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1.
Nat Commun ; 15(1): 4046, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744961

ABSTRACT

The ability to electrically manipulate antiferromagnetic magnons, essential for extending the operating speed of spintronic devices into the terahertz regime, remains a major challenge. This is because antiferromagnetic magnetism is challenging to perturb using traditional methods such as magnetic fields. Recent developments in spin-orbit torques have opened a possibility of accessing antiferromagnetic magnetic order parameters and controlling terahertz magnons, which has not been experimentally realised yet. Here, we demonstrate the electrical manipulation of sub-terahertz magnons in the α-Fe2O3/Pt antiferromagnetic heterostructure. By applying the spin-orbit torques in the heterostructure, we can modify the magnon dispersion and decrease the magnon frequency in α-Fe2O3, as detected by time-resolved magneto-optical techniques. We have found that optimal tuning occurs when the Néel vector is perpendicular to the injected spin polarisation. Our results represent a significant step towards the development of electrically tunable terahertz spintronic devices.

2.
South Asian J Cancer ; 13(1): 57-62, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38721103

ABSTRACT

Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves. This was a prospective study of all COVID-19-positive cancer patients attending our specialty out-patient department at Rajiv Gandhi Cancer Institute and Research Centre between March 2020 and November 2020 (1st wave) and April 2021 and June 2021 (second wave). All patients diagnosed to have COVID-19 by real-time polymerase chain reaction (RT-PCR) with a biopsy-proven solid organ malignancy attending the medical oncology out-patient department were included during both the waves. A total of 300 patients with proven SARS-CoV-2 infection by either RT-PCR or cartridge based nucleic acid amplification test were encountered, of which 123 were encountered during the first wave of the pandemic and 177 during the second wave. The case fatality rate of the first wave was 9.8%, with a 15-day case fatality rate of 5.6%, whereas for the second wave, it was 13% and 7.2%, respectively. Twelve patients succumbed to COVID-19 disease in the first wave and 23 succumbed in the second. There were no statistically significant correlations; however, the death in the second wave tended to occur more in younger male patients, with comorbidities and history of smoking. There was no relation with ongoing cancer-directed treatment or chemotherapy. Our study is unique in comparing characteristics of the two most important COVID-19 waves and treatment patterns in cancer patients from a single center. The second wave showed a higher CFR, hospital admission rate, and higher frequency of respiratory complications; however, there was no relation to cancer-directed therapy and COVID-19, thus reiterating the fact that cancer treatment should not be halted in the event of a COVID-19 infection.

3.
Int J Appl Basic Med Res ; 14(1): 17-22, 2024.
Article in English | MEDLINE | ID: mdl-38504846

ABSTRACT

Background: The Ring Finger 43 (RNF43) is a tumor suppressor gene that negatively regulates the Wnt/ß-catenin signaling. The p.G659fs is a recurrent RNF43 C-terminal truncating variant frequent in colorectal cancer (CRC) patients. We aimed to identify this hotspot variant in CRC patients and assessed the relationship between the mutation, clinical characteristics, and tumor ß-catenin localization. Materials and Methods: Formalin-fixed, paraffin-embedded tissue samples of upfront, surgically resected, sporadic colorectal adenocarcinoma cases were selected. The p.G659fs mutation was determined by capillary sequencing with sequence-specific primers. Tissue microarray and immunohistochemistry were employed to analyze nuclear ß-catenin expression and the expression of mismatch repair (MMR) proteins, respectively. In addition, clinical details were retrieved from the hospital medical records and data were analyzed. Results: The RNF43 p.G659fs mutation was observed in 8% of CRC patients. In total, 25% of tumors showed a loss of immunostaining for one or more MMR proteins and 14.6% of tumors showed positive nuclear ß-catenin staining. The p.G659fs variant was significantly enriched in MMR-deficient tumors (P = 0.04). Importantly, no correlation was observed between the variant and nuclear ß-catenin localization (P = 0.48), indicating a Wnt-independent role of this variant in CRC tumors. Conclusions: To the best of our knowledge, this is the first study from North India to show the involvement of RNF43 p.G659fs variant in CRC patients. The mutation correlated with MMR protein deficiency and seems to be conferring tumorigenicity independent of the Wnt pathway.

4.
Sci Adv ; 9(44): eadh9853, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37910622

ABSTRACT

Quantitative magnetic resonance imaging (MRI) techniques are powerful tools for the study of human tissue, but, in practice, their utility has been limited by lengthy acquisition times. Here, we introduce the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework in the context of myelin water imaging (MWI); a quantitative MRI technique generally regarded as the most rigorous approach for noninvasive, in vivo measurement of myelin content. The CALIPR framework exploits data redundancy to recover high-quality images from a small fraction of an imaging dataset, which allowed MWI to be acquired with a previously unattainable sequence (fully sampled acquisition 2 hours:57 min:20 s) in 7 min:26 s (4.2% of the dataset, acceleration factor 23.9). CALIPR quantitative metrics had excellent precision (myelin water fraction mean coefficient of variation 3.2% for the brain and 3.0% for the spinal cord) and markedly increased sensitivity to demyelinating disease pathology compared to a current, widely used technique. The CALIPR framework facilitates drastically improved MWI and could be similarly transformative for other quantitative MRI applications.


Subject(s)
Myelin Sheath , Water , Humans , Myelin Sheath/pathology , Magnetic Resonance Imaging/methods , Spinal Cord/diagnostic imaging , Brain/diagnostic imaging
5.
Front Aging Neurosci ; 15: 1266859, 2023.
Article in English | MEDLINE | ID: mdl-37876875

ABSTRACT

Non-invasive methods of detecting early-stage Alzheimer's disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer's pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles. We used template-based analyzes of NOE MRI data and the characteristic Z-spectrum, with parameters optimized for increase specificity to NOE, to detect changes in lipids and proteins in an AD mouse model that recapitulates features of human AD. We find changes in NOE contrast in the hippocampus, hypothalamus, entorhinal cortex, and fimbria, with these changes likely attributed to disruptions in the phospholipid bilayer of cell membranes in both gray and white matter regions. This study suggests that NOE MRI may be a useful tool for monitoring early-stage changes in lipid-mediated metabolism in AD and other disorders with high spatial resolution.

6.
Mol Biotechnol ; 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37410258

ABSTRACT

Candida albicans is known for its pathogenicity, although it lives within the human body as a commensal member. The commensal nature of C. albicans is well controlled and regulated by the host's immune system as they live in the harmonized microenvironment. However, the development of certain unusual microhabitat conditions (change in pH, co-inhabiting microorganisms' population ratio, debilitated host-immune system) pokes this commensal fungus to transform into a pathogen in such a way that it starts to propagate very rapidly and tries to breach the epithelial barrier to enter the host's systemic circulations. In addition, Candida is infamous as a major nosocomial (hospital-acquired infection) agent because it enters the human body through venous catheters or medical prostheses. The hysterical mode of C. albicans growth builds its microcolony or biofilm, which is pathogenic for the host. Biofilms propose additional resistance mechanisms from host immunity or extracellular chemicals to aid their survival. Differential gene expressions and regulations within the biofilms cause altered morphology and metabolism. The genes associated with adhesiveness, hyphal/pseudo-hyphal growth, persister cell transformation, and biofilm formation by C. albicans are controlled by myriads of cell-signaling regulators. These genes' transcription is controlled by different molecular determinants like transcription factors and regulators. Therefore, this review has focused discussion on host-immune-sensing molecular determinants of Candida during biofilm formation, regulatory descriptors (secondary messengers, regulatory RNAs, transcription factors) of Candida involved in biofilm formation that could enable small-molecule drug discovery against these molecular determinants, and lead to disrupt the well-structured Candida biofilms effectively.

7.
Microb Drug Resist ; 29(9): 423-437, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37428599

ABSTRACT

One of the ubiquitous hospital-acquired infections is associated with Candida albicans fungus. Usually, this commensal fungus causes no harm to its human host, as it lives mutually with mucosal/epithelial tissue surface cells. Nevertheless, due to the activity of various immune weakening factors, this commensal starts reinforcing its virulence attributes with filamentation/hyphal growth and building an absolute microcolony composed of yeast, hyphal, and pseudohyphal cells, which is suspended in an extracellular gel-like polymeric substance (EPS) called biofilms. This polymeric substance is the mixture of the secreted compounds from C. albicans as well as several host cell proteins. Indeed, the presence of these host factors makes their identification and differentiation process difficult by host immune components. The gel-like texture of the EPS makes it sticky, which adsorbs most of the extracolonial compounds traversing through it that aid in penetration hindrance. All these factors further contribute to the multidrug resistance phenotype of C. albicans biofilm that is spotlighted in this article. The mechanisms it employs to escape the host immune system are also addressed effectively. The article focuses on cellular and molecular determinants involved in the resistance of C. albicans biofilm against multidrug and the host immune system.


Subject(s)
Anti-Bacterial Agents , Candida albicans , Humans , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Candida , Biofilms
8.
Magn Reson Med ; 89(6): 2295-2304, 2023 06.
Article in English | MEDLINE | ID: mdl-36744726

ABSTRACT

PURPOSE: Nuclear Overhauser effect (NOE) is based on dipolar cross-relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of NOE magnetization transfer ratio (NOEMTR ) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T). METHODS: We optimized the B 1 + $$ {\mathrm{B}}_1^{+} $$ amplitude and length of the saturation pulse by acquiring NOE images with different B 1 + $$ {\mathrm{B}}_1^{+} $$ values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities. To isolate the individual contributions from z-spectra, we have fit the NOE z-spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast. RESULTS: We found that a saturation amplitude of 0.72 µT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were ∼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%-4.2%, and rNOE range was 2.9%-10.5%. CONCLUSION: This work has demonstrated an excellent reproducibility of both inter- and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.


Subject(s)
Algorithms , Brain Neoplasms , Humans , Reproducibility of Results , Image Interpretation, Computer-Assisted/methods , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Protons
9.
Magn Reson Med ; 89(4): 1357-1367, 2023 04.
Article in English | MEDLINE | ID: mdl-36372994

ABSTRACT

PURPOSE: The nuclear Overhauser effect (NOE) quantification from the steady-state NOE imaging suffers from multiple confounding non-NOE-specific sources, including direct saturation, magnetization transfer, and relevant chemical exchange species, and is affected by B0 and B1 + inhomogeneities. The B0 -dependent and B1 + -dependent data needed for deconvolving these confounding effects would increase the scan time substantially, leading to other issues such as patient tolerability. Here, we demonstrate the feasibility of brain lipid mapping using an easily implementable transient NOE (tNOE) approach. METHODS: This 7T study used a frequency-selective inversion pulse at a range of frequency offsets between 1.0 and 5.0 parts per million (ppm) and -5.0 and -1.0 ppm relative to bulk water peak. This was followed by a fixed/variable mixing time and then a single-shot 2D turbo FLASH readout. The feasibility of tNOE measurements is demonstrated on bovine serum albumin phantoms and healthy human brains. RESULTS: The tNOE measurements from bovine serum albumin phantoms were found to be independent of physiological pH variations. Both bovine serum albumin phantoms and human brains showed broad tNOE contributions centered at approximately -3.5 ppm relative to water peak, with presumably aliphatic moieties in lipids and proteins being the dominant contributors. Less prominent tNOE contributions of approximately +2.5 ppm relative to water, presumably from aromatic moieties, were also detected. These aromatic signals were free from any CEST signals. CONCLUSION: In this study, we have demonstrated the feasibility of tNOE in human brain at 7 T. This method is more scan-time efficient than steady-state NOE and provides NOE measurement with minimal confounders.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Algorithms , Brain/diagnostic imaging , Brain/metabolism , Feasibility Studies , Magnetic Resonance Imaging/methods , Sensitivity and Specificity , Serum Albumin, Bovine , Water/metabolism , Phantoms, Imaging
10.
Front Pharmacol ; 13: 1025591, 2022.
Article in English | MEDLINE | ID: mdl-36532778

ABSTRACT

Background: Ayurveda, the indigenous medical system of India, has chemosensory property (rasa) as one of its major pharmacological metric. Medicinal plants have been classified in Ayurveda under six rasas/tastes-sweet, sour, saline, pungent, bitter and astringent. This study has explored for the first time, the use of Electronic tongue for studies of rasa-based classification of medicinal plants. Methods: Seventy-eight medicinal plants, belonging to five taste categories (sweet, sour, pungent, bitter, astringent) were studied along with the reference taste standards (citric acid, hydrochloric acid, caffeine, quinine, L-alanine, glycine, ß-glucose, sucrose, D-galactose, cellobiose, arabinose, maltose, mannose, lactose, xylose). The studies were carried out with the potentiometry-based Electronic tongue and the data was analysed using Principle Component Analysis, Discriminant Function Analysis, Taste Discrimination Analysis and Soft Independent Modeling of Class Analogy. Results: Chemosensory similarities were observed between taste standards and the plant samples-citric acid with sour group plants, sweet category plants with sucrose, glycine, ß-glucose and D-galactose. The multivariate analyses could discriminate the sweet and sour, sweet and bitter, sweet and pungent, sour and pungent plant groups. Chemosensory category of plant (classified as unknown) could also be identified. Conclusion: This preliminary study has indicated the possibility of fingerprinting the chemosensory-based ayurvedic classification of medicinal plants using E-tongue coupled with multivariate statistical analysis.

11.
J Biomol Struct Dyn ; 40(14): 6211-6227, 2022 09.
Article in English | MEDLINE | ID: mdl-33538239

ABSTRACT

New thiazole-thiazolidinedione hybrids (5a-k) were efficiently synthesized and evaluated for their in-vitro antimicrobial activity against four fungal and bacterial strains. The chemical structures of the compounds were elucidated by FTIR, 1H NMR, and 13C NMR spectral data. Most of the synthesized compounds were sensitive against gram positive, gram negative bacterial and fungal strains. Among the synthesized molecules, compounds 5h, and 5i exhibited promising inhibitory activity against all selected fungal strains and gram positive bacteria namely, Staphylococcus aureus, and Enterococcus faecalis. The molecular docking results predicted that the thiazole-thiazolidinedione derivatives bind to the active site protein ATP-binding pocket from E. coli, S. aureus and C. albicans with good interaction energy scores. Ct-DNA was used to evaluate the binding interactions of the selected compounds by means of absorption spectroscopy. To further characterize the drug-likeness and ADME properties were calculated using the Qikprop, the result of present study suggests that thiazole-thiazolidinedione hybrid could be an interesting approach for the design of new antimicrobial agents.Communicated by Ramaswamy H. Sarma.


Subject(s)
Anti-Infective Agents , Thiazolidinediones , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacteria , Escherichia coli , Fungi , Microbial Sensitivity Tests , Molecular Docking Simulation , Staphylococcus aureus , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacology , Thiazolidinediones/chemistry , Thiazolidinediones/pharmacology
12.
Pol J Pathol ; 72(2): 117-125, 2021.
Article in English | MEDLINE | ID: mdl-34706518

ABSTRACT

Tag-sequencing is a modified next-generation sequencing (NGS) approach wherein targeted regions are tagged with unique molecular identifiers enabling error-free detection of rare genomic alterations. We aimed to perform this high- fidelity sequencing to identify actionable variants from the plasma of lung cancer patients. Targeted sequencing was performed from plasma-derived cell-free nucleic acid in twenty-one advanced, treatment naïve, non-small-cell lung cancer (NSCLC) patients. Clinically significant genetic alterations were compared with matched tumor NGS profile for each patient (patient-level), and separately for each alteration (variant-level). Cross-platform validation was done for EGFR and KRAS mutations (real-time PCR) and ALK1 rearrangement (immunohistochemistry). Forty-seven alterations (26 in plasma and 21 in tumor tissue) were detected in 19/21 tested cases. Overall-concordance between the two assays was 94.87% (κ of 0.71, 95% CI: 0.54-0.89). Patient-level and genic-concordance was 57.1% (12/21 cases) and 67.86%, respectively. Almost perfect agreement was reached for detecting actionable EGFR mutations and ALK1 rearrangement (κ of 0.89 and κ of 1, respectively), which was confirmed by single-gene testing. Substantial agreement between the assays makes Tag-sequencing a viable option for identifying multibiomarkers from the plasma of advanced NSCLC patients in special circumstances where tissue has depleted/tumor is inaccessible/high risk of biopsy due to existing comorbidities.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Biopsy , Carcinoma, Non-Small-Cell Lung/genetics , High-Throughput Nucleotide Sequencing , Humans , Lung Neoplasms/genetics , Mutation
13.
J Pathol Transl Med ; 55(5): 324-329, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34465078

ABSTRACT

BACKGROUND: A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as "MET exon 14 skipping" (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing. METHODS: This is a home brew assay which was developed with the concept that the transcripts from true ΔMET14 will be shorter by ~140 bases than their wild type counterparts. The cases which were called MET exon 14 skipping positive on next-generation sequencing (NGS) were subjected to this assay, along with 13 healthy controls in order to establish the validity for true negatives. RESULTS: Thirteen cases of ΔMET14 mutation were detected on NGS using RNA-based sequencing. Considering NGS as a gold standard, the sizing assay using both gel and capillary electrophoresis that showed 100% specificity for both with concordance rates of 84.6% and 88.2% with NGS, respectively, were obtained. CONCLUSIONS: Owing to the cost-effective nature and easy to use procedures, this assay will prove beneficial for small- and medium-sized laboratories where skilled technical personnel and NGS platforms are unavailable.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-21263331

ABSTRACT

BackgroundWe report the findings of a large follow-up community-based serosurvey and correlating it with the COVID-19 test-positivity rate and the case load observed during the peak of the second wave of the Covid-19 pandemic in Delhi, India. MethodsIndividuals of age [≥]5 years were recruited from 274 wards of the state (population [~] 19.6 million) during January 11 to January 22 2021. A total of 100 participants each were included from all the wards for a net sample size of [~]28,000. A multi-stage sampling technique was applied for selection of participants for the household serosurvey. Anti SARS CoV-2 IgG antibodies were detected by using the VITROS assay (90% Sn, 100% Sp). ResultsAntibody positivity was observed in 14,298 (50.76%) of the 28,169 samples. The age, sex and district population weighted seroprevalence of the IgG SARS-CoV-2 was 50.52% (95% C.I. 49.94-51.10) and after adjustment for assay characteristics was 56.13% (95% C.I. 55.49-56.77). On adjusted analysis, participants aged [≥]50 years, of female gender, housewives, having ever lived in containment zones, urban slum dwellers, and diabetes or hypertensive patients had significantly higher odds of SARS-CoV-2 antibody positivity. The peak infection rate and the test positivity rate since October 2020 were initially observed in mid-November 2020 with a subsequent steep declining trend, followed by a period of persistently low case burden lasting until the first week of March 2021. This was followed by a steady increase followed by an exponential surge in infections from April 2021 onwards culminating in the second wave of the pandemic. ConclusionsThe presence of infection induced immunity from SARS-CoV-2 even in more than one in two people can be ineffective in protecting the population.

15.
ESC Heart Fail ; 8(4): 2698-2712, 2021 08.
Article in English | MEDLINE | ID: mdl-33991175

ABSTRACT

AIMS: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants. METHODS AND RESULTS: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak ), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t1/2, Cr ) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak , VT, and VO2 efficiency than either control group (all P < 0.05). The t1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF. CONCLUSIONS: Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF.


Subject(s)
Heart Failure , Exercise Tolerance , Heart Failure/diagnosis , Heart Failure/metabolism , Humans , Muscle, Skeletal/metabolism , Oxygen Consumption , Proteomics , Stroke Volume
17.
Cancer Rep (Hoboken) ; 4(4): e1348, 2021 08.
Article in English | MEDLINE | ID: mdl-33660436

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy followed by brachytherapy is the standard of care in locally advanced carcinoma cervix. There is no prognostic factor at present to predict the outcome of disease in locally advanced carcinoma cervix. AIM: Differential expression of microRNAs can be used as biomarkers to predict clinical response in locally advanced carcinoma cervix patients. METHODS: Thirty-two patients of locally advanced carcinoma cervix with International Federation of Gynecology and Obstetrics Stage IB-IVA were enrolled from 2017 to 2018. Expression of microRNA-9 5p, -31 3p, -100 5p, -125a 5p, -125b-5p, and -200a 5p in formalin-fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pretreatment evaluation was done with clinical examination and MRI pelvis. All patients received concurrent chemoradiotherapy followed by brachytherapy. Patients were evaluated for the clinical response after 3 months of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Patients with no residual disease were classified as Complete responders (CR) and with residual or progressive disease were classified as Nonresponders (NR). Results were statistically analyzed using Mann Whiney U test to examine significant difference between the expression of microRNA between complete responders (CR) and nonresponders (NR). RESULTS: microRNA-100 5p was upregulated in complete responders (CR) which showed a trend towards statistical significance (p value = 0.05). CONCLUSION: microRNA-100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix. Its role should be further investigated in a larger study population.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/therapy , Chemoradiotherapy/statistics & numerical data , MicroRNAs/metabolism , Uterine Cervical Neoplasms/therapy , Adult , Aged , Biomarkers, Tumor/analysis , Biopsy , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Cervix Uteri/pathology , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/analysis , Middle Aged , Response Evaluation Criteria in Solid Tumors , Up-Regulation , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
18.
NMR Biomed ; 34(6): e4503, 2021 06.
Article in English | MEDLINE | ID: mdl-33749037

ABSTRACT

Glutamate-weighted CEST (gluCEST) imaging is nearly unique in its ability to provide non-invasive, spatially resolved measurements of glutamate in vivo. In this article, we present an improved correction for B1 inhomogeneity of gluCEST images of the human brain. Images were obtained on a Siemens 7.0 T Terra outfitted with a single-volume transmit/32-channel receive phased array head coil. Numerical Bloch-McConnell simulations, fitting and data processing were performed using in-house code written in MATLAB and MEX (MATLAB executable). "Calibration" gluCEST data was acquired and fit with a phenomenological functional form first described here. The resulting surfaces were used to correct experimental data in accordance with a newly developed method. Healthy volunteers of varying ages were used for both fitted "calibration" data and corrected "experimental" data. Simulations allowed us to describe the dependence of CEST at 3.0 ppm (gluCEST) on saturation B1 using a new functional form, whose validity was confirmed by successful fitting to real human data. This functional form was used to parameterize surfaces over the space (B1 , T1 ), which could then be used to correct the signal from each pixel. The resulting images show less signal loss in areas of low B1 and greater contrast than those generated using the previously published method. We demonstrate that, using this method with appropriate nominal saturation B1 , the major limitation of correcting for B1 inhomogeneity becomes the effective flip angle of the acquisition module, rather than inability to correct for inhomogeneous saturation. The lower limit of our correction ability with respect to both saturation and acquisition B1 is about 40% of the nominal value. In summary, we demonstrate a more rigorous and successful approach to correcting gluCEST images for B1 inhomogeneity. Limitations of the method and further improvements to enable correction in regions with severe pathology are discussed.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Glutamic Acid/metabolism , Magnetic Resonance Imaging , Adult , Aged , Computer Simulation , Humans , Image Processing, Computer-Assisted , Middle Aged , Young Adult
19.
J Ayurveda Integr Med ; 12(2): 238-244, 2021.
Article in English | MEDLINE | ID: mdl-33551338

ABSTRACT

BACKGROUND: Although Electronic tongue is used in pharmaceutical, food and beverage industries for objective evaluation of taste, its use in medicinal plants from an ayurvedic perspective is novel. Control experiments are therefore necessary to standardise and optimise parameters. OBJECTIVE: The aim is to optimise the use of solvent and standardise sample concentration for study of plants from an ayurvedic standpoint of rasa. The major objectives are two-fold: (i) evaluate sensor response to different types of solvent water (ii) explore use of E-tongue in taste ranking of medicinal plants used in ayurveda. MATERIALS AND METHODS: Single, double and triple distilled, reverse osmosis and milliQ waters were evaluated separately and as a medium for preparing plant extracts. For taste ranking, standard addition method using d-glucose as sweet taste standard was used for different brands of mango juices (case in point study) and eight medicinal plants from sweet category. The effect of sample concentration and taste standard on taste ranking were evaluated. RESULTS: MQ and TD water demonstrated similar organoleptic properties whereas plant extracts prepared in DD and MQ water showed maximum taste-based differentiation. The mango juices were taste discriminated by E-tongue and ranked based on their sweetness scores. The relative ranking of plant samples showed concentration dependence and also varied with the concentration range of taste standard. CONCLUSION: Milli-Q and double distilled water can be used for E-tongue studies of medicinal plants. While the results open up the possibility of taste ranking of medicinal plants, they also demonstrate the importance of standardising and optimising the concentration of samples and taste standards in the context of ayurvedic rasa based studies.

20.
J Ayurveda Integr Med ; 12(2): 234-237, 2021.
Article in English | MEDLINE | ID: mdl-33514460

ABSTRACT

There is growing interest in understanding how ayurveda, the indigenous medical system of India, uses plants for therapeutic purpose. The aim of this two parts article is to explore how the analytical technique of Electronic tongue (E-tongue) can be used for studying rasa, one of the major ayurvedic parameter in the study of medicinal and nutritional plants. Although E-tongue is widely used in pharmaceutical, food and beverage industries for objective evaluation of taste, its use in plants from an ayurvedic perspective is novel. This first of the two parts article introduces the technique of E-tongue, positioning it in context for the following part. The latter discusses crucial control experiments required prior using E-tongue for studies on medicinal plants from an ayurvedic standpoint.

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