Publications by authors named "Sai M"

Background: Disproportionately enlarged subarachnoid space hydrocephalus (DESH) is one of the neuroradiological characteristics of idiopathic normal pressure hydrocephalus (iNPH), which makes statistical analyses of brain images difficult. This study aimed to develop and validate methods of accurate brain segmentation and spatial normalisation in patients with DESH by using the Computational Anatomy Toolbox (CAT12).

Methods: Two hundred ninety-eight iNPH patients with DESH and 25 healthy controls (HCs) who underwent cranial MRI were enrolled in this study.

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Occupational radiation exposure to the eye lens of medical staff during endoscopic retrograde cholangiopancreatography (ERCP) should be kept low so as not to exceed annual dose limits. Dose should be low to avoid tissue reactions and minimizing stochastic effects. It is known that the head and neck of the staff are exposed to more scattered radiation in an over-couch tube system than in a C-arm system (under-couch tube).

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Article Synopsis
  • The activation of nuclear retinoid X receptors (RXRs) involves releasing corepressors and recruiting coactivators, influencing gene activation or repression.
  • Research identified a synthetic agonist that significantly increases the binding of PGC1α (a coactivator) to RXR, unlike the natural ligand 9-cis retinoic acid.
  • The study produced three related RXR agonists with varying abilities to enhance PGC1α recruitment, suggesting potential new therapies through targeted RXR-PGC1α interactions via selective coregulator modulation.
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The human tailless homologue receptor (TLX) is a ligand-activated transcription factor acting as a master regulator of neural stem cell homeostasis. Despite its promising potential in neurodegenerative disease treatment, TLX ligands are rare but required to explore phenotypic effects of TLX modulation and for target validation. We have systematically studied and optimized a TLX agonist scaffold obtained by fragment fusion.

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Article Synopsis
  • - Colorectal adenocarcinoma is the most common type of colorectal cancer in the U.S., driven by genetic mutations like APC, KRAS, HER-2 IHC3+, CHEK-2, and TP53 that result in cancer development.
  • - Standard treatment for metastatic colorectal cancer often includes chemotherapy and targeted therapies, but many patients endure disease progression, prompting the search for new treatments like fruquintinib, a selective VEGFR inhibitor.
  • - A case report describes a patient with metastatic colorectal cancer who suffered a cerebellar hemorrhage after starting fruquintinib, emphasizing the importance of close monitoring and personalized risk assessments for patients on this medication.
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The neuroprotective transcription factor nuclear receptor-related 1 (Nurr1) has shown great promise as a therapeutic target in Parkinson's and Alzheimer's disease as well as multiple sclerosis but high-quality chemical tools for pharmacological target validation of Nurr1 are rare. We have employed the weak Nurr1 modulator amodiaquine (AQ) and AQ-derived fragments as templates to design a new Nurr1 agonist chemotype by scaffold hopping and fragment growing strategies. Systematic structural optimization of this scaffold yielded Nurr1 agonists with nanomolar potency and binding affinity.

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Diagnostic reference level (DRL) for mammography for 2015 and 2020 has been published by J-RIME. More new dose studies are needed to revise the next DRL. In preparation for the next revision of the DRL for mammography, this study investigated data from the Japan Central Organization on Quality Assurance of Breast Cancer Screening on the mean average glandular dose (AGD) for institutional image accreditation in 2019-2023 and the relationship between the average at eligible institutions to date and the type of breast X-ray system.

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Photo-switchable nuclear receptor modulators ("photohormones") enable spatial and temporal control over transcription factor activity and are valuable precision tools for biological studies. We have developed a new photohormone chemotype by incorporating a light-switchable motif in the scaffold of a cinalukast-derived PPARα ligand and tuned light-controlled activity by systematic structural variation. An optimized photohormone exhibited PPARα agonism in its light-induced (Z)-configuration and strong selectivity over related lipid-activated transcription factors representing a valuable addition to the collection of light-controlled tools to study nuclear receptor activity.

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In this study, an extensive exploration survey of wild progeny was conducted which yielded 18 candidate plus trees (CPTs) of . Seeds of these CPTs were collected from diverse locations between 10°54' and 28°07' E longitude, and 76°27' and 95°32' N latitude, covering 18 different locations across 5 states of the Indian subcontinent. The objective of the progeny trial was to assess genetic associations and variability in growth and physio-chemical characteristics.

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Retinoid X receptors (RXRs, NR2B1-3) hold therapeutic potential in oncology, neurodegeneration, and metabolic diseases, but traditional RXR agonists mimicking the natural ligand 9- retinoic acid exhibit poor physicochemical properties, pharmacokinetics, and safety profiles. Improved RXR ligands are needed to exploit RXR modulation as a promising therapeutic concept in various indications beyond its current role in second-line cancer treatment. Here, we report the co-crystal structure of RXR in complex with a novel pyrimidine-based ligand and the structure-informed optimization of this scaffold to highly potent and highly soluble RXR agonists.

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Article Synopsis
  • Researchers discovered that the transcription factor Nurr1 binds to a dopamine metabolite called 5,6-dihydroxyindole (DHI), which can help in designing new drugs targeting Nurr1.
  • They screened a custom set of 14,000 DHI analogues and selected 24 candidates for testing, leading to the identification of three promising Nurr1 agonists with strong binding affinity.
  • The study showed that these DHI derivatives effectively engage cellular targets and work well together, hinting at multiple binding sites that could be exploited for new therapeutic strategies involving Nurr1.
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Introduction: The objective was to perform placental ultrasound image texture (UPIA) in first (T1), second(T2) and third(T3) trimesters of pregnancy using machine learning( ML).

Methods: In this prospective observational study the 2D placental ultrasound (US) images from 11-14 weeks, 20-24 weeks, and 28-32 weeks were taken. The image data was divided into training, validating, and testing subsets in the ratio of 80%, 10%, and 10%.

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Previously reported syntheses of 3-functionalized silyl enol ethers using allyloxysilanes are hindered by undesirable reactions owing to retro Brook rearrangements. In this study, various 3-functionalized ()-silyl enol ethers were synthesized from readily available 1-arylallylic alcohols using (trimethylsilyl)methylpotassium as a base. ,-Difunctionalization of the -generated dipotassio α,β-dianion with electrophiles and silyl chlorides is key to the success of this transformation.

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Background: Diabetes mellitus (DM) is a chronic disease, which requires optimal glycemic control to prevent its ensuing vascular complications. Pathway to optimal glycemic control in T2DM has a complex socio-behavioral construct, especially in vulnerable populations, like slum dwellers, who have reduced health-care access and lower prioritization of health needs.

Objective: The study aimed to map trajectories of glycemic control amongst individuals with T2DM living in urban slums and identify key determinants associated with unfavourable glycaemic trajectory.

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This paper describes the regio- and diastereoselective synthesis of unsymmetrical 1,4-diketone-derived ()-monosilyl enol ethers from 1-arylallyloxysilanes and Weinreb amides using (trimethylsilyl)methylpotassium as a base. The metalation of 1-arylallyloxysilanes to generate siloxyallylpotassiums is the key step in this transformation. The products can be transformed into diverse α-monofunctionalized unsymmetrical 1,4-diketones.

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Neuroblastoma is the most common extracranial solid tumor in children. When metastasis to the falx cerebri is present, it is classified as stage M; however, its behavior has not been well characterized. Here we present a case of stage M infantile neuroblastoma (NB) with involvement of the falx cerebri, and also summarize the clinical profiles of previously reported cases.

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Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS).

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Microbial synthesized surfactants are used in contaminated soil bioremediation processes and have multiple applications in various industries. These compounds minimize the negative influences in soil via absorption by detoxifying the toxic metals or compounds. Further, applications of biosurfactants are detected in treating chronic diseases or synthetic drugs alternatives in current periods.

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Respiratory viruses are transmitted via respiratory particles that are emitted when people breath, speak, cough, or sneeze. These particles span the size spectrum from visible droplets to airborne particles of hundreds of nanometers. Barrier face coverings ("cloth masks") and surgical masks are loose-fitting and provide limited protection from airborne particles since air passes around the edges of the mask as well as through the filtering material.

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This study reports the first base-promoted aldol-Tishchenko reactions of allylic alcohols with aldehydes initiated by allylic isomerization. The reaction enables the diastereoselective synthesis of a variety of 1,3-diols with three contiguous stereogenic centers. Unlike commonly reported systems, our method allows the use of readily available allylic alcohols as nucleophiles instead of enolizable aldehydes and ketones.

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Quantification of long term changes in cloud distribution and properties is critical for the proper assessment of future climate. We show contrasting trends in cloud properties and cloud radiative effects over Northwest Indian Ocean (NWIO) in south Asian summer monsoon. Cloud top height (CTH) decreases in June (- 69 ± 3 myr) and July (- 44 ± 3 myr), whereas it increases in August (106 ± 2 myr) and September (37 ± 1 myr).

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Diabetic peripheral neuropathy (DPN), a chronic neurological complication of diabetes mellitus, remains scantily addressed area of research. Many lacunae in the temporal sequence between cause and effect of DPN still remain unfilled and therefore treatment of DPN remains unsatisfactory. This is largely due to the conventional glucocentric focus to resolve the problem.

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The recent outbreak of coronavirus disease (COVID-19) has challenged the survival of human existence in the last 1 year. Frontline healthcare professionals were struggling in combating the pandemic situation and were continuously supported with literature, skill set, research activities, and technologies developed by various scientists/researchers all over the world. To handle the continuously mutating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requires amalgamation of conventional technology with emerging approaches.

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We report a novel s-tetrazine based covalent organic framework (TZA-COF) and its hybrid nanocomposites with reduced graphene oxide (TZA-COF-rGO) and Co metal to illustrate novel structure-activity relationships in this class of compounds for electrocatalytic oxygen reduction reaction (ORR). The Co-impregnated hybrid composites (TZA-COF-rGO-Co) were further annealed to yield Co-encapsulated nitrogen doped graphitic carbon (Co@NC-600), which exhibited excellent ORR activity comparable to that of the state-of-the art Pt/C in terms of onset potential, E1/2 (half-wave potential), 4e- reduction selectivity and methanol tolerance. Sequential mechanistic analyses of activity enhancement and electron transfer pathways for the ORR, at different stages of controlled catalyst engineering, elucidated the crucial role of active sites and overall catalyst nature in tuning the ORR mechanism.

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