Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty.

OBJECTIVES: This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. METHODS: Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. RESULTS: Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. CONCLUSION: Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.

Impact of ambient air pollution on colorectal cancer risk and survival: insights from a prospective cohort and epigenetic Mendelian randomization study.

BACKGROUND: This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. METHODS: Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene-environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification. FINDINGS: During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI = 1.01-1.06; P = 0.016) and poorer survival (HR, 1.13, 95% CI = 1.03-1.23; P = 0.010), particularly among participants with insufficient physical activity and ever smokers (Pinteraction > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM2.5 exposure (per 10 µg/m3 increment) and elevated CRC risk (RR,1.42, 95% CI = 1.12-1.79; P = 0.004; I2 = 90.8%). Genetically predicted methylation at PM2.5-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO2-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival. INTERPRETATION: Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110. FUNDING: Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).

Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer.

BACKGROUND: We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. METHODS: Metabolite quantitative trait loci were derived from two published metabolomics genome-wide association studies (GWASs), and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (100,204 cases; 154,587 controls) and the FinnGen cohort (4,957 cases; 304,197 controls). Mendelian randomization (MR) and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable MR and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC. RESULTS: The study identified 30 plasma metabolites and four urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, Olipudase alfa, Tilactase). Thirteen modifiable risk factors were associated with nine metabolites and eight of these modifiable risk factors were associated with CRC risk. These nine metabolites mediated the effect of modifiable risk factors (Actinobacteria, BMI, waist-hip ratio, fasting insulin, smoking initiation) on CRC. CONCLUSION: This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.

Evaluating the Clinical Utility of Semi-Quantitative Luciferase Immunosorbent Assay Using Treponema pallidum Antigens in Syphilis Diagnosis and Treatment Monitoring.

OBJECTIVE: To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. METHOD: LISA for detection of anti-TP15, TP17, and TP47 antibodies was developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). 90 serial serum samples from six syphilis rabbit models (three treated, three untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as reference. RESULTS: Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89-0.93) with TPPA were observed. In serial serum samples from rabbit models, significant difference in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31-51) and LISA-TP47 (days 41). In paired serum samples form syphilis patients, TRUST titers and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post treatment (P < 0.001). When TRUST titers decreased by 0, 2, 4, or ≥8-folds, the RLU decreased by 17.53%, 31.34%, 48.62%, and 72.79% for LISA-TP15; 8.84%, 17.00%, 28.37%, and 50.57% for LISA-TP17; 22.25%, 29.79%, 51.75%, and 70.28% for LISA-TP47, respectively. CONCLUSION: Semi-quantitative LISA performs well for syphilis diagnosis while LISA-TP17 is more effective for monitoring syphilis treatment in rabbit models and clinical patients.

Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Risk and Incidence of Cardiovascular Disease Associated with Polycystic Ovary Syndrome.

AIMS: We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD. METHODS: We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. Global incidence of PCOS-associated CVD was calculated by a population attributable fraction (PAF) modelling using the pooled RR, PCOS prevalence, CVD incidence number and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. RESULTS: The risk of CVD was significantly increased in the women with PCOS for all-age group (pooled RR 1.51, 95% CI 1.36-1.69), and 10- to 54-year-old (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS associated CVD cases in women across all-age group has rised from 102 530 to 235 560. The most affected regions were East Asia & Pacific (108 430, 66 090-166 150) in 2019. The South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%; 0.41-0.56) is faster than that of the all-age group (0.34; 0.27-0.42). The middle- or low-middle sociodemographic index countries, experienced higher increase trend of CVD due to PCOS in the past thirty years. CONCLUSIONS: Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with high PCOS-associated CVD burden, especially premature CVD in women under 55 years.

Studies have reported cardiovascular disease (CVD) is the leading cause of mortality for women. Meanwhile, women with polycystic ovary syndrome (PCOS) substantially elevate the risk of CVD. However, no studies have quantified the impact of PCOS on the overall CVD burden. This study performed a meta-analysis to assess the risk of CVD in all-age group and 10 to 54 years old women, living with PCOS with 17 articles, and estimated the burdens of PCOS-associated CVD burden, by global, 7 World-bank defined regions, and 204 countries, from 1990 to 2019, using a PAF modelling. Our study implicated women in all-age group, and 10 to 54 years old with PCOS face a 1.51-fold, and 1.37-fold increased risk of CVD compared those without, respectively. Globally, approximately 0.85% of CVD new cases in 2019 were associated with PCOS, corresponded a more than 2-fold increase of PCOS-associated CVD cases from 1990. However, the burden of PCOS-associated CVD varies widely by region; for instance, nearly 1.49% of CVD new cases were attributed to PCOS in North America. Meanwhile, the East Asia & Pacific region had the highest PCOS-associated new CVD case, and the South Asia experienced the highest increase in age-standardised incidence rates of CVD due to PCOS. Notably, we found higher worldwide PAFs, and annual increase ASIR than that in all-age group women. This result suggests that premature CVD in women with PCOS under 55 years deserve more attention.

Global, regional, and national burden and quality of care of multiple myeloma, 1990-2019.

Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.

Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease.

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P < 2 × 10-16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.

Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS: This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS: During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51-1.65), peptic ulcer (HR 1.56, 95% CI 1.43-1.71), diverticular disease (HR 1.19, 95% CI 1.14-1.24), pancreatitis (HR 1.45, 95% CI 1.24-1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25-2.69), liver cirrhosis (HR 2.92, 95% CI 2.58-3.30), biliary disease (HR 1.18, 95% CI 1.10-1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17-1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01-2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS: In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.

Single-cell RNA sequencing highlights epithelial and microenvironmental heterogeneity in malignant progression of pancreatic ductal adenocarcinoma.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Single-cell transcriptomics provides a unique perspective for dissecting the epithelial and microenvironmental heterogeneity that accompanies progression from benign IPMNs to invasive PDAC. Single-cell RNA sequencing was performed through droplet-based sequencing on 35 693 cells from three high-grade IPMNs and two IPMN-derived PDACs (all surgically resected). Analysis of single-cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of noninvasive dysplasia to invasive cancer. For epithelial cells, we identified acinar-ductal cells and isthmus-pit cells enriched in IPMN lesions and profiled three types of PDAC-unique ductal cells. Notably, a proinflammatory immune component was distinctly observed in IPMNs, comprising CD4+ T cells, CD8+ T cells, and B cells, whereas M2 macrophages were significantly accumulated in PDAC. Through the analysis of cellular communication, the osteopontin gene (SPP1)-CD44 pathway between macrophages and epithelial cells were particularly strengthened in the PDAC group. Further prognostic analysis revealed that SPP1 is a biomarker of IPMN carcinogenesis for surveillance. This study demonstrates the ability to perform high-resolution profiling of single cellular transcriptomes during the progression of high-grade IPMNs to cancer. Notably, single-cell analysis provides an unparalleled insight into both epithelial and microenvironmental heterogeneity associated with early cancer pathogenesis and provides practical markers for surveillance and targets for cancer interception.

CD44-targeting hyaluronic acid-selenium nanoparticles boost functional recovery following spinal cord injury.

BACKGROUND: Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery. RESULTS: The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI. CONCLUSIONS: These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.

Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers.

BACKGROUND: The proteome is an important reservoir of potential therapeutic targets for cancer. This study aimed to examine the causal associations between plasma proteins and cancer risk and to identify proteins with cross-cancer effects. METHODS: Genetic instruments for 3991 plasma proteins were extracted from a large-scale proteomic study. Summary-level data of 13 site-specific cancers were derived from publicly available datasets. Proteome-wide Mendelian randomization and colocalization analyses were used to investigate the causal effect of circulating proteins on cancers. Protein-protein interactions and druggability assessment were conducted to prioritize potential therapeutic targets. Finally, systematical Mendelian randomization analysis between healthy lifestyle factors and cancer-related proteins was conducted to identify which proteins could act as interventional targets by lifestyle changes. RESULTS: Genetically determined circulating levels of 58 proteins were statistically significantly associated with 7 site-specific cancers. A total of 39 proteins were prioritized by colocalization, of them, 11 proteins (ADPGK, CD86, CLSTN3, CSF2RA, CXCL10, GZMM, IL6R, NCR3, SIGLEC5, SIGLEC14, and TAPBP) were observed to have cross-cancer effects. Notably, 5 of these identified proteins (CD86, CSF2RA, CXCL10, IL6R, and TAPBP) have been targeted for drug development in cancer therapy; 8 proteins (ADPGK, CD86, CXCL10, GZMM, IL6R, SIGLEC5, SIGLEC14, TAPBP) could be modulated by healthy lifestyles. CONCLUSION: Our study identified 39 circulating protein biomarkers with convincing causal evidence for 7 site-specific cancers, with 11 proteins demonstrating cross-cancer effects, and prioritized the proteins as potential intervention targets by either drugs or lifestyle changes, which provided new insights into the etiology, prevention, and treatment of cancers.

Endoscopic endonasal transpterygoid nasopharyngectomy: Anatomical considerations and technical note.

BACKGROUND: The study was designed to identify new landmarks in the parapharyngeal segment of the internal carotid artery (ICA) for nasopharyngectomy and describe a surgical procedure of endoscopic endonasal transpterygoid nasopharyngectomy (EETPN). METHODS: Four cadaveric specimens were injected with colored silicone and subjected to CT scanning before dissection. The nasopharyngeal skull base was exposed using the endoscopic endonasal transpterygoid approach. The clinical data of four patients with nasopharyngeal malignances who underwent EETPN were reviewed. RESULTS: The lateral edge of the longus capitis muscle medially; the foramen lacerum, petrous apex spine and the stump of the levator veli palatini muscle superior laterally; and the upper parapharyngeal ICA laterally constitute the ICA-longus capitis muscle-petrous apex spine triangle which was a novel landmark for the upper parapharyngeal segment of the ICA. CONCLUSION: The ICA-longus capitis muscle-petrous apex spine triangle are important landmarks of the upper parapharyngeal segment of the ICA.

Digestive System Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study.

INTRODUCTION: Although digestive system disease affects gut microbiota and their metabolites associated with dementia risk, the association between digestive system diseases and incident dementia has not yet been established. METHODS: This cohort analysis included 458,181 participants free of baseline dementia in the UK Biobank (2006-2021). The associations of 14 digestive system diseases with dementia incidence were examined in 2022 using Cox proportional hazards regression models. Analyses were performed to differentiate the associations for early-onset (age <65 years) and late-onset (age ≥65 years) dementia. Interaction and stratification analyses were performed for polygenic risk score and APOE. RESULTS: During a median follow-up of 12.4 years, 6,415 incident dementia cases were diagnosed. Eleven digestive system diseases showed significant associations with an increased risk of dementia after controlling for covariates and multiple testing. Compared with hazard ratios for individuals without digestive system diseases, the hazard ratios of dementia increased from 1.15 (95% confidence interval=1.09, 1.23) for patients with intestinal diverticular disease to 2.31 (95% confidence interval=1.98, 2.70) for patients with cirrhosis. The associations were different between certain digestive system diseases and dementia by onset age. The associations appeared to be stronger for cirrhosis (Q=0.001), irritable bowel syndrome (Q<0.001), gastritis and duodenitis (Q=0.002), gastroesophageal reflux disease (Q<0.001), ulcerative colitis (Q=0.047), gallbladder disease (Q=0.012), and peptic ulcer (Q=0.030) with early-onset dementia. There were no interactions for polygenic risk score or APOE (p>0.05). CONCLUSIONS: These findings suggest an increased need for dementia prevention among patients with digestive system diseases.

Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study.

Background: Human immunodeficiency virus (HIV) significantly increases the risk of non-Hodgkin lymphoma (NHL) development, yet the population-level impact on NHL burden is unquantified. We aim to quantify this association and estimate the global burden of HIV-associated NHL. Methods: In this meta-analysis, we searched five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) from database inception up to September 13, 2023, identifying cohort, case-control, or cross-sectional studies with an effective control group to assess NHL risk among individuals with HIV infection, with two authors extracting summary data from reports. Global and regional HIV-associated population attributable fraction (PAF) and NHL disease burden were calculated based on the pooled risk ratio (RR). HIV prevalence and NHL incidence were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Trends in NHL incidence due to HIV were assessed using age-standardised incidence rate (ASIR) and estimated annual percentage change (EAPC). This study was registered with PROSPERO (CRD42023404150). Findings: Out of 14,929 literature sources, 39 articles met our inclusion criteria. The risk of NHL was significantly increased in the population living with HIV (pooled RR 23.51, 95% CI 17.62-31.37; I2 = 100%, p < 0.0001), without publication bias. Globally, 6.92% (95% CI 2.18%-11.57%) of NHL new cases in 2019 were attributable to HIV infection (30,503, 95% CI 9585-52,209), which marked a more than three-fold increase from 1990 (8340, 95% CI 3346-13,799). The UNAIDS region of Eastern and Southern Africa was the highest affected region, with 44.46% (95% CI 19.62%-58.57%) of NHL new cases attributed to HIV infection. The Eastern Europe and Central Asia region experienced the highest increase in ASIR of NHL due to HIV in the past thirty years, wherein the EAPC was 8.74% (95% CI 7.66%-9.84%), from 2010 to 2019. Interpretation: People with HIV infection face a significantly increased risk of NHL. Targeted prevention and control policies are especially crucial for countries in Eastern and Southern Africa, Eastern Europe and Central Asia, to achieve the UNAIDS's '90-90-90' Fast-Track targets. Limited studies across diverse regions and heterogeneity between research have hindered precise estimations for specific periods and regions. Funding: Sichuan Provincial People's Hospital, Chengdu, China; Health Care for Cadres of Sichuan Province, Chengdu, China; Science and Technology Department of Sichuan Province, Chengdu, China.

Nanomaterials as therapeutic agents to modulate astrocyte-mediated inflammation in spinal cord injury.

Promoting the recovery of neurological function in patients with traumatic spinal cord injury (TSCI) remains challenging. The balance between astrocyte-mediated neurotrophic and pro-inflammatory responses is critical for TSCI repair. Recently, the utilization of nanomaterials has been considerably explored in immunological reconstructive techniques that specifically target astrocyte-mediated inflammation, yielding positive outcomes. In this review, we aim to condense the present knowledge regarding the astrocyte-mediated inflammation following TSCI. We then review the various categories of nanomaterials utilized in the management of astrocyte-mediated inflammation in TSCI and conclude by summarizing their functions and advantages to offer novel insights for the advancement of effective clinical strategies targeting TSCI.

Superlow Power Consumption Memristor Based on Borphyrin-Deoxyribonucleic Acid Composite Films as Artificial Synapse for Neuromorphic Computing.

Memristor synapses based on green and pollution-free organic materials are expected to facilitate biorealistic neuromorphic computing and to be an important step toward the next generation of green electronics. Metalloporphyrin is an organic compound that widely exists in nature with good biocompatibility and stable chemical properties, and has already been used to fabricate memristors. However, the application of metalloporphyrin-based memristors as synaptic devices still faces challenges, such as realizing a high switching ratio, low power consumption, and bidirectional conductance modulation. We developed a memristor that improves the resistive switching (RS) characteristics of Zn(II)meso-tetra(4-carboxyphenyl) porphine (ZnTCPP) by combining it with deoxyribonucleic acid (DNA) in a composite film. The as-fabricated ZnTCPP-DNA-based device showed excellent RS memory characteristics with a sufficiently high switching ratio of up to ∼104, super low power consumption of ∼39.56 nW, good cycling stability, and data retention capability. Moreover, bidirectional conductance modulation of the ZnTCPP-DNA-based device can be controlled by modulating the amplitudes, durations, and intervals of positive and negative pulses. The ZnTCPP-DNA-based device was used to successfully simulate a series of synaptic functions including long-term potentiation, long-term depression, spike time-dependent plasticity, paired-pulse facilitation, excitatory postsynaptic current, and human learning behavior, which demonstrates its potential applicability to neuromorphic devices. A two-layer artificial neural network was used to demonstrate the digit recognition ability of the ZnTCPP-DNA-based device, which reached 97.22% after 100 training iterations. These results create a new avenue for the research and development of green electronics and have major implications for green low-power neuromorphic computing in the future.

Risk of incident cardiovascular disease among patients with gastrointestinal disorder: a prospective cohort study of 330,751 individuals.

BACKGROUND AND AIMS: The associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations. METHODS: This study included 330 751 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), heart failure (HF) and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD. RESULTS: During a median follow-up of 11.8 years, 31 605 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.37; 95% confidence interval 1.34-1.41, P < 0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, Barrett's esophagus, gastroesophageal reflux disease, peptic ulcer, celiac disease, diverticulum, appendicitis, and biliary disease. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2. CONCLUSIONS: This large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.

High-Performance Neuromorphic Computing and Logic Operation Based on a Self-Assembled Vertically Aligned Nanocomposite SrTiO3:MgO Film Memristor.

Neuromorphic computing based on memristors capable of in-memory computing is promising to break the energy and efficiency bottleneck of well-known von Neumann architectures. However, unstable and nonlinear conductance updates compromise the recognition accuracy and block the integration of neural network hardware. To this end, we present a highly stable memristor with self-assembled vertically aligned nanocomposite (VAN) SrTiO3:MgO films that achieve excellent resistive switching with low set/reset voltage variability (4.7%/-5.6%) and highly linear conductivity variation (nonlinearity = 0.34) by spatially limiting the conductive channels at the vertical interfaces. Various synaptic behaviors are simulated by continuously modulating the conductance. Especially, convolutional image processing using diverse crossbar kernels is demonstrated, and the artificial neural network achieves an overwhelming recognition accuracy of up to 97.50% for handwritten digits. Even under the perturbation of Poisson noise (λ = 10), 6% Salt and Pepper noise, and 5% Gaussian noise, the high recognition accuracies are retained at 95.43%, 94.56%, and 95.97%, respectively. Importantly, the logic memory function is proven experimentally based on the nonvolatile properties. This work provides a material system and design idea to achieve high-performance neuromorphic computing and logic operation.