Impact of Rituximab maintenance on outcomes in Follicular lymphoma: An Indian experience

Background: Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) and comprises 9 % of total NHL in India. Rituximab maintenance (RM) after induction immunochemotherapy improves PFS. However, currently, no data exists from the Indian continent regarding the impact of Rituximab maintenance (RM) on overall survival (OS) & progression-free survival (PFS). Our study aims to assess if RM improves the outcomes in FL patients. Methods: This retrospective study included 95 patients diagnosed with FL meeting GELF criteria and registered at our institute All India Institute of Medical Sciences Delhi between January 2012 -December 2023. Among these, forty -four (46 %) patients received 2 years of RM every 2 months after induction immunochemotherapy. The primary outcome were overall survival (OS) and progression-free survival. Secondary outcomes were factors affecting OS & PFS. Results: Out of the 95 patients who met GELF criteria, 52 were male and 43 were female, with a median age of 53 years (range: 27–81). Advanced Ann Arbor stage III/IV comprises 82 (86 %) patients. Bone marrow involvement and bulky disease were observed in 36 (38 %) and 29 (31 %) patients respectively. Based on the Follicular Lymphoma International Prognostic Index (FLIPI-1), 27 (28 %) were low risk, 9 (10 %) intermediate risk, and 59 (62 %) were high risk. The complete remission (CR) was achieved in 71 % of patients. During follow-up, 27 (28 %) patients experienced relapsed and 8 patients transformed to diffuse large B-cell lymphoma (DLBCL). At a median follow-up of 63 months, the median OS was not reached. The median PFS was 122 months in the RM group and 94 months in the non-RM group, with 5-year PFS of 91.6 % vs 59.3 %, respectively (log-rank p = 0.017). Rituximab maintenance was independently associated with improved PFS (adjusted HR 0.28, 95 % CI: 0.12–0.65, p = 0.003). Failure to attain CR (aHR 2.49, 95 % CI: 1.20–5.19, p = 0.015) and bone marrow involvement (aHR 2.92, 95 % CI: 0.99–8.63, p = 0.05) were independently associated with inferior PFS. Conclusions: Rituximab maintenance after induction immunochemotherapy significantly improved PFS. This is the first study from India demonstrating the impact of rituximab maintenance in FL

Regional responses to oceanic variability constrain global drought synchrony

Synchronized droughts threaten global food security, with concerns about increased frequency and duration under climate change. However, their long-term evolution and physical limits remain unknown. We analyze 61 drought networks over 120 years (1901–2020) of Self Calibrating palmer drought severity index (sc-PDSI) data, employing a suite of network synchronization measures and empirical orthogonal functions to unravel the physical drivers and limiters of drought synchrony. Our results show that, contrary to claims that synchronized droughts could affect up to one sixth of the global land mass, the maximum synchronized area fluctuates between 1.84% and 6.5% of the total land mass. Although we observe a strong dependence between drought onset and local crop failures, global drought synchrony is shaped by a dichotomy: temperature trends exacerbate it, while precipitation variability, modulated by sea surface temperature oscillations, limits it. This suggests that although drought hubs are increasing, large-scale synchronization across multiple agricultural regions is less widespread than expected, affecting global food security strategies

Treatment of leather industry effluents by membrane-based technologies.

Membrane processes represent useful approaches for the treatment of industrial wastewater due to their advantages over conventional separation processes that include mild operating conditions of temperature and pressure, high selectivity towards target solutes, non-use of additives and consequently reduced risk of contamination, ease scale-up and low energy consumption. This chapter provides an overview of membrane-based technologies of practical and potential interest for the treatment of spent effluents from beamhouse, tanning and post-tanning operations as well of global effluents of the leather industry. Typical advantages over conventional methodologies and process designs in agreement with zero discharge approaches and circular economy principles are highlighted and discussed

Development of multimodel-based hydrologic outlook for India

Real-time monitoring and early warning systems for hydrological variables are essential for the decision making for managing water resources and agricultural activities. Notwithstanding the considerable progress in operational weather and climate forecast in India, efforts to develop a multimodel-based hydrological outlook utilizing the meteorological forecast have been lacking. Here using gridded observations, meteorological forecast, and ensemble of three hydrological models (VIC, Noah-MP, and H08), we examine the potential of meteorological forecast for the development of a hydrologic outlook at a short-to-subseasonal lead time. We evaluate the role of multivariate bias correction that ensures co-variability of precipitation and temperature in the monsoonal climate on the prediction skills of hydrologic outlook components (precipitation, temperature, evapotranspiration, runoff, soil moisture, and streamflow). The raw forecast from the Extended Range Forecast System (ERFS) showed overall wet bias in precipitation and warm bias in maximum and minimum temperatures, which was significantly improved after the multivariate bias correction. As the bias correction of meteorological forecast and post-processing of streamflow resulted in the best prediction skills, we used it to develop the hydrologic outlook. The developed hydrologic outlook demonstrated reasonable forecast skills at 1-30 day lead time for extreme dry and wet conditions. The multimodel-based hydrologic outlook can assist the decision making in water resources and agriculture in India

Plasma levels of hydroxychloroquine and seroconversion in health care workers during COVID prophylaxis: Retrospective evaluation using pharmacokinetic simulation

Objectives: Hydroxychloroquine (HCQ) was repurposed for prophylactic use against coronavirus disease-19. However, justification for the different regimens used for prophylaxis lacks rationale. Thus, this study retrospectively assessed the therapeutic plasma levels of HCQ using simulation-based pharmacokinetic estimates for rationalising the dose of HCQ. Materials and Methods: A total of 246 healthcare workers (HCWs) took the HCQ prophylaxis as per the Indian Council of Medical Research (ICMR) dosing. Besides, healthy volunteers (HWs) consumed HCQ following the ICMR regimen. Serum levels of HCQ in HCWs and HWs were analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The detected HCQ levels pharmacokinetic parameters were derived and used for the simulation studies to predict free drug and lung (tissue) levels. The HCQ levels were correlated with seroconversion, and adverse effects and correlated with predicted levels. Results: The HCQ plasma concentration of HCWs falls into the therapeutic window of HCQ as predicted by the simulation studies. The simulated data showed that the ratio of plasma to lung (tissue levels) as well as to epithelial lining fluid levels (free drug levels) could reach in adequate levels of reported IC50. Poor correlation was observed for the HCQ concentration and duration of prophylactic treatment in HCWs, while the seropositivity was negatively correlated with the HCQ levels in non-responders in HCWs. Conclusion: The study revealed that adequate plasma HCQ levels were reached following the prophylaxis schedule to exhibit protection against severe acute respiratory syndrome coronavirus 2. However, the lack of any advantages in the clinical studies highlights the paradox of the absence of in vitro-in vivo correlation

Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma

T cells are essential for tumor immunosurveillance and disease regulation in Multiple Myeloma (MM), but their role in disease pathogenesis is not well understood. To investigate this, we analyzed T cell subsets for activation status, relative distribution of naïve and memory T cell populations, regulatory T cells (Tregs), and circulating follicular helper T cells (cTFH) in the peripheral blood of 40 newly diagnosed MM (NDMM) patients. We also assessed inhibitory receptor expression CD160, ICOS/CD278, CD152/CTLA-4, and PD-1/CD279 on T cells in peripheral blood. Our results showed reduced T cell numbers, an imbalance between naïve and effector CD4+ T cells, and decreased memory Tregs in newly diagnosed MM patients compared to healthy controls. Furthermore, plasma cells in the bone marrow correlated with percentage of activated cTFH cells and inhibitory receptor expressing T cells in peripheral blood indicating that disrupted T cell homeostasis and immune-mediated processes may drive disease progression in NDMM

BBX22 enhances the accumulation of antioxidants to inhibit DNA damage and promotes DNA repair under high UV‐B

Under changing climatic conditions, plant exposure to high-intensity UV-B can be a potential threat to plant health and all plant-derived human requirements, including food. It's crucial to understand how plants respond to high UV-B radiation so that proper measures can be taken to enhance tolerance towards high UV-B stress. We found that BBX22, a B-box protein-coding gene, is strongly induced within one hour of exposure to high-intensity UV-B. Our metabolomics data indicated that BBX22 promotes the accumulation of antioxidants like ascorbic acid and proline. These antioxidants play a vital role in shielding plants exposed to high UV-B from the detrimental effects of Reactive Oxygen Species (ROS), including DNA damage. Additionally, BBX22 promotes DNA damage repair by inducing the expression of DNA repair genes like UVR1 and UVR3. BBX22 directly binds to the promoter of UVR1 to regulate its expression. Furthermore, BBX22 indirectly induces the expression of UVR1 and UVR3 by enhancing the binding of HY5 to their promoters. Together, these results suggest a multi-pronged role of BBX22 in protection against high-intensity UV-B. Enhancing BBX22 levels or its orthologs in different plant species can potentially offer DNA damage protection and tolerance against intense UV radiation

Caregiver Burden and Quality of Life Among Parents of Children With Cancer: A Cross-Sectional Study

Background Parents caring for children with cancer face substantial physical, emotional, social, and financial challenges, especially in low- and middle-income countries like India. Objective In this study, we aimed to assess caregiver burden and quality of life among parents of children with cancer in the Indian context, and to describe the socio-cultural and economic factors influencing these outcomes. Methods In this cross-sectional study, 200 primary caregivers of paediatric oncology patients were assessed using the Zarit Burden Interview (ZBI), WHOQoL-BREF, and the Multidimensional Scale of Perceived Social Support (MSPSS). Socio-demographic and clinical data were collected through interviews and review of medical records. Results The median ZBI score was 66 (IQR 23.5), with 66% of caregivers experiencing severe burden. Caregiver burden was higher among mothers, caregivers with lower education, those unemployed, and those living in nuclear families. Burden negatively correlated with duration of illness (r = −0.75, P < 0.05) and quality of life across all domains. Perceived social support was low, particularly among caregivers living alone or in nuclear families. Conclusions High caregiver burden and impaired quality of life were observed among caregivers in a resource-limited setting. Strengthening social support and implementing family-centred interventions may help reduce the burden and improve outcomes

Precision targeting of fat metabolism in triple negative breast cancer with a biotinylated copolymer.

Mitochondrial 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

Contrast enhanced ultrasound versus MRI for response assessment of extra-abdominal desmoid Fibromatosis- A feasibility study

Background 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