Publications by authors named "T Siva Kumar"

1,126 Publications

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Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage.

J Cereb Blood Flow Metab 2021 Jun 10:271678X211020865. Epub 2021 Jun 10.

The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.
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http://dx.doi.org/10.1177/0271678X211020865DOI Listing
June 2021

Peptide-based delivery vectors with pre-defined geometrical locks.

RSC Med Chem 2020 Nov 13;11(11):1303-1313. Epub 2020 Aug 13.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati Guwahati-781039 Assam India

Design of peptide-based targeted delivery vectors with attributes of specificity and selective cellular targeting by fixing their topology and resulting electrostatic fingerprint is the objective of this study. We formulated our peptide design platform by utilizing the possibilities of side-chain induced geometric restrictions in a typical peptide molecule. Conceptually, we locked the conformation of the RGD/NGR motif of tumor homing peptides (THPs) by mutating glycine in these motifs with d-proline and tailed the peptides with a syndiotactic amphipathic segment for cellular penetration. The designed peptides were synthesized, characterized, and tested on various cell lines, including breast cancer (MDA-MB-231), cervical cancer (HeLa), osteosarcoma (U2-OS) and non-cancer mammary epithelial cells (MCF-10A), by flow cytometry and confocal microscopy. The results showed differential cellular uptake in different cell types, as a result of the distinct electrostatic fingerprint encoded in their design. The uptake of serum pre-treated peptides by cells reveals the retention of peptide activity even after the incubation with serum. In addition, peptide-methotrexate (MTX) conjugates compared to the methotrexate drug showed enhanced apoptotic cell death in MTX-resistant MDA-MB-231 cells, indicating the increase in MTX bioavailability.
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http://dx.doi.org/10.1039/d0md00229aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126890PMC
November 2020

A deep-learning based multimodal system for Covid-19 diagnosis using breathing sounds and chest X-ray images.

Appl Soft Comput 2021 Sep 26;109:107522. Epub 2021 May 26.

School of Design, Avantika University, Ujjain, India.

Covid-19 has become a deadly pandemic claiming more than three million lives worldwide. SARS-CoV-2 causes distinct pathomorphological alterations in the respiratory system, thereby acting as a biomarker to aid its diagnosis. A multimodal framework (Ai-CovScan) for Covid-19 detection using breathing sounds, chest X-ray (CXR) images, and rapid antigen test (RAnT) is proposed. Transfer Learning approach using existing deep-learning Convolutional Neural Network (CNN) based on Inception-v3 is combined with Multi-Layered Perceptron (MLP) to develop the CovScanNet model for reducing false-negatives. This model reports a preliminary accuracy of 80% for the breathing sound analysis, and 99.66% Covid-19 detection accuracy for the curated CXR image dataset. Based on Ai-CovScan, a smartphone is conceptualised as a mass-deployable screening tool, which could alter the course of this pandemic. This 's deployment could minimise the number of people accessing the limited and expensive confirmatory tests, thereby reducing the burden on the severely stressed healthcare infrastructure.
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http://dx.doi.org/10.1016/j.asoc.2021.107522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149173PMC
September 2021

Venezia applicator with oblique needles improves clinical target volume coverage in distal parametrial tumor residue compared to parallel needles only.

J Contemp Brachytherapy 2021 Feb 18;13(1):24-31. Epub 2021 Feb 18.

Radiation Therapy Department, Gustave Roussy, Villejuif, France.

Purpose: Residual distal parametrial involvement after radiochemotherapy is a true challenge for brachytherapists since the width and asymmetry of high-risk clinical target volume (HR-CTV) are difficult to cover properly with a standard implant.

Material And Methods: Dosimetric plans of five patients treated with Venezia advanced gynecological applicator at our institution were reviewed. For each patient, we compared the original plan with a new plan where oblique needles were removed and re-optimized manually. Optimization process was halted when EQD2 D HR-CTV reached 90 Gy, when one hard constraint to organs at risk (OARs) was reached according to the EMBRACE II protocol, or when dose-rate of one of OARs exceeded 0.6 Gy/h.

Results: Tumors were large; median HR-CTV volume was 64 cc and median distance between tandem and outer contour of HR-CTV was 40 mm. For the five patients, HR-CTV EQD2 D was superior in the plan using oblique needles, with a median difference of 6.5 Gy (range, 1.7-8.5 Gy). Median D HR-CTV and intermediate-risk CTV (IR-CTV) were significantly increased with oblique needles: 85.9 Gy (range, 83.2-90.3 Gy) vs. 81.5 Gy (range, 77.4-84 Gy), and 68.7 Gy (range, 66.3-72.3 Gy) vs. 67 Gy (range, 64.3-69.1 Gy), = 0.006 for both. There were no significant differences in the dose to OARs. Plans with only parallel needles had less favorable dose distribution, with cold spots on the outer parametria and higher vaginal activation to compensate parametrial coverage in its inferior part.

Conclusions: Venezia applicator permits reproducible application to increase CTV coverage in patients with distal parametrial tumor residue during brachytherapy, while maintaining acceptable dose to OARs.
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http://dx.doi.org/10.5114/jcb.2021.103583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117708PMC
February 2021

Association of ovarian response with picoAMH in women undergoing controlled ovarian hyperstimulation.

Clin Biochem 2021 May 14. Epub 2021 May 14.

Department of Pathology, Texas Children's Hospital, Houston, TX, United States. Electronic address:

Objective: Our study aims to evaluate the diagnostic performance of a high-sensitivity picoAnti-Müllerian Hormone (picoAMH) for predicting ovarian response in women undergoing controlled ovarian hyperstimulation and occurrence of ovarian hyperstimulation syndrome.

Methods: Retrospective cohort study at a single academic fertility center including all patients with picoAMH ELISA who underwent controlled ovarian hyperstimulation. The primary outcome was the number of oocytes retrieved, and secondary outcomes included cycle cancellation and ovarian hyperstimulation syndrome. Patients were grouped into poor, normal, and hyper-responders based on number of oocytes retrieved.

Results: The mean AMH and antral follicle count (AFC) were significantly different between normal response vs. hyper response group (p < 0.0001). Only serum AMH and not AFC was significantly increased in patients diagnosed with ovarian hyperstimulation syndrome (OHSS). For prediction of OHSS, receiver operating characteristic (ROC) analysis revealed that AMH (area under the ROC curve [AUC] = 0.85) was significantly better than the AFC (AUC = 0.64). The serum AMH cut-off at sensitivity of 80% for predicting OHSS among hyper responders from ROC curve was 3.67 ng/ml. Serum AMH measured by picoAMH ELISA showed superior correlation to number of oocytes retrieved when compared to AFC in the age group over 40 years old (r = 0.74 and r = 0.4, respectively) CONCLUSION: This study shows great utility of picoAMH ELISA for predicting ovarian response to controlled ovarian hyperstimulation (COH). Diagnostic performance of picoAMH for prediction of OHSS is superior to the AFC in our cohort.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.05.007DOI Listing
May 2021