Publications by authors named "S VijayaBhaskara Gupta"

19,667 Publications

Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

ESMO Open 2022 May 13;7(3):100483. Epub 2022 May 13.

Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: https://facebook.com/https://www.facebook.com/BIGagainstbreastcancer/.

Background: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally.

Patients And Methods: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site.

Results: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific.

Conclusions: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.
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http://dx.doi.org/10.1016/j.esmoop.2022.100483DOI Listing
May 2022

The respiratory lipoquinone, menaquinone, functions as an inducer of genes regulated by the repressor MSMEG_2295.

Microbiology (Reading) 2022 May;168(5)

Department of Microbiology, Bose Institute, P-1/12 C.I.T. Scheme VIIM, Kolkata 700054, India.

A previous study reported that the (Msm) protein MSMEG_2295 is a repressor controlling the expression of several genes, including that for MSMEG_5125, a putative isoprenoid binding protein belonging to the YceI family, and DinB2, a DNA damage repair enzyme. This repressor is encoded by the first gene of the operon that also expresses the gene for DinB2. Targeted inhibition of MSMEG_5125 using CRISPRi technology resulted in a significant loss of Msm's respiratory activity and viability. Since this protein has been predicted to be an isoprenoid binding protein, we suspected a role of menaquinones, which are isoprenoid naphthoquinones, in the observed phenomenon. Accordingly, we tested whether MSMEG_5125's deficiency-induced lethality could be reversed by adding menaquinone. The result was positive, implying cooperation between MSMEG_5125 and menaquinone in bringing about respiration. Inhibition of expression led to the induction of and , two hallmark genes of the MSMEG_2295 regulon. This result suggests that when MSMEG_5125 becomes limiting, a feedback-loop derepresses the MSMEG_2295 regulon genes, including its own. Interestingly, menaquinone functioned as an inducer of , indicating that it is likely to mediate the feedback mechanism. This result also strengthens our hypothesis that the functions of menaquinone and MSMEG_5125 are interrelated. Menaquinone also induced the MSMEG_2295-controlled operon () not induced following the inactivation of . Therefore, the activation mechanism of MSMEG_2295-regulated genes may not be the same for all, although derepression is likely to be a common feature. , menaquinone abolished MSMEG_2295's DNA binding activity by interacting with it, confirming its role as an inducer. Therefore, a menaquinone-MSMEG_5125-regulated gene expression circuit controls Msm respiration and possibly oxidative stress-induced DNA damage repair.
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http://dx.doi.org/10.1099/mic.0.001192DOI Listing
May 2022

Performance of Multidetector Computed Tomography and Negative Versus Positive Enteric Contrast for Evaluation of Gastrointestinal Neuroendocrine Neoplasms.

J Comput Assist Tomogr 2022 May-Jun 01;46(3):333-343. Epub 2022 Mar 4.

From the Department of Abdominal Radiology, University of Texas MD Anderson Cancer Center, Houston, TX.

Background: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN.

Methods: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test.

Results: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers.

Conclusions: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.
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http://dx.doi.org/10.1097/RCT.0000000000001291DOI Listing
March 2022

Design and Synthesis of Shikimoylated-Polypeptides for Nuclear Specific Internalization.

ACS Macro Lett 2022 Mar 9;11(3):289-295. Epub 2022 Feb 9.

Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur Campus, Nadia, West Bengal-741246, India.

Targeted delivery of therapeutics such as small molecule drugs or nucleic acids exclusively to the nucleus of diseased mammalian cells poses a significant challenge. The development of targeting ligands that can specifically enter certain cancer cells via a specific receptor-mediated endocytosis and then traffic exclusively to the nucleus to deliver the cargo inside it can achieve this goal. We have developed an end-functionalized shikimoylated-polypeptide with pendant shikimoyl moieties that can enter mammalian cells via the mannose receptors and are then exclusively trafficked into the nucleus. The presence of the shikimoyl group in the polypeptide, which traffics it exclusively to the nucleus, contrasts with the mannosylated or galactosylated glycopolypeptides that are distributed all over the cytoplasm or the mannose-6-phosphate containing polypeptide that is exclusively trafficked to the lysosome. Using challenge experiments, we demonstrate that these polypeptides can enter both dendritic and cancer cells through mannose-receptors and subsequently enter the cell nucleus via the interaction with a nuclear pore complex (NPC) protein importin-α/β1. To the best of our knowledge, this represents the first example of a synthetic polyvalent glycopolypeptide mimic that performs the dual function of entering mammalian cells through specific receptors and subsequently traffics into the nucleus. The conjugation of these end-functionalized shikimoylated-polypeptides to other biological entities, such as recombinant anticancer drugs, DNA, RNA, and CRISPR-Cas9, may be a suitable alternative for delivery of these biological entities into cells affected by cancer and other genetic diseases.
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http://dx.doi.org/10.1021/acsmacrolett.1c00740DOI Listing
March 2022

Vitamin D: The Missing Nutrient Behind the Two Deadly Pandemics, COVID-19 and Cardiovascular Diseases.

Cureus 2022 Apr 14;14(4):e24133. Epub 2022 Apr 14.

Nephrology, Temple University Hospital, Philadelphia, USA.

The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently.  This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.
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http://dx.doi.org/10.7759/cureus.24133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106532PMC
April 2022
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