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Recently, the concerns about micro- and nano-plastics (NPs) toxicity have been increasing constantly, however the investigations are quiet meager. The present study provides evidences on the toxicological prospectives of virgin-, coronated- and isolated-NPs on human blood cells and Allium cepa root tip, respectively. Several plasma proteins displayed strong affinity towards NPs and produced multi-layered corona of 13 nm to 600 nm size. The coronated-NPs often attracted each other via non-specific protein-protein attraction which subsequently induced protein-induced coalescence in NPs. In the protein point of view, the interaction caused conformational changes and denaturation of protein thereby turned it as bio-incompatible. The coronated-NPs with increased protein confirmation changes caused higher genotoxic and cytotoxic effect in human blood cells than the virgin-NPs. On the other hand, virgin-NPs and the NPs isolated from facial scrubs hindered the root growth and caused chromosome aberration (ring formation, C-mitotic and chromosomal breaks, etc.) in root of Allium cepa . At the outset, the present study highlights the urgent need of scrutinization and regulation of NPs use in medical applications and pre-requisition of additional studies for assessing the bio-accumulation and bio-magnification of NPs.

Extreme temperature events are one of the most serious threats resulting from climatic change across the globe. Quantifying the intensity, duration, and frequency of temperature extremes is of huge societal and scientific interest. Recent evidence in climate change challenges the stationarity assumption conventionally followed while performing temperature-duration-frequency (TDF) analysis. India has distinct climate zones and topography, distributing climate threats unevenly. In this study, stationary (S) and non-stationary (NS) TDF analysis for India and its seven temperature homogenous areas is performed using a gridded (1° × 1°) daily maximum temperature dataset from 1951 to 2019. Time is employed as a covariate to incorporate linear, quadratic, and exponential trends in the location and/or scale parameters of the generalized extreme value distribution to demonstrate the impact of non-stationarity in developing TDF curves. According to the findings, NS TDF models provide a better fit to the dataset when compared to the S TDF model. More than 55% of the grid points have NS Model-1, viz., location parameter linearly varying with time, as the best-fit model. In contrast to their stationary counterparts, NS temperature return levels were consistently higher across all return periods. Furthermore, temperature homogenous zones in the North-West, North Central, and Interior Peninsula are more susceptible to temperature rises beyond 45°C. While envisioning long-term solutions in a changing climate scenario, considering non-stationarity significantly improved the accuracy of TDF curves. This will indeed support more robust predictions, which will ultimately aid in the mitigation of future extreme temperature events.

Letter to the Editor

The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively ( p  = 0.23). At a median follow-up of 3.5 months (range, 0.39–10.92), the estimated 3 month and 6 month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. 78 unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64 ; p  = 0.001).

Large-scale global climatic oscillations (GCOs) play a vital role in modulating the hydrometeorological patterns across the Globe. Recently, Kerala, the southwest coastal State of India has been increasingly impacted by consecutive extreme weather events highlighting the State’s increased vulnerability to climate variability. This study presents a comprehensive evaluation of multiscale teleconnections between five key hydrometeorological variables: temperature, rainfall and drought (represented using Standardised precipitation index at 3-, 6-, and 12-month scales) and five major GCOs: El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), Indian Ocean Dipole (IOD), North Atlantic Oscillation (NAO) and Atlantic Multidecadal Oscillation (AMO). The analysis covers a 41-year period (1980–2020) across three major urban cities of Kerala: Trivandrum, Kochi, and Kozhikode, with the help of bivariate and multivariate wavelet coherence analysis to capture the localised and time-varying associations between GCOs and hydrometeorological variables. The study proposes a percentage of significant coherence differencing (PSD) scheme to quantify the relative significance of each GCO in the multivariate framework, addressing the limitations of traditional additive methods. The ENSO consistently emerged as a dominant modulator for all the hydroclimatic patterns across all the cities. However, the addition of AMO and/or IOD with ENSO play variable but significant roles in modulating the rainfall and temperature patterns whereas addition of NAO and/or PDO is found to be influential for drought analysis. The PSD scheme offers a refined approach for understanding climate teleconnections and the study findings underscore the need for location-specific analyses to support climate resilience strategies in monsoon-dependent regions like Kerala.

We assessed differences in survival between non-Hispanic black (NHB) and non-Hispanic white (NHW) patients with multiple myeloma (MM), and the sequential effects of patient characteristics, and diagnosis and treatment-related factors on the survival disparity using data from 3319 NHB and 20,831 NHW MM patients in the SEER-Medicare (1999–2017) database. Four sets of 3319 NHWs were matched sequentially to the same set of 3319 NHBs, based on demographics (age, sex, year of diagnosis, marital status, and SEER site), socioeconomic status (SES, demographics plus SES), presentation factors (SES variables plus comorbidity), and treatment factors (presentation variables plus antimyeloma therapies). We found NHBs were less likely to receive treatment than NHWs even among patients matched for demographics, SES, and comorbidities. The absolute difference in 5-year survival between NHBs and NHWs was not significant in the demographics match (0.6%; P = 0.30) and remained non-significant after matching for SES (1.4%, P = 0.17). When matching for presentation, NHBs had significantly longer 5-year survival than NHWs (absolute difference = 3.8%, P = 0.003). Additional matching on treatment-related factors further enlarged the racial difference in 5-year survival to 4.6% (P < 0.001). Our findings reinforce the importance of equitable access to effective treatment modalities to further improve the survival of NHB patients with MM.

The proteasome inhibitor (PI) \"bortezomib\" has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination. It is well tolerated and can be administered in the outpatient setting with manageable toxicity. The key to good results is managing side effects so that patients remain on therapy with minimal interruptions. Therefore, proactive management of peripheral neuropathy and thrombocytopenia is advised using dose delay and reduction strategies. The recent introduction of second- and third-generation PIs with different chemical and biological properties has resulted in a plethora of new clinical studies and has confirmed the ongoing role of this class of drugs in future myeloma therapy.

Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses the current reporting trends of +1q, the efficacy of existing regimens on +1q, and its prognostic implications in MM randomized controlled trials (RCTs). Pubmed, Embase and Cochrane Registry of RCTs were searched from January 2012 to December 2022. Only MM RCTs were included. A total of 124 RCTs were included, of which 29 (23%) studies reported on +1q. Among them, 10% defined thresholds for +1q, 14% reported survival data separately for gain and amp, and 79% considered +1q a high-risk cytogenetic abnormality. Amongst RCTs that met the primary endpoint showing improvement in progression free survival (PFS), lenalidomide maintenance (Myeloma XI), selinexor (BOSTON), and isatuximab (IKEMA and ICARIA) were shown to improve PFS for patients with evidence of +1q. Some additional RCT’s such as Myeloma XI+ (carfilzomib), ELOQUENT-3 (elotuzumab), and HOVON-65/GMMG-HD4 (bortezomib) met their endpoint showing improvement in PFS and also showed improvement in PFS in the +1q cohort, although the confidence interval crossed 1. All six studies that reported HR for +1q patients vs. without (across both arms) showed worse OS and PFS for +1q. There is considerable heterogeneity in the reporting of +1q. All interventions that have shown to be successful in RCTs and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention. A more standardized approach to reporting this abnormality is needed.