Publications by authors named "Hari D"

Background: Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.

Methods: We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models.

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Spirocyclobutyl oxindoles have garnered substantial attention in drug discovery and pharmaceuticals owing to their wide range of biological activities. Strain-release in small-ring compounds is a powerful strategy to enable efficient access to complex molecules. In this study, we successfully realized a photoredox-catalyzed strain-release radical spirocyclization approach to attain functionalized spirocyclobutyl oxindoles.

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Spirocyclobutane derivatives have gained significant attention in drug discovery programs due to their broad spectrum of biological activities and clinical applications. Ring-strain in organic molecules is a powerful tool to promote reactivity by releasing strain energy, allowing the construction of complex molecules selectively and efficiently. Herein, we report the first strain-enabled radical spirocyclization cascades for the synthesis of functionalized spirocyclobutyl lactones and - lactams, which are finding increasing applications in medicinal chemistry.

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Difluoro(methylene)cyclopropanes (F2MCPs) show better anti-cancer properties and chemical reactivities compared to their nonfluorinated analogues. However, catalytic stereoselective methods to access these privileged motifs still remain a challenging goal. The Doyle-Kirmse reaction is a powerful strategy for the concomitant formation of carbon-carbon and carbon-sulfur bonds.

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Background: Increasing financial risk protection is a key feature of Universal Health Coverage and the path towards health for all. Publicly Funded Health Insurance Schemes (PFHIS) have been considered as one of the pathways to safeguard against financial shocks and potentially reduce Out-of-Pocket Expenditure (OOPE). The south Indian state of Kerala has roughly a decade-long experience in implementing PFHIS.

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The Dowd-Beckwith reaction, a ring-expansion of carbonyl compounds alkoxy radicals, is a powerful approach for synthesizing medium to large-sized carbocyclic scaffolds, which takes advantage of existing ring structures and avoids entropic and enthalpic factors that arise from the end-to-end cyclization strategies. However, the Dowd-Beckwith ring-expansion followed by H-atom abstraction is still the dominating pathway, which hampers its synthetic applications, and there currently exist no reports on the functionalization of ring-expanded radicals using non-carbon based nucleophilic reagents. Herein, we report a redox-neutral decarboxylative Dowd-Beckwith/radical-polar crossover (RPC) sequence that delivers functionalized medium-sized carbocyclic compounds with broad functional group tolerance.

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A temperature-regulated catalyst-free photoinduced selective carbene C-H insertion strategy was realized to efficiently synthesize spiro--lactones and -lactams, which hold considerable promise in drug discovery programs. The reaction shows broad applicability across a range of α-diazo esters and amides with various ring sizes and substituents and has been demonstrated to successfully achieve the late-stage spirocyclization of natural/bioactive compounds. The obtained products could be transformed into spiro-oxetanes, -azetidines, and -cyclopropanes, privileged scaffolds with broad utility in medicinal chemistry.

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Background: Kerala, a south Indian state, has a long and strong history of mobilisation of people's participation with institutionalised mechanisms as part of decentralisation reforms introduced three decades ago. This history formed the backdrop of the state's COVID-19 response from 2020 onwards. As part of a larger health equity study, we carried out an analysis to understand the contributions of people's participation to the state's COVID-19 response, and what implications this may have for health reform as well as governance more broadly.

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Background: Pre-procedural COVID-19 testing in patients scheduled for elective cases have become routine to reduce the risk of COVID-19 exposure and pulmonary complications related to perioperative COVID-19 infection, and to reduce the use of specific hospital resources among other reasons. This study evaluates the efficacy of universal COVID-19 testing for elective procedures.

Methods: Single institution retrospective observational study from July 2020 through August 2021.

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Background: Literature on the epidemiology of gastric cancer metastasis is limited, although outcomes are known to be poor. We describe patterns of gastric cancer metastasis and treatment in the United States.

Methods: Patients with metastatic gastric adenocarcinoma were identified in the NCDB from 2004 to 2016.

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Introduction: Psychosocial distress screening of cancer patients is an American College of Surgeons Commission on Cancer mandate for accredited cancer programs. We evaluated psychosocial distress in breast cancer patients to characterize risk factors for high distress scores at a safety net hospital.

Materials And Methods: The psychosocial distress screening form includes a list of potential issues and a distress score scaled from 1 through 10.

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We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co-solvent or removal of oxygen, either at 37 °C or room temperature. The transformation led to a significant increase of peptide lipophilicity and worked for aromatic thiols, homocysteine, cysteine, and peptides containing 4 to 18 amino acids.

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Allylboration of carbonyl compounds is one of the most widely used methods in the stereoselective synthesis of natural products. However, these powerful transformations are so far limited to allyl- or crotylboron reagents; ring-strained substituents in the α-position have not been investigated. Such substrates would lead to an increase in strain energy upon allylboration and as such cause a significant increase in the activation barrier of the reaction.

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Tracheal tumor is a rare entity. Tracheal tumor may be a primary tracheal tumor or secondary to invasion from a mediastinal tumor (or a lymph node). These tumors are prone to cause critical airway obstruction which may require urgent care.

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Background: Cholelithiasis referrals often present with concomitant or isolated atypical symptoms such as reflux, bloating, or epigastric pain. We sought to identify the impact of preoperative symptomatology of atypical or dyspepsia-type biliary colic on operative and non-operative clinical outcomes.

Methods: A retrospective review of patients referred for gallstone disease from 2014 to 2018 at a single institution in Los Angeles County was performed.

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The intramolecular [4+2] cycloaddition between arenes and allenes first reported by Himbert gives rapid access to rigid polycyclic scaffolds. Herein, we report a one-pot oxyalkynylation/cycloaddition reaction proceeding under mild conditions (23-90 °C) and providing complex polycyclic architectures with high efficiency, and atom and step economy. The bicyclo[2.

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The broad synthetic utility of organoboron compounds stems from their ready ability to undergo 1,2-migrations. Normally, such shifts are induced by α-leaving groups or by reactions of alkenyl boronates with electrophiles. Herein, we present a new strategy to induce 1,2-metalate rearrangements, via ring expansion of vinylcyclopropyl boronate complexes activated by electrophiles.

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Background: Lipomatous masses are the most common soft tissue tumors. While the majority are benign lipomas, it is important to identify those masses that are malignant prior to excision. Current guidelines recommend core needle biopsy (CNB) for all lipomatous masses larger than 3-5 cm.

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Ethynylbenziodoxol(on)e (EBX) cyclic hypervalent iodine reagents are now established reagents for the alkynylation of radicals and nucleophiles, yet they present limited possibilities for further structure and reactivity modification. Herein, the first synthesis is reported for the corresponding ethynylbenziodazolone (EBZ) reagents, in which the oxygen atom in the iodoheterocycle is replaced by a nitrogen atom. The substituent on the nitrogen enables further fine-tuning of the reagent structure and reactivity.

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While significant advances have been made in the treatment of many different solid tumors, pancreatic cancer remains a glaring exception. Overall 5-year survival rates for pancreatic cancer remain in the single digits. While newer chemotherapy regimens such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated modest improvement in survival benefit for metastatic disease and have improved the resectability rates of previously borderline or locally advanced tumors, clinically significant improvements from immunotherapy and targeted therapy remain to be demonstrated.

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TiO-ZnO heterogeneous catalytic system provides a good replacement of a homogeneous catalytic reaction due to its easier recovery. In this study, biodiesel was produced from Ulva lactuca seaweeds using TiO-ZnO nanocomposite catalysts with particle size of ~12 nm. The size controlled TiO-ZnO nanocomposite was characterized by powder XRD analysis and TEM.

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Background: Robotic surgery is increasingly adopted into surgical practice, but it remains unclear what level of robotic training general surgery residents receive. The purpose of our study was to assess the variation in robotic surgery training amongst general surgery residency programs in the United States.

Methods: A web-based survey was sent to 277 general surgery residency programs to determine characteristics of resident experience and training in robotic surgery.

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The efficient synthesis of organic compounds is an important field of research, which sets the basis for numerous applications in medicine or materials science. Based on the polarity induced by functional groups, logical bond disconnections can be deduced for the elaboration of organic compounds. Nevertheless, this classical approach makes synthesis rigid, as not all bond disconnections are possible.

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