130553 research outputs found
Sort by
Contrast enhanced ultrasound versus MRI for response assessment of extra-abdominal desmoid Fibromatosis- A feasibility study
No full textBackground
Desmoid Fibromatosis (DF) is a locally aggressive soft tissue tumor which was traditionally managed with surgical excision. However due to high rates of local recurrence and insights about its behavior, there is now a paradigm shift towards active surveillance and medical management. Imaging plays a crucial role in surveillance and treatment response; however, conventional RECIST criteria are not adequate for DF. MRI is the preferred modality but faces limitation in availability and uniformity. Although ultrasound (US) is not optimal for evaluation, contrast enhanced US has shown promising results in many solid tumors.
Objectives
To explore the role of Contrast Enhanced Ultrasound (CEUS) as a response assessment tool in DF.
Materials and Methods
This was a prospective study conducted between March 2022 and December 2023 and included 21 adults with DF who received medical line of treatment. A combination of clinical evaluation for symptom relief, and imaging modalities using MRI and CEUS, were utilized for response assessment. Statistical analysis was performed using non parametric tests.
Results
Out of 21, 19 patients underwent pre as well as post-treatment evaluation. Clinical improvement was reported by 73.68 % while MRI indicated response only in 41.18 %; whereas only 29.41 % met the criteria for partial response according to RECIST 1.1. All responders on MRI exhibited continued enhancement on CEUS with a significant decrease in Mean Transit Time (MTT, p = 0.047).
Conclusion
CEUS demonstrates potential as an effective treatment response tool in DF, providing real-time information of microvascular changes within the mass
Dual-functional antibiotic adjuvant displays potency against complicated gram-negative bacterial infections and exhibits immunomodulatory properties
No full textThe treatment of Gram-negative bacterial infections is challenged by antibiotic resistance and complicated forms of infection like persistence, multispecies biofilms, intracellular infection, as well as infection-associated hyperinflammation and sepsis. To overcome these challenges, a dual-functional antibiotic adjuvant has been developed as a novel strategy to target complicated forms of bacterial infection and exhibit immunomodulatory properties. The lead adjuvant, D-LBDiphe showed multimodal mechanisms of action like weak outer membrane permeabilization, weak membrane depolarization, and inhibition of efflux machinery, guided primarily by hydrogen bonding and electrostatic interactions, along with weak van der Waals forces. D-LBDiphe potentiated antibiotics up to ∼4100-fold, targeted phenotypic forms of antibiotic tolerance, and revitalized antibiotics against topical and systemic infections of P. aeruginosa in mice. The aromatic moiety in D-LBDiphe was instrumental for interaction with lipopolysaccharide (LPS) micelles, and this interaction was the driving factor in reducing pro-inflammatory cytokines by 61.8–79% in mice challenged with LPS. Such multifarious properties of a weak-membrane perturbing, nonactive and nontoxic adjuvant have been discussed for the first time, supported by detailed mechanistic understanding and elucidation of structure-guided properties. This work expands the scope of antibiotic adjuvants and validates them as a promising approach for treatment of complicated bacterial infections and inflammation
463 Lipid metabolism reprogramming in eyelid sebaceous gland carcinoma
No full textBackground
Eyelid sebaceous gland carcinoma (SGC) is an aggressive malignancy.The status of lipid metabolism in SGC is not known. This study investigates Stearoyl-CoA desaturase (SCD1) and CD36 in eyelid SGC. SCD1 is the key rate-limiting enzyme of lipid metabolism and desaturates the saturated fatty acids (SFAs) to generate monounsaturated fatty acids (MUFAs). CD36 is a high-affinity receptor for long-chain fatty acids (FA) which facilitates FA uptake into the cell. CD36 functions as both a signal transducer and a fatty acid transporter. Both are upregulated in various cancers.
Design
This study evaluated 31 cases of histopathologically confirmed eyelid SGC and 10 normal controls (skin).Comprehensive qPCR gene expression profiles of SCD1 and CD36 and western blotting of SCD1 was done in all cases and controls. Patients were followed up for 25.71 ± 17.68 months. Statistical analysis was applied to determine the clinical significance of SCD-1 and CD-36.
Results
The mean age was 58.74 ±12.01 years, with a slight male predominance (55%). Tumors >2 cm were present in 25.8%, pagetoid spread in 45.1% and well differentiation was observed in 64.5% of the cases. There were 29% cases in AJCC T3/T4 stage. Four cases of recurrences, 2 with lymph nodes metastasis, one case each with distant metastasis and death. SCD1 and CD36 mRNA overexpression was observed in 67.7% and 61.2% patients respectively, 69.5% with age >50 years showed a high mRNA expression of SCD1 and 65.2% had high CD36. Females showed high SCD1 (85.7%) and CD36 (78.5%) expression and 57.1% of cases with pagetoid spread overexpressed both SCD-1 and CD-36. 62.5% of cases in T3/T4 stages showed high SCD-1 and 55.6% had high CD36 expression. Overexpression of SCD1 and CD36 was observed in 70% and 60% poorly differentiated tumors respectively. The single patient who died and 75% recurrent cases had high SCD1.CD36 overexpressed in all 4 recurrent cases and the patient who died. The mRNA expression of SCD1 correlated with mRNA expression of CD36 in 67.7% (21/31) cases. The protein expression of SCD1 by western blot correlated with the mRNA expression of SCD1.
Conclusions
In this first preliminary study on lipid metabolism in eyelid SGC patients, we observed upregulation of both SCD1 and CD36 in patients with poor prognostic features. A longer follow-up is warranted to confirm their roles as potential markers for identifying high-risk patients. SCD1 and CD36 could serve as molecular targets for therapeutic intervention in drug-resistant cases
79P Prospective study of endocrine effects and quality of life in paediatric and young CML patients on tyrosine kinase inhibitors: An experience from a tertiary care centre in India
No full textBackground
Chronic myeloid leukaemia (CML) is a rare form of childhood cancer, accounting for just 2-3% of paediatric leukaemia’s. While the introduction of tyrosine kinase inhibitors (TKIs) has significantly improved treatment outcomes, their long-term impact on endocrine functions and quality of life (QoL) in children is still not fully understood. This study investigates the off-target effects of TKIs on growth, bone health, metabolism, and QoL in paediatric CML patients.
Methods
This prospective observational study includes 82 paediatric and young adult CML patients who began TKI therapy before 18 years of age between 2004-2024 at AIIMS and NCI, India. Of these, 71 were on TKI therapy for over 2 years, and 11 were newly initiated during the study. Excluding those treated with chemotherapy or undergoing bone marrow transplant, the study assesses endocrine functions (BMD, thyroid, growth, pubertal development, gonadal, adrenal function, glucose/lipid metabolism) and QoL (EORTC QLQ-C30 for adults, PedsQL for children).
Results
A majority of patients were male (80.5%), and the median age at diagnosis was 12 years, with 66% presenting in chronic phase. The median age of the patients during study was 20 years, and the median duration of TKI exposure was 7.5 years. Short stature occurred in 15% of patients, mostly prepubertal at TKI initiation, linked to low IGF-1 levels but not growth hormone deficiency. Low BMD was noted in 35.2%, and 93% had vitamin D deficiency. Subclinical hypothyroidism was observed in 10% of patients, while dysglycemia and dyslipidaemia affected 11% and 8%, respectively. Infertility was noted in only one patient. QoL assessment revealed good physical and emotional functioning in younger patients, but poorer social functioning and older patients reported financial concerns and fatigue.
Conclusions
Prolonged TKI use in paediatric CML patients causes significant endocrine and metabolic complications, especially affecting growth and bone health. These effects are more severe in prepubertal patients. Regular monitoring of growth, bone density and thyroid function is vital and evaluation of all other endocrine functions can be done as clinically indicated
Evaluating the efficacy of Hip1R, Vimentin, and H3K27me3 as surrogate markers for 1p/19q co-deletion in oligodendrogliomas
No full textBackground
Assessment of the chromosomal 1p/19q status is essential to distinguish between IDH-mutant astrocytoma and oligodendroglioma. Genetic analyses, however, are expensive, time-consuming, and not widely accessible. Immunohistochemical loss of ATRX is currently the only established surrogate marker for a non-1p/19q co-deleted genotype. To find cost-effective approaches and improve risk stratification, we aimed to assess the immunohistochemical expression HIP1R, Vimentin, and H3K27me3 as surrogate markers in predicting 1p/19q status for oligodendrogliomas.
Methods
A total of 182 adult-type-diffuse gliomas were analyzed for IDH1 R132H, ATRX, P 53, MIB-1-LI, HIP1R, Vimentin, and H3K27me3 expression using immunohistochemistry. 1p/19q co-deletion was assessed by fluorescence in situ hybridization (FISH) assay. IDH sequencing was performed in IDH1 R132H negative cases. Histomorphological and molecular classification of these gliomas was performed according to World Health Organization (WHO) 2021 CNS5 classification.
Results
In this study, 102 IDH-mutant oligodendrogliomas, 44 IDH-mutant astrocytomas, and 36 IDH-wild-type glioblastomas exhibited distinct patterns of the IHC markers. In oligodendrogliomas, HIP1R showed either homogeneous or homogenous with mosaic staining, Vimentin was negative and H3K27me3 was lost in all cases. In Astrocytoma and glioblastomas, HIP1R was predominantly mosaic, Vimentin was widely positive, and H3K27me3 was variable. Combining these markers, especially the positivity of HIP1R, negative Vimentin, and complete loss of H3K27me3, achieved perfect diagnostic accuracy, making them highly reliable for differentiating oligodendroglioma from astrocytoma, and glioblastomas.
Conclusions
The study demonstrates that the combinations of the three immunohistochemical markers HIP1R, Vimentin, and H3K27me3 can accurately predict 1p/19q co-deletion status in IDH-mutant gliomas. This method offers a reliable, robust, cost-effective alternative to complex techniques like FISH
Uttarakhand: A Hotspot for Extreme Events?
No full textThis study investigates the spatial and temporal climate variability, particularly focusing on extreme hydrometeorological events, over Uttarakhand, India. Located within the Central Himalaya, the region is characterised by frequent extreme rainfall events during the Indian Summer Monsoon (ISM) and winter western disturbances (WDs). To understand the relationship between climate variability and global teleconnections (North Atlantic Oscillation (NAO), El Niño-Southern Oscillation (ENSO), Dipole Mode Index (DMI), we analysed four decades (1982–2020) of observational data, including rainfall, surface radiative temperature, and surface runoff, alongside teleconnection indices. A composite analysis of 140 hydro-meteorological events is performed to correlate climate variations. The results demonstrate significant spatial variability in rainfall and surface runoff between western and eastern Uttarakhand. A marked increase in extreme events, particularly during the monsoon season, is observed after 2010. Notably, the period 1998-2009 shows increased annual temperatures and decreased precipitation and surface runoff, coinciding with periods of low amplitudes in the considered global teleconnections
Assessing the role of regional characteristics in estimating the volume of glacial lakes in the upper Indus-Ganga-Brahmaputra basins, Hindu Kush Himalaya
No full textGlacial lakes have exponentially increased in the recent decades across the world’s mountains, particularly in the Hindu Kush Himalaya (HKH), caused by rapid melting of glaciers. Consequently, their water volume and hence the hazard potential had also increased in recent decades. Robust water volumes of hazardous glacial lakes located in remote locations are rarely available, limiting the accuracy of current glacial lake outburst flood (GLOF) models that heavily rely on empirical water volume estimation equations. The majority of presently used equations are mainly based on data collected in the European Alps and have limited applicability in the HKH region. Thus, accurately predicting GLOF extents and likely damages in the downstream regions remains a critical challenge in the HKH region. In this study, we developed eight empirical equations to estimate mean depth (4) and volume (4) of glacial lakes in the upper Indus-Ganga-Brahmaputra (IGB) river basins. The study is based on a field-based bathymetric dataset of 25 glacial lakes from different parts of the upper IGB river basins. Separate equations were formulated for the major basins to understand the influence of regional lake characteristics on depth and volume estimations of glacial lakes. Our analysis revealed a non-linear negative relationship between the circularity ratio of glacial lakes and their mean depth, indicating that elongated lakes tend to be deeper than the circular ones. The average circularity ratio of glacial lakes in the upper IGB basins was 0.51 (as of 2020). We estimated the mean depth and total volume for a dataset comprising 19,284 glacial lakes in the upper IGB basins. The estimated mean depth and total estimated volume of these lakes in 2020 was 7.20 m and 28.88 km3, respectively. The empirical equations generated in the study based on the field-based bathymetry will be helpful in assessing the GLOF threats from continuously expanding glacial lakes in the upper IGB basins
A Priori and A Posteriori Error Identities for the Scalar Signorini Problem
No full textIn this paper, on the basis of a (Fenchel) duality theory on the continuous level, we derive an a posteriori error identity for arbitrary conforming approximations of the primal formulation and the dual formulation of the scalar Signorini problem. In addition, on the basis of a (Fenchel) duality theory on the discrete level, we derive an a priori error identity that applies to the approximation of the primal formulation using the Crouzeix–Raviart element and to the approximation of the dual formulation using the Raviart–Thomas element, and leads to quasi-optimal error decay rates without imposing additional assumptions on the contact set and in arbitrary space dimensions
Convergence of an AFEM for a non-local nonlinear problem of Kirchhoff type
No full textIn this article, plain convergence of an adaptive finite element method is shown for a non-local problem of Kirchhoff type under the same assumptions on the data as in the paper of T. Gudi (2012) [21]. Then by imposing some additional assumptions on the data, convergence and quasi-optimality of an AFEM is proved for the Kirchhoff type problem. The theoretical results are illustrated by some numerical experiments
Demystifying the solvent sensitive onset of complexity and chirality transition in hierarchically organized co‐assembled organic‐inorganic superstructures
No full textProgramming the solvent mediated hierarchical organization and chirality transition in organic-inorganic co-assembled hybrid materials is attractive but still a challenge. The work presented in the manuscript reveals the development of solvent responsive R/S-Pyra-CEA building block which exhibited distinct absorption and chiroptical behavior in presence of Lewis base good co-solvents (THF/1,4-dioxane/DMSO) in self-assembled/co-assembled state in mixed aqueous media. The work proposes a simple strategy to employ subtle differences in the solvent characteristics as the control to direct the co-assembly of well-designed organic building block, inorganic component [Au (III) ions)], and chiral inducer (cysteine) through multiple hierarchical growth pathways for generating diverse chiral superstructures in mixed aqueous media which is unprecedented. The outcome of this study is expected to provide fresh insights for designing solvent sensitive building blocks to prepare nature mimic complex hierarchically organized chiral hybrid materials