Socioeconomic inequalities in cancer incidence and mortality: An analysis of GLOBOCAN 2022.

BACKGROUND: Given the recent updates in cancer burden estimates by GLOBOCAN 2022, this study was undertaken to provide pertinent perspectives within the context of the Human Development Index (HDI) and major world economies. METHODS: Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022, alongside projections up to 2050. Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined. The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group. RESULTS: In males, prostate cancer predominated in countries with low, high (except China), and very high HDI. Prostate and liver cancers were prominent causes of death in countries with low HDI. In females, breast and cervical cancers predominated in countries with low-to-medium HDI. Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes. ASIRs and ASMRs for breast, prostate, lung, and colorectal cancers in the top 10 economies were higher than the global average. However, liver, stomach, and cervical cancers in most Western countries exhibited lower rates. In China, hematologic malignancies (43%) were prevalent among children aged 0-14 years, whereas thyroid cancer led among adolescents and young adults aged 15-39 years. Regarding incidence and mortality, lung cancer predominated for individuals over 40 years, except for females aged 40-59 years, in whom breast cancer predominated. Projected trends indicated substantial increases in new cancer cases (76.6%) and deaths (89.7%) over the next three decades. CONCLUSIONS: Infection- and poverty-related cancer burdens are offset by increased prostate, breast, colorectal, and lung cancer incidence associated with rapid societal and economic transitions. Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries, necessitating tailored, evidence-based, and comprehensive strategies for effective cancer prevention and control.

Clinical Benefit from Docetaxel +/- Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy.

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

Application of Intramedullary Calcar Support Plate and Lateral Locking Plate in Elderly Patients with Neer 3 and 4-Part Fractures of Proximal Humerus Through a Deltoid Splitting Approach.

Background: The reduction and fixation of Medial humeral calcar is difficult in the treatment of elderly proximal humerus Neer 3 and 4-part fractures with a single lateral locking plate. Our study investigated the efficacy of an intramedullary calcar supporting plate combined with a lateral locking plate for the treatment of 3- and 4-part fractures of the proximal humerus in the elderly through a deltoid splitting approach. Methods: From June 2022 to December 2022, we treated six elderly patients with Neer 3 and 4-part fractures using proximal humeral intramedullary calcar support plate in combination with lateral locking plate through a deltoid splitting approach. Follow-up time was 6-12 months. Assessment indicators included fracture union, quality of reduction, and complication rate. The Constant-Murley score was used to record shoulder function at 6 months postoperatively. Results: All 6 patients showed fracture union and anatomic reduction. Constant-Murley score was 79.5 (70-90) at 6 months postoperatively. There was no incision non-healing, internal fixation failure, bone non-union or surgical site infection, secondary surgery, or death. Shoulder impingement occurred in 1 case. Conclusion: Proximal humeral intramedullary calcar support plate combined with lateral locking plate fixation through a deltoid splitting approach can effectively maintain fracture reduction, prevent inversion collapse of humeral head and internal fixation failure, and provide satisfactory clinical results at an early stage. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01098-3.

Internet addiction and health-related quality of life in adolescents: The mediating role of sleep disturbance.

BACKGROUND: Internet addiction (IA) has emerged as a recognized risk factor associated with impaired health-related quality of life (HRQOL) in adolescents. However, the role of sleep disturbance in this association remains unclear. This study aimed to investigate the association of IA with HRQOL in Chinese adolescents and to evaluate the potential mediating role of sleep disturbance. METHODS: A cross-sectional study was conducted among adolescents attending six randomly selected middle schools in Guangzhou, China. Adolescents self-reported their internet use using the Young Diagnostic Questionnaire. HRQOL and sleep disturbance were assessed by the Pediatric Quality of Life Inventory version 4.0 and the Pittsburgh Sleep Quality Index, respectively. Multivariate linear regression analysis was employed to assess the association between IA and HRQOL. Baron and Kenny's causal steps method was used to examine the possible mediating role of sleep disturbance. RESULTS: Of the 6473 adolescents included, 23.5% had maladaptive internet use (MIU) and 16.6% had pathological internet use (PIU). Compared to adolescents with adaptive internet use (AIU), those with IA had significantly lower scores across all HRQOL dimensions and summary scales. Mediation analysis revealed that sleep disturbance was a significant mediator. Specifically, sleep disturbance mediated 34.55% of the effects of MIU and 34.06% of the effects of PIU on the HRQOL total scale score , respectively. CONCLUSIONS: IA was associated with poorer HRQOL, indicating the needs of preventing IA in Chinese adolescents. Additionally, our findings underscored the importance of enhancing sleep quality to mitigate the adverse impact of IA on adolescents' well-being.

Riding practices of e-bike riders after the implementation of electric bike management regulations: An observational study in Hangzhou, China.

Objective: This study aimed to understand the riding behaviors of electric bike (e-bike) users in Hangzhou after the "Regulations of Zhejiang Province on the Administration of Electric Bicycles". Methods: The study consisted of two parts, including a questionnaire survey of local e-bike users in Shangcheng District and Jiande County in Hangzhou City, and a cross-sectional observational study of 16 intersections. Results: A total of 789 e-bike riders participated in the questionnaire survey, and the riding behavior of 99,407 e-bike users was observed. The main purpose of using e-bike was work and daily life, 46.0% of them used e-bikes more than 5 days a week, and 58.5% used e-bikes for less than 30 min each time. A vast majority (81.7%) of e-bike riders believe that the implementation of Zhejiang Regulations has significantly improved the safety level of e-bike riding in the region. The field survey found that the correct rates of helmet wearing by e-bike riders and passengers were 78.83% and 42.27%. The main violations were invalid/non-helmet wearing (21.17%), followed by carrying passengers and running red lights (7.94% and 4.26%). The rates of invalid/non-helmet wearing and running red lights were significantly higher during non-morning rush hour, weekends, and roads without separate non-motorized vehicle lanes than in other conditions (all P < 0.05). Additionally, sunny days and crossroads were risk factors for passenger-carrying and invalid/non-helmet wearing compared to rainy/cloudy days and T-intersections. Conclusions: The phenomenon that e-bike users' correct practice lags far behind the awareness of various violations has shown some improvement. To further enhance safety measures for e-bike riders, it is necessary to promote education, improve infrastructure, and strengthen law enforcement, in support of the "Zhejiang Regulations" and behavioral interventions.

Porcine Mandibular Bone Marrow-Derived Mesenchymal Stem Cell (BMSC)-Derived Extracellular Vesicles Can Promote the Osteogenic Differentiation Capacity of Porcine Tibial-Derived BMSCs.

OBJECTIVE: Existing research suggests that bone marrow-derived mesenchymal stem cells (BMSCs) may promote endogenous bone repair. This may be through the secretion of factors that stimulate repair processes or directly through differentiation into osteoblast-progenitor cells. However, the osteogenic potential of BMSCs varies among different tissue sources (e.g., mandibular versus long BMSCs). The main aim of this study was to investigate the difference in osteogenic differentiation capacity between mandibular BMSCs (mBMSCs) and tibial BMSCs (tBMSCs). MATERIALS AND METHODS: Bioinformatics analysis of the GSE81430 dataset taken from the Gene Expression Omnibus (GEO) database was performed using GEO2R. BMSCs were isolated from mandibular and tibial bone marrow tissue samples. Healthy pigs (n = 3) (registered at the State Office for Nature, Environment, and Consumer Protection, North Rhine-Westphalia (LANUV) 81-02.04.2020.A215) were used for this purpose. Cell morphology and osteogenic differentiation were evaluated in mBMSCs and tBMSCs. The expression levels of toll-like receptor 4 (TLR4) and nuclear transcription factor κB (NF-κB) were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot (WB), respectively. In addition, mBMSC-derived extracellular vesicles (mBMSC-EVs) were gained and used as osteogenic stimuli for tBMSCs. Cell morphology and osteogenic differentiation capacity were assessed after mBMSC-EV stimulation. RESULTS: Bioinformatic analysis indicated that the difference in the activation of the TLR4/NF-κB pathway was more pronounced compared to all other examined genes. Specifically, this demonstrated significant downregulation, whereas only 5-7 upregulated genes displayed significant variances. The mBMSC group showed stronger osteogenic differentiation capacity compared to the tBMSC group, confirmed via ALP, ARS, and von Kossa staining. Furthermore, qPCR and WB analysis revealed a significant decrease in the expression of the TLR4/NF-κB pathway in the mBMSC group compared to the tBMSC group (TLR4 fold changes: mBMSCs vs. tBMSCs p < 0.05; NF-κB fold changes: mBMSCs vs. tBMSCs p < 0.05). The osteogenic differentiation capacity was enhanced, and qPCR and WB analysis revealed a significant decrease in the expression of TLR4 and NF-κB in the tBMSC group with mBMSC-EVs added compared to tBMSCs alone (TLR4 fold changes: p < 0.05; NF-κB fold changes: p < 0.05). CONCLUSION: Our results indicate that mBMSC-EVs can promote the osteogenic differentiation of tBMSCs in vitro. The results also provide insights into the osteogenic mechanism of mBMSCs via TLR4/NF-κB signaling pathway activation. This discovery promises a fresh perspective on the treatment of bone fractures or malunions, potentially offering a novel therapeutic method.

Increased incidence risks of cardiovascular disease among cancer patients: Evidence from a population-based cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) is becoming a major concern among cancer patients, leading to the development of a new field named cardio-oncology. However, previous studies were mainly based on the western population and focused on CVD mortality. Evidence from the Chinese population is limited. Furthermore, few studies investigated the incidence risks of CVD among cancer patients. METHODS: 85,787 eligible cancer patients were included from Hangzhou city, China. Age-standardized standard incidence ratio (SIR) was used to reflect the incidence risks of CVD among cancer patients as compared with the standard population, which was defined as all residents in Hangzhou city during the same period. RESULTS: After three years of follow-up, cancer patients showed elevated incidence risks of CVD (SIR = 1.41, 95%CI: 1.35-1.47) as compared with the standard population. The elevated risks of CVD were highest in the first year after cancer diagnosis (SIR = 1.68, 95%CI: 1.58-1.78), then followed by the second (SIR = 1.21, 95%CI: 1.11-1.31) and the third (SIR = 1.18, 95%CI: 1.07-1.29) year. These results were consistent in males and females. Furthermore, different risks of CVD were observed among different cancer sites. Patients with pancreatic cancer showed the highest risks of CVD, then followed by liver cancer, lung cancer, kidney cancer, gastric cancer, bladder cancer, prostate cancer, and colorectal cancer. CONCLUSIONS: Cancer patients have increased incidence risks of CVD, especially in the first year after cancer diagnosis. The increased risks of CVD vary by different cancer sites. Our findings highlight the importance of paying close attention to the CVD risks among cancer patients.

A facile dual-mode immunosensor based on speckle Ag-doped nanohybrids for ultrasensitive detection of Ochratoxin A.

Ochratoxin A (OTA) is a potent carcinogen, and is among the most dangerous mycotoxins in agricultural products. In this study, an ultrasensitive dual-mode immunosensor was developed for naked-eye and fluorescence detection of OTA based on Ag-doped core-shell nanohybrids (Ag@CSNH). Complete antigen-labeled Ag@CSNH (CA-Ag@CSNH) were used as a competitive bind and dual-mode probe. The diffused doping structure of CA-Ag@CSNH provided improved stability, color and fluorescence quencher performance. Antibodies modified magnetic beads were used as a capture probe. The competitive binding between OTA and CA-Ag@CSNH produced both color change and fluorescence quenching. Ultraviolet and fluorescence intensitie correlated linearly with OTA concentration ranges of 0.03-3 ng/mL and 10-10000 pg/mL, and limits of detection of 0.0235 ng/mL and 0.9921 pg/mL, respectively. The practical applicability of proposed strategy was demonstrated by analysis of OTA in spiked corn, soybean and flour samples. This study offers a new insight on multi-mode platforms for various applications.

In situ Hg2+ improved the peroxidase-like activity and triggered "ON" the oxidase-like activity of yolk-shell Co3S4 microspheres for the detection of Hg2.

Exploring highly active nanozymes is an important task to realize the real-time detection of some heavy metal ions in water. In this work, yolk-shell Co3S4 microspheres have been verified to possess excellent peroxidase-like activity, which can be further improved by adding Hg2+. Very interestingly, Hg2+ can trigger "ON" the oxidase-like activity of Co3S4 microspheres. The dual peroxidase-/oxidase-like activity of the yolk-shell Co3S4 microspheres is evaluated by using the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Furthermore, comprehensive studies verify that the enhanced peroxidase-like activity, together with the "ON" oxidase-like activity of the yolk-shell Co3S4 microspheres, is attributed to the in situ generation of HgS on the surface of Co3S4 microspheres and then the release of more active sites. Importantly, the in situ generated HgS on the surface of Co3S4 microspheres can form a heterojunction, which also accelerates the catalytic process. During the catalytic reaction, some active species (O2- and h+) can be detected by ESR. Thus, a colorimetric sensing platform based on Hg2+-triggered signal amplification has been successfully constructed, which can be validated by the detection of Hg2+ residue in environmental water.

The whole-blood Epstein-Barr virus DNA can serve as a valuable molecular marker for diagnosis and prognosis prediction of nasopharyngeal carcinoma.

The clinical significance and prognostic role of whole-blood EBV-DNA in EBV-associated nasopharyngeal carcinoma (NPC) have not been thoroughly investigated. This study aims to explore the diagnostic and prognostic value of EBV-DNA for NPC in a non-endemic region of China. We enrolled patients with chronic active EBV infection (CAEBV), nasopharyngitis (NA), extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), and NPC. Demographic and clinical data were collected and the diagnostic and prognostic values of EBV-DNA were analyzed. Immunohistochemistry was performed to detect EBV-encoded small ribonucleic acids (EBER), as well as the expression of p53, Ki-67, and epidermal growth factor receptor (EGFR). The levels of pretreatment Epstein-Barr virus DNA (preEBV-DNA) in new NPC cases were found to differ from those in other diseases and exhibited varying age distributions. The threshold value of preEBV-DNA for distinguishing NPC from CAEBV and NA was determined. We confirmed that epistaxis, diabetes mellitus, T3N2 or T4N0-2 stage, and IgM positivity were associated with higher levels of preEBV-DNA, and identified risk factors associated with the prognosis of locoregionally advanced NPC (La-NPC). Patients with intermittently or persistently positive EBV-DNA (IPCP), higher preEBV-DNA levels, and positive Epstein-Barr virus-encoded small RNA (EBER) status (EBERpos) had worse survival. New cases of NPC with elevated levels of EBV in the whole-blood and positive EBER status were shown to have a poor prognosis upon progression to La-NPC. EBV-DNA was found to be an indicator for predicting prognosis in La-NPC and could also be used to distinguish new NPC cases.

Extracellular vesicles derived from endothelial cells modulate macrophage phenotype in vitro.

Extracellular vesicles (EVs) mediate cell-to-cell communication by horizontally transferring biological materials from host cells to target cells. During exposure to pathogens, pathogen-associated molecular patterns (e.g., lipopolysaccharide, LPS) get in contact with endothelial cells and stimulate the secretion of endothelial cell-derived EVs (E-EVs). The triggered EVs secretion is known to have a modulating influence on the EVs-receiving cells. Macrophages, a major component of innate immunity, are polarized upon receiving external inflammatory stimuli, in which toll-like receptor4 (TLR4)-nuclear factor kappa B (NFκB) pathway plays a key role. However, the functions of LPS-induced E-EVs (ELPS-EVs) in modulating macrophage phenotype and activation remain elusive. We collected the EVs from quiescent endothelial cells (ENor-EVs) and ELPS-EVs to detect their stimulatory role on NR8383 macrophages. Isolated EVs were characterized by transmission electron microscopy (TEM), western blot assay, and nanoparticle tracking analysis (NTA). NR8383 macrophages were stimulated with ELPS-EVs, ENor-EVs, or PBS for 24 h. Hereafter, the uptake of EVs by the macrophages was investigated. Upon EVs stimulation, cellular viability was determined by MTT assay, while macrophage phenotype was analyzed by flow cytometry and immunofluorescence analysis. Furthermore, a western blot assay was conducted to evaluate the potentially involved TLR4-NFκB pathway. Interestingly, upon exposure to LPS, endothelial cells secreted significantly higher amounts of EVs (i.e., ELPS-EVs) when compared to quiescent cells or cells in PBS. The ELPS-EVs were also better internalized by NR8383 macrophages than ENor-EVs. The cellular viability of ELPS-EVs-treated macrophages was 1.2 times higher than those in the ENor-EVs and PBS groups. In addition, ELPS-EVs modulated NR8383 macrophages towards a proinflammatory macrophage M1-like phenotype. This was indicated by the significantly upregulated expressions of proinflammatory macrophage biomarkers CD86 and inducible nitric oxide synthase (iNOS) observed in ELPS-EVs-treated macrophages. The TLR4-NFκB signaling pathway was substantially activated in ELPS-EVs-treated macrophages, indicated by the elevated expressions of makers TLR4 and phosphorylated form of nuclear factor kappa B p65 subunit (p-NFκBp65). Overall, our results indicate that E-EVs play a crucial role in macrophage phenotype modulation under inflammatory conditions.

Use of magnetic powder to effectively improve the denitrification employing the activated sludge fermentation liquid as carbon source.

Nitrogen removal is often limited in municipal wastewater treatment due to the lack of sufficient carbon source. Utilizing volatile fatty acids (VFAs) from waste activated sludge (WAS) fermentation broth as a carbon source is an ideal alternative to reduce the cost for wastewater treatment plants (WWTPs) and improve denitrification efficiency simultaneously. In this study, an anaerobic system was applied for simultaneous denitrification and WAS fermentation and the addition of magnetic microparticles (MMP) were confirmed to enhance both denitrification and WAS fermentation. Firstly, the addition of MMP increased the nitrate reduction rate by over 25.36% and improve the production of N2. Additionally, the equivalent chemical oxygen demand (COD) of the detected VFAs increased by 7.06%-14.53%, suggesting that MMP promoted the WAS fermentation. The electron transfer efficiency of denitrifies was accelerated by MMP via electron-transporting system (ETS) activity and cyclic voltammetry (CV) experiments, which might result in the promotional denitrification and WAS fermentation performance. Furthermore, the high-throughput sequencing displayed that, MMP enriched key microbes capable of degrading the complex organics (Chloroflexi, Synergistota and Spirochaetota) as well as the typical denitrifies (Bacteroidetes_vadinHA17 and Denitratisoma). Therefore, this study provides a novel strategy to realize simultaneous WAS utilization and denitrification for WWTPs.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

Characterization of the microbial community and prediction of metabolic functions in an anaerobic/oxic system with magnetic micropolystyrene as a biocarrier.

Polystyrene (PS) and magnetic polystyrene (MPS) materials have been used extensively in wastewater treatment. In this research, a 55-day anaerobic/oxic process was carried out to evaluate the effects of PS and MPS on microorganisms under aerobic and anaerobic conditions. Scanning electron microscopy results revealed differences in the entanglement state of the sludge with the biocarrier due to differences in surface morphology. High-throughput sequencing analysis showed that the microbial communities differed considerably in the presence of PS and MPS addition under both aerobic and anaerobic conditions. The highest abundance and diversity were observed in the PS reactor, with 929 observed species and a PD_whole_tree index of 91.58 under anaerobic conditions. MPS promoted the enrichment of bacteria related to nitrogen recycling such as Nitrospirota which increased from 1.13% in the seeding sludge to 3.48% and 10.07% in the aerobic reactors with PS and MPS, respectively. Moreover, advanced analysis showed that PS inhibited many microbial functions (e.g., protein export, nitrogen metabolism), and MPS alleviated this inhibition. This study provides significant insights into the microbial effects of PS and MPS and may shed light on biocarrier selection in future studies.

Adverse childhood experiences and depressive symptoms among middle-aged or older adults in China and the mediating role of short sleep duration.

BACKGROUND: Limited research has simultaneously examined the link between adverse childhood experiences (ACEs), short sleep duration, and depressive symptoms among middle-aged or older Chinese adults. This study aims to investigate the association between ACEs and later-life depressive symptoms, and to examine the mediating role of short sleep duration (<6 h/night) in this association. METHODS: Data of 11,452 participants aged ≥45 years were obtained from the China Health and Retirement Longitudinal Study. Information on ACEs, depressive symptoms, and sleep duration were reported via questionnaires. The mediating effect of short sleep duration in the association between ACEs and depressive symptoms was examined by Baron and Kenny's causal steps method and Karlson/Holm/Breen (KHB) method. RESULTS: Compared to non-exposed group, exposure to ACEs was significantly associated with increased odds of depressive symptoms in a dose-response pattern. The odds ratio of depressive symptoms increased from 1.27 (95 % CI: 1.11-1.46) for one ACE to 3.38 (95 % CI: 2.92-3.90) for ≥4 ACEs. The KHB method identified significant mediating role of short sleep duration in the association between experiencing three or more ACEs and depressive symptoms, with the proportional mediation estimated at 8.96 % and 8.85 % for the groups with 3 ACEs and ≥4 ACEs, respectively. The results were consistent across genders and gender did not moderate these associations. LIMITATIONS: The cross-sectional design limited the ability to make causal inference. CONCLUSIONS: ACEs were positively associated with depressive symptoms, and short sleep duration partially mediated this association. Promoting optimal sleep duration among ACE-exposed individuals might improve their mental health.

Functionalized magnetic nanobeads for SERS-based detection of Staphylococcus aureus.

In this study, we introduced a Raman detection technique based on a combination of functionalized magnetic beads and surface-enhanced Raman scattering (SERS) tags to develop a rapid and sensitive strategy for the detection of Staphylococcus aureus (S. aureus), a typical foodborne pathogen. Polyethylene glycol (PEG) and bovine serum albumin (BSA) dual-mediated teicoplanin functionalized magnetic beads (TEI-BPBs) were prepared for separation of target bacteria. SERS tags were used to immobilize antibodies on gold surfaces with bifunctional linker proteins to ensure specific recognition of S. aureus. Under optimal conditions, the combination of TEI-BPBs and SERS tags showed reliable performance, exhibiting good capture efficiency even in the presence of 106 CFU mL-1 of non-target bacteria. The SERS tag provided an effective hot spot for subsequent Raman detection, presenting good linearity in the range of 102-107 CFU mL-1. Good performance has also been shown in detecting target bacteria in milk samples, where it has a recovery of 95.5-101.3%. Thus, the highly sensitive Raman detection technique combined with TEI-BPBs capture probes and SERS tags is a promising method for the detection of foodborne pathogens in food or clinical samples.

Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study.

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context. METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from Jan 1, 2014, to Feb 29, 2020. We built and tested an ensemble deep learning model on pretreatment CTs (Deep-CT) to predict overall survival and progression-free survival after treatment with immune checkpoint inhibitors. We also evaluated the added predictive value of the Deep-CT model in the context of existing clinicopathological and radiological metrics. FINDINGS: Our Deep-CT model demonstrated robust stratification of patient survival of the MD Anderson testing set, which was validated in the external Stanford set. The performance of the Deep-CT model remained significant on subgroup analyses stratified by PD-L1, histology, age, sex, and race. In univariate analysis, Deep-CT outperformed the conventional risk factors, including histology, smoking status, and PD-L1 expression, and remained an independent predictor after multivariate adjustment. Integrating the Deep-CT model with conventional risk factors demonstrated significantly improved prediction performance, with overall survival C-index increases from 0·70 (clinical model) to 0·75 (composite model) during testing. On the other hand, the deep learning risk scores correlated with some radiomics features, but radiomics alone could not reach the performance level of deep learning, indicating that the deep learning model effectively captured additional imaging patterns beyond known radiomics features. INTERPRETATION: This proof-of-concept study shows that automated profiling of radiographic scans through deep learning can provide orthogonal information independent of existing clinicopathological biomarkers, bringing the goal of precision immunotherapy for patients with NSCLC closer. FUNDING: National Institutes of Health, Mark Foundation Damon Runyon Foundation Physician Scientist Award, MD Anderson Strategic Initiative Development Program, MD Anderson Lung Moon Shot Program, Andrea Mugnaini, and Edward L C Smith.

Adverse childhood experiences, problematic internet use, and health-related quality of life in Chinese adolescents.

Background: The influence of adverse childhood experiences (ACEs) on an individual's health is substantial. However, the associations between ACEs, problematic internet use (PIU), and health-related quality of life (HRQOL) in adolescents remain underexplored.Objective: To assess the association between ACEs and HRQOL in Chinese adolescents and to evaluate the mediating role of PIU in this association.Method: A sample of 6,639 adolescents (3,457 boys and 3,182 girls) aged between 11-20 years (mean [SD] age: 14.5 [1.6] years) were recruited from 6 junior and senior middle schools using a proportional sampling approach in a cross-sectional study. Data on ACE exposure was collected through the short form of Childhood Trauma Questionnaire, the ACE-International Questionnaire, and two additional questions. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0. The associations between ACEs and HRQOL were estimated using linear regression models. Mediation analysis was further conducted to explore the possible mediating role of PIU in the association between ACEs and HRQOL.Results: Our study collected 13 different ACEs. We found that adolescents exposed to any ACE had significantly lower scores in all HRQOL dimensions, psychosocial health summary scale, and total scale, than those without such exposure. Specifically, adolescents with ≥ 3 ACE exposure had a total scale score that was 14.70 (95%CI: 15.53 to 13.87) points lower than their non-exposed counterparts. Mediation analysis identified PIU as a significant mediator, with the proportion of the total effect attributable to PIU ranging from 14.38% for social functioning to 17.44% for physical functioning.Conclusions: Exposure to ACEs was associated with poorer HRQOL in Chinese adolescents, underscoring the importance to prevent ACEs and their negative impacts on adolescent well-being. These findings also highlighted the need of promoting appropriate internet use among adolescents exposed to ACEs, in order to avert potential impairment in their HRQOL.HIGHLIGHTSAdolescents with adverse childhood experiences have poorer health-related quality of life.The association between adverse childhood experiences and health-related quality of life shows a dose-response pattern.Problematic internet use partially mediates the associations between adverse childhood experiences and health-related quality of life in adolescents.