Blood-based molecular and cellular biomarkers of early response to neoadjuvant PD-1 blockade in patients with non-small cell lung cancer.

BACKGROUND: Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response. METHODS: Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model. RESULTS: The gene expression of hundreds of DEGs (FDR p < 0.05, fold change < -2 or > 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p < 0.05) and heightened responsiveness to anti-PD-1 treatment in patient cohort and co-cultured cell lines. CONCLUSION: This study discovered and validated peripheral blood-based biomarkers with evident predictive efficacy for early therapy response and patient stratification before treatment for neoadjuvant PD-1 blockade in NSCLC patients.

Supramolecular engineering cascade regulates NIR-II J-aggregates to improve photodynamic therapy.

Rational design of small organic molecule-based NIR-II photosensitizers (PSs) with high singlet oxygen quantum yield in aqueous solution for deep tissue imaging and cancer therapy still presents challenges. Herein, we devised a general synthesis strategy to obtain six NIR-II region PSs with tunable aggregation states by adjusting the steric effect, and all PSs possess longer NIR absorption/emission wavelengths with tails extending beyond 1200 nm. Notably, ATX-6 possessed a singlet oxygen quantum yield of 38.2% and exhibited concentration-dependent J-aggregation properties upon self-assembly in an aqueous solution. What's more, supramolecular engineering with DSPE-PEG2000 further enhanced its degree of J-aggregation, which was attributed to the dimer-excited reduction of the energy levels of the single-linear/triple-linear states and the facilitation of intersystem crossover processes. In addition, ATX-6 NPs showed superior photodynamic therapy effects and great potential in high-contrast in vivo bioimaging of the NIR-II region. These results provide valuable insights for achieving the diagnostic and therapeutic integration of tumors.

Integrative analysis of the transcriptome and proteome reveals the molecular responses of tobacco to boron deficiency.

BACKGROUND: Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. RESULTS: We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. CONCLUSION: Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

A Semi-Supervised Adaptive Matrix Machine Approach for Fault Diagnosis in Railway Switch Machine.

The switch machine, an essential element of railway infrastructure, is crucial in maintaining the safety of railway operations. Traditional methods for fault diagnosis are constrained by their dependence on extensive labeled datasets. Semi-supervised learning (SSL), although a promising solution to the scarcity of samples, faces challenges such as the imbalance of pseudo-labels and inadequate data representation. In response, this paper presents the Semi-Supervised Adaptive Matrix Machine (SAMM) model, designed for the fault diagnosis of switch machine. SAMM amalgamates semi-supervised learning with adaptive technologies, leveraging adaptive low-rank regularizer to discern the fundamental links between the rows and columns of matrix data and applying adaptive penalty items to correct imbalances across sample categories. This model methodically enlarges its labeled dataset using probabilistic outputs and semi-supervised, automatically adjusting parameters to accommodate diverse data distributions and structural nuances. The SAMM model's optimization process employs the alternating direction method of multipliers (ADMM) to identify solutions efficiently. Experimental evidence from a dataset containing current signals from switch machines indicates that SAMM outperforms existing baseline models, demonstrating its exceptional status diagnostic capabilities in situations where labeled samples are scarce. Consequently, SAMM offers an innovative and effective approach to semi-supervised classification tasks involving matrix data.

Hypolipidemic effect of polysaccharide from Sargassum fusiforme and its ultrasonic degraded polysaccharide on zebrafish fed high-fat diet.

Sargassum fusiforme is a brown seaweed that grows abundantly along the rocky coastlines of Asian countries. The polysaccharides derived from Sargassum fusiforme (SFPS) have received much interest due to their various bioactivities, such as hypolipidemic, hypoglycemic, and antioxidant activities. In this study, we extracted and purified SFPS, and obtained the ultrasonic degradation product (SFPSUD). The lipid regulatory effects of SFPS and SFPSUD were investigated in a zebrafish model fed a high-fat diet. The results showed that SFPS significantly decreased the levels of total cholesterol (TC) and triglycerides (TG), and increased the activities of lipoprotein lipase (LPL) and hepatic lipase (HL). SFPSUD was more effective than the SFPS in reducing the TC and TG levels in zebrafish, as well as increasing the LPL and HL activities. Histopathological observations of zebrafish livers showed that SFPSUD significantly improved lipid metabolism disorder in the hepatocytes. The possible lipid-lowering mechanism in zebrafish associated with SFPS and SFPSUD may involve acceleration of the lipid metabolism rate by increasing the activities of LPL and HL. Thus, SFPSUD could be tested as a highly effective hypolipidemic drug. Our results suggest that SFPS and SFPSUD have potential uses as functional foods for the prevention and treatment of hyperlipidemia. Ultrasound can be effectively applied to degrade SFPS to improve its physicochemical properties and bioactivities.

Landscape fragmentation and regularity lead to decreased carbon stocks in basins: Evidence from century-scale research.

Landscapes evolution have significantly altered the Earth's energy balance and biogeochemical cycles, thereby exacerbating climate change. This, in turn, affects surface characteristics and the provision of ecosystem services, especially carbon storage. While recent centuries have witnessed unprecedented landscape changes, limited long-term studies have offered insights into the comparison between present-day features and historical conditions. This study utilized historical reconstruction data and remote sensing imagery to assess landscape evolution and its consequences for carbon stocks over 300 years. Employing multiple regression and random forest models were selected to quantify the influence of key landscape metrics on carbon stocks in the Dongting Lake basin, allowing for a thorough analysis across different sub-basins and land types. The results revealed that intensified human disturbances led to increased landscape fragmentation (+82%), regularity (+56%), and diversity (+37%) within the basin. Moreover, carbon stocks decreased from 4.13 Gt to 3.66 Gt, representing an 11.4% loss, with soil carbon stock experiencing the most considerable reduction (0.24 Gt, 51%). These changes in carbon stock metrics corresponded to shifts in landscape patterns, both undergoing significant transitions at the turn of the 21st century. Meanwhile, fragmentation and regularity played a vital role in explaining carbon stock changes, as their increase contributes to greater carbon losses. Likewise, an increase in landscape diversity correlated with decreased carbon stocks, challenging the prevailing notion that enhanced diversity promotes carbon stocks. The influence of landscape patterns on carbon stocks varies notably across distinct land types. An increase in the dominance of farmland and built-up land led to decreased carbon stocks, while the opposite holds true for forestland. Similarly, a decrease in regularity for farmland, forestland, and built-up land benefits carbon storage, while grassland demonstrates the opposite trend. These findings offer insights for countries and regions in the early stages of development or approaching development, suggesting improvements in land use practices and strategies to address climate change. This involves offsetting land-based carbon emissions through changes in landscape spatial configuration.

Application value of laparoscopic surgery in elderly patients (≥ 75 years) with colorectal cancer and prognostic factors influencing 5-year overall survival.

OBJECTIVE: To investigate the application value of laparoscopic surgery in elderly patients (≥ 75 years) with colorectal cancer, and to identify the prognostic factors influencing the long-term survival in this demographic, and to establish a predictive nomogram model. METHODS: A retrospective analysis was conducted on 146 elderly (≥ 75 years old) colorectal cancer patients who underwent radical surgery in Baoji People's Hospital from August 2016 to February 2018, including 55 patients who underwent laparotomy and 91 patients who underwent laparoscopic surgery. Survival curves were plotted using the Kaplan-Meier method, and differences in prognosis were assessed using the Log-rank test. Prognostic impacts of various factors on 5-year survival were analyzed using a Cox proportional hazards model. Significant predictors identified in the Cox model were used to construct a nomogram for predicting survival, which was then validated for accuracy and clinical utility. RESULTS: Laparoscopic surgery was associated with shorter hospital stays (P = 0.022), although at a higher cost (P = 0.011). The laparoscopic group also had less intraoperative bleeding (P < 0.001), incision length (P < 0.001), time to first postoperative expectoration (P < 0.001), time to first postoperative feeding (P = 0.002), and time to postoperative peritoneal drainage (P = 0.003) compared to the open surgery group. Additionally, the rate of postoperative wound complications was also lower in the laparoscopic group (P = 0.014). There was no significant difference in the 5-year post-treatment survival between the two groups (P = 0.150). Multifactorial Cox regression analysis revealed that a history of diabetes mellitus (P = 0.037), vascular infiltration (P = 0.026), nerve bundle invasion (P = 0.001), and TNM stage (P = 0.001) were independent prognostic factors affecting the 5-year survival of patients with advanced colorectal cancer. The constructed nomogram showed high predictive accuracy for 1-, 3-, and 5-year survival, with AUC values of 0.91, 0.87, and 0.79, respectively. Calibration curves and decision curve analysis confirmed the model's clinical utility. Risk formula: History of diabetes mellitus * -0.696194503 + Vascular infiltration * -0.769736513 + Nerve bundle invasion * -1.1709777 + TNM staging * 1.201933691. CONCLUSION: Laparoscopic surgery can reduce intraoperative trauma and accelerate postoperative recovery in elderly colorectal cancer patients (≥ 75 years) compared to open surgery. The developed nomogram model based on independent prognostic factors such as diabetes history, vascular infiltration, nerve bundle invasion, and TNM staging, facilitates tailored prognostic assessment, enhancing individual patient management.

The associations between interparental conflict and adolescent adjustment: a cross-lagged panel network analysis.

Extensively studied in interparental relationship literature suggests interparental conflict is a risk factor for adolescent adjustment, but the specific, dimension level relationships between interparental conflict and adolescent adjustment remain unclear. This study explored the interactions between the various dimensions of interparental conflict and adolescent adjustment in Chinese adolescents. A total of 1870 Chinese adolescents (42.27% males; Mage = 16.18, SD = 0.43, range = 15-18) completed a survey at two time points spaced three months apart. Data was analyzed using both cross-sectional and longitudinal network analysis. The cross-sectional network analysis found that resolution has the greatest connections with the dimensions of adolescent adjustment, suggesting that adolescents reporting high resolution are more prone to experience concurrent poor adjustment and therefore should be a primary focus of attention. The longitudinal network analysis revealed that, in general, previous hyperactivity-inattention is a significant and strong predictor of future interparental conflict, underscoring a child-driven effect. Meanwhile, prosocial behavior contributes to decreases in both interparental conflict and adjustment problems over time. These findings highlight the importance of addressing hyperactivity-inattention and cultivating prosocial behavior in adolescents as key intervention points-these can help resolve conflicts between parents and reduce adjustment problems for adolescents.

The precision of technical aspects in the minimally invasive Broström-Gould procedure: a cadaveric anatomical study.

BACKGROUND: A comprehensive understanding of the anatomy of the anterolateral ankle joint and its interrelationships is essential for advancing the development of minimally invasive Broström-Gould procedure, thereby enhancing surgical efficacy and minimizing postoperative complications. METHODS: Ten fresh human ankle specimens were dissected to observe the shape and trajectory of the lateral bundle of the inferior extensor retinaculum (IER) and its relationship with the deep fascia. To observe the relationship between the ankle capsule and the anterior talofibular ligament (ATFL). The center of the insertion point of ATFL at the lateral malleolus was used as the reference point. The vertical distance from the reference point to the fibula tip, the horizontal distance from the reference point to the lateral branch of the superficial peroneal nerve, the shortest distance from the reference point to IER, the narrowest width of the IER, the angle between the line connecting the shortest distance from the reference point to the IER and the longitudinal axis of the fibula were measured. The tension and elasticity of ATFL was understood. To describe the minimally invasive Broström-Gould procedure according to the anatomical characteristics of the anterolateral ankle joint. RESULTS: Among the 10 cases, 8 cases (80%) had double bundles of ATFL, 2 cases (20%) had single bundle of ATFL, and no outer superior oblique bundle was observed in IER. The vertical distance from the reference point to the fibula tip was 1.2 ± 0.3 (range 1.1-1.3) mm. The shortest distance from the reference point to the level of the superficial peroneal branch was 28.2 ± 4.3 (range 24.5-32.4) mm. The shortest distance from the reference point to IER was 12.5 ± 0.6 (range 12.1-12.9) mm, and the width of IER at this point was 7.2 ± 0.3 (range 7.0-7.6) mm. The angle between the line connecting the shortest distance from the reference point to the IER and the longitudinal axis of the fibula was about 60° ± 2.8° (range 58.1°-62.1°) mm. The space between the anterolateral deep fascia of the ankle joint and the ankle capsule is very small, and only a few fat granules are separated between them. The ATFL is largely fused to the ankle capsule. The ATFL exhibited high tension and poor elasticity after traction with the probe hook. CONCLUSIONS: The results showed that in the minimally invasive Broström-Gould technique for lateral ankle stabilization, the Broström procedure actually sutured the insertion of the ATFL together with the ankle capsule to the anterior edge of the lateral malleolus. In the Gould procedure, the deep fascia was mostly reinforced with the ankle capsule. The minimum suture span was obtained when the Gould suture needle direction was at an Angle of 60° to the longitudinal axis of the fibula.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

The effect of choice on memory across development.

Numerous studies have demonstrated the role of making choices as an internal motivator to improve performance, and recent studies in the domain of memory have focused on adults. To chart the developmental trend of the choice effect on memory, we conducted a series of seven experiments involving children, adolescents, and young adults. Participants (N = 512) aged 5 to 26 years performed a choice encoding task that manipulated the opportunities to choose and then took a memory test. Using different types of experimental materials and corroborated by a mini meta-analysis, we found that the choice effect on memory was significant in childhood and early adolescence but not significant in late adolescence and early adulthood. The developmental changes were statistically significant, particularly evident during the transition from early to late adolescence. These findings suggest that the internal value of choice decreases across development and contributes to our understanding of developmental differences in the role of choice in memory.

Chemotherapy-induced PTEN-L secretion promotes the selection of PTEN-deficient tumor cells.

BACKGROUND: PTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression. METHODS: PTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms. RESULTS: The chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy. CONCLUSIONS: In summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment.

A modified "outside-in" Broström-Gould procedure yielding favorable outcomes for the management of chronic lateral ankle instability-a retrospective study with mid-term follow-up.

Purpose: There are various surgical interventions available for the management of Chronic lateral ankle instability (CLAI). The Broström-Gould procedure has gained widespread recognition among foot and ankle specialists for its favorable surgical outcomes. However, with advancements in anatomical understanding and medical technology, further enhancements to the effectiveness of the Gould procedure are warranted. This study introduces a all-inside modified "outside-in" Broström -Gould procedure as an alternative approach for addressing lateral ankle instability. Methods: From August 2020 to October 2022, 40 patients with lateral ankle instability who underwent arthroscopic repair of the modified "outside-in" Broström-Gould procedure were retrospectively analyzed. All patients received standard non-surgical treatment before surgery for more than 6 months without symptom relief. Visual Analogue Scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) and Karlsson-Peterson score were used to evaluate the postoperative effect. Results: All patients were followed up for (14.62 ± 2.04) months. One year after operation, all patients could walk normally, ankle instability sensation disappeared, varus stress test and anterior drawer test were negative. The VAS , AOFAS and Karlsson-Peterson scores of all patients were significantly better compared with those before operation, and the difference between before and after operation was statistically significant. Conclusions: The modified "outside-in" Broström-Gould procedure can effectively treat CLAI, which can obtain satisfactory results. The procedure is straightforward, the impact is minimal, and the aesthetics are pleasing.

Genetic Inactivation of the ß1 adrenergic receptor prevents Cerebral Cavernous Malformations in zebrafish.

Propranolol reduces experimental murine cerebral cavernous malformations (CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in zebrafish that follow mosaic inactivation of ccm2. Because morpholino silencing of the ß1 adrenergic receptor (adrb1) prevents the embryonic CVP lesion, we proposed that adrb1 plays a role in CCM pathogenesis. Here we report that adrb1 -/- zebrafish exhibited 86% fewer CVP lesions and 87% reduction of CCM lesion volume relative to wild type brood mates at 2dpf and 8-10 weeks stage, respectively. Treatment with metoprolol, a ß1 selective antagonist, yielded a similar reduction in CCM lesion volume. Adrb1 -/- zebrafish embryos exhibited reduced heart rate and contractility and reduced CVP blood flow. Similarly, slowing the heart and eliminating the blood flow in CVP by administration of 2,3-BDM suppressed the CVP lesion. In sum, our findings provide genetic and pharmacological evidence that the therapeutic effect of propranolol on CCM is achieved through ß1 receptor antagonism.

Warming-driven increased synchrony of tree growth across the southernmost part of the Asian boreal forests.

Climate change has profoundly affected the synchrony of tree growth at multiple scales, thereby altering the structure and function of forest ecosystems. The Asian boreal forests extend southward to the Greater Khingan Range in northeast China. Given the ecological importance and susceptibility to climate change, the impacts of warming on this marginal forest community have been extensively investigated. Nonetheless, how tree growth synchrony changes across this region remains less understood. Focusing on this knowledge gap, we compiled a contiguously-distributed tree-ring network, containing 18 sampling populations and 475 individual larch trees, to explore the changes in multiple-scale growth synchrony across this region. We found increasing growth synchrony at both the individual and population levels over the past decades. The increasing trend of the regional inter-population growth synchrony was well in line with the increasing temperature and PDSI. Furthermore, 11 of the 18 sampling populations showed significant increases in their intra-population growth synchrony. We further associated the sliding intra-population growth synchrony with local climates. Intra-population growth synchrony of 13 and 11 sampling populations were significantly positively correlated with local temperature, and negatively correlated with local PDSI, respectively, demonstrating the driving role of warming-induced drought on growth synchrony. The linear regression model quantifying this relationship suggested that an increase of 1 °C in annual mean temperature would drive the intra-population growth synchrony to increase by 0.047. As warming trends in the study area are projected to continue over this century, our study warns of the further consequences of the increasing growth synchrony may have on the functioning, resilience, and persistence of forests.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

A prospective cohort study exploring the joint influence of sunlight exposure and tanning bed use on basal cell carcinoma, squamous cell carcinoma, and melanoma risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR = 1.53, 95% CI 1.37-1.71, Pinteraction=0.01; vs. low sun exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR = 1.62, 95% CI 1.47-1.79, Pinteraction=0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

Aberrant auditory metabolite levels and topological properties are associated with cognitive decline in presbycusis patients.

Presbycusis has been reported as related to cognitive decline, but its underlying neurophysiological mechanism is still unclear. This study aimed to investigate the relationship between metabolite levels, cognitive function, and node characteristics in presbycusis based on graph theory methods. Eighty-four elderly individuals with presbycusis and 63 age-matched normal hearing controls underwent magnetic resonance spectroscopy, functional magnetic resonance imaging scans, audiological assessment, and cognitive assessment. Compared with the normal hearing group, presbycusis patients exhibited reduced gamma-aminobutyric acid and glutamate levels in the auditory region, increased nodal characteristics in the temporal lobe and precuneus, as well as decreased nodal characteristics in the superior occipital gyrus and medial orbital. The right gamma-aminobutyric acid levels were negatively correlated with the degree centrality in the right precuneus and the executive function. Degree centrality in the right precuneus exhibited significant correlations with information processing speed and executive function, while degree centrality in the left medial orbital demonstrated a negative association with speech recognition ability. The degree centrality and node efficiency in the superior occipital gyrus exhibited a negative association with hearing loss and speech recognition ability, respectively. These observed changes indicate alterations in metabolite levels and reorganization patterns at the brain network level after auditory deprivation.

Spatially selective p-type doping for constructing lateral WS2 p-n homojunction via low-energy nitrogen ion implantation.

The construction of lateral p-n junctions is very important and challenging in two-dimensional (2D) semiconductor manufacturing process. Previous researches have demonstrated that vertical p-n junction can be prepared simply by vertical stacking of 2D materials. However, interface pollution and large area scalability are challenges that are difficult to overcome with vertical stacking technology. Constructing 2D lateral p-n homojunction is an effective strategy to address these issues. Spatially selective p-type doping of 2D semiconductors is expected to construct lateral p-n homojunction. In this work, we have developed a low-energy ion implantation system that reduces the implanted energy to 300 eV. Low-energy implantation can form a shallow implantation depth, which is more suitable for modulating the electrical and optical properties of 2D materials. Hence, we utilize low-energy ion implantation to directly dope nitrogen ions into few-layer WS2 and successfully realize a precise regulation for WS2 with its conductivity type transforming from n-type to bipolar or even p-type conduction. Furthermore, the universality of this method is demonstrated by extending it to other 2D semiconductors, including WSe2, SnS2 and MoS2. Based on this method, a lateral WS2 p-n homojunction is fabricated, which exhibits significant rectification characteristics. A photodetector based on p-n junction with photovoltaic effect is also prepared, and the open circuit voltage can reach to 0.39 V. This work provides an effective way for controllable doping of 2D semiconductors.

Deep Learning Model for Grading and Localization of Lumbar Disc Herniation on Magnetic Resonance Imaging.

BACKGROUND: Methods for grading and localization of lumbar disc herniation (LDH) on MRI are complex, time-consuming, and subjective. Utilizing deep learning (DL) models as assistance would mitigate such complexities. PURPOSE: To develop an interpretable DL model capable of grading and localizing LDH. STUDY TYPE: Retrospective. SUBJECTS: 1496 patients (M/F: 783/713) were evaluated, and randomly divided into training (70%), validation (10%), and test (20%) sets. FIELD STRENGTH/SEQUENCE: 1.5T MRI for axial T2-weighted sequences (spin echo). ASSESSMENT: The training set was annotated by three spinal surgeons using the Michigan State University classification to train the DL model. The test set was annotated by a spinal surgery expert (as ground truth labels), and two spinal surgeons (comparison with the trained model). An external test set was employed to evaluate the generalizability of the DL model. STATISTICAL TESTS: Calculated intersection over union (IoU) for detection consistency, utilized Gwet's AC1 to assess interobserver agreement, and evaluated model performance based on sensitivity and specificity, with statistical significance set at P < 0.05. RESULTS: The DL model achieved high detection consistency in both the internal test dataset (grading: mean IoU 0.84, recall 99.6%; localization: IoU 0.82, recall 99.5%) and external test dataset (grading: 0.72, 98.0%; localization: 0.71, 97.6%). For internal testing, the DL model (grading: 0.81; localization: 0.76), Rater 1 (0.88; 0.82), and Rater 2 (0.86; 0.83) demonstrated results highly consistent with the ground truth labels. The overall sensitivity of the DL model was 87.0% for grading and 84.0% for localization, while the specificity was 95.5% and 94.4%. For external testing, the DL model showed an appreciable decrease in consistency (grading: 0.69; localization: 0.66), sensitivity (77.2%; 76.7%), and specificity (92.3%; 91.8%). DATA CONCLUSION: The classification capabilities of the DL model closely resemble those of spinal surgeons. For future improvement, enriching the diversity of cases could enhance the model's generalization. TECHNICAL EFFICACY: Stage 2.