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Floatable artificial leaf to couple oxygen-tolerant CO2 conversion with water purification
Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma
Abstract Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.
CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells
The mediating effect of emotional schemas in the relationship between online gaming addiction and life satisfaction
Study of the spatial strength distribution patterns and microstructure characteristics of ultra-fine tailings cemented paste backfill
AbstractIn this study, the spatial distribution of the mechanical strength of ultra-fine tailings cemented paste backfill (UCPB) in underground stopes was examined, and the micro-mechanism responsible for differences in spatial strength performance via changes in particle deposition was elucidated. To better understand this phenomenon, we constructed a similar backfilling stope model using the ultra-fine tailings of a gold mine. We manufactured specimens at different spatial locations and conducted a novel series of tests, including uniaxial compressive strength, shear strength, and conventional triaxial tests, to obtain the strength parameters in different spatial distributions. The strength parameters for the different UCPB locations in this model were revealed and examined along with the original pore and particle size distributions. Computer tomography (CT) and scanning electron microscopy (SEM) observations before and after the UCPB failed revealed that the particle deposition effect at different positions was the primary cause of the size effect. The strength distribution pattern demonstrated that the UCPB material has an apparent spatial effect. Consequently, considering the position relationship between the stope and filling mouth is crucial when designing the strength of adjacent mining rooms. This research may guide both backfill study and design.
Discretized representations in V1 predict suboptimal orientation discrimination
XLSA breakthrough: gene therapy potential
Crowd counting in domain generalization based on multi-scale attention and hierarchy level enhancement
AbstractIn order to solve the problem of weak single domain generalization ability in existing crowd counting methods, this study proposes a new crowd counting framework called Multi-scale Attention and Hierarchy level Enhancement (MAHE). Firstly, the model can focus on both the detailed features and the macro information of structural position changes through the fusion of channel attention and spatial attention. Secondly, the addition of multi-head attention feature module facilitates the model’s capacity to effectively capture complex dependency relationships between sequence elements. In addition, the three-stage encoding and decoding processing mode enables the model to effectively represent crowd density information. Finally, the fusion of multi-scale features derived from different receptive fields is further enhanced through multi-scale hierarchy level feature fusion, thereby enabling the model to learn high-level semantic information and low-level multi-scale visual field feature information. This method enhances the model’s capacity to capture key feature information, even in highly differentiated datasets, thereby improving the model’s generalization ability on a single domain. The model has demonstrated strong generalization capabilities through extensive experiments on different datasets. This study not only improves the accuracy of crowd counting, but also introduces a new research approach for single domain generalization of crowd counting.
pACP-HybDeep: predicting anticancer peptides using binary tree growth based transformer and structural feature encoding with deep-hybrid learning
A nomogram predicting the risk of venous thromboembolism in patients following urologic surgeries
L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer
Vitamin C deprivation puts stem cells to sleep
CHST3, PGBD5, and SLIT2 can be identified as potential genes for the diagnosis and treatment of osteoporosis and sarcopenia
Research and application of multi-frequency electromagnetic technology in real-time online characterization of steel microstructures and mechanical properties
Restoring small water bodies to improve lake and river water quality in China
AbstractClimate change, population growth, and agricultural intensification are increasing nitrogen (N) inputs, while driving the loss of inland water bodies that filter excess N. However, the interplay between N inputs and water body dynamics, and its implications for water quality remain poorly understood. Analyzing data from 1995 to 2015 across China, here, we find a 71% reduction in the area of small (<104.5 m2) water bodies (SWB), primarily in high-N-input agricultural regions. Preferential loss of SWBs, the most efficient nutrient filters, places 42% of China at high water quality risk due to increasing N inputs and declining SWB density. Currently, N removal by water bodies is 986 kilotonnes year−1, but restoring 2.3 million hectares of SWB could increase removal by 21%, compared to just 5% for equivalent restoration of large water bodies. Targeted SWB restoration is crucial for improving water quality and mitigating N pollution in China.
Ascorbate deficiency increases quiescence and self-renewal in hematopoietic stem cells and multipotent progenitors
Abstract Ascorbate (vitamin C) limits hematopoietic stem cell (HSC) function and suppresses leukemia development, partly by promoting the function of the Tet2 tumor suppressor. In humans, ascorbate is obtained from the diet, whereas in mice, it is synthesized in the liver. In this study, we show that deletion of the Slc23a2 ascorbate transporter from hematopoietic cells depleted ascorbate to undetectable levels in HSCs and multipotent hematopoietic progenitors (MPPs) without altering the plasma ascorbate levels. Slc23a2 deficiency increased HSC reconstituting potential and self-renewal potential upon transplantation into irradiated mice. Slc23a2 deficiency also increased the reconstituting and self-renewal potentials of MPPs, conferring the ability to reconstitute irradiated mice long term. Slc23a2-deficient HSCs and MPPs divided much less frequently than control HSCs and MPPs. Increased self-renewal and reconstituting potential were observed particularly in quiescent Slc23a2-deficient HSCs and MPPs. The effect of Slc23a2 deficiency on MPP self-renewal was not mediated by reduced Tet2 function. Ascorbate thus regulates quiescence and restricts self-renewal potential in HSCs and MPPs such that ascorbate deficiency confers MPPs with long-term self-renewal potential.
The appropriate nutrient conditions for methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro
AbstractPolymicrobial biofilms, the reason for most chronic wound infections, play a significant role in increasing antibiotic resistance. The in vivo effectiveness of the new anti-biofilm therapy is conditioned by the profound evaluation using appropriate in vitro biofilm models. Since nutrient availability is crucial for in vitro biofilm formation, this study is focused on the impact of four selected cultivation media on the properties of methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilms. To reflect the wound environment, Tryptic soy broth, RPMI 1640 with and without glucose, and Lubbock medium were supplemented with different amounts of host effector molecules present in human plasma or sheep red blood cells. The study demonstrates that the Lubbock medium provided the most appropriate amount of nutrients regarding the biomass structure and the highest degree of tolerance to selected antimicrobials with the evident contribution of the biofilm matrix. Our results allow the rational employment of nutrition conditions within methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro for preclinical research. Additionally, one of the potential targets of a complex antibiofilm strategy, carbohydrates, was revealed since they are prevailing molecules in the matrices regardless of the cultivation media.
Application of the Lasso regularisation technique in mitigating overfitting in air quality prediction models
SOX2+ sustentacular cells are stem cells of the postnatal adrenal medulla
AbstractRenewal of the catecholamine-secreting chromaffin cell population of the adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence for the presence or absence of an adrenomedullary stem cell has been enigmatic. In this work, we demonstrate that a subset of sustentacular cells endowed with a support role, are in fact adrenomedullary stem cells. Through genetic tracing and comprehensive transcriptomic data of the mouse adrenal medulla, we show that cells expressing Sox2/SOX2 specialise as a unique postnatal population from embryonic Schwann Cell Precursors and are also present in the normal adult human adrenal medulla. Postnatal SOX2+ cells give rise to chromaffin cells of both the adrenaline and noradrenaline lineages in vivo and in vitro. We reveal that SOX2+ stem cells have a second, paracrine role in maintaining adrenal chromaffin cell homeostasis, where they promote proliferation through paracrine secretion of WNT6. This work identifies SOX2+ cells as a true stem cell for catecholamine-secreting chromaffin cells.