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TCL-637: Outcome of peripheral T-Cell lymphomas-not otherwise specified (PTCL-NOS): An analysis from Northern India
No full textContext:
Peripheral T-cell lymphomas (PTCLs) represent a diverse category of non-Hodgkin lymphomas (NHLs), with PTCLnot otherwise specified (PTCL-NOS) being the predominant variant.
Objective:
This study aimed to present data on the demographics and outcomes of patients with PTCL who received treatment at a single institution in North India.
Design, Setting, and Participants:
This study was conducted on patients aged ≥18 years diagnosed with PTCL-NOS from January 2014 to December 2023 at AIIMS in New Delhi. Data regarding clinical characteristics, treatment modalities, tumor response, and survival outcomes were retrospectively obtained.
Results:
A total of 90 patients were recruited during the study period, and 80 patients were taken for response evaluation and outcome analysis. The median age was 46 years (range 18–81 years). An intermediate- to high- international prognosis index (IPI) score was 66.25%, bone marrow involvement was 12.5%, extranodal involvement was 60%, and elevated LDH was 50%. Moreover, 70% of patients had B symptoms and advanced (stage III/IV), and 60% had a performance status (PS) of >1. The majority of patients received anthracycline-based multiagent chemotherapy and etoposide-based chemotherapy. Complete remission (CR) rate was 70%, while the overall response rate was 82.3%. Only 12 patients underwent stem cell transplantation due to various logistical reasons. The median follow-up duration was 27 months. The 5-year event-free survival and overall survival rates were 35% and 44%, respectively. Univariate analyses indicated that performance status >1, age ≥60 years, serum albumin levels <3.5 g/dL, failure to achieve complete remission, extranodal involvement, and the presence of B symptoms were significantly correlated with poorer survival outcomes. In the multivariate analysis, only serum albumin levels <3.5 g/dL and failure to achieve CR significantly impacted survival. Two patients received brentuximab vedotin for advanced disease without autologous stem cell transplant and at the time of our analysis were in remission.
Conclusions:
Patients with PTCL in our Northern India cohort tend to present at a younger age and with more advanced disease stages compared with patients from Western countries. The poor prognosis for PTCL patients in our cohort emphasizes the need for standardized procedures for prompt diagnosis, referral, and treatment
Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche
No full textMetastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs from female mice harboring Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogates metastatic outgrowth. These findings implicate Brd7 and PBAF in triggering metastatic outgrowth in cancer, pointing to targetable underlying mechanisms involving specific immune cell compartments
Abstract 5931: Unraveling the genetic complexity of Ph-like ALL: development of a cost-effective diagnostic qPCR panel
No full textBackground:
Advancements in high-throughput sequencing have significantly expanded our understanding of B-cell Acute Lymphoblastic Leukemia (B-ALL). In particular, whole-transcriptome sequencing (WTS) has facilitated the discovery of the Ph-like ALL subtype. However, clinical integration of WTS remains challenging due to high costs and lack of standardized workflows. Ph-like ALL is marked by genetic heterogeneity, including diverse fusions and mutations, which complicates its diagnosis and limits targeted therapeutic options. This genetic complexity correlates with poor prognosis, emphasizing the need for accessible and effective diagnostic approaches.
Aim:
To develop a cost-effective, qPCR-based diagnostic panel for its detection and classification in clinical settings.
Methods:
A cohort of 394 newly diagnosed B-ALL cases were analyzed using RT-PCR and FISH for initial genetic screening. WTS was employed for comprehensive fusion detection, mutation analysis, and subtype classification. Kaplan-Meier survival analysis was used to evaluate patient outcomes, and a qPCR-based likelihood scoring model was developed based on differential gene expression (DEGs) to identify Ph-like ALL.
Results:
Whole transcriptome sequencing revealed that 13.1% of the B-ALL cases have Ph-like phenotype, found in different age groups: 9.7% in pediatric patients (n=15), 20.5% in adolescents and young adults (AYA, n=8), and 50% in adults (n=3). Ph-like ALL cases predominantly exhibited fusions involving JAK-STAT pathway genes (n=10), ABL-class genes (n=9), or NTRK1 (n=1), in addition to a novel RUNX1::FGF13 fusion (n=2). Differentially expressed genes were tested for diagnostic potential, with 9 genes (FZH2, PON2, CA6, OLFML2A, BAALC, PRKCZ, ZFPM2, TCFL5 and ENPP2) demonstrating significant ROC (p<0.0001 and sensitivity and specificity >80%) curves in a discovery cohort (n=79). This likelihood model also effectively distinguished Ph-like ALL in a validation cohort (n=150). Additionally, survival analysis revealed significantly worse event-free survival (EFS) and overall survival (OS) in Ph-like ALL patients compared to non-Ph-like patients (EFS: 0% vs. 43.3%, HR 3.40, p=0.006; OS: 0% vs. 45.4%, HR 3.57, p=0.005).
Conclusion:
This study underscores the genetic diversity of Ph-like ALL. The poor prognosis of Ph-like ALL, marked by significantly reduced EFS and OS, highlights the need for targeted therapeutic approaches. The cost-effective qPCR-based diagnostic panel provides a promising tool for the early detection of Ph-like ALL, offering potential for improved patient outcomes through timely intervention
First principle based delignification mechanism and kinetics of pine needles using Protic Ionic Liquid and Deep Eutectic Solvent in microwave and oil-bath reactors.
No full textBiomass and bio-based products play an important role in addressing anthropogenic climate change, presenting both opportunities and challenges [1]. Replacing fossil-based materials, like, plastics and chemicals by bio-based alternatives can significantly reduce emissions from production and disposal processes [2]. Additionally, many bio-based products are biodegradable, minimizing the landfill use and the associated greenhouse gas emissions [3]. However, the growing demand for bioenergy and bio-based products could put pressure on land resources, impacting food security and biodiversity [4].
Cellulose has traditionally been the primary focus of biomass utilization, comprehensive valorization of all major biopolymers, including lignin, is becoming increasingly important for the success of lignocellulosic biorefineries [5]. Lignin makes up a substantial portion of biomass—up to 40% on a dry basis [6]—and
Polymer-grafted silica based hybrid macrobeads for Pb(II) and Cr(VI) removal from water.
No full textThe presence of heavy metals in water deters its usability for drinking purposes. Indiscriminate disposal of industrial effluent into water bodies further complicates the situation. Accordingly, there is a dire need for a treatment system that can effectively remove the contaminants from water. Although there are solutions like the utilization of membrane and other powder-based adsorbers, challenges like high cost, fouling, scaling, the generation of a new class of waste (post usage), and limited recyclability often limit their usage. Hence, there is a critical need to develop a system that demonstrates high adsorption capacity, is reusable, and is easy to develop. Accordingly, we synthesized silylated polyethyleneimine, grafted it onto silica particles, and tested its efficacy in removing heavy metal contaminants like lead and hexavalent chromium from water. The resultant modified polyethyleneimine modified silica particles (termed as SiEP) outperformed many adsorber materials, including metal–organic framework, zeolite, clay, etc., and it demonstrated a staggering adsorption capacity (Langmuir) of 442 mg/g (pH 6) and 182 mg/g (pH 5) for lead and chromium, respectively at 30 °C. The developed nanopowder was further encapsulated inside polyacrylonitrile macrobeads and tested for its efficacy. Although the encapsulation resulted in a decrease in adsorption capabilities, common problems like high-pressure build-up and inefficient contact associated with powder-based adsorber were avoided upon encapsulation. The macrobeads exhibited 37 mg/g and 20 mg/g adsorption capacities for lead and chromium, respectively. For both the powder and the macrobeads, the adsorption capacity was tested in the presence of mixed ions and both the adsorber demonstrated their unique capability to be selective against targeted ions. They were further tested against a real groundwater matrix synthetically spiked with lead and chromium. Such findings open up a new avenue to developing water treatment materials that demonstrate selectivity and recyclability, indicating their potential for large-scale water treatment applications in industrial settings
Improving the accuracy of remotely sensed TSS and turbidity using quality enhanced water reflectance by a statistical resampling technique
No full textSatellite-based optical Remote Sensing (RS) presents a unique opportunity for monitoring the water quality of complex riverine systems stretching over large regions. However, due to the weak reflectance and resulting low signal-to-noise ratio of water bodies, interference of clouds and cloud shadows significantly impacts the accuracy of remotely sensed water quality parameters. This study presents a scalable, innovative cloud and cloud-shadow masking using the Gaussian Mixture Model (GMM) combined with a spatially aggregated reflectance sampling approach that can robustly monitor the Total Suspended Solids (TSS) and turbidity over selected sections of the study site, the Hooghly River in West Bengal, India. The statistical resampling approach based on GMM was applied to Sentinel-2 (S2) imagery to produce input to Machine Learning (ML) algorithms to retrieve the TSS and turbidity for target river sections. The resampled reflectance data was spatially aggregated over the selected regions of interest to further improve the input quality. Out of 80 cloud-contaminated images, we were able to use 70 images with 40%–50% clouds/cloud shadows for TSS and turbidity retrievals after applying the GMM-based masking and spatial aggregation. The resampled spectral data and in-situ TSS and turbidity measurements were used to train four ML models: Partial Least Squares Regression (PLSR), Random Forest Regression (RFR), Extreme Gradient Boosting (XGBoost), and Support Vector Regression (SVR). Our approach improved the estimation accuracy of the TSS by 33% and turbidity by 28% compared to the input processed using the built-in Sentinel-2 cloud and cloud shadow masks. This work emphasizes the importance of careful satellite image preparation for cloud and cloud-shadow screening and the utility of spatially aggregated reflectance samples over homogeneous regions of interest to enable robust water quality assessment under variable atmospheric conditions
Visual homogeneity computations in the brain enable solving property-based visual tasks
No full textMost visual tasks involve looking for specific object features. But we also often perform property-based tasks where we look for specific property in an image, such as finding an odd item, deciding if two items are same, or if an object has symmetry. How do we solve such tasks? These tasks do not fit into standard models of decision making because their underlying feature space and decision process is unclear. Using well-known principles governing multiple object representations, we show that displays with repeating elements can be distinguished from heterogeneous displays using a property we define as visual homogeneity. In behavior, visual homogeneity predicted response times on visual search, same-different and symmetry tasks. Brain imaging during visual search and symmetry tasks revealed that visual homogeneity was localized to a region in the object-selective cortex. Thus, property-based visual tasks are solved in a localized region in the brain by computing visual homogeneity
Western disturbances and climate variability: a review of recent developments
No full textWestern disturbances (WDs) are synoptic-scale weather systems embedded within the subtropical westerly jet. Manifesting as upper-level troughs often associated with a lower-tropospheric low over western or northern India, they share some dynamical features with extratropical cyclones. WDs are most common during the boreal winter (December to March), during which they bring the majority of precipitation – both rain and snow – to the western Himalaya, as well as to surrounding areas of north India, Pakistan, and the Tibetan Plateau. WDs are also associated with weather hazards such as heavy snowfall, hailstorms, fog, cloudbursts, avalanches, frost, and cold waves.
In this paper, we review recent developments in understanding WDs and their impacts. Over the last decade, recent studies have collectively made use of novel data, novel analysis techniques such as tracking algorithms, and the increasing availability of high-resolution weather and climate models. This review is separated into six main sections – structure and thermodynamics, precipitation and impacts, teleconnections, modelling experiments, forecasting at a range of scales, and paleoclimate and climate change – each motivated with a brief discussion of the accomplishments and limitations of previous research.
A number of step changes in understanding are synthesised. Use of new modelling frameworks and tracking algorithms has significantly improved knowledge of WD structure and variability, and a more frequentist approach can now be taken. Improved observation systems have helped quantification of water security over the western Himalaya. Convection-permitting models have improved our understanding of how WDs interact with the Himalaya to trigger natural hazards. Improvements in paleoclimate and future climate modelling experiments have helped to explain how WDs and their impacts over the Himalaya respond to large-scale natural and anthropogenic forcings. We end by summarising unresolved questions and outlining key future WD research topics
Precision targeting of fat metabolism in triple negative breast cancer with a biotinylated copolymer.
No full textMitochondrial CPT1-mediated fatty acid β-oxidation (FAO) critically contributes to the accelerated metastatic expansion of triple negative breast cancer (TNBC). Hence, inhibition of FAO through active CPT1 targeting could be a promising therapeutic approach in anti-TNBC therapies. Herein, we strategically synthesized a pyrene chain end labelled copolymer bearing biotin pendants, CP4, that actively targets CPT1 and efficiently blocks FAO in metastatic TNBC. Following the comprehensive characterization and synthesis of CP4, in silico negative docking score and Ramachandran plot analyses confirmed its on-target binding potential to CPT1. As a result, CP4 disrupts mitochondrial membrane potential, generates excessive ROS, and restricts excessive ATP production by impairing mitochondrial respiration, glycolytic function, and FAO. Subsequently, CP4 suppressed FA uptake and regulated FAO-associated gene expressions, exhibiting successive metastatic growth inhibition and apoptosis induction. Also, in an animal model, CP4 demonstrated active binding to CPT1, as evidenced by the significant depletion of CPT1A expression in tumor and liver tissue, akin to the specific CPT1-targeted drug. This active targeting of CPT1 has further consolidated the healing of altered lipid and oxidative stress, resulting in remarkable tumor regression, highlighting CP4 as a promising anticancer therapy focused on mitochondrial FAO, advancing future breast cancer treatments
Visible light‐triggered precision so<sub>2</sub> release from polymeric nanomedicine for cancer therapy
No full textA number of polymeric sulfur dioxide (SO2)-releasing nanomedicines have demonstrated promise in cancer treatment by enabling controlled SO2 release, triggered by endogenous (redox) stimuli. However, the heterogeneous distribution of these endogenous stimuli across different organs presents a significant challenge to clinical translation. To overcome this limitation, developing SO2 donors that respond to exogenous triggers offers a promising strategy for therapeutic advancement. Herein, an exogenous stimuli-responsive strategy is presented for generating SO2 from a series of amphiphilic block copolymers (BCPx) under visible light irradiation (427 nm) in a biological environment, aiming to evaluate their potential for cancer therapy. The coumarin-based, water-soluble polymers form well-defined nanostructures (BCPxNs) in aqueous media, releasing 70–85% of the theoretical SO2 within 4 h. Moreover, the BCPxNs nanostructures exhibit self-reporting behavior upon SO2 release. In vitro cellular assays with BCP2Ns nanostructures demonstrate an enhanced antiproliferative effect in cervical carcinoma HeLa cells under visible light irradiation (427 nm), with an IC50 value of 0.3 mg mL−1. Investigations using confocal microscopy and flow cytometry confirm SO2-induced cell death. Overall, this strategy underscores the potential of light-responsive polymeric SO2 donors with spatiotemporal control for cancer therapy