Evaluating Occupational Workforce and Practices in New York Metropolitan Nail Salons.

This study investigated workforce characteristics, work practices, protective measures, and health symptoms among nail salon workers in New York and New Jersey following the implementation of local exhaust ventilation (LEV) regulations in New York. An online survey conducted from 2022 to 2023 targeted registered nail salons and manicurists in both states (N = 146). The majority of respondents were Asian, primarily Korean (52.1%) and Chinese (26%). In New York, 79% of salons had a mechanical ventilation system, including LEV, while in New Jersey, where no ventilation regulation exists, only 52% of nail salons had mechanical ventilation systems. A substantial proportion of manicurists reported health-related concerns (40.5%) and symptoms related to chemical exposure (67.6%). The study emphasizes the need for continuous and improved illness prevention strategies, including the use of safer products, comprehensive health and safety training, and effective ventilation practices, to better protect nail salon workers.

Plasma genome-wide mendelian randomization identifies potentially causal genes in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease with a very poor prognosis. Existing drugs for the treatment of IPF are still insufficient. Therefore, there is still a need to explore new drug targets for preventing and treating IPF. METHODS: We included quantitative trait loci (QTL) for genes, DNA methylation, and proteins in plasma, as well as the summary statistics for IPF. Genetic variants located within 500 kb of the gene and strongly associated with plasma exposure were used as instrumental variables. The causal association between plasma exposures and IPF was primarily estimated using summary-data-based Mendelian randomization (SMR) analysis. Five other MR methods and sensitivity analyses were employed to validate the SMR results. Bayesian tests for colocalization between QTL and IPF risk loci further strengthen the MR results. RESULTS: We identified three genes and five DNA methylation sites causally associated with IPF by SMR analysis, validation of MR analysis, sensitivity analysis, and colocalization analysis. BTRC and LINC01252 were negatively associated with IPF risk (OR: 0.30, 95% CI: 0.17-0.54, FDRSMR = 0.029; OR: 0.85, 95% CI: 0.78-0.92, FDRSMR = 0.043), and RIPK4 was positively associated with IPF risk (OR: 2.60, 95% CI: 1.64-4.12, FDRSMR = 0.031). cg00045227 (OR8U8, OR: 1.16, 95% CI: 1.08-1.24, FDRSMR = 0.010), cg00577578 (GBAP1, OR: 1.23, 95% CI: 1.12-1.36, FDRSMR = 0.014), cg14222479 (ARPM1, OR: 3.17, 95% CI: 1.98-5.08, FDRSMR = 0.001), and cg19263494 (PMF1, OR: 1.20, 95% CI: 1.10-1.30, FDRSMR = 0.012) were positively associated with the risk of IPF, whereas cg07163735 (MAPT, OR: 0.22, 95% CI: 0.11-0.45, FDRSMR = 0.013) was negatively correlated with the risk of IPF. CONCLUSIONS: This study demonstrated that genetically determined plasma levels of the BTRC, RIPK4, and LINC01252 genes, as well as methylation levels of cg00045227 (OR8U8), cg00577578 (GBAP1), cg07163735 (MAPT), cg14222479 (ARPM1), and cg19263494 (PMF1), have causal influences on the risk of IPF.

Trimetallic MOF-derived Fe-Mn-Sn oxide heterostructure enabling exceptional catalytic degradation of organic pollutants.

Developing efficient and environmentally benign heterogeneous catalysts that activate peroxymonosulfate (PMS) for the degradation of persistent organic contaminants remains a challenge. Metal-organic frameworks (MOFs)-derived metal oxide catalysts in advanced oxidation processes (AOPs) have received considerable attention research fraternity. Herein, we report an innovative magnetic trimetallic MOF-derived Fe-Mn-Sn oxide heterostructure (FeMnO@Sn) with adjustable morphology, size and Sn content, prepared through an impregnation-calcination strategy. The formation of a novel magnetic Fe2O3/Fe3O4/Mn3O4 heterostructure induces the generation of abundant Fe2+ and Mn2+ sites on the FeMnO@Sn surface. Meanwhile, the introduction of SnO2 into the Fe2O3/Fe3O4/Mn3O4 heterostructure facilitates the cleavage of the OO bond in adsorbed PMS. The synergy among the different functionalities of each metal oxide plays a vital role in the swift and effective degradation of pollutants. In addition, the uniquely designed catalyst exhibits magnetic properties that facilitate easy recycling and repeated use, thereby meeting environmental protection requirements. Overall, this research highlights the design of heterogeneous catalysts for the effective activation of PMS and provides valuable insights for the advancement of future environmental catalysts.

IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.

Type I interferon (IFN-I) and its downstream genes play a profound role in HIV infection. In this study, we found that an IFN-inducible gene, IFI27, was upregulated in HIV-1 infection, which in turn efficiently suppressed HIV-1 replication, specially degraded the viral gag protein, including p24 and p55 subunits. Notably, the anti-HIV-1 activity of IFI27 in Old World monkeys surpassed that in New World monkeys, and IFI27 has a higher potentially inhibitory effect on HIV-1 than simian immunodeficiency virus (SIV). Our initial observations showed that NPM-IFI27, the IFI27 variant in northern pig-tailed macaque (Macaca leonina, NPM), exhibited a strong anti-HIV-1 activity. Further investigation demonstrated that NPM-IFI27 degraded p24 and p55 via the ubiquitin-proteasome pathway, with NPM-IFI27-37-115 interacting with the p24-N domain, and the NPM-IFI27-76-122 domain was closely associated with K48 ubiquitin recruitment. Additionally, Skp2 was identified as the probable E3 ubiquitin ligase responsible for the degradation of p24 and p55. Similarly, human IFI27 (Hu-IFI27) showed a mechanism similar to NPM-IFI27 in HIV-1 inhibition. These findings underscore the pivotal role of NPM-IFI27 in HIV-1 infection and provide a potential strategy for clinical anti-HIV-1 therapy.IMPORTANCEHIV-1 infection can trigger the production of IFN-I, which subsequently activates the expression of various IFN-stimulated genes (ISGs) to antagonize the virus. Therefore, discovering novel host antiviral agents for HIV-1 treatment is crucial. Our previous study revealed that IFI27 can influence HIV-1 replication. In this study, we observed that the NPM-IFI27 complex specifically inhibited HIV-1 by targeting its Gag protein. Further exploration demonstrated that IFI27 interacted with the HIV-1 p24 and p55 proteins, leading to their degradation through the ubiquitin-proteasome pathway. Notably, the NPM-IFI27-37-122 variant exhibited potent anti-HIV-1 activity, comparable to that of SAMHD1. These findings highlight the critical role and inhibitory mechanism of NPM-IFI27 in HIV-1 infection, providing a potential strategy for clinical antiviral therapy.

Venous aneurysms in unruptured supratentorial brain arteriovenous malformations: a protective factor against hemorrhagic stroke and insights into hemodynamic mechanisms.

OBJECTIVE: This study endeavors to clarify the impact of venous aneurysms (VA) on hemorrhagic risk in brain arteriovenous malformations (AVMs) and uncover potential hemodynamic mechanisms, utilizing quantitative digital subtraction angiography (QDSA) technology and survival dataset. METHODS: Patients were enrolled in a multicenter prospective collaboration registry between August 2011 and August 2021, and subsequently categorized into the VA and non-VA cohorts. Using propensity score-matched survival analysis, we quantitatively assessed the natural risk of hemorrhagic stroke in these two cohorts. Additionally, a quantitative hemodynamic analysis was conducted to explore the distinctions in hemodynamic characteristics between these two cohorts. RESULTS: Among 3758 consecutive AVMs documented at a single center from the registry, 820 unruptured AVMs who maintained conservation management over 1 month were identified. Following a two-step matching process, 504 cases were retained for survival analysis and 408 cases for hemodynamic analysis. Overall, the presence of VA emerged as a protective factor, associated with a decreased risk of hemorrhagic stroke (HR, 0.21 [95% CI: 0.07-0.62], p = 0.004). Distinct hemodynamic characteristics were observed in AVMs with VA, showing a lower stasis index in two components of AVMs-the nidus (p = 0.014) and the main draining vein (p = 0.018). CONCLUSION: In this observational prospective cohort study, the presence of VA is associated with a decreased risk of hemorrhagic stroke in AVMs, suggesting an underlying hemodynamic mechanism involving the redistribution of excessive pressure loads within the AVM nidus by the VA. KEY POINTS: Questions What impact, if any, does VA have on the hemorrhagic risk in brain AVMs? Findings Presence of VA is associated with a decreased hemorrhagic stroke risk through the redistribution of pressure loads. Critical relevance VA in brain AVMs emerges as a protective factor against hemorrhagic stroke. Understanding this association and the underlying hemodynamic mechanisms offers valuable guidance for preventive strategies and informs clinical decision-making, improving overall patient care.

Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients.

Rheumatoid arthritis (RA) is marked by joint damage and inflammation, with B cells playing a key role by generating autoantibodies. This study shows that G protein-coupled receptor 40 (GPR40) deficiency in B cells leads to increased activation, proliferation, antibody production, germinal center formation, and class switch recombination. GPR40 regulates Plcγ2 phosphorylation and intracellular calcium flux downstream of the B cell receptor by binding to the Gαq protein. In GPR40-deficient mice, susceptibility to collagen-induced arthritis was higher. GPR40 agonists showed potential as therapeutic agents, and their reduced expression in patients with RA correlated with disease onset, suggesting GPR40 as a potential therapeutic target and diagnostic marker.

Association of the combined stereotactic radiosurgery and embolization strategy and long-term outcomes in brain arteriovenous malformations with a volume >10 ml: A nationwide multicenter observational prospective cohort study.

BACKGROUND: To assess the long-term outcome of large brain arteriovenous malformations (AVMs) (volume > 10 ml) underwent combined embolization and stereotactic radiosurgery (E+SRS) versus SRS alone. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (MATCH study, August 2011-August 2021) and categorized into E+SRS and SRS alone cohorts. Propensity score-matched survival analysis was employed to control for potential confounding variables. The primary outcome was a composite event of non-fatal hemorrhagic stroke or death. Secondary outcomes were favorable patient outcomes, AVM obliteration, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes (RIC), and embolization complications. Furthermore, the efficacy of distinct embolization strategies was evaluated. Hazard ratios (HRs) were computed utilizing Cox proportional hazard models. RESULTS: Among 1063 AVMs who underwent SRS with or without prior embolization, 176 patients met the enrollment criteria. Following propensity score matching, the final analysis encompassed 98 patients (49 pairs). Median (interquartile range) follow-up duration for primary outcomes spanned 5.4 (2.7-8.4) years. Overall, the E+SRS strategy demonstrated a trend toward reduced incidence of primary outcomes compared to the SRS alone strategy (1.44 vs 2.37 per 100 patient-years; HR, 0.58 [95 % CI, 0.17-1.93]). Regardless of embolization degree or strategy, stratified analyses further consistently revealed a similar trend, albeit without achieving statistical significance. Secondary outcomes generally exhibited equivalence, but the combined approach showed potential superiority in most measures. CONCLUSIONS: This study suggests a trend toward lower long-term non-fatal hemorrhagic stroke or death risks with the E+SRS strategy when compared to SRS alone in large AVMs (volume > 10 ml).

The correlation between social adaptability and academic procrastination of undergraduate nursing students: the mediating role of resilience.

BACKGROUND: How to mobilize nurses students' learning initiative, reduce the incidence of academic procrastination, and improve their social adaptability is a key factor in lowering nursing brain drain and improving nursing quality. OBJECTIVE: To explore the mediating role of resilience in the correlation between social adaptability and academic procrastination of undergraduate nursing students. METHODS: This study is a cross-sectional survey. The researchers conducted an electronic questionnaire survey of 962 nursing undergraduates in Guanzhong District, Shaanxi Province from November 2022 to April 2023, and adopted the intention sampling method. And make the following assumptions: (1) There is a significant negative correlation between academic procrastination and social adaptability. (2) Academic procrastination can directly affect the social adaptability of undergraduate nursing students, and it has a significant negative predictive effect. (3) Resilience can directly affect academic procrastination and social adaptability. At the same time, resilience plays an intermediary role between the two. In this study, the Aitken procrastination scale, the resilience scale, and the social adaptability diagnostic scale were used to evaluate undergraduate nursing students. SPSS27.0 software is used to analyze the data statistically, and the Hayes PROCESS Macro method is used to test the model. RESULTS: The study's findings are as follows: 1) Academic procrastination significantly and negatively impacts social adaptability (c = -0.292, t = -6.407, p < 0.001). 2) Even when accounting for resilience, academic procrastination still significantly predicts lower social adaptability (c'= -0.204, t = -4.338, p < 0.001). 3) The Bootstrap method test of percentile bias correction indicates that resilience serves as a significant mediator between academic procrastination and social adaptability. Bootstrap SE = 0.018, 95% CI = (-0.124, -0.055). The indirect effect contributes to 29.79% of the total effect. CONCLUSION: Resilience not only directly affects the academic procrastination and social adaptability of nursing students, but also partially intermediate the relationship between academic procrastination and social adaptability.

Optimizing the nested PCR method for Decapod iridescent virus 1 (DIV1) targeting ATPase gene by reselecting the inner primers.

DIV1 has the characteristics of fast transmission and a broad host range. Its infection leads to a high mortality rate, posing a serious threat to the global crustacean aquaculture industry. In order to increase the accuracy of DIV1 detection and reduce the difficulty of result interpretation, this study modified the original nested PCR method targeting the DIV1 ATPase gene. The internal primers for the nested PCR were redesigned to produce a 338 bp amplification product in the second step PCR, effectively distinguishing the target band from primer dimers. The newly established nested PCR method exhibits strong specificity and high sensitivity, with a detection limit as low as 1.37 × 101 copies/reaction. The developed nested PCR assay provides new technical support for the accurate detection of DIV1 in global crustacean aquaculture.

Protective effect of hydroxysafflor yellow a on thioacetamide-induced liver injury and osteopenia in zebrafish.

Hydroxysafflor yellow A (HSYA) is the main water-soluble compound of safflower. It is commonly used in liver disease treatment and has anti-osteoporotic activity. However, the specific mechanism of HSYA is not yet fully understood. Thioacetamide (TAA) has toxic effects on the liver and is widely used in establishing animal models of cirrhosis and liver fibrosis. In research of liver-related diseases and bone deformation in vivo, the zebrafish has become a frequently utilized animal model. In establishing a TAA-induced zebrafish liver injury model, we found that TAA-induced zebrafish also developed osteopenia. The aim of our study is to investigate the protective effect of HSYA on TAA-induced liver injury and osteopenia in zebrafish. The findings demonstrated that HSYA alleviated hepatic oxidative stress, inhibited the release of inflammatory factors, and promoted in vivo skeletal mineralization in zebrafish larvae. Further Real-time Polymerase Chain Reaction and Western blotting analyses showed that HSYA altered the expression levels of SIRT1, HMGB1, TLR4, MYD88 and NF-ΚB, ameliorated TAA-induced liver injury, reduced the release of inflammation-related factors IL-6, IL-1ß, TNF-α, regulated the ratio of RANKL/OPG, ameliorated TAA-induced osteopenia. In conclusion, our study demonstrated that HSYA exhibited a noteworthy beneficial influence on TAA-induced liver injury and osteopenia in zebrafish, this finding provide a foundation for the application of HSYA in clinical research.

A comparative study on the immune response in the head and trunk kidney of yellow catfish infected with Edwardsiella ictaluri.

The teleost kidneys are anatomically divided into head kidney and trunk kidney, each performing distinct physiological functions. Although previous research has elucidated the role of the head kidney in immune responses, there is a paucity of literature on the comparative studies of the head and trunk kidney response to bacterial infection. Therefore, an Edwardsiella ictaluri infection model of yellow catfish was constructed to investigate and compare the immune responses between the two kidney types. The findings indicated that E. ictaluri infection induced significant pathological changes in both the head and trunk kidney. Despite variances in structure, both the head and trunk kidney of yellow catfish exhibit robust immune responses following E. ictaluri infection. Unexpectedly, the up-regulation level of IgM was found to be higher in the trunk kidney compared to the head kidney. Additionally, both the IgM+ and IgD+ B cells were increased after bacterial infection. This research elucidates the parallels and distinctions in immune functions between both the head and trunk kidney in fish, enriching the immune theory of the fish kidney, and also providing a theoretical basis for the immune response of teleost kidney against bacterial infections.

ALK-positive large B-cell lymphoma: a clinicopathological and molecular characteristics analysis of seven cases.

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK+ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK+ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.

Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 ( IRF4 ) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL- IRF4 -R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL- IRF4 -R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL- IRF4 -R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.

Spatial and temporal patterns of cortical mean diffusivity in Alzheimer's disease and suspected non-Alzheimer's disease pathophysiology.

INTRODUCTION: The spatial and temporal patterns of cortical mean diffusivity (cMD), as well as its association with Alzheimer's disease (AD) and suspected non-Alzheimer's pathophysiology (SNAP), are not yet fully understood. METHODS: We compared baseline (n = 617) and longitudinal changes (n = 421) of cMD, cortical thickness, and gray matter volume and their relations to vascular risk factors, amyloid beta (Aß), and tau positron emission tomography (PET), and longitudinal cognitive decline in Aß PET negative and positive older adults. RESULTS: cMD increases were more sensitive to detecting brain structural alterations than cortical thinning and gray matter atrophy. Tau-related cMD increases partially mediated Aß-related cognitive decline in AD, whereas vascular disease-related increased cMD levels substantially mediated age-related cognitive decline in SNAP. DISCUSSION: These findings revealed the dynamic changes of microstructural and macrostructural indicators and their associations with AD and SNAP, providing novel insights into understanding upstream and downstream events of cMD in neurodegenerative disease. HIGHLIGHTS: Cortical mean diffusivity (cMD) was more sensitive to detecting structural changes than macrostructural factors. Tau-related cMD increases partially mediated amyloid beta-related cognitive decline in Alzheimer's disease (AD). White matter hyperintensity-related higher cMD mainly explained the age-related cognitive decline in suspected non-Alzheimer's pathophysiology (SNAP). cMD may assist in tracking earlier neurodegenerative signs in AD and SNAP.

Integrating ATAC-Seq and RNA-Seq Reveals the Signal Regulation Involved in the Artemia Embryonic Reactivation Process.

Embryonic diapause is a common evolutionary adaptation observed across a wide range of organisms. Artemia is one of the classic animal models for diapause research. The current studies of Artemia diapause mainly focus on the induction and maintenance of the embryonic diapause, with little research on the molecular regulatory mechanism of Artemia embryonic reactivation. The first 5 h after embryonic diapause breaking has been proved to be most important for embryonic reactivation in Artemia. In this work, two high-throughput sequencing methods, ATAC-seq and RNA-seq, were integrated to study the signal regulation process in embryonic reactivation of Artemia at 5 h after diapause breaking. Through the GO and KEGG enrichment analysis of the high-throughput datasets, it was showed that after 5 h of diapause breaking, the metabolism and regulation of Artemia cyst were quite active. Several signal transduction pathways were identified in the embryonic reactivation process, such as G-protein-coupled receptor (GPCR) signaling pathway, cell surface receptor signaling pathway, hormone-mediated signaling pathway, Wnt, Notch, mTOR signaling pathways, etc. It indicates that embryonic reactivation is a complex process regulated by multiple signaling pathways. With the further protein structure analysis and RT-qPCR verification, 11 GPCR genes were identified, in which 5 genes function in the embryonic reactivation stage and the other 6 genes contribute to the diapause stage. The results of this work reveal the signal transduction pathways and GPCRs involved in the embryonic reactivation process of Artemia cysts. These findings offer significant clues for in-depth research on the signal regulatory mechanisms of the embryonic reactivation process and valuable insights into the mechanism of animal embryonic diapause.

The Changes of Mitochondria during Aging and Regeneration.

Aging and regeneration are opposite cellular processes. Aging refers to progressive dysfunction in most cells and tissues, and regeneration refers to the replacement of damaged or dysfunctional cells or tissues with existing adult or somatic stem cells. Various studies have shown that aging is accompanied by decreased regenerative abilities, indicating a link between them. The performance of any cellular process needs to be supported by the energy that is majorly produced by mitochondria. Thus, mitochondria may be a link between aging and regeneration. It should be interesting to discuss how mitochondria behave during aging and regeneration. The changes of mitochondria in aging and regeneration discussed in this review can provide a timely and necessary study of the causal roles of mitochondrial homeostasis in longevity and health.

Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer.

BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

Causal relationships between lung cancer and sepsis: a genetic correlation and multivariate mendelian randomization analysis.

Background: Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear. Method: This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness. Results: LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, p = 8.29 × 10-5, P fdr = 2.49 × 10-4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, p = 0.012, P fdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, p = 0.009, P fdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p > 0.05 and P fdr > 0.05). Conclusion: The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients.

Association of tumor immune infiltration and prognosis with homologous recombination repair genes mutations in early triple-negative breast cancer.

The aim of this study was to evaluate the mutation spectrum of homologous recombination repair (HRR) genes and its association with tumor immune infiltration and prognosis in triple-negative breast cancer (TNBC). TNBC patients (434 patients from Ruijin cohort) were evaluated with targeted next-generating sequencing for mutations in HRR genes. The frequencies of mutations were compared with public reference cohorts (320 TNBC patients from METABRIC, 105 from TCGA, and 225 from MSKCC 2018). Associations between mutation status and tumor immune infiltration and prognosis were analyzed. HRR genes mutations were seen in 21.89% patients, with BRCA1/2 mutations significantly enriched in tumors with breast/ovarian cancer family history (P = 0.025) and high Ki-67 levels (P = 0.018). HRR genes mutations were not related with recurrence-free survival (RFS) (adjusted P = 0.070) and overall survival (OS) (adjusted P = 0.318) for TNBC patients, regardless of carboplatin treatment (P > 0.05). Moreover, tumor immune infiltration and PD-L1 expression was positively associated with HRR or BRCA1/2 mutation (all P < 0.001). Patients with both HRR mutation and high CD8+ T cell counts had the best RFS and OS, whereas patients with no HRR mutation and low CD8+ T cell counts had the worst outcomes (RFS P < 0.001, OS P = 0.019). High frequency of HRR gene mutations was found in early TNBC, with no prognostic significance. Immune infiltration and PD-L1 expression was positively associated with HRR mutation, and both HRR mutation and high CD8+ T cell infiltration levels were associated with superior disease outcome.

[18F]-D3FSP ß-amyloid PET imaging in older adults and alzheimer's disease.

PURPOSE: [18F]-D3FSP is a new ß-amyloid (Aß) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear. METHODS: We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [18F]-D3FSP Aß PET imaging. We analyzed plasma Aß42/Aß40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated. RESULTS: Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau181 (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aß42/Aß40 (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings. CONCLUSION: This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aß plaques in the brain. [18F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [18F]-D3FSP PET images with other validated Aß PET tracers or postmortem results are crucial.