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OBJECTIVE: To investigate Covid-19 vaccination as a potential secondary public health benefit of case management for Medicaid beneficiaries with health and social needs. DATA SOURCES AND STUDY SETTING: The CommunityConnect case management program for Medicaid beneficiaries is run by Contra Costa Health, a county safety net health system in California. Program enrollment data were merged with comprehensive county vaccination records. STUDY DESIGN: Individuals with elevated risk of hospital and emergency department use were randomized each month to a case management intervention or usual care. Interdisciplinary case managers offered coaching, community referrals, healthcare connections, and other support based on enrollee interest and need. Using survival analysis with intent-to-treat assignment, we assessed rates of first-dose Covid-19 vaccination from December 2020 to September 2021. In exploratory sub-analyses we also examined effect heterogeneity by gender, race/ethnicity, age, and primary language. DATA COLLECTION AND EXTRACTION METHODS: Data were extracted from county and program records as of September 2021, totaling 12,866 interventions and 25,761 control enrollments. PRINCIPAL FINDINGS: Approximately 58% of enrollees were female and 41% were under age 35. Enrollees were 23% White, 12% Asian/Pacific Islander, 20% Black/African American, and 36% Hispanic/Latino, and 10% other/unknown. Approximately 35% of the intervention group engaged with their case manager. Approximately 56% of all intervention and control enrollees were vaccinated after 9 months of analysis time. Intervention enrollees had a higher vaccination rate compared to control enrollees (adjusted hazard ratio [aHR]: 1.06; 95% confidence interval [CI]: 1.02-1.10). In sub-analyses, the intervention was associated with stronger likelihood of vaccination among males and individuals under age 35. CONCLUSIONS: Case management infrastructure modestly improved Covid-19 vaccine uptake in a population of Medicaid beneficiaries that over-represents social groups with barriers to early Covid-19 vaccination. Amidst mixed evidence on vaccination-specific incentives, leveraging trusted case managers and existing case management programs may be a valuable prevention strategy.

The cellular components of tumors and their microenvironment play pivotal roles in tumor progression, patient survival, and the response to cancer treatments. Unveiling a comprehensive cellular profile within bulk tumors via single-cell RNA sequencing (scRNA-seq) data is crucial, as it unveils intrinsic tumor cellular traits that elude identification through conventional cancer subtyping methods. Our contribution, scBeacon, is a tool that derives cell-type signatures by integrating and clustering multiple scRNA-seq datasets to extract signatures for deconvolving unrelated tumor datasets on bulk samples. Through the employment of scBeacon on the The Cancer Genome Atlas (TCGA) cohort, we find cellular and molecular attributes within specific tumor categories, many with patient outcome relevance. We developed a tumor cell-type map to visually depict the relationships among TCGA samples based on the cell-type inferences.

This study explores the relationship between the governance of architecturally embedded applications and their longevity in organizational use. Using a contingency-fit logic, it posits that alignment between application governance (distribution of decision rights) and architectural contingencies contributes to sustained durations of organizational use. Architectural contingencies include internal application modularity, application inter-connectedness, and governance of surrounding application clusters. Evidence for the governance-architecture fit hypothesis is derived from analyzing temporally ordered data about applications (n = 225, n = 498, n = 193) from organizations in the media, banking, and utilities sectors over five years. Using a two-step approach with ordinal regression, along with Cox proportional hazards and logistic regression models, our findings indicate that a fit between observed governance and the governance induced by architectural contingencies reduces the likelihood of application decommissioning. The study advances the fields of information systems (IS) governance and architecture by offering a micro-level perspective on the longevity of organizational IS use while also shedding light on the importance of governance choices aligned with unique architectural application properties. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies report on the outcome performance of posterior composite restorations. However, there are fewer studies providing data for anterior restorations. The aim of this study was to evaluate the clinical outcome performance of anterior permanent restorations by analyzing a large dataset from a German national health insurance company. Materials and Methods: Routine claims data from a major German national health insurance company were assessed. Fee codes were used for tracing restoration careers on a day-count basis. The treatment was defined as a placed restoration (Class III and IV) on a mesial or distal tooth surface, irrespective of the extension. The restorations were placed between January 1, 2010 and December 31, 2013. Statistical analyses were conducted using Kaplan-Meier survival analysis to determine cumulative 4-year survival rates. The primary outcome was re-intervention on the same surface. Secondary outcomes were crowning and extraction which were analyzed separately. Results: A total of 2,417,791 restorations involving mesial surfaces and a number of 2,409,031 restorations involving distal surfaces were observed. At 4 years, the cumulative survival rates concerning the primary outcome "re-intervention" were 79.9% for mesial and 80.9% for distal restorations. The respective annual failure rates (AFR) were 5.5% and 5.2%. Fouryear survival rates for the secondary outcome "crown" were 93.8% for mesial and 94.1% for distal anterior restorations. The respective AFRs were 1.6% and 1.5%. For the secondary outcome "extraction," the respective rates were 94.6% for mesial and 93.9% for distal restorations. The respective AFRs were 1.4% and 1.6%. Conclusion: The performance of permanent anterior restorations which were placed in general dental practices in Germany can be rated as acceptable. [ABSTRACT FROM AUTHOR]

We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. METHODS: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

INTRODUCTION: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. RESULTS: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p

Caenorhabditis elegans is highly important in current research, serving as a pivotal model organism that has greatly advanced the understanding of fundamental biological processes such as development, cellular biology, and neurobiology, helping to promote major advances in various fields of science. In this context, the survival of a nematode under various conditions is commonly investigated via statistical survival analysis, which is typically based on hypothesis testing, providing valuable insights into the factors influencing its longevity and response to various environmental factors. The extensive reliance on hypothesis testing is acknowledged as a concern in the scientific analysis process, emphasizing the need for a comprehensive evaluation of alternative statistical approaches to ensure a rigorous and unbiased interpretation of research findings. In this work, we propose an alternative method to hypothesis testing for evaluating differences in nematode survival. Our approach relies on a clustering technique that takes into account the complete structure of survival curves, enabling a more comprehensive assessment of survival dynamics. The proposed methodology helps to identify complex effects on nematode survival and enables us to derive the probability that treatment induces a specific effect. To highlight the application and benefits of the proposed methodology, it is applied to two different datasets, one simple and one more complex. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited. Materials and methods: We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests. Results: With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3–19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2–0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05). Conclusions: IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes. [ABSTRACT FROM AUTHOR]

The number of cancer survivors worldwide is increasing every year, making secondary primary cancers (SPC) is a growing health threat. Studies have been conducted to investigate the risk of occurrence between digestive system tumors (DST) and thyroid cancer (TC). However, existing studies have tended to focus more on the risk of developing SPC and less on the impact of SPC on the survival of cancer survivors. In this study, using the Surveillance, Epidemiology, and End Results database, we aimed to explore the impact of TC on the survival of patients with DST by data between 2000 and 2018. The study employed the standardized incidence ratio to assess the relative risk of SPC, propensity score matching was conducted to mitigate confounding effects, Kaplan-Meier, Cox proportional risk model and competitive risk model were used to analyze the factors affecting the overall survival and cancer-specific survival. We furthermore explored the influence of pathological types and radiotherapy of TC on the survival of DST patients. 518,901 patients with DST only, 801 patients with TC occurring earlier than DST (TC-1st), and 744 patients with DST occurring earlier than TC (DST-1st) were included. The total incidence rate of small intestine cancer after TC was higher than that of the general population, and the incidence of TC after DST was higher than in the general population. DST patients with a history of TC had better overall survival and lower cancer-specific mortality and this difference was particularly significant in patients with DST-1st. In addition, radiotherapy for TC had no effect on cancer-specific mortality in patients with DST. [ABSTRACT FROM AUTHOR]

An improved DeepSurv model is proposed for predicting the prognosis of colorectal cancer patients at stage IV. Our model, called as PseudoDeepSurv, is optimized by a novel loss function, which is the combination of the average negative log partial likelihood and the mean-squared error derived from the pseudo-observations approach. The public BioStudies dataset including 999 patients was utilized for performance evaluation. Our PseudoDeepSurv model produced a C-index of 0.684 and 0.633 on the training and testing dataset, respectively. While for the original DeepSurv model, the corresponding values are 0.671 and 0.618, respectively. [ABSTRACT FROM AUTHOR]

AbstractElectronic health records offer abundant data on various diseases and health conditions, enabling researchers to explore the relationship between disease onset age and underlying risk factors. Unlike mortality data, the event of interest is non-terminal, hence individuals can retrospectively report their disease-onset-age upon recruitment to the study. These individuals, diagnosed with the disease before entering the study, are termed “prevalent”. The ascertainment imposes a left truncation condition, also known as a “delayed entry”, because individuals had to survive a certain period before being eligible for enrollment. The standard method to accommodate delayed entry conditions on the entire history up to recruitment, hence the retrospective prevalent failure times are conditioned upon and cannot participate in estimating the disease-onset-age distribution. Other methods that condition on less information and allow the incorporation of the prevalent observations either bring about numerical and computational difficulties or require statistical assumptions that are violated by most biobanks. This work presents a novel estimator of the coefficients in a regression model for the age-at-onset, successfully utilizing the prevalent data. Asymptotic results are provided, and simulations are conducted to showcase the substantial efficiency gain. In particular, the method is highly useful in leveraging large-scale repositories for replication analysis of genetic variants. Indeed, analysis of urinary bladder cancer data reveals that the proposed approach yields about twice as many replicated discoveries compared to the popular approach. [ABSTRACT FROM AUTHOR]

Background: Choline alfoscerate, a cholinergic precursor with limited evidence of efficacy in dementia management, has been used for various cognitive impairments in Korea. Partly due to its insurance coverage, this agent appears to incur significant expense for the insurance system. Thus, we aimed to describe choline alfoscerate prescription patterns and analyze their long-term effects in an older adult cohort with dementia. Methods: This observational study used the National Health Insurance Service Senior Cohort Dataset. Choline alfoscerate -naïve patients who were diagnosed with dementia between 2003 and 2014 with at least 12 months of follow-up were selected. Time-dependent Cox regression was employed to estimate the association between drug exposure and the risk of treatment failure events. Results: There were 11,463 eligible participants, of whom approximately 73% were female, and 19% had been exposed to choline alfoscerate. According to the main regression survival analysis, the association between longitudinal choline alfoscerate use and the risk of progression events related to treatment failure was unclear. However, a significant decrease of nearly 20% in the risk of all-cause mortality was associated with choline alfoscerate exposure, and a slight reduction in progression regarding treatment failure was observed with CA use only during the early stages of diagnosis. Age, sex, insurance premiums, several comorbidities and concurrent medications were significantly associated with the probability of the events according to the multivariate models. Conclusions: Further analyses are needed to confirm the early-stage and long-term effectiveness of choline alfoscerate in specific populations, which will help in considering its reimbursement. [ABSTRACT FROM AUTHOR]

Background: Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is considered an important factor in the progression of cancer, acting as a modulator of cellular migration, adhesion, and metastatic potential. Its significance as a prognostic factor, however, remains unclear, which necessitated a comprehensive review and meta-analysis. Methods: Our study followed the PRISMA guidelines, analyzing studies from major databases including PubMed, Embase, and Cochrane. Our eligibility criteria included studies evaluating NEDD9 expression in relation to cancer prognosis and outcomes such as overall survival (OS), progression-free survival (PFS), disease-free Survival (DFS), recurrence-free survival (RFS), and cancer-specific survival (CSS). We used random-effects and fixed-effect models for meta-analysis, and we validated our findings by comparative analysis using data from external cohorts like The Cancer Genome Atlas (TCGA). Results: The analysis of 27 studies with 3915 patients demonstrated a significant relationship between NEDD9 expression and poor OS as indicated by the pooled meta-analysis outcome across all included cancers (HR: 1.81, 95% CI: 1.38-2.37). A significant effect on PFS/DFS/RFS/CSS was also found (HR: 2.14, 95% CI: 1.42-3.23). Variations in survival across different types of cancer were indicated by subgroup analysis. NEDD9 expression was correlated with various immune cells across cancer types according to immune infiltration analysis. Protein-protein interaction (PPI) analysis indicated significant interactions involving NEDD9, suggesting mechanisms which influence tumor behavior and response to treatment. Conclusion: Our results suggest that NEDD9 is a significant prognostic marker in several human cancers. As a result of its central role in cancer progression and prognosis, it presents a promising target for therapeutic interventions. Our study highlights the importance of further research into the biology of NEDD9 and its therapeutic potential. [ABSTRACT FROM AUTHOR]

Most current studies use body mass index (BMI) or waist circumference (WC) to define obesity, and BMI, which reflects subcutaneous fat independent of visceral fat, is the most commonly used indicator of obesity. WC reflects subcutaneous and visceral fat. This research aims to investigate the effect of obesity on mortality in people with digestive diseases. According to BMI and WC, we divided patients with obesity into the following four groups: general obesity, abdominal obesity, combined obesity, and non-obese. The effects of different obesity types on mortality in a population with digestive diseases were analysed via Cox regression and inverse probability-weighted Cox regression. Our research employed multivariate imputation via the chained equations method to interpolate missing values. A total of 254,445 participants, with a mean age of 57.8 ± 7.8 years, were included in the analysis. Of these participants, 227,111 (89.3%) participants were censored, and 27,334 (10.7%) participants died. Abdominal obesity and combined obesity were independent predictors of mortality in patients with digestive diseases. The combination of BMI and WC was valuable and significant for considering the type of obesity. In addition, our study revealed that sex, socioeconomic status, lifestyle habits, and physical activity were also associated with death in people with digestive disorders. Combined obesity, which is determined by both BMI and WC, is an important factor that influences mortality in a population with digestive diseases, and it plays a stronger role than abdominal obesity alone. These modifiable risk factors for mortality can provide guidance to populations with digestive diseases to avoid poor lifestyles and prolong survival time. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer. Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020. Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien–Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan–Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892–37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076–8.340; p = 0.036) were independent prognostic factors for disease-free survival. Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival. [ABSTRACT FROM AUTHOR]

Introduction: Ependymoma is the third most frequent central malignant nervous system tumor in the pediatric age group. There is scarce data in the literature on survival of these patients, especially in upper and lower middle-income countries. We aimed to describe the clinical and demographic characteristics, treatment, and outcome of pediatric patients with ependymoma admitted to a public cancer hospital. Methods: Retrospective analysis of medical records of patients with ependymoma, admitted to the Pediatric Oncology department (0-20 years) during the period of 2000-2022. Data on patient, disease characteristics, and treatment were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Seventy-two patients were evaluated; median age at diagnosis was 6.5 years (range: 1-20), 63% were male, 54% of the tumors were in the posterior fossa (PF-EPN), 45% were classified as WHO grade 3, and 68% were operated on in other institutions before referral. Regarding treatment, 72% underwent radiotherapy and 33% of patients underwent chemotherapy. Almost 70% percent of the patients had relapses. The median follow-up time was 5.2 years (Range: 0,1-21,4). The OS in 5 years was 67%. Totally resected tumors had OS in 5 years of 88% (p: 0.028). Conclusion: The results achieved in this series show a survival gap between UMIC and HIC. Relapses occurred mainly in the first ten years and then reached a plateau, with the majority of patients experiencing endocrinological and neurological sequelae. [ABSTRACT FROM AUTHOR]

Purpose: DNA primase subunit 2 (PRIM2) is a component of the DNA polymerase α‐primase complex involved in DNA replication. Previous studies have implicated PRIM2 in cancer progression, but a comprehensive pan‐cancer analysis is lacking. Here, we systematically analyzed PRIM2 across various cancer types to elucidate its potential role in cancer biology. Methods: The expression data of PRIM2 was obtained from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression Project (GTEx) databases. A range of bioinformatics tools were employed to analyze the expression of PRIM2 with the correlation of clinical data, diagnosis, prognosis, subtypes, immunomodulatory, and drug sensitivity. Further validation experiments were performed in HT‐29 and HepG2 cell lines. Results: PRIM2 expression was elevated in most tumor tissues, indicating its potential diagnostic value. Elevated PRIM2 levels affected prognosis and survival and varied with clinical status. Mutations and methylation events drove the aberrant expression of PRIM2 in various cancers. Furthermore, PRIM2 was linked to key immunoregulatory genes such as PD‐L1 and infiltration of Th2 cells in tumor tissues. Our findings suggested that PRIM2 is correlated to immunotherapy and may be sensitive to specific small molecule PLK1 inhibitors. Knocking down PRIM2 in HT‐29 and HepG2 cell lines reduced their proliferation, migration, invasion, and epithelial‐mesenchymal transition. Conclusion: This research highlights the potential of PRIM2 as a biomarker for cancer diagnosis and prognosis, and as a target for immunomodulatory therapy, offering valuable insights for clinical applications. [ABSTRACT FROM AUTHOR]

Many experience sampling (ESM) studies suggested that high resilience is reflected by quickly recovering one’s emotional baseline. However, former studies relied on coarse data and did not look into differential recovery from emotional ups and downs. This preregistered proof-of-concept study therefore used high-resolution data collected in 2022 to compute emotional recovery after high levels of positive versus negative emotions. Adults (N = 68) participated in a three-week ESM study with eight assessments per day, complemented by short-spaced burst assessments. Resilience was assessed at baseline (trait-level; TR) and daily (day-level; DR). Multilevel survival analyses showed that high DR predicted faster returns from negative emotions, but also delayed returns following positive emotions (exp(β) = 1.32, p = 0.006). Instead, TR did not relate to emotional recovery (exp(β) = 0.85, p = 0.067). These findings were generally robust across different sensitivity analyses. This illustrates how innovative ESM designs combined with time-to-event analyses may further our insight in emotional recovery and the timescale at which it unfolds. [ABSTRACT FROM AUTHOR]

Background: Gaucher's disease (GD), a lysosomal storage disorder, poses significant treatment challenges. This 23-year study assesses survival rates and treatment efficacy in Brazilian GD patients, integrating data from a 16-year cohort (2000–2015) and the TABNET/DATASUS medicines distribution data (1999–2022). Objective: To investigate the survival of GD patients in Brazil, identifying key risk factors and evaluating the impact of treatments funded by the Brazilian National Health System (SUS). Methodology: A 16-year retrospective cohort study was conducted using the National Database of SUS. Patients diagnosed with GD and treated with Enzyme Replacement Therapy (ERT) or Substrate Synthesis Inhibition (SSI) from 2000 to 2015 were included. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards model. The data from TABNET/DATASUS system from 1999 to 2022 was used to assess the trend in drug distribution beyond the main cohort. Results: The study included 1,234 patients. Survival rates at 5 and 10 years were 93.2% and 88.5%, respectively, with age and comorbidities like diabetes, cardiovascular diseases, and Parkinson's disease significantly affecting survival. Patients who received doses lower than DDD (n = 880) demonstrated a survival probability of 91.8%. In contrast, those with doses equal to the DDD (n = 15) showed a 100% survival probability, as no events were observed in this group. The greater than DDD group (n = 339) exhibited a survival probability of 81%. A log-rank test indicated a borderline statistical significance (p = 0.058) in the survival distributions among the different DDD adherence, with the lower dose group showing a favorable trend. Conclusion: This study provides insights into the survival rates and associated risk factors for GD patients in Brazil, contributing to the global understanding of GD and its management. While we acknowledge the inherent limitations of relying largely on electronic medical records and categorical codes, our findings underscore the need for early diagnosis, timely initiation of treatment, effective management of comorbidities, and personalized dosing strategies to improve patient outcomes. Future studies should aim to incorporate clinical verification of electronic data to further enhance the reliability and applicability of these findings. [ABSTRACT FROM AUTHOR]

Pear psyllid (Cacopsylla pyri) is a persistent pest to the pear industry; with an estimated cost of £5 million per annum in the UK alone. This phloem feeding insect is resistant to a large proportion of approved pesticides, necessitating the use of alternative control strategies. Many pear growers practice integrated pest management (IPM) of pear psyllid, focusing on maximizing natural enemy populations, whilst minimizing the use of agrochemical sprays. The anthocorid Anthocoris nemoralis and the European earwig Forficula auricularia are particularly effective at controlling pear psyllid populations during the summer months. Despite the effectiveness of both natural enemies, there is a lack of understanding on whether both species should be promoted together or separately, due to the risk of intraguild predation (IGP) or interference competition. Furthermore, abiotic factors including temperature may influence both behaviors, altering activity level and niche overlap. Although IGP and interference competition have been documented between multiple species of natural enemies neither have been studied between these two specific predators. Using microcosm experiments, olfactometer assays and survival analyses this study demonstrated whether A. nemoralis and F. auricularia can be used in synchrony to control pear psyllid. Results indicated that IGP is present; F. auricularia will consume A. nemoralis when predators are not spatially separate and in absence of psyllid prey. There was no evidence for interference competition, although both predators consumed more prey at higher temperatures. This confirms that pear growers can encourage both predators for the control of pear psyllid without losing predation efficacy. [ABSTRACT FROM AUTHOR]

Objective: A recent update of the French cohort of uranium miners added seven years of follow-up data. We use these new data to look for new possible radon-related increased risks and refine the estimation of the potential association between cumulative radon exposure and four cancer sites: lung cancer, kidney cancer, brain and central nervous system (CNS) cancer and leukemia (excluding chronic lymphocytic leukemia, which is not radiation-induced). Methods: Several parametric survival models are proposed, fitted and compared under the Bayesian paradigm, to perform new and original exposure-risk analyses. In line with recent UNSCEAR recommendations, we consider time-related effect modifiers and exposure rate as potential effect modifying factors. We use Bayesian model selection criteria to identify radon-related increased hazard rates. Results: Under the assumption of a linear exposure-risk relationship, we found a substantial evidence for a strictly positive effect of cumulative radon exposure on the hazard rate of death by lung cancer among French uranium miners. Given the current available data under the assumptions of a linear or log-linear exposure-risk relationship, it is not possible to conclude in favour of the absence or the existence of a strictly positive effect of chronic exposure to radon on the hazard rate of death by kidney cancer. Regarding death by brain and CNS cancer, there is a substantial evidence for the absence of radon-related effect. Finally, under the assumption of a log-linear exposure-risk relationship, a small positive radon-related effect appears when looking at the risk of death by leukemia (excluding CLL). Conclusion: This study investigates the existence of radon-related increased risk of death by lung cancer, kidney cancer, brain and CNS cancer and leukemia under a Bayesian framework and assumptions of linear and log-linear exposure-risk relationships. If there is no doubt in the interpretation of the results for lung cancer and brain and CNS cancer, the conclusion is less clear-cut in the case of kidney cancer and leukemia (excluding CLL). A future update of the French cohort, increasing the follow-up time for miners, may help to reach a clearer conclusion for these two cancer sites. [ABSTRACT FROM AUTHOR]

Purpose: Early-onset colorectal cancer (CRC) (EOCRC, < 50 years) has distinct clinicopathological features from late-onset CRC (LOCRC, ≥ 50 years). However, evidence on survival outcomes is contradictory. We aimed to analyse the differences in 5-year overall survival (OS) between EOCRC and LOCRC. Methods: A retrospective cohort study was conducted during 2018–2022. Individuals aged ≥ 18 years diagnosed with CRC at two hospitals in Medellín, Colombia were included. Clinicopathological and survival data were retrieved from the medical records and a public government database. Patients were categorized into EOCRC and LOCRC groups. Five-year OS rates were calculated using the Kaplan-Meier method and prognostic factors for OS were identified through Cox regression models. Results: Among 1022 patients, 52.5% were female, and 13.5% (n = 138) had EOCRC. Patients with EOCRC showed higher 5-year OS rates than LOCRC patients (54% vs. 32%). Univariable analyses indicated a 37% lower risk of death for EOCRC compared to LOCRC (HR: 0.633, 95%CI: 0.476–0.840, p = 0.002). After multivariable analyses, advanced staging and higher tumour grading were prognostic factors for worse OS (HR: 2.127, 95% CI:1.405–3.220, p = 0.0001; and HR: 12.896, 95%CI: 6.310-26.355, p = 0.000; respectively), and being in the EOCRC group remained as a prognostic factor for higher OS (HR: 0.482, 95% CI: 0.336–0.690, p = 0.000). Conclusion: EOCRC is associated with significantly better 5-year OS rates and prognosis compared to LOCRC. Advanced stage and higher tumour grading are predictors of lower OS among all CRC patients. These findings highlight the importance of age-related risk stratification and personalized therapeutic approaches in CRC. [ABSTRACT FROM AUTHOR]

Bruton's Tyrosine Kinase (BTK), a soluble tyrosine kinase plays an essential role in the growth, development, and signalling of B cells. It is a non-receptor kinase that is crucial for leukemic cell survival, proliferation, and oncogenic signalling in many B cell malignancies. The enhanced metastasis caused by BTK expression may be reduced by BTK inhibitors, which also have powerful therapeutic effects. The goal of the study is to identify potential inhibitors which have good binding affinity with BTK. The current study also aims to investigate the expression pattern and the prognostic significance of BTK across all cancer types. Interestingly, it was found that BTK was highly overexpressed in numerous cancer types including; clear cell renal carcinoma, glioblastoma, head and neck, liver and breast cancer. BTK was found to reduce the relapse-free and overall survival rate. Furthermore, using in silico approach two structural analogues of Pirtobrutinib namely; 163207918 and 129269825 that bind to BTK with higher affinity were identified. Using drug-likeness analysis the therapeutic possibility of screened Pirtobrutinib analogues were evaluated. The Molecular docking and dynamic analysis revealed that the new Pirtobrutinib analogues could be potent inhibitors with higher binding affinity and stability in comparison with the parent compound. In conclusion, after preclinical and clinical research, the identified analogues may open the door for their prospective use in cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. Material and methods: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. Results: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). Conclusion: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. Clinical relevance statement: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. Key Points: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes. [ABSTRACT FROM AUTHOR]

Background A low-protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD. Methods The EQUAL study is a prospective, observational study including patients ≥65 years of age with an incident estimated glomerular filtration rate <20 ml/min/1.73 m2 in six European countries with follow-up through 6 years. Nutritional status was assessed by a 7-point subjective global assessment (SGA) every 3–6 months. Prescribed diet (g protein/kg of bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease of ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights. Results Of 1738 adults (631 prescribed LPD at any point during follow-up), there were 1319 with repeated SGA measurements, of which 267 (20%) decreased in SGA ≥2 points and 565 (32.5%) who died. There was no difference in survival or decrease in nutritional status for patients prescribed a LPD ≤0.8 g/kg ideal bodyweight {odds ratio [OR] for mortality 1.15 [95% confidence interval (CI) 0.86–1.55)] and OR for decrease in SGA 1.11 [95% CI 0.74–1.66]} in the adjusted models. In patients prescribed a LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and older age >75 years, lower SGA and higher comorbidity burden for both mortality and nutritional status decline. Conclusions In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between adolescents' adherence to attention‐deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. Methods: Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12–18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. Results: High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64–0.71) or ≥6 months (HR 0.62, CI 0.59–0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non‐stimulant medication, different offense categories and further sensitivity analyses. Conclusions: Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents. [ABSTRACT FROM AUTHOR]

Intimate partner homicide (IPH) can be viewed as the ultimate result of a potential spectrum of violence that can occur between intimate or former partners. The goal of this study is to identify the criminal career and contextual indicators that precede IPH. This study utilized a database encompassing all criminal events documented by the police in the province of Quebec from 1990 to 2022. Cox regression models indicate that the violent assault in a non-IPV context, variety of criminal offenses and general lambda of crimes influence the likelihood of IPH offender criminal career survival. The results indicate a linear distribution of risk, highlighting the complexity of predicting IPH. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

Discrete-time survival analysis (DTSA) models are a popular way of modeling events in the social sciences. However, the analysis of discrete-time survival data is challenged by missing data in one or more covariates. Negative consequences of missing covariate data include efficiency losses and possible bias. A popular approach to circumventing these consequences is multiple imputation (MI). In MI, it is crucial to include outcome information in the imputation models. As there is little guidance on how to incorporate the observed outcome information into the imputation model of missing covariates in DTSA, we explore different existing approaches using fully conditional specification (FCS) MI and substantive-model compatible (SMC)-FCS MI. We extend SMC-FCS for DTSA and provide an implementation in the smcfcs R package. We compare the approaches using Monte Carlo simulations and demonstrate a good performance of the new approach compared to existing approaches. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment. METHODS: Given the genetic susceptibility of AD, a multi‐factorial pseudotime approach was proposed to integrate amyloid imaging and genotype data for estimating a risk score. Validation involved association with cognitive decline and survival analysis across risk‐stratified groups, focusing on patients with mild cognitive impairment (MCI). RESULTS: Our risk score outperformed amyloid composite standardized uptake value ratio in correlation with cognitive scores. MCI subjects with lower pseudotime risk score showed substantial delayed onset of AD and slower cognitive decline. Moreover, pseudotime risk score demonstrated strong capability in risk stratification within traditionally defined subgroups such as early MCI, apolipoprotein E (APOE) ε4+ MCI, APOE ε4– MCI, and amyloid+ MCI. DISCUSSION: Our risk score holds great potential to improve the precision of early risk assessment. Highlights: Accurate early risk assessment is critical for the success of clinical trials.A new risk score was built from integrating amyloid imaging and genetic data.Our risk score demonstrated improved capability in early risk stratification. [ABSTRACT FROM AUTHOR]

Limited information exists regarding the epidemiology, metastasis, and survival of dermatofibrosarcoma protuberans (DFSP). To measure DFSP incidence and assess metastasis and survival outcomes. Incidence rate, overall and DFSP-specific survival outcomes for primary DFSP tumors contained in the Surveillance, Epidemiology, and End Results (SEER) registry were analyzed via quasi-Poisson regression, Cox, and competing risk analyses. DFSP incidence rate was 6.25 (95% CI, 5.93-6.57) cases per million person-years with significantly higher incidence observed among Black individuals than White individuals (8.74 vs 4.53). DFSP with larger tumor size (≥3 cm, odds ratio [OR]: 2.24; 95% CI, 1.62-3.12; P <.001) and tumors located on the head and neck (OR: 4.88; 95% CI, 3.31-7.18; P <.001), and genitalia (OR: 3.16; 95% CI, 1.17-8.52; P =.023) were associated with significantly increased risk of metastasis whereas higher socioeconomic status was associated with significantly decreased risk of metastasis. Larger tumor size (≥3 cm), regardless of location, and age (≥60 years) were associated with significantly worse overall and cancer-specific survival. Retrospective design of SEER. DFSP incidence is 2-fold higher among Black than White individuals. The risk of DFSP metastasis is significantly increased with tumor size ≥3 cm and tumors located on head and neck, and genitalia. Larger tumor size (≥ 3 cm), regardless of location, and age (≥60 years) are the most important prognostic indicators of survival. [ABSTRACT FROM AUTHOR]

Several studies have reported short- and intermediate-term outcomes after thoracic endovascular aortic repair (TEVAR) for descending thoracic aortic aneurysm (DTAA); however, reports on long-term (10 years) outcomes are sparse. Therefore, the aim of this study was to analyze predictors impacting long-term outcome after TEVAR for DTAA. Databases from four academic institutions were reviewed and consecutive cases of TEVAR for DTAA between 1999 and 2021 were included in this retrospective multicenter study (case series). Ethical approval from the institutional review board was obtained and patient demographics and treatment data, as well as follow-up information were retrieved and analyzed. We identified 305 patients (mean age, 72 ± 10 years) who were treated with TEVAR for degenerative DTAA with a mean aortic diameter of 64 mm. Altogether 445 endografts were implanted via femoral access (93%) with a technical success of 94%. Operative mortality, stroke rate, and rate of spinal cord ischemia were 6% (5% for intact, 12% for ruptured DTAA), 4%, and 3%, respectively. Kaplan-Meier estimates for overall survival rates were 76%, 59% and 34% at 1, 5 and 10 years and freedom from reintervention rates were 84%, 73% and 58% at 1, 5 and 10 years, respectively. In multivariate analysis, American Society of Anesthesiologists grade 3 to 5 and nonelective case were identified as predictors for death, whereas as fusiform DTAA, proximal landing zone 2, and hypertension, but not device generation, were predictive for reintervention. This study is, to date, the largest reporting long-term (10 years) outcome on TEVAR for DTAA. We found acceptable rates for long-term survival and freedom from reintervention that were independent of endovascular device generation. [ABSTRACT FROM AUTHOR]

Aim: This article provides an overview of time‐to‐event (TTE) analysis in pharmacoepidemiology. Materials & Methods: The key concept of censoring is reviewed, including right‐, left‐, interval‐ and informative censoring. Simple descriptive statistics are explained, including the nonparametric estimation of the TTE distribution as per Kaplan–Meier method, as well as more complex TTE regression approaches, including the parametric Accelerated Failure Time (AFT) model and the semi‐parametric Cox Proportional Hazards and Restricted Mean Survival Time (RMST) models. Additional approaches and various TTE model extensions are presented as well. Finally, causal inference for TTE outcomes is addressed. Results: A thorough review of the available concepts and methods outlines the immense variety of available and useful TTE models. Discussion: There may be underused TTE concepts and methods, which are highlighted to raise awareness for researchers who aim to apply the most appropriate TTE approach for their study. Conclusion: This paper constitutes a modern summary of TTE analysis concepts and methods. A curated list of references is provided. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification. Methods The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent. Results The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P  = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P  = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P  = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P  = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P  = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P  = .0761) was associated with EFS. Conclusion Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties. [ABSTRACT FROM AUTHOR]

Backgrounds There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. Methods Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. Results Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P  < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P  < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P  = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P  = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P  < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P  < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P  < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P  < .05). Conclusion ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Contemporary injury tolerance of the lumbar spine for under-body blast references axial compression and bending moments in a limited range. Since injuries often occur in a wider range of flexion and extension with increased moment contribution, this study expands a previously proposed combined loading injury criterion for the lumbar spine. Fifteen cadaveric lumbar spine failure tests with greater magnitudes of eccentric loading were incorporated into an existing injury criterion to augment its applicability and a combined loading injury risk model was proposed by means of survival analysis. A loglogistic distribution was the most representative of injury risk, resulting in optimized critical values of Fr,crit = 6011 N, and My,crit = 904 Nm for the proposed combined loading metric. The 50% probability of injury resulted in a combined loading metric value of 1, with 0.59 and 1.7 corresponding to 5 and 95% injury risk, respectively. The inclusion of eccentric loaded specimens resulted in an increased contribution of the bending moment relative to the previously investigated flexion/extension range (previous My,crit = 1155 Nm), with the contribution of the resultant sagittal force reduced by nearly 200 N (previous Fr,crit = 5824 N). The new critical values reflect an expanded flexion/extension range of applicability of the previously proposed combined loading injury criterion for the human lumbar spine during dynamic compression. [ABSTRACT FROM AUTHOR]

This study utilized data from 140,294 prostate cancer cases from the Surveillance, Epidemiology, and End Results (SEER) database. Here, 10 different machine learning algorithms were applied to develop treatment options for predicting patients with prostate cancer, differentiating between surgical and non‐surgical treatments. The performances of the algorithms were measured using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value. The Shapley Additive Explanations (SHAP) method was employed to investigate the key factors influencing the prediction process. Survival analysis methods were used to compare the survival rates of different treatment options. The CatBoost model yielded the best results (AUC = 0.939, sensitivity = 0.877, accuracy = 0.877). SHAP interpreters revealed that the T stage, cancer stage, age, cores positive percentage, prostate‐specific antigen, and Gleason score were the most critical factors in predicting treatment options. The study found that surgery significantly improved survival rates, with patients undergoing surgery experiencing a 20.36% increase in 10‐year survival rates compared with those receiving non‐surgical treatments. Among surgical options, radical prostatectomy had the highest 10‐year survival rate at 89.2%. This study successfully developed a predictive model to guide treatment decisions for prostate cancer. Moreover, the model enhanced the transparency of the decision‐making process, providing clinicians with a reference for formulating personalized treatment plans. [ABSTRACT FROM AUTHOR]

Ludhiana, a pollution hot spot in North India, has seen a rapid deterioration in air quality over the years due to urbanization and industrialization. This study interprets the variations of particulate matter (PM) and gaseous pollutants (Nitrogen oxide, Nitrogen dioxide, NOX, Sulphur dioxide, Carbon monoxide, Benzene, Toluene, Ozone, and Ammonia) for the data observed from 2017 to 2023 in Ludhiana. This also covers the analysis focused on capturing the changes that occurred at the times of lockdown imposed during the Coronavirus Disease (COVID-19). The maximum 24-h averaged mass concentration values exceeded the National Ambient Air Quality Standards (NAAQS) of 100 µg/m3 for PM10 concentration and 60 µg/m3 for PM2.5 concentration in 2018 by the factor of 5 and 8. With the onset of the COVID-19 lockdown in 2020 year, PM10 and PM2.5 reached the minimum level while CO, T, O3, and NO2 increased by the factor of 3.9, 1.9, 1.4, and 1.3 from their previous year. This NO2 is a precursor of ozone formation, a higher NO2 to NO ratio observed during the lockdown, confirms the role of nitrogen compounds in the higher ozone formation rate. Based on the NO2/NO ratio, the probability rate of ozone formation determined using survival analysis is observed to be 94% from 2017 to 2023. The local sources' contribution to these air pollutants during Pre-Lockdown, Lockdown, and Post-Lockdown are analyzed using principal component analysis. The impact of the lockdown on ozone concentration sources has been observed. During the Pre- and Post-Lockdown phases, three sources (PC1, PC2, and PC3) were positively identified. Ozone levels are linked to PC3 in these phases, but during the lockdown, a negative loading in PC3 and positive loadings in PC1 and PC2 indicate a decrease in ozone from reduced emissions and an increase from secondary reactions involving nitrogen compounds. Moreover, the Toluene to Benzene concentration ratio is > 2, indicating the source of their origin from industrial emission or other non-traffic sources. Health assessment for the years 2017–2019 reveals a significant decrease in the number of cases of all-cause mortality, ischemic heart disease, stroke, and chronic obstructive pulmonary disease associated with reducing PM2.5 concentrations to national and international standards. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the characteristics of newly diagnosed marginal zone lymphoma (MZL) patients, evaluate the efficacy of different treatment regimens, and explore prognostic factors in the era of immunotherapy. Methods: We reviewed the clinical data of newly diagnosed MZL patients treated at the Department of Hematology, The First Hospital of Jilin University, from October 2013 to October 2023. Survival differences between groups were analyzed using the log-rank test, and prognostic factors were identified. Results: A total of 265 newly diagnosed MZL patients were included, with a median age of 59 years (range 22-90). The most common pathological type was mucosaassociated lymphoid tissue (MALT) lymphoma, accounting for 66.0% of cases. Among the 147 MZL patients included in the efficacy analysis, the median followup was 43.4 months. Both the median progression-free survival (PFS) and overall survival (OS) were not reached. The 5-year PFS and OS rates were 76.0% and 86.6%, respectively. Patients who achieved complete response (CR) after induction therapy had significantly better PFS (P=0.0045), OS (P<0.001), and time to next treatment (TTNT) (P=0.0045) compared to those who did not achieve CR. A subgroup analysis was conducted on 51 MZL patients with high tumor burden who received ≥4 cycles of treatment. It was found that the CR rate (CRR) in patients receiving obinutuzumab (G) ± chemotherapy was significantly higher than in those receiving rituximab (R) ± chemotherapy (93.8% vs. 48.6%, P=0.002). Multivariate analysis revealed that disease progression or death within 24 months of initial treatment (POD24) was an independent risk factor affecting OS (P<0.001). Patients who experienced POD24 had a median survival of only 19.7 months, with a 3-year OS rate of just 37.6%, whereas those without POD24 had a 3-year OS rate of 97.3%. Conclusion: MZL is predominantly seen in middle-aged and elderly patients and is a specific indolent B-cell lymphoma, with MALT lymphoma being the most common subtype. Achieving CR after induction therapy significantly prolongs survival in MZL patients. Compared to R ± chemotherapy, G ± chemotherapy achieves a higher CRR in high tumor burden MZL patients. In the era of immunotherapy, POD24 is an independent prognostic factor for MZL. [ABSTRACT FROM AUTHOR]

Objective To identify key gene mutations and explore their mechanisms in bladder urothelial carcinoma (BLCA) through bioinformatics analysis combined with clinical sample testing. Methods Gene mutation data, transcriptome data, and clinical data for all BLCA cases were downloaded from the TCGA database(406 tumor tissues and 19 adjacent non-cancer tissues) and GTEx database (21 adjacent non-cancer tissues). A total of 32 clinical samples from BLCA surgeries were collected, and gene expression was measured using real-time quantitative polymerase chain reaction (PCR). Results Mutations were found in 91. 42% of the patients, with missense mutations, single nucleotide variants, and CT transitions being the predominant types. The top five mutated genes were TP53 (47%), TTN (45%), KMT2D (29%), MUC16 (28%), and KDM6A (26%). In both TCGA and clinical samples, the expression levels of mutant KDM6A were significantly higher than those of the wild type (P=0.008,0.007). The patients with wild-type KDM6A had a longer overall survival (OS) and progression-free survival (PFS) than those with the mutation (P=0.028.0.035). Further studies revealed that the expression of KDM6A was significantly positively correlated with the levels of CD8+T cells (r=0.22,P=0.039), macrophages (r=0.31,P=0.032), and endothelial cells (r=0.26, P = 0.002). Conclusion Mutations in KDM6A are closely associated with prognosis and the immune microenvironment in BLCA, suggesting that KDM6A mutations may serve as potential therapeutic targets for BLCA. [ABSTRACT FROM AUTHOR]

Accurate prediction of remaining useful life (RUL) for in‐service systems plays an important role in ensuring efficient operation of industrial equipment and in preventing unexpected equipment failures. In this paper, we present a prognostic framework for real‐time RUL prediction based on joint modeling of both degradation signals and time‐to‐event data. The proposed model employs a change point‐based general path model to capture signal non‐linearity and Neural network (NN) based Cox model to link the time‐to‐event data with the estimated degradation trend. An empirical two‐step scheme for hyperparameter estimation is proposed to enhance prognostic accuracy. Furthermore, an efficient Bayesian model updating procedure, integrated with recursive particle filtering, is used to facilitate online prediction, achieving accurate RUL prediction in real‐time and accounting for uncertainties in RUL prediction. Simulation and real‐life case studies demonstrate the advantages of the proposed method over existing approaches. [ABSTRACT FROM AUTHOR]

Subsampling is a practical strategy for analyzing vast survival data, which are progressively encountered across diverse research domains. While the optimal subsampling method has been applied to inferences for Cox models and parametric accelerated failure time (AFT) models, its application to semi‐parametric AFT models with rank‐based estimation have received limited attention. The challenges arise from the non‐smooth estimating function for regression coefficients and the seemingly zero contribution from censored observations in estimating functions in the commonly seen form. To address these challenges, we develop optimal subsampling probabilities for both event and censored observations by expressing the estimating functions through a well‐defined stochastic process. Meanwhile, we apply an induced smoothing procedure to the non‐smooth estimating functions. As the optimal subsampling probabilities depend on the unknown regression coefficients, we employ a two‐step procedure to obtain a feasible estimation method. An additional benefit of the method is its ability to resolve the issue of underestimation of the variance when the subsample size approaches the full sample size. We validate the performance of our estimators through a simulation study and apply the methods to analyze the survival time of lymphoma patients in the surveillance, epidemiology, and end results program. [ABSTRACT FROM AUTHOR]