The effect of gastrointestinal graft-versus-host disease and diarrhea on the pharmacokinetic profile of sotrovimab in hematopoietic stem cell transplant recipients.

BACKGROUND: Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics (PK) of the long-acting mAb sotrovimab targeting SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients. METHODS: All participants received an intravenous infusion of sotrovimab within one week prior to initiating the pre-transplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks post-transplant. RESULTS: Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal (GI) graft-versus-host disease (GVHD) post-transplant. CONCLUSIONS: These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased GI clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations.

Synthesis, Characterization, and Properties of a Novel Hyperbranched Polymers with Polyacrylamide Side Chains.

A novel hyperbranched polymer with polyacrylamide side chains (HAPAM) was synthesized by aqueous solution polymerization using acrylic acid, acrylamide, 2-acrylamido-2-methyl-1-propanesulfonic acid, hydrophobic monomer of dimethyl octadecyl ammonium chloride, and the homemade skeleton monomer of modified-M2.0 as raw materials and (NH4)2S2O8-NaHSO3 as initiator. The molecular structure, functional groups, and surface morphology of HAPAM were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and scanning electron microscopy. It was found that the performance of HAPAM solution was higher than that of ordinary polyacrylamide solution in terms of thickening ability, shearing resistance, thermal endurance, salt-resistance, resistance-coefficient and residual-resistance-coefficient, ability to reduce interfacial tension between polymer solution and crude oil, and oil-displacement-efficiency. In particular, the enhanced oil recovery of the HAPAM solution was 13.03%, and the improvement of shearing resistance and immunity to chromatographic separation were simultaneously achieved by the HAPAM solution. These results indicate that the successful synthesis of the novel HAPAM opens a promising strategy for developing new high-performance oil-displacing polymers.

Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Molecular mechanisms for selective action of afidopyropen to Myzus persicae and Coccinella septempunctata.

BACKGROUND: Afidopyropen is a novel insecticide with high selectivity between sucking insects such as the peach aphids Myzus persicae and natural enemies like the seven-spotted lady beetle Coccinella septempunctata. However, the mechanisms of selective action for afidopyropen remain unknown. RESULTS: The LC50 values of afidopyropen to the 1st-4th instar larvae and adult C. septempunctata were 372- to more than 7267-fold higher than that to adult M. persicae. Though the activity of cytochrome P450s in M. persicae was 6.1- to 7.5-fold higher than that in C. septempunctata, the latter has much higher activities of carboxylesterase (CarEs) and glutathione S-transferases (GSTs), and the crude enzyme of C. septempunctata and M. persicae showed similar metabolism efficiency to afidopyropen. Molecular docking results demonstrated that afdopyropen showed higher binding affinity to the vanilloid-type transient receptor potential (TRPV) channel of M. persicae (-9.1 kcal/mol) than to that of C. septempunctata (-8.2 kcal/mol). And the EC50 value of afdopyropen to the TRPV channel of C. septempunctata (41 360 nM) was 19 885-fold higher than that in M. persicae (2.08 nM). CONCLUSIONS: Our results demonstrated that the significantly different sensitivity of M. persicae and C. septempunctata TRPV channel to afidopyropen play a key role in the high selectivity of afidopyropen. These findings provide new insights into the selective mechanisms of afidopyropen against insect pests and natural enemies as well as the theory support for coordinated application of chemical control and biological control. © 2024 Society of Chemical Industry.

Dynamic alterations in M2 macrophage subtypes enhance flap expansion efficiency and tissue regeneration.

Dilatation of soft skin tissue is a common surgical procedure in plastic surgery. M2 macrophages play a critical role in reducing inflammation, promoting epithelial and vascular endothelial cell proliferation, enhancing collagen synthesis in fibroblasts, and orchestrating extracellular matrix remodelling by promoting angiogenesis, epithelialisation, and fibrosis. Macrophages improve flap survival by promoting microangiogenesis and collagen remodelling. However, the role of macrophages in flap expansion has not yet been investigated. Improving the expansion efficiency of dilatation flaps and promoting flap vascularisation are the pressing problems in the fields of plastic and reconstruction surgery. In the present study, we used a mouse model to assess the effects of macrophage activation on skin expansion, thickness, ultrastructure, intradermal angiogenesis, and collagen and cytokine levels. Our findings revealed dynamic changes in the macrophage content and subtypes within the expansion flaps. The enrichment of M2 macrophages significantly enhanced the efficiency of flap expansion, vascularisation, and collagen synthesis. Our findings underline the pivotal role of M2 macrophages in tissue regeneration at the molecular and biochemical levels. These findings provide a basis for improving flap expansion efficiency using M2 macrophages.

PlexinA1 promotes gastric cancer migration through preventing MICAL1 protein ubiquitin/proteasome-mediated degradation in a Rac1-dependent manner.

Metastasis promotes the development of tumors and is a significant cause of gastric cancer death. For metastasis to proceed, tumor cells must become mobile by modulating their cytoskeleton. MICAL1 (Molecule Interacting with CasL1) is known as an actin cytoskeleton regulator, but the mechanisms by which it drives gastric cancer cell migration are still unclear. Analysis of gastric cancer tissues revealed that MICAL1 expression is dramatically upregulated in stomach adenocarcinoma (STAD) samples as compared to noncancerous stomach tissues. Patients with high MICAL1 expression had shorter overall survival (OS), post-progression survival (PPS) and first-progression survival (FPS) compared with patients with low MICAL1 expression. RNAi-mediated silencing of MICAL1 inhibited the expression of Vimentin, a protein involved in epithelial-mesenchymal transition. This effect correlates with a significant reduction in gastric cancer cell migration. MICAL1 overexpression reversed these preventive effects. Immunoprecipitation experiments and immunofluorescence assays revealed that PlexinA1 forms a complex with MICAL1. Importantly, specific inhibition of PlexinA1 blocked the Rac1 activation and ROS production, which, in turn, impaired MICAL1 protein stability by accelerating MICAL1 ubiquitin/proteasome-dependent degradation. Overexpression of PlexinA1 enhanced Rac1 activation, ROS production, MICAL1 and Vimentin expressions, and favored cell migration. In conclusion, this study identified MICAL1 as an important facilitator of gastric cancer cell migration, at least in part, by affecting Vimentin expression and PlexinA1 promotes gastric cancer cell migration by binding to and suppressing MICAL1 degradation in a Rac1/ROS-dependent manner.

shinyTempSignal: an R shiny application for exploring temporal and other phylogenetic signals.

The molecular clock model is fundamental for inferring species divergence times from molecular sequences. However, its direct application may introduce significant biases due to sequencing errors, recombination events, and inaccurately labeled sampling times. Improving accuracy necessitates rigorous quality control measures to identify and remove potentially erroneous sequences. Furthermore, while not all branches of a phylogenetic tree may exhibit a clear temporal signal, specific branches may still adhere to the assumptions, with varying evolutionary rates. Supporting a relaxed molecular clock model better aligns with the complexities of evolution. The root-to-tip regression method has been widely used to analyze the temporal signal in phylogenetic studies and can be generalized for detecting other phylogenetic signals. Despite its utility, there remains a lack of corresponding software implementations for broader applications. To address this gap, we present shinyTempSignal, an interactive web application implemented with the shiny framework, available as an R package and publicly accessible at https://github.com/YuLab-SMU/shinyTempSignal. This tool facilitates the analysis of temporal and other phylogenetic signals under both strict and relaxed models. By extending the root-to-tip regression method to diverse signals, shinyTempSignal helps in the detection of evolving features or traits, thereby laying the foundation for deeper insights and subsequent analyses.

Development and validation of outcome prediction model for reperfusion therapy in acute ischemic stroke using nomogram and machine learning.

OBJECTIVE: To develop logistic regression nomogram and machine learning (ML)-based models to predict 3-month unfavorable functional outcome for acute ischemic stroke (AIS) patients undergoing reperfusion therapy. METHODS: Patients undergoing reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) were prospectively recruited. Unfavorable outcome was defined as 3-month modified Rankin Scale (mRS) score 3-6. The independent risk factors associated with unfavorable outcome were obtained by regression analysis and included in the prediction model. The performance of nomogram was assessed by the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). ML models were compared with nomogram using AUC; the generalizability of all models was ascertained in an external cohort. RESULTS: A total of 505 patients were enrolled, with 256 in the model construction, and 249 in the external validation. Five variables were identified as prognostic factors: baseline NIHSS, D-dimer level, random blood glucose (RBG), blood urea nitrogen (BUN), and systolic blood pressure (SBP) before reperfusion. The AUC values of nomogram were 0.865, 0.818, and 0.779 in the training set, test set, and external validation, respectively. The calibration curve and DCA indicated appreciable reliability and good net benefits. The best three ML models were extra trees (ET), CatBoost, and random forest (RF) models; all of them showed favorable discrimination in the training cohort, and confirmed in the test and external sets. CONCLUSION: Baseline NIHSS, D-dimer, RBG, BUN, and SBP before reperfusion were independent predictors for 3-month unfavorable outcome after reperfusion therapy in AIS patients. Both nomogram and ML models showed good discrimination and generalizability.

Safe utilization of bioresources in gentamicin mycelial residues by thermal treatment: Antibiotic degradation, resistance gene inactivation and available nutrients promotion.

Gentamicin mycelium residues (GMRs) abundant in organic substances were generated during the production of gentamicin. Inappropriate handling techniques not only waste valuable resources, they could also result in residual gentamicin into the natural environment, leading to the generation of antibiotic resistance genes (ARGs), which would cause a significant threat to ecological system and human health. In the present work, the effects of thermal treatment on the removal of residual gentamicin in GMRs, as well as the changes of associated ARGs abundance, antimicrobial activity and bioresources properties were investigated. The results indicated that the hazards of GMRs was significantly reduced through thermal treatment. The degradation rate of residual gentamicin in GMRs reached 100 %, the total abundance of gentamicin resistance genes declined from 8.20 to 1.14 × 10-5 and the antibacterial activity of the decomposition products of GMRs on Vibrio fischeri was markedly reduced at 200 °C for 120 min. Additionally, the thermal treatment remarkably influenced the bioresource properties of GMRs-decomposition products. The release of soluble organic matters including soluble carbohydrates and soluble proteins have been enhanced in GMRs, while excessively high temperatures could lead to a reduction of nutrient substances. Generally, thermal treatment technology was a promising strategy for synergistic reducing hazards and utilizing bioresources of GMRs.

High -Sensitive Detection of Malachite Green Based on Surface-Enhanced Electrochemiluminescence.

This article introduces a novel unlabeled surface-enhanced electrochemiluminescence (SEECL) sensor for malachite green (MG) detection. The SEECL sensor was prepared by modifying the Ru(bpy)32+ doped gold-SiO2 core-shell nanocomposites (Au@SiO2-Ru(bpy)32+) on the gold electrode. Ru(bpy)32+ of nanocomposites can not only emit electrochemiluminescence (ECL) with electrochemical reaction, but also induce the local surface plasmon resonance (LSPR) of gold core. That is beneficial to enhance the ECL signa of sensor. However, in the existence of MG, the luminescence of sensor would be quenched by the fluorescence resonance energy transfer (FRET) between MG and Ru(bpy)32+. In this paper, both fluorescence and ECL of the Au@SiO2-Ru(bpy)32+ were investigated for MG detection. And the results show that the SEECL sensor has high sensitive to MG. Under the optimal experimental conditions, the minimum detection concentration could be achieved about 1.0 nM of MG, which fully meets the China national standard detection requirements of veterinary drug residue in seafood.

Community assembly and microbial interactions in an alkaline vanadium tailing pond.

Intensive development of vanadium-titanium mines leads to an increasing discharge of vanadium (V) into the environment, imposing potential risks to both environmental system and public health. Microorganisms play a key role in the biogeochemical cycling of V, influencing its transformation and distribution. In addition, the characterization of microbial community patterns serves to assess potential threats imposed by elevated V exposure. However, the impact of V on microbial community remains largely unknown in alkaline V tailing areas with a substantial amounts of V accumulation and nutrient-poor conditions. This study aims to explore the characteristics of microbial community in a wet tailing pond nearby a large-scale V mine. The results reveal V contamination in both water (0.60 mg/L) and sediment tailings (340 mg/kg) in the tailing pond. Microbial community diversity shows distinctive pattern between environmental metrices. Genera with the functional potential of metal reduction\resistance, nitrogen metabolism, and carbon fixation have been identified. In this alkaline V tailing pond, V and pH are major drivers to induce community variation, particularly for functional bacteria. Stochastic processes primarily govern the assemblies of microbial community in the water samples, while deterministic process regulate the community assemblies of sediment tailings. Moreover, the co-occurrence network pattern unveils strong selective pattern for sediment tailings communities, where genera form a complex network structure exhibiting strong competition for limited resource. These findings reveal the patterns of microbial adaptions in wet vanadium tailing ponds, providing insightful guidelines to mitigate the negative impact of V tailing and develop sustainable management for mine-waste reservoir.

Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study.

Background: This study aimed to investigate the correlations of serum vitamin D insufficiency with quadriceps neuromuscular function in patients with anterior cruciate ligament (ACL) injury. Methods: A cross-sectional study was conducted. Eighteen patients with a primary, unilateral ACL injury who had insufficient serum vitamin D concentrations (<30 ng/ml) were recruited for the study. Bilateral quadriceps neuromuscular function, including maximal strength, the speed of rapid contraction, and inhibition, were measured on an isokinetic dynamometer with the hip and the knee joint flexion at 90° and 45°, respectively. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC); the speed of rapid contraction was quantified by the rate of torque development (RTD), which was divided into the early (RTD0-50) and the late phase (RTD100-200); quadriceps inhibition was quantified by the central activation ratio (CAR). Serum vitamin D concentration was quantitatively determined by serum 25(OH)D concentration measured by the 25(OH)D ELISA kit. The Spearman rank correlation analysis was used to examine the correlation between the vitamin D concentration and bilateral quadriceps MVIC, RTD0-50, RTD100-200, and CAR, respectively. Results: The results of Spearman rank correlation analyses showed that the serum 25(OH)D concentration was significantly correlated with bilateral quadriceps MVIC (injured: r = 0.574, p = 0.013; uninjured: r = 0.650, p = 0.003) and RTD0-50 (r = 0.651, p = 0.003), and CAR (r = 0.662, p = 0.003) on the uninjured limb. However, no significant correlations were found between the serum 25(OH)D concentration and the other outcomes. Conclusions: The serum vitamin D concentration correlates with quadriceps neuromuscular function in patients with ACL injury who had vitamin D insufficiency.

Metabolic regulation of homologous recombination repair by MRE11 lactylation.

Lactylation is a lactate-induced post-translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient-derived xenograft and organoid models. A cell-penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.

In-situ production and activation of H2O2 over hydroxyapatite modified CuFeO2 for self-sufficient heterogeneous photo-Fenton degradation of doxycycline hydrochloride.

The self-sufficient heterogeneous photo-Fenton (SH-PF) system was constructed for doxycycline hydrochloride (DOH) degradation with hydroxyapatite (Hap) modified CuFeO2 (Hap/CuFeO2) composites through H2O2 in-situ production. The modification of Hap could improve the specific surface area, visible-light response, light conversion efficiency, photoelectron lifetime and oxygen vacancies (OVs) of CuFeO2, which was conducive to H2O2 production and DOH degradation in SH-PF system. Notably, Hap/CuFeO2 fabricated with 0.5 g Hap (Hap/CuFeO2-0.5) displayed more superior performance for DOH degradation compared to other synthesized catalysts. The Hap/CuFeO2-0.5 load and initial solution pH for DOH degradation in SH-PF system were optimized, and the Hap/CuFeO2-0.5 had good reusability and stability. The •OH was the main active species for DOH degradation, and the facilitation effect of •O2- and photoelectrons on DOH degradation was associated with the H2O2 production in the present work. In addition, the capture of photogenerated holes suppressed the recombination of photogenerated carriers, elevating the production of photoelectrons and thereby enhancing H2O2 production and DOH degradation. The degradation pathways for DOH were proposed and the comprehensive toxicities of DOH were relieved after degradation in SH-PF system.

Heat and carbon co-activated persulfate to regenerate gentamicin-laden activated carbon: Performance, mechanism, and safety assessment.

Activated carbon enriched with high concentrations of gentamicin (ACG) was generated in the production process of gentamicin. Inappropriate handling methods for ACG not only squanders carbon resource, but also seriously hinders achieving global carbon neutrality and hazardous to human health. In the present work, thermal and carbon co-activated persulfate method (TC-PS) was developed to regenerate ACG with degrading gentamicin. The results showed that ACG was effectively regenerated by TC-PS, restoring the adsorption performance for gentamicin. When the treatment temperature was 80 °C, the persulfate dosage was 20 mM and the initial pH was 3.0, the degradation efficiency of gentamicin reached 100%. The HO• and SO4•- were the major reactive species for gentamicin degradation. The possible degradation routes of gentamicin were proposed and the safety assessment indicated that the produced intermediates during the regeneration process of ACG by TC-PS have insignificant impact on the biological and ecological environment.

Synergistic anticancer effect by targeting CDK2 and EGFR-ERK signaling.

The EGFR-RAS-ERK pathway is one of the most important signaling cascades in cell survival, growth, and proliferation. Aberrant activation of this pathway is a common mechanism in various cancers. Here, we report that CDK2 is a novel regulator of the ERK pathway via USP37 deubiquitinase (DUB). Mechanistically, CDK2 phosphorylates USP37, which is required for USP37 DUB activity. Further, USP37 deubiquitinates and stabilizes ERK1/2, thereby enhancing cancer cell proliferation. Thus, CDK2 is able to promote cell proliferation by activating USP37 and, in turn, stabilizing ERK1/2. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity. Indeed, our patient-derived xenograft (PDX) results suggest that targeting both ERK1/2 stability and activity kills cancer cells more efficiently even at lower doses of these two inhibitors, which may reduce their associated side effects and indicate a potential new combination strategy for cancer therapy.

Effect of eccentric isokinetic exercise on muscle strength and functional recovery after anterior cruciate ligament reconstruction.

Background: Previous studies have shown isokinetic exercise forms an important part in reconditioning the patients after anterior cruciate ligament reconstruction (ACLR) in regaining muscle strength and knee function. Although eccentric isokinetic training has been shown to enhance quadriceps muscle strength, the application toward benefiting patients after ACLR remains controversial. The present study aims to investigate the benefits of eccentric over concentric isokinetic exercises on knee muscle strength and its value in later stage of rehabilitation, including the return-to-sport. Methods: Thirty-six patients who had undergone ACLR for 4-to-6 months were assigned to receive either eccentric or concentric isokinetic training weekly for six weeks on top of their standardized post-operative exercise programme. The assessments include isokinetic test on the peak torques of quadriceps and hamstrings, single-leg hop test and ability to return-to-sport. Results: Both groups demonstrated significant gains on peak torques in quadriceps and hamstrings after training. At post-intervention, the peak torques for both quadriceps (p = 0.005) and hamstrings (p = 0.017) of the ACL-reconstructed limb from eccentric training were significantly higher than concentric training. The significant improvement was similarly demonstrated in the limb symmetry index (LSI) in hamstrings (p = 0.016) of the ACL-reconstructed limb from eccentric training. Moreover, eccentric group performed significantly better in single-leg hop tests (p = 0.042). Most importantly, eccentric group have higher percentages of return-to-sport (55.6 %) than concentric group (27.8 %). Conclusion: A 6-week course of eccentric isokinetic training was more effective than concentric isokinetic training in increasing quadriceps and hamstrings strength in terms of peak torques. Importantly, the better functional performance after the eccentric isokinetic exercise account for higher return-to-sport ratio.

DRAVA: Aligning Human Concepts with Machine Learning Latent Dimensions for the Visual Exploration of Small Multiples.

Latent vectors extracted by machine learning (ML) are widely used in data exploration (e.g., t-SNE) but suffer from a lack of interpretability. While previous studies employed disentangled representation learning (DRL) to enable more interpretable exploration, they often overlooked the potential mismatches between the concepts of humans and the semantic dimensions learned by DRL. To address this issue, we propose Drava, a visual analytics system that supports users in 1) relating the concepts of humans with the semantic dimensions of DRL and identifying mismatches, 2) providing feedback to minimize the mismatches, and 3) obtaining data insights from concept-driven exploration. Drava provides a set of visualizations and interactions based on visual piles to help users understand and refine concepts and conduct concept-driven exploration. Meanwhile, Drava employs a concept adaptor model to fine-tune the semantic dimensions of DRL based on user refinement. The usefulness of Drava is demonstrated through application scenarios and experimental validation.

Causal associations of sleep traits with cancer incidence and mortality.

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00-1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06-1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11-1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08-1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15-9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27-1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Flash-Based Computing-in-Memory Architecture to Implement High-Precision Sparse Coding.

To address the concerns with power consumption and processing efficiency in big-size data processing, sparse coding in computing-in-memory (CIM) architectures is gaining much more attention. Here, a novel Flash-based CIM architecture is proposed to implement large-scale sparse coding, wherein various matrix weight training algorithms are verified. Then, with further optimizations of mapping methods and initialization conditions, the variation-sensitive training (VST) algorithm is designed to enhance the processing efficiency and accuracy of the applications of image reconstructions. Based on the comprehensive characterizations observed when considering the impacts of array variations, the experiment demonstrated that the trained dictionary could successfully reconstruct the images in a 55 nm flash memory array based on the proposed architecture, irrespective of current variations. The results indicate the feasibility of using Flash-based CIM architectures to implement high-precision sparse coding in a wide range of applications.