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Breast cancer remains a pervasive global health concern, necessitating continuous efforts to attain effectiveness of recurrence prediction schemes. This work focuses on breast cancer recurrence prediction using two advanced architectures such as Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU), integrated with feature selection techniques utilizing Logistic Regression (LR) and Analysis of Variance (ANOVA). The well-known Wisconsin cancer registry dataset, which contains vital diagnostic data from breast mass fine-needle aspiration biopsies, was employed in this study. The mean values of accuracy, precision, recall and F1-score for the proposed LR-CNN-LSTM model were calculated as 98.24%, 99.14%, 98.30% and 98.14% respectively. The mean values of accuracy, precision, recall and F1-score for the proposed ANOVA-GRU model were calculated as 96.49%, 97.04%, 96.67% and 96.67% respectively. The comparison with traditional methods showcases the superiority of our proposed approach. Moreover, the insights gained from feature selection contribute to a deeper understanding of the critical factors influencing breast cancer recurrence. The combination of LSTM and GRU models with feature selection methods not only enhances prediction accuracy but also provides valuable insights for medical practitioners. This research holds the potential to aid in early diagnosis and personalized treatment strategies.

The efficiency of solar cells is strongly influenced by factors such as durability, cost-effectiveness, environmental compatibility, and overall performance. Recent advancements in kesterite-based CZTSSe solar cells have revealed a persistent challenge of low open-circuit voltage (V OC ), which significantly limits device efficiency. This work focuses on optimizing absorber and interface properties to enhance the simulated performance of CZTSSe solar cells. The thermal stability of the proposed structure is also evaluated by examining the effect of operating temperature on key photovoltaic parameters. To address performance limitations, a BaSi₂-based back surface field (BSF) layer is incorporated, and numerical simulations are carried out using the SCAPS-1D software. The introduction of the BaSi₂-based BSF layer effectively reduces V OC -related losses and enhances the overall device efficiency. The model’s validity is supported through comparison with previously published experimental and simulation data. Incorporating BaSi₂ as the BSF layer increases the simulated efficiency from 12.54% to 16.37%. In parallel, a systematic study of the CZTSSe absorber layer was conducted to determine the optimal thickness and doping concentration for further improving solar cell performance. The values can be varied systematically, such as the absorber’s layer thickness from 0.5 to 3 μm, and the doping concentration is modified from 10 12 to 10 18 cm − 3 . An efficiency of 19.61% can be achieved for the recently improved configuration using a CZTSSe thickness of just only 0.5 μm under idealized conditions but not experimentally realistic. This reduction of the thickness of the CZTSSe solar cells is an important factor in the decline of performance, but it can improve the lifetime of minority carriers.

The Asian Summer Monsoon (ASM) exhibit different modes of variability in which the active and break phases is one of the most prominent intraseasonal scale variability of the ASM. The shift in convective centres to more polluted regions coupled with the associated circulation features during these phases results in a redistribution of trace species in the upper troposphere and lower stratosphere (UTLS) region. Apropos to this, this study presents a quantitative assessment of the variability in the spatial distribution of ozone, carbon monoxide (CO) and water vapour (H 2 O) in the UTLS during the active and break phase of ASM with respect to the seasonal mean background using fifteen years (2005–2019) of Aura-MLS observations in conjunction with reanalysis data sets, cloud-top brightness temperatures and trajectory analysis. These 15-years of data is used to make composite maps of tracer anomalies to investigate the varying influence of monsoon convection, transport and ASMA dynamics in the UTLS region during the active/break phase. This study shows that, while the distribution of trace species during both phases is determined by the combined role of convection and transport in the upper troposphere, changes in ASMA modes, transport and tropopause dynamics during the active/break phases controls the spatial pattern of both tropospheric and stratospheric species near the tropopause level.

Smooth muscle cells (SMCs) play a key role in atherogenesis. However, mechanisms regulating expansion and fate of pre-existing SMCs in atherosclerotic plaques remain poorly defined. Here we show that multiple SMC progenitors mix to form the aorta during development. In contrast, during atherogenesis, a single SMC gives rise to the smooth muscle-derived cells that initially coat the cap of atherosclerotic plaques. Subsequently, highly proliferative cap cells invade the plaque core, comprising the majority of plaque cells. Reduction of integrin β3 (Itgb3) levels in SMCs induces toll-like receptor 4 expression and thereby enhances Cd36 levels and cholesterol-induced transdifferentiation to a macrophage-like phenotype. Global Itgb3 deletion or transplantation of Itgb3 (−/−) bone marrow results in recruitment of multiple pre-existing SMCs into plaques. Conditioned medium from Itgb3-silenced macrophages enhances SMC proliferation and migration. Together, our results suggest SMC contribution to atherogenesis is regulated by integrin β3-mediated pathways in both SMCs and bone marrow-derived cells. Smooth muscle cells (SMCs) invade atherosclerotic lesions and expand, contributing to plaque progression. Here Misra et al. show that SMC-derived plaque cells come from a single SMC and integrin β3 in SMCs and macrophages regulate the fate, expansion and migration of SMCs during plaque formation.

Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. The glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes and in particular ALDH1A3, were enriched in Mes GSCs. Glycolytic activity and ALDH activity were significantly elevated in Mes GSCs but not in PN GSCs. Expression of ALDH1A3 was also increased in clinical HGG compared with low-grade glioma or normal brain tissue. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs. Last, radiation treatment of PN GSCs up-regulated Mes-associated markers and down-regulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3-mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature.

Balloon-borne cryogenic frost-point hygrometer (CFH) observations over two tropical stations Trivandrum (8.53° N, 76.87° E) and Hyderabad (17.47° N, 78.58° E) [2014–2017] along with Microwave Limb Sounder (MLS) observations [2011–2017] are used to examine the signatures of local and regional dynamics in the distribution of lower stratospheric water vapour over the Indian region. The column-integrated water vapour in the lower stratosphere (IWVLS) varies in the range 2.5–5 g/m2 with low values during winter and high values during summer monsoon and post monsoon seasons. About 50–75% of IWVLS lies in the lower regime of the lower stratosphere, the region from cold point tropopause (CPT) to 21 km (LS1). Hygropause is very near to the CPT in winter and pre-monsoon and 2–3 km above the CPT in summer-monsoon and post-monsoon. The CPT and the minimum in saturated mixing ratio (SMRmin) altitudes show a positive correlation, with SMRmin mostly occurring below the CPT. Though water vapour mixing ratio (WVMR) at CPT increases with increase in SMRmin, it is mostly less than the corresponding SMRmin value. CFH observations showed that the tape recorder signal in the LS1 is disturbed by the local/regional dynamics. While the amount of water vapour entering the lower stratosphere is higher over Hyderabad in winter and summer monsoon, it is higher over Trivandrum in the other two seasons. Hydration at the tropopause level is mainly determined by the overshooting/deep convection, monsoon dynamics and horizontal transport and dehydration is determined by temperature variations in the tropical tropopause layer (TTL).

Ozone in the troposphere is a prominent pollutant whose production is sensitive to the emissions of nitrogen oxides (NOx) and volatile organic compounds (VOCs). Here, we assess the variation of tropospheric ozone levels, trends, ozone photochemical regimes and radiative effects using the ECHAM6–HAMMOZ chemistry–climate model for the period 1998–2019 and satellite measurements. The global mean simulated trend in tropospheric column ozone (TRCO) for the study period (1998–2019) is 0.89 ppb decade−1. During the overlapping period with Ozone Monitoring Instrument/Microwave Limb Sounder (OMI/MLS) observations (2005–2019), the simulated global mean TRCO trends (1.58 ppb decade−1) show fair agreement with OMI/MLS estimates (1.4 ppb decade−1). The simulations for doubling emissions of NOx (DoubNOx), VOCs (DoubVOC), and halving emissions of NOx (HalfNOx) and VOCs (HalfVOC) show nonlinear responses to ozone trends and tropospheric ozone photochemical regimes. The DoubNOx simulations show VOC-limited regimes over the Indo-Gangetic Plain, eastern China, western Europe and the eastern US, while HalfNOx simulations show NOx-limited regimes over North America and Asia. Emissions changes in NOx (DoubNOx/HalfNOx) influence the shift in tropospheric ozone photochemical regimes compared to VOCs (DoubVOC/HalfVOC). The estimated global mean TO3RE during 1998–2019 from the control (CTL) simulations is 1.21 W m−2. The global mean TO3RE shows enhancement by 0.36 W m−2 in DoubNOx simulations compared to CTL. While TO3RE shows a reduction in other simulations compared to CTL (DoubVOC: −0.005 W m−2, HalfNOx: −0.12 W m−2 and HalfVOC: −0.03 W m−2). We show that emission changes in anthropogenic NOx cause more significant changes in TO3RE than anthropogenic VOCs.

During lung fibrosis, the epithelium induces signaling to underlying mesenchyme to generate excess myofibroblasts and extracellular matrix; herein, we focus on signaling in the mesenchyme. Our studies indicate that platelet-derived growth factor receptor (PDGFR)-β + cells are the predominant source of myofibroblasts and Kruppel-like factor (KLF) 4 is upregulated in PDGFR-β + cells, inducing TGFβ pathway signaling and fibrosis. In fibrotic lung patches, KLF4 is down-regulated, suggesting KLF4 levels decrease as PDGFR-β + cells transition into myofibroblasts. In contrast to PDGFR-β + cells, KLF4 reduction in α-smooth muscle actin (SMA) + cells non-cell autonomously exacerbates lung fibrosis by inducing macrophage accumulation and pro-fibrotic effects of PDGFR-β + cells via a Forkhead box M1 to C-C chemokine ligand 2—receptor 2 pathway. Taken together, in the context of lung fibrosis, our results indicate that KLF4 plays opposing roles in PDGFR-β + cells and SMA + cells and highlight the importance of further studies of interactions between distinct mesenchymal cell types. The pluripotency factor KLF4 has been described as pro-fibrotic or anti-fibrotic in various diseases. Herein, the authors show that during lung fibrosis, these distinct effects can be attributed to mesenchymal cell-type specific functions of KLF4.

Background Liquid cultures have been commonly used in space, toxicology, and pharmacology studies of Caenorhabditis elegans . However, the knowledge about transcriptomic alterations caused by liquid cultivation remains limited. Moreover, the impact of different genotypes in rapid adaptive responses to environmental changes (e.g., liquid cultivation) is often overlooked. Here, we report the transcriptomic and phenotypic responses of laboratory N2 and the wild-isolate AB1 strains after culturing P 0 worms on agar plates, F 1 in liquid cultures, and F 2 back on agar plates. Results Significant variations were found in the gene expressions between the N2 and AB1 strains in response to liquid cultivation. The results demonstrated that 8–34% of the environmental change-induced transcriptional responses are transmitted to the subsequent generation. By categorizing the gene expressions for genotype, environment, and genotype-environment interactions, we identified that the genotype has a substantial impact on the adaptive responses. Functional analysis of the transcriptome showed correlation with phenotypical changes. For example, the N2 strain exhibited alterations in both phenotype and gene expressions for germline and cuticle in axenic liquid cultivation. We found transcript evidence to approximately 21% of the computationally predicted genes in C. elegans by exposing the worms to environmental changes. Conclusions The presented study reveals substantial differences between N2 and AB1 strains for transcriptomic and phenotypical responses to rapid environmental changes. Our data can provide standard controls for future studies for the liquid cultivation of C. elegans and enable the discovery of condition-specific genes.

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable. Metastatic uveal melanoma is poorly responsive to immune checkpoint inhibition. Here, the authors analyse 100 uveal melanoma metastases using bulk and single cell RNA-seq, TCR analysis, and immune reactivity to show potent, yet, quiescent tumour infiltrating lymphocytes that can be harnessed by adoptive transfer to confer tumour immunity.