Multiple reports on the causal relationship between various chronic pain and gut microbiota: a two-sample Mendelian randomization study.

Background: Previous evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood. Methods: We categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations. Results: We have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR p = 0.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR p = 0.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (p > 0.05), as confirmed by the Cochrane's Q-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (p > 0.05). Conclusion: Our MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.

Analysis of lumbar spine loading during walking in patients with chronic low back pain and healthy controls: An OpenSim-Based study.

Low back pain (LBP) is one of the most prevalent and disabling disease worldwide. However, the specific biomechanical changes due to LBP are still controversial. The purpose of this study was to estimate the lumbar and lower limb kinematics, lumbar moments and loads, muscle forces and activation during walking in healthy adults and LBP. A total of 18 healthy controls and 19 patients with chronic LBP were tested for walking at a comfortable speed. The kinematic and dynamic data of the subjects were collected by 3D motion capture system and force plates respectively, and then the motion simulation was performed by OpenSim. The OpenSim musculoskeletal model was used to calculate lumbar, hip, knee and ankle joint angle variations, lumbar moments and loads, muscle forces and activation of eight major lumbar muscles. In our results, significant lower lumbar axial rotation angle, lumbar flexion/extension and axial rotation moments, as well as the muscle forces of the four muscles and muscle activation of two muscles were found in patients with LBP than those of the healthy controls (p < 0.05). This study may help providing theoretical support for the evaluation and rehabilitation treatment intervention of patients with LBP.

MiR-3682-3p promotes esophageal cancer progression by targeting FHL1 and activating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Esophageal cancer (EC) is highly ranked among all cancers in terms of its incidence and mortality rates. MicroRNAs (miRNAs) are considered to play key regulatory parts in EC. Multiple research studies have indicated the involvement of miR-3682-3p and four and a half LIM domain protein 1 (FHL1) in the achievement of tumors. The aim of this research was to clarify the significance of these genes and their possible molecular mechanism in EC. METHODS: Data from a database and the tissue microarray were made to analyze the expression and clinical significance of miR-3682-3p or FHL1 in EC. Reverse transcription quantitative PCR and Western blotting were used to detect the expression levels of miR-3682-3p and FHL1 in EC cells. CCK8, EdU, wound healing, Transwell, flow cytometry, and Western blotting assays were performed to ascertain the biological roles of miR-3682-3p and FHL1 in EC cells. To confirm the impact of miR-3682-3p in vivo, a subcutaneous tumor model was created in nude mice. The direct interaction between miR-3682-3p and FHL1 was demonstrated through a luciferase assay, and the western blotting technique was employed to assess the levels of crucial proteins within the Wnt/ß-catenin pathway. RESULTS: The noticeable increase in the expression of miR-3682-3p and the decrease in the expression of FHL1 were observed, which correlated with a negative impact on the patients' overall survival. Upregulation of miR-3682-3p expression promoted the growth and metastasis of EC, while overexpression of FHL1 partially reversed these effects. Finally, miR-3682-3p motivates the Wnt/ß-catenin signal transduction by directly targeting FHL1. CONCLUSION: MiR-3682-3p along the FHL1 axis activated the Wnt/ß-catenin signaling pathway and thus promoted EC malignancy.

Multimodal detection and analysis of microplastics in human thrombi from multiple anatomically distinct sites.

BACKGROUND: Microplastic (MP) pollution has emerged as a significant environmental concern worldwide. While extensive research has focused on their presence in marine organisms and ecosystems, their potential impact on human health, particularly on the circulatory system, remains understudied. This project aimed to identify and quantify the mass concentrations, polymer types, and physical properties of MPs in human thrombi surgically retrieved from both arterial and venous systems at three anatomically distinct sites, namely, cerebral arteries in the brain, coronary arteries in the heart, and deep veins in the lower extremities. Furthermore, this study aimed to investigate the potential association between the levels of MPs and disease severity. METHODS: Thrombus samples were collected from 30 patients who underwent thrombectomy procedures due to ischaemic stroke (IS), myocardial infarction (MI), or deep vein thrombosis (DVT). Pyrolysis-gas chromatography mass spectrometry (Py-GC/MS) was employed to identify and quantify the mass concentrations of the MPs. Laser direct infrared (LDIR) spectroscopy and scanning electron microscopy (SEM) were used to analyse the physical properties of the MPs. Demographic and clinical information were also examined. A rigorous quality control system was used to eliminate potential environmental contamination. FINDINGS: MPs were detected by Py-GC/MS in 80% (24/30) of the thrombi obtained from patients with IS, MI, or DVT, with median concentrations of 61.75 µg/g, 141.80 µg/g, and 69.62 µg/g, respectively. Among the 10 target types of MP polymers, polyamide 66 (PA66), polyvinyl chloride (PVC), and polyethylene (PE) were identified. Further analyses suggested that higher concentrations of MPs may be associated with greater disease severity (adjusted ß = 7.72, 95% CI: 2.01-13.43, p < 0.05). The level of D-dimer in the MP-detected group was significantly higher than that in the MP-undetected group (8.3 ± 1.5 µg/L vs 6.6 ± 0.5 µg/L, p < 0.001). Additionally, LDIR analysis showed that PE was dominant among the 15 types of identified MPs, accounting for 53.6% of all MPs, with a mean diameter of 35.6 µm. The shapes of the polymers detected using LDIR and SEM were found to be heterogeneous. INTERPRETATION: This study presents both qualitative and quantitative evidence of the presence of MPs, and their mass concentrations, polymer types, and physical properties in thrombotic diseases through the use of multimodal detection methods. Higher concentrations of MPs may be associated with increased disease severity. Future research with a larger sample size is urgently needed to identify the sources of exposure and validate the observed trends in the study. FUNDING: This study was funded by the SUMC Scientific Research Initiation Grant (SRIG, No. 009-510858038), Postdoctoral Research Initiation Grant (No. 202205230031-3), and the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (No. 2020LKSFG02C).

Segmenting Ischemic Penumbra and Infarct Core Simultaneously on Non-Contrast CT of Patients with Acute Ischemic Stroke Using Novel Convolutional Neural Network.

Differentiating between a salvageable Ischemic Penumbra (IP) and an irreversibly damaged Infarct Core (IC) is important for therapy decision making for acute ischemic stroke (AIS) patients. Existing methods rely on Computed Tomography Perfusion (CTP) or Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery (DWI-FLAIR). We designed a novel Convolutional Neural Network named I2PC-Net, which relies solely on Non-Contrast Computed Tomography (NCCT) for the automatic and simultaneous segmentation of the IP and IC. In the encoder, Multi-Scale Convolution (MSC) blocks were proposed to capture effective features of ischemic lesions, and in the deep levels of the encoder, Symmetry Enhancement (SE) blocks were also designed to enhance anatomical symmetries. In the attention-based decoder, hierarchical deep supervision was introduced to address the challenge of differentiating between the IP and IC. We collected 197 NCCT scans from AIS patients to evaluate the proposed method. On the test set, I2PC-Net achieved Dice Similarity Scores of 42.76 ± 21.84%, 33.54 ± 24.13% and 65.67 ± 12.30% and lesion volume correlation coefficients of 0.95 (p < 0.001), 0.61 (p < 0.001) and 0.93 (p < 0.001) for the IP, IC and IP + IC, respectively. The results indicated that NCCT could potentially be used as a surrogate technique of CTP for the quantitative evaluation of the IP and IC.

Genome sequencing and analysis of Bacillus velezensis VJH504 reveal biocontrol mechanism against cucumber Fusarium wilt.

One major issue in reducing cucumber yield is the destructive disease Cucumber (Cucumis sativus L.) wilt disease caused by Fusarium oxysporum f. sp. cucumerinum (Foc). When using the isolate VJH504 isolated from cucumber rhizosphere soil and identified as Bacillus velezensis, the growth of Foc in the double culture experiment was effectively inhibited. Phenotypic, phylogenetic, and genomic analyses were conducted to enhance understanding of its biocontrol mechanism. According to the result of the phenotype analysis, B. velezensis VJH504 could inhibit cucumber fusarium wilt disease both in vitro and in vivo, and significantly promote cucumber seed germination and seedling growth. Additionally, the tests of growth-promoting and biocontrol characteristics revealed the secretion of proteases, amylases, ß-1,3-glucanases, cellulases, as well as siderophores and indole-3-acetic acid by B. velezensis VJH504. Using the PacBio Sequel II system, we applied the complete genome sequencing for B. velezensis VJH504 and obtained a single circular chromosome with a size of 3.79 Mb. A phylogenetic tree was constructed based on the 16S rRNA gene sequences of B. velezensis VJH504 and 13 other Bacillus species, and Average Nucleotide Identity (ANI) analysis was performed using their whole-genome sequences, confirming isolateVJH504 as B. velezensis. Following this, based on the complete genome sequence od B. velezensis VJH504, specific functional analysis, Carbohydrate-Active Enzymes (CAZymes) analysis, and secondary metabolite analysis were carried out, predicting organism's abilities for biofilm formation, production of antifungal CAZymes, and synthesis of antagonistic secondary metabolites against pathogens. Afterwards, a comparative genomic analysis was performed between B. velezensis VJH504 and three other B. velezensis strains, revealing subtle differences in their genomic sequences and suggesting the potential for the discovery of novel antimicrobial substances in B. velezensis VJH504. In conclusion, the mechanism of B. velezensis VJH504 in controlling cucumber fusarium wilt was predicted to appear that B. velezensis VJH504is a promising biocontrol agent, showcasing excellent application potential in agricultural production.

Development of a fabrication process for production of diffractive optics.

In this study, a novel fabrication process, to the best of our knowledge, was developed to fabricate a glass harmonic diffractive lens. In this process, a polymethylmethacrylate master of the diffractive lens was machined using single-point diamond turning. Then an electrolytic plating process was conducted to grow a reverse nickel (Ni) mold. Precision compression molding was performed using the Ni mold to replicate the diffractive lens structures onto a glass surface. Surface measurements and optical testing show that the replicated diffractive lenses by the proposed method have high tolerances and require optical performance, demonstrating a high-volume, high-precision, and cost-effective process. The proposed method will be critical for consumer products where glass optics are increasingly used in lens assemblies.

Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer.

BACKGROUND: Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients. METHODS: The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0). RESULTS: Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death. CONCLUSION: Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.

High-repetition-rate and high-beam-quality all-solid-state nanosecond pulsed deep-red Raman laser.

We report on a high-repetition-rate and high-beam-quality all-solid-state nanosecond pulsed deep-red laser source by intracavity second harmonic generation of the actively Q-switched Nd:YVO4/KGW Raman laser. The polarization of the 1342 nm fundamental laser was aligned with the Ng and Nm axes of KGW crystal for accessing the eye-safe Raman lasers at 1496 and 1526 nm, respectively. With the aid of the elaborately designed V-shaped resonator and the composite Nd:YVO4 crystal, excellent mode matching and good thermal diffusion have been confirmed. Under an optimal pulse repetition frequency of 25 kHz, the average output powers of the Raman lasers at 1496 and 1526 nm were measured to be 3.7 and 4.9 W with the superior beam quality factor of M2 = 1.2, respectively. Subsequently, by incorporating a bismuth borate (BIBO) crystal, the deep-red laser source was able to lase separately two different spectral lines at 748 and 763 nm, yielding the maximum average output powers of 2.5 and 3.2 W with the pulse durations of 15.6 and 11.3 ns, respectively. The resulting beam quality was determined to be near-diffraction-limited with M2 = 1.28.

Effects of Rhizosphere Microbial Communities on Cucumber Fusarium wilt Disease Suppression.

Cucumber Fusarium wilt is a worldwide soil-borne disease that seriously restricts the yield and quality of cucumber. The rhizosphere soil microbiome, as the first line of defense against pathogens invading plant roots, plays a key role in rhizosphere immune formation and function. The purpose of this study was to reveal the key microecological factors and dominant microbial flora affecting cucumber resistance and susceptibility to Fusarium wilt by analyzing the physical and chemical properties and microbial flora of rhizosphere soil with different degrees of susceptibility and resistance to cucumber Fusarium wilt, thereby laying a foundation to establish cucumber resistance to the Fusarium wilt rhizosphere core microbiome. Firstly, Illumina Miseq sequencing technology was used to evaluate the physical and chemical properties and microbial groups of cucumber rhizosphere soil at different health levels, and the key environmental factors and microbial factors related to cucumber Fusarium wilt were screened out. Subsequently, PICRUSt2 and FUNGuild were used to predict the functions of rhizosphere bacteria and fungi. Combined with functional analysis, the possible interactions among soil physical and chemical properties, cucumber rhizosphere microorganisms, and Fusarium wilt were summarized. The results showed that the available potassium content in the rhizosphere soil of healthy cucumber decreased by 10.37% and 0.56%, respectively, compared with the rhizosphere soil of severely susceptible cucumber and mildly susceptible cucumber. Exchangeable calcium content increased by 25.55% and 5.39%; the α diversity Chao1 index of bacteria and fungi in the rhizosphere soil of healthy cucumber was significantly lower than that in the rhizosphere soil of seriously infected cucumber, and the MBC content of its physical and chemical properties was also significantly lower than that in the rhizosphere soil of seriously infected cucumber. There was no significant difference in the Shannon and Simpson diversity indexes between healthy cucumber rhizosphere soil and seriously infected cucumber rhizosphere soil. The results of the ß diversity analysis showed that the bacterial and fungal community structure of healthy cucumber rhizosphere soil was significantly different from that of severely and mildly infected cucumber rhizosphere soil. At the genus level, through statistical analysis, LEfSe analysis, and RDA analysis, the key bacterial and fungal genera with potential biomarker values were screened out as SHA_26, Subgroup_22, MND1, Aeromicrobium, TM7a, Pseudorhodoplanes, Kocuria, Chaetomium, Fusarium, Olpidium, and Scopulariopsis, respectively. The bacteria SHA_26, Subgroup_22, and MND1 related to cucumber Fusarium wilt inhibition belong to Chloroflexi, Acidobacteriota, and Proteobacteria, respectively. Chaetomiacea belongs to Sordariomycates. The results of functional prediction showed that changes to the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway in the bacterial microbiota were concentrated in tetracycline biosynthesis, selenocompound metabolism, lipopolysaccharide biosynthesis, etc., which were mainly involved in the metabolism of terpenoids and polyketides, energy metabolism, metabolism of other amino acids, glycan biosynthesis and metabolism, lipid metabolism, cell growth and death, transcription, metabolism of cofactors and vitamins, and biosynthesis of other secondary metabolites. The difference in fungi was mainly dung saprotroph-ectomycorrhizal-soil saprotroph-wood saprotroph. Through the correlation analysis and functional predictions of the key environmental factors, microbial flora, and cucumber health index in cucumber rhizosphere soil, we determined that the inhibition of cucumber Fusarium wilt was a synergistic effect of environmental factors and microbial flora, and a model diagram was drawn to briefly explain its mechanism. This work will provide a basis for the biological control of cucumber Fusarium wilt in the future.

Knowledge Graph: Applications in Tracing the Source of Large-Scale Outbreak - Beijing Municipality, China, 2020-2021.

Introduction: Tracing transmission paths and identifying infection sources have been effective in curbing the spread of coronavirus disease 2019 (COVID-19). However, when facing a large-scale outbreak, this is extremely time-consuming and labor-intensive, and resources for infection source tracing become limited. In this study, we aimed to use knowledge graph (KG) technology to automatically infer transmission paths and infection sources. Methods: We constructed a KG model to automatically extract epidemiological information and contact relationships from case reports. We then used an inference engine to identify transmission paths and infection sources. To test the model's performance, we used data from two COVID-19 outbreaks in Beijing. Results: The KG model performed well for both outbreaks. In the first outbreak, 20 infection relationships were identified manually, while 42 relationships were determined using the KG model. In the second outbreak, 32 relationships were identified manually and 31 relationships were determined using the KG model. All discrepancies and omissions were reasonable. Discussion: The KG model is a promising tool for predicting and controlling future COVID-19 epidemic waves and other infectious disease pandemics. By automatically inferring the source of infection, limited resources can be used efficiently to detect potential risks, allowing for rapid outbreak control.

Circ_0011385 knockdown inhibits cell proliferation, migration and invasion, whereas promotes cell apoptosis by regulating miR-330-3p/MYO6 axis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Recent studies have showed circular RNA (circRNA) participates in the development of CRC. The study was designed to reveal the role of circ_0011385 in CRC progression and underneath mechanism. METHODS: The expression circ_0011385, microRNA-330-3p (miR-330-3p) and myosin VI (MYO6) mRNA were determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot assay. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), cell colony formation and flow cytometry assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by wound-healing assay and transwell invasion assay, respectively. The binding sites between miR-330-3p and circ_0011385 or MYO6 were predicted by CircInteractome or starBase online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Circ_0011385 and MYO6 expression were dramatically upregulated, while miR-330-3p expression was downregulated in CRC tissues or cells compared with control groups. Circ_0011385 expression was associated with tumor size, tumor-node-metastasis stage (TNM) stage and lymph node metastasis of CRC patients. Circ_0011385 silencing or MYO6 absence repressed cell proliferation, migration and invasion, whereas induced cell apoptosis in CRC. Additionally, miR-330-3p inhibitor or MYO6 overexpression attenuated the repressive impacts of circ_0011385 silencing on CRC process. Circ_0011385 was associated with miR-330-3p, and miR-330-3p targeted MYO6. Circ_0011385 knockdown inactivated MEK1/2/ERK1/2 signaling pathway by miR-330-3p/MYO6 axis. Furthermore, circ_0011385 knockdown suppressed tumor growth in vivo. CONCLUSION: Circ_0011385 regulated CRC process by miR-330-3p/MYO6 axis through MEK1/2/ERK1/2 signaling pathway, providing a novel therapeutic target for CRC.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Association between physical activity and health-related quality of life: time to deterioration model analysis in lung adenocarcinoma.

BACKGROUND AND PURPOSE : Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD). METHODS: We conducted a hospital-based prospective study. The International Physical Activity Questionnaire long-form (IPAQ-L) was used to investigate the pre-treatment physical activity levels, and the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) were used to assess HRQoL at baseline and during follow-up. The QoLR package was used to calculate the HRQoL scores and determine TTD events (minimal clinically important difference=5 points). The effect of physical activity on the HRQoL was assessed using Cox regression analysis. RESULTS: For EORTC QLQ-C30, TTD events of physical functioning (PF) and dyspnea (DY) in functional scales and symptom scales were the most common during follow-up. Pre-treatment physical activity was found to significantly delay TTD of insomnia (HR=0.635, 95%CI: 0.437-0.922, P=0.017) and diarrhea (HR=0.475, 95%CI: 0.291-0.774, P=0.003). For EORTC QLQ-LC13 scales, deterioration of dyspnea (LC-DY) was the most common event. Physical activity was found to delay the TTD of dyspnea (HR=0.654, 95%CI: 0.474-0.903, P=0.010), sore mouth (HR=0.457, 95%CI: 0.244-0.856, P=0.015), and dysphagia (HR=0.315, 95%CI: 0.172-0.580, P<0.001). CONCLUSIONS: Pre-treatment physical activity of LUAD patients may delay the TTD of multiple HRQoL indicators in EORTC QLQ-C30 and EORTC QLQ-LC13. IMPLICATION FOR CANCER SURVIVORS: Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors (someone who is living with or beyond cancer), that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD).

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90). CONCLUSIONS: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3.

Using head-mounted eye trackers to explore children's color preferences and perceptions of toys with different color gradients.

This study investigated how color gradients affect the attraction and visual comfort of children aged 4 to 7 years. We analyzed 108 eye-tracking datasets, including the color attraction index (COI), visual comfort index (PUI), and saccade rate (SR). The findings revealed that children are more attracted to colors as saturation decreases and brightness increases within a specific range. Beyond this range, reduced saturation diminishes color appeal. Moderate brightness and contrast enhance visual comfort during play, while extremely low contrast hinders concentration. Warm colors (red, orange, and yellow) slightly dominate preferences; however, the roles of hue, saturation, and brightness in children's color preferences remain inconclusive. These insights have practical implications for age-appropriate toy design and marketing. Future research should explore age-specific color preferences for more targeted design strategies.

Experimental demonstration of 16QAM/QPSK OFDM-NOMA VLC with LDPC codes and analog pre-equalization.

Non-orthogonal multiple access (NOMA) via power domain multiplexing is widely deployed in bandwidth-limited light-emitting-diode-based visible-light-communication (VLC) systems due to its excellent spectral efficiency. However, quadrature phase-shift keying (QPSK) or even lower-order modulation formats are dominant; therefore, the spectral efficiency can be further improved with the higher-order quadrature amplitude modulation (QAM) modulation. Besides, error propagation (EP) deteriorates the system performance of lower power users during demodulation with imperfect successive interference cancellation. In this paper, we experimentally demonstrate a low-density parity-check (LDPC) codes-enabled 16QAM/QPSK modulation scheme for the orthogonal frequency-division multiplexing-based NOMA-VLC transmission system. Moreover, the analog pre-equalization technique is employed to enhance the modulation bandwidth. The experimental results exhibit that the EP can be significantly mitigated, and the bit error rate performance of lower power users can be improved by up to about 2 orders of magnitude by using LDPC codes and an analog pre-equalization technique.

Bandwidth enhancement with DAC-enabled pre-equalization and real-valued precoding for a FBMC-VLC.

Modulation bandwidth limitation is one of the major drawbacks in light-emitting diode (LED)-based visible light communication (VLC) systems. Various advanced physical-layer modulation formats with digital/analog pre-equalization or adaptive modulation techniques are usually employed to improve the transmission rate of VLC systems. In this Letter, we use a radio frequency (RF) digital-to-analog converter (DAC) to directly realize signal pre-equalization without additional digital or analog signal processing. In addition, low-complexity real-valued precoding techniques are applied to reduce the peak-to-average power ratio (PAPR) and equalize the subcarrier signal-to-noise ratio (SNR). The proposed hybrid scheme is experimentally investigated in a spectral-efficient filter bank multi-carrier (FBMC)-based VLC transmission system. The results exhibit that the PAPR can be reduced by more than 3 dB at the complementary cumulative distribution function of 1 × 10-4 with the real-valued precoding techniques. By using the proposed hybrid scheme, the modulation bandwidth can be increased to 515 MHz for 16QAM-FBMC with a bit error rate below 3.8 × 10-3 after 2.3-m free-space transmission. The net bit rate is improved by more than 45% compared with the conventional FBMC-VLC.

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems.

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. RESULTS AND SIGNIFICANCE: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. CONCLUSIONS: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Protein phosphatase 2A-B56γ-Drp1-Rab7 signaling axis regulates mitochondria-lysosome crosstalk to sensitize the anti-cancer therapy of hepatocellular carcinoma.

Mitochondria-lysosome crosstalk is an intercellular communication platform regulating mitochondrial quality control (MQC). Activated dynamin-related protein 1 (Drp1) with phosphorylation at serine 616 (p-Drp1Ser616) plays a critical role in mitophagy-dependent cell survival and anti-cancer therapy for hepatocellular carcinoma (HCC). However, the underlying mechanisms that p-Drp1Ser616 involved in regulating mitochondria-lysosome crosstalk and mediating anti-HCC therapy remain unknown. HCC cells and mouse xenograft models were conducted to evaluate the relationship between p-Drp1Ser616 and Ras-associated protein 7 (Rab7) and the underlying mechanism by protein phosphatase 2A (PP2A)-B56γ regulating mitophagy via dephosphorylation of p-Drp1Ser616 in HCC. Herein, we found that Drp1 was frequently upregulated and was associated with poor prognosis in HCC. Mitochondrial p-Drp1Ser616 was a novel inter-organelle tethering protein localized to mitochondrion and lysosome membrane contact sites (MCSs) via interaction with Rab7 to trigger an increase in the mitochondria-lysosome crosstalk, resulting in PINK1-Parkin-dependent mitophagy and anti-apoptosis in HCC cells under the treatment of chemotherapy drugs. Moreover, we demonstrate that B56γ-mediated direct dephosphorylation of p-Drp1Ser616 inhibited mitophagy and thus increased mitochondria-dependent apoptosis. Overall, our findings demonstrated that activation of B56γ sensitizes the anti-cancer effect of HCC chemoprevention via dephosphorylated regulation of p-Drp1Ser616 in inhibiting the interaction between p-Drp1Ser616 and Rab7, which may provide a novel mechanism underlying the theranostics for targeting intervention in HCC.