity among caries active and caries free individuals.

Design: This review followed the PRISMA guidelines and registered in PROSPERO (CRD42024518973). A comprehensive search across various research databases until January 31, 2024 yielded 1031 articles, where multiple screening ultimately narrowed it to 13 articles.

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  • The study investigates how social determinants of health (SDOH) impact pediatric-onset multiple sclerosis (POMS), particularly in terms of adverse SDOH frequency and their effects on treatment and outcomes.
  • Researchers conducted a retrospective analysis of data from the United States Network of Pediatric MS Centers, focusing on various demographic and clinical outcomes related to SDOH hardships.
  • Findings indicated that 66% of participants faced social hardships, which influenced factors such as age at symptom onset, steroid treatment likelihood, study attrition risk, and overall health scores.
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Background: One of the major inflammatory markers, C-reactive protein (CRP), is often elevated in people who have had a heart attack, vascular problems, stroke, or sudden cardiac death. Obesity is associated with higher CRP levels because adipose tissue activates cytokines. Obesity and overweight increase the risk of heart disease, as does an elevated CRP level.

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  • Right ventricle-pulmonary artery (RV-PA) coupling analyzes how the right ventricle's strength and resistance impact each other, traditionally assessed through invasive pressure-volume loop measurements.
  • Researchers examined the effectiveness of the TAPSE/PASP ratio, a non-invasive method using echocardiography, against the standard PV loop metrics, through a systematic review of existing studies.
  • Their meta-analysis of ten selected studies showed only a moderate correlation (0.52) between TAPSE/PASP and the gold standard, indicating that while non-invasive methods are widely used, they fall short in accurately capturing the nuances of RV-PA coupling for managing right ventricular dysfunction.
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During the last three decades, technological advancements in high-throughput next-generation sequencing have resulted in an increased understanding of proteomic and genomic data, aptly termed proteogenomics. Efforts in developing such approaches have not only been limited but also focused on protein identification and subcellular localization. These approaches, however, have also been explored for their broad understanding of how genomics/transcriptomics data have yielded measures, for example, gene expression regulation/signal cascading and diseasome studies.

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  • - This study introduces a new model using nonlinear ordinary differential equations to analyze Hepatitis C Virus (HCV) dynamics across six groups: Susceptible, Treatment, Responder, Non-Responder, Cured, and Fibrosis.
  • - A comprehensive numerical analysis was performed over 20 years to evaluate the model's predictive accuracy, aiming to offer a non-invasive alternative for monitoring liver fibrosis progression.
  • - The model incorporates various parameters that help understand treatment effects on fibrosis progression and distinguishes the disease's natural course for non-responders, which could improve patient management and outcomes.
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Cancer is one of the major life-threatening diseases in the world and oral cancer is the 8th most common type of deadly cancers in Asian countries. Despite many causes, tobacco is the main causative agent as 90% of oral cancer cases were due to daily consumption of tobacco and its products. The major drawback of the conventional therapies for oral cancer including chemotherapy, surgery and radiotherapy or combination of these is the dose limiting toxicity.

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  • The study analyzed genetic alterations in cerebrospinal fluid (CSF) from 711 patients to help classify CNS cancers and guide targeted therapies.
  • They found detectable circulating tumor DNA (ctDNA) in over half of CSF samples from patients with CNS tumors, while none was found in samples from patients without CNS tumors.
  • The research also revealed clonal evolution and resistance mechanisms over time, with ctDNA presence linked to poorer overall survival rates for these patients.
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DHODH inhibition represents an attractive approach to overcome differentiation blockade for the treatment of AML. In a previous communication, we described our efforts leading to the discovery of compound 3 (JNJ-74856665), an orally bioavailable, potent, and selective DHODH inhibitor for clinical development. Guided by the co-crystal structures bound to human DHODH, other fused six-membered constructs were explored as isosteric replacements of the isoquinolinone central core.

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Arsenic contamination in groundwater poses a significant threat to human health, affecting millions worldwide. This study presents a novel approach for simultaneous remediation of both As(III) and As(V) by using iron-functionalized polythiophene (PTh@Fe) composites. The PTh@Fe composite was synthesized by a reduction process involving FeCl/FeCl byproducts of polymerization, resulting in a highly efficient adsorbent for both As(III) and As(V) species.

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Background: We evaluated the association of achieving endoscopic outcomes at week 12 of induction with improvements in clinical outcomes and quality of life (QoL) at week 52 of maintenance in patients with moderately to severely active Crohn's disease (CD) treated with upadacitinib (UPA).

Methods: This post hoc analysis evaluated data from 2 phase 3 induction trials (NCT03345836 and NCT03345849) and 1 maintenance (NCT03345823) trial. Clinical responders to 12-week induction therapy with UPA who also received 52-week maintenance treatment with UPA were included.

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  • Aberrant expression of HOX and MEIS1 family genes in certain leukemias disrupts normal blood cell differentiation and contributes to leukemia development.
  • Menin inhibitors can target the interaction between KMT2A and menin, reducing the abnormal expression of key factors and promoting differentiation in these leukemias.
  • A collaborative effort among pediatric and adult specialists aims to advance menin inhibitors in treatment, offering a comprehensive overview of clinical trials and advocating for inclusive trial designs for youth.
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Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) have poor outcomes compared with newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children with relapsed/refractory B-cell ALL (n = 7) after ≥2 relapses, and children and young adults with T-cell ALL (children, n = 24; young adults, n = 5) or LL (n = 10) after first relapse. The primary end point was complete response (CR) in the B-cell ALL (end of cycle 2) and T-cell ALL (end of cycle 1) cohorts, after which patients could proceed off study to allogeneic hematopoietic stem cell transplant (HSCT).

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This study investigated the impact of feeding 17% moringa leaf meal (MLM) on the ruminal and fecal microbial composition and body weight gain (BWG) performance of lambs (Ovis aries) and kids (Capra hircus). A total of n = 28 lambs (n = 14, no-moringa, n = 14, 17% moringa) and 24 kids (n = 12, no-moringa, n = 12, 17% moringa) were involved in the experiment and body weight was recorded fortnightly. Metagenomic shotgun sequencing was performed on 28, 22, and 26 ruminal solid, liquid fraction, and fecal samples from lambs, and 23, 22, and 23 samples from kids.

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  • New-onset refractory status epilepticus (NORSE) is a serious condition that can cause significant disability, often not responding well to standard treatments.
  • An 11-year-old girl with anti-GAD 65 encephalitis who experienced NORSE showed minimal improvement with regular anti-seizure medications and first-line therapies.
  • After receiving intrathecal dexamethasone (IT-DEX) along with rituximab, her neuroinflammation decreased, seizure frequency dropped, and she could reduce anesthesia, suggesting IT-DEX could be beneficial early on for various causes of refractory status epilepticus.
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Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with -rearranged () acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) acute leukemia.

Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.

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Extracellular vesicles (EVs) can transfer antigens and immunomodulatory molecules, and such EVs released by antigen-presenting cells equipped with immunostimulatory functions have been utilized for vaccine formulations. A prior high-throughput screening campaign led to the identification of compound (), which enhanced EV release and increased intracellular Ca influx. Here, we performed systematic structure-activity relationship (SAR) studies to investigate the scaffold for its potency as a vaccine adjuvant.

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Background: Understanding nutrition's role in multiple sclerosis (MS) can guide recommendations and intervention-based studies.

Objective: Evaluate the association between nutrition and pediatric-onset MS outcomes.

Methods: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers.

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Background: With advanced virtual reality (VR) technology, its usage in health care is creating an impact on patient outcomes. Patients undergoing knee replacement surgery are already anxious due to the surgery, anaesthesia, and unfamiliar environment of the operation theatre. In addition to that, the unpleasant noise of tools makes it worse.

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  • The study uses density functional theory simulations to analyze the electronic and magnetic properties of hydrogenated borophenes, particularly when doped with 3d transition metals.
  • It finds that hydrogenating 2-borophene creates a Dirac cone, enhancing its stability and suggesting its potential use as a Dirac material.
  • The research highlights that Cr-doped hydrogenated borophene exhibits the highest magnetic moment, opening avenues for applications in electronics and spintronics, while providing insights for future experimental work on tunable 2D materials.
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Summary: perox-per-cell automates cumbersome, image-based data collection tasks often encountered in peroxisome research. The software processes microscopy images to quantify peroxisome features in yeast cells. It uses off-the-shelf image processing tools to automatically segment cells and peroxisomes and then outputs quantitative metrics including peroxisome counts per cell and spatial areas.

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