Rank Statistics Research Articles

Adaptive rank-based tests for high dimensional mean problems

The Wilcoxon signed-rank test and the Wilcoxon–Mann–Whitney test are commonly employed in one sample and two sample mean tests for one-dimensional hypothesis problems. For high-dimensional mean test problems, we calculate the asymptotic distribution of the maximum of rank statistics for each variable and suggest a max-type test. This max-type test is then merged with a sum-type test, based on their asymptotic independence offered by stationary and strong mixing assumptions. Our numerical studies reveal that this combined test demonstrates robustness and superiority over other methods, especially for heavy-tailed distributions.

GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists. We focused on two key topics to showcase GeneRaMeN: virus host factors and cancer dependencies. Using GeneRaMeN 'Rank Aggregation', we integrated 24 published and new flavivirus genetic screening datasets, including dengue, Japanese encephalitis, and Zika viruses. This meta-analysis yielded a consensus list of flavivirus host factors, elucidating the significant influence of cell line selection on screening outcomes. Similar analysis on 13 SARS-CoV-2 CRISPR screening datasets highlighted the pivotal role of meta-analysis in revealing redundant biological pathways exploited by the virus to enter human cells. Such redundancy was further underscored using GeneRaMeN's 'Rank Correlation', where a strong negative correlation was observed for host factors implicated in one entry pathway versus the alternate route. Utilizing GeneRaMeN's 'Rank Uniqueness', we analyzed human coronaviruses 229E, OC43, and SARS-CoV-2 datasets, identifying host factors uniquely associated with a defined subset of the screening datasets. Similar analyses were performed on over 1000 Cancer Dependency Map (DepMap) datasets spanning 19 human cancer types to reveal unique cancer vulnerabilities for each organ/tissue. GeneRaMeN, an efficient tool to integrate and maximize the usability of genetic screening datasets, is freely accessible via https://ysolab.shinyapps.io/GeneRaMeN.

Acute diverticulitis: beyond the diagnosis: predictive role of CT in assessing risk of recurrence and clinical implications in non-operative management of acute diverticulitis

PurposeThe aim of the study is to identify CT findings that are predictive of recurrence of acute uncomplicated colonic diverticulitis, to better risk-stratify these patients for whom guidelines recommend a conservative outpatient treatment and to determine the appropriate management with an improvement of health costs.Materials and MethodsOver the past year, 33 patients enrolled in an outpatient integrated care pathway (PDTA) for uncomplicated acute diverticulitis with 1-year follow-up period, without recurrence, and 33 patients referred to Emergency Department for a recurrent acute diverticulitis were included. Images of admission CT were reviewed by two radiologists and the imaging features were analyzed and compared with Chi-square and Student t tests. Univariate and multivariate Cox regression models were employed to identify parameters that significantly predicted recurrence in 1-year follow-up period and establish cutoff and recurrence-free rates. The maximally selected rank statistics (MSRS) were used to identify the optimal wall thickening cutoff for the prediction of recurrence.ResultsPatients with recurrence showed a greater mean parietal thickness compared to the group without recurrence (16 mm vs. 11.5 mm; HR 1.25, p < 0.001) and more evidence of grade 4 of peridiverticular inflammation (40% vs. 12%, p = 0.009, HR 3.44). 12-month recurrence-free rates progressively decrease with increasing thickness and inflammation. In multivariate analysis, only parietal thickness maintained its predictive power with an optimal cutpoint > 15 mm that causes a sixfold increased risk of recurrence (HR 6.22; 95% CI, 3.05–12.67; p < 0.001). Beyond thickness and peridiverticular inflammation, predictive value of early recurrence within 90 days from the 1st episode resulted also an Hinchey Ib on admission CT.ConclusionsThe maximum wall thickening and the grade of peridiverticular inflammation can be considered as predictive factors of recurrence and may be helpful in selecting patients for a tailored treatment to prevent the risk of recurrence.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study

BackgroundThe hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms.MethodsClinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan–Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms.ResultsA total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405–0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538–0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS.ConclusionPreoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.

Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis

The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21–1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04–2.18, P = 0.030) compared to a lower SII. Kaplan–Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (Pall-cause mortality < 0.0001 and Pcardiovascular mortality = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.

Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols

BackgroundGrade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.MethodsKi67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.ResultsIn initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).ConclusionsG2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.

HaN-Seg: The head and neck organ-at-risk CT and MR segmentation challenge

Background and purposeTo promote the development of auto-segmentation methods for head and neck (HaN) radiation treatment (RT) planning that exploit the information of computed tomography (CT) and magnetic resonance (MR) imaging modalities, we organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge. Materials and methodsThe challenge task was to automatically segment 30 organs-at-risk (OARs) of the HaN region in 14 withheld test cases given the availability of 42 publicly available training cases. Each case consisted of one contrast-enhanced CT and one T1-weighted MR image of the HaN region of the same patient, with up to 30 corresponding reference OAR delineation masks. The performance was evaluated in terms of the Dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95), and statistical ranking was applied for each metric by pairwise comparison of the submitted methods using the Wilcoxon signed-rank test. ResultsWhile 23 teams registered for the challenge, only seven submitted their methods for the final phase. The top-performing team achieved a DSC of 76.9 % and a HD95 of 3.5 mm. All participating teams utilized architectures based on U-Net, with the winning team leveraging rigid MR to CT registration combined with network entry-level concatenation of both modalities. ConclusionThis challenge simulated a real-world clinical scenario by providing non-registered MR and CT images with varying fields-of-view and voxel sizes. Remarkably, the top-performing teams achieved segmentation performance surpassing the inter-observer agreement on the same dataset. These results set a benchmark for future research on this publicly available dataset and on paired multi-modal image segmentation in general.

Endoxifen Concentration is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.

The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dosage. However, the clinical significance of endoxifen on the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics. Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.

D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors.

This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

Systemic inflammatory biomarkers are novel predictors of all-cause and cardiovascular mortality in individuals with osteoarthritis: a prospective cohort study using data from the NHANES

BackgroundChronic inflammation may contribute to increased mortality risk in individuals with osteoarthritis (OA), but research on the prognostic value of inflammatory biomarkers is limited. We aimed to evaluate the associations of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) with all-cause and cardiovascular mortality among US adults with OA.MethodsThis cohort study included 3545 adults with OA aged ≥ 20 years from the National Health and Nutrition Examination Survey 1999–2020. The SII and SIRI were calculated using complete blood cell count data. Participants were categorized as having a higher or lower SII and SIRI using cutoff points derived by the maximally selected rank statistics method. Cox proportional hazards models, Fine–Gray competing risk regression models and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the associations between the SII/SIRI and mortality in OA patients.ResultsOver a median follow-up of 5.08 (3.42–9.92) years, 636 (17.94%) deaths occurred, including 149 (4.20%) cardiovascular deaths. According to multivariable-adjusted models involving demographic, socioeconomic, and health factors, OA patients with a higher SII had a twofold greater risk of all-cause mortality than patients with a lower SII (HR 2.01; 95% CI: 1.50–2.68). Similarly, a higher SIRI was associated with an 86% increased risk of all-cause mortality relative to a lower SIRI (HR 1.86; 95% CI: 1.46–2.38). Similar to the trend found with all-cause mortality, patients with an elevated SII and SIRI had a 88% and 67% increased risk of cardiovascular mortality, respectively, compared to patients with a lower SII (HR 1.88; 95% CI: 1.16–3.03) and SIRI (HR 1.67; 95% CI: 1.14–2.44). Time-dependent ROC curves showed that both the SII and SIRI have moderate and valid performance in predicting short- and long-term mortality in patients with OA.ConclusionsHigher SII and SIRI values were associated with greater all-cause and cardiovascular mortality among US adults with OA.

Association of muscle mass and radiodensity assessed by chest CT with all-cause and cardiovascular mortality in hemodialysis patients.

This study investigates the prognostic value of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) measured by chest CT in relation to all-cause and cardiovascular disease (CVD) mortality among hemodialysis (HD) patients. A retrospective study was conducted from January 2015 to December 2021 involving HD patients at a dialysis center. Chest CT scans at the twelfth thoracic vertebra level (T12) were analyzed to assess SMI and SMD. Sex-specific cut-off values for two metrics were determined using maximally selected rank statistics. Hazard ratios (HRs) were calculated to evaluate the associations of SMI and SMD with mortality. The discrimination of prognostic models was also compared. The study included 603 patients with a median age of 58years. Of these, 187 (31.0%) patients with SMI < 30.00 cm2/m2 (male) or < 25.04 cm2/m2 (female) and 192 (31.8%) patients with SMD < 32.25 HU (male) or < 30.64 HU (female) were categorized as lower SMI and SMD, respectively. Over a median follow-up of 3.8years, 144 deaths occurred. Multivariate Cox regression analysis showed that lower SMI and SMD were independently associated with all-cause mortality (SMI: HR = 1.47, 95% CI 1.03-2.10; SMD: HR = 1.75, 95% CI 1.20-2.54) and CVD mortality (SMI: HR = 1.74, 95% CI 1.03-2.94; SMD: HR = 1.72, 95% CI 1.02-2.95). Adding SMI and SMD to the established risk model improved the C-index from 0.82 to 0.87 (P < 0.001). Decision curve analysis showed that the prognostic model incorporating both SMI and SMD offered the highest net benefit for predicting all-cause mortality. Muscle metrics derived from CT scans at T12 level provide valuable prognostic information which could enhance the role of chest CT in muscle assessment among HD patients.

Apolipoprotein A-I levels in the survival of patients with colorectal cancer: a retrospective study.

Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.

Novel pretreatment nomograms based on pan-immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma.

The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.

QFD with Statistical Ranking – a Hydropower Turbine Case Study

QFD with Statistical Ranking – a Hydropower Turbine Case Study

The Combined Shewhart-CUSUM Wilcoxon Signed-rank Control Charts for Process Location

Nonparametric one- and two-sided combined Shewhart-CUSUM (CSC) control charts for process location based on the Wilcoxon signed rank (WSR) statistic are proposed. The statistical performances of these charts are investigated through Monte Carlo simulations, when the underlying process distributions are normal, uniform and Laplace. It is observed that a CSC WSR chart can be designed so as to exhibit a trade-off statistical performance between the performances of the Shewhart WSR and CUSUM WSR charts for identifying a location shift of any size. Hence, it is a viable alternative to these two charts in a case where efficient detections of the small as well as large-sized location shifts are equally important. Computations of the control statistics of a one-sided CSC WSR chart are illustrated using simulated-data example.. KEYWORDS :Statistical process control, Average run length, Distribution-free control chart

Local Community Participation Under Proboscis Monkey Conservation-Based Ecotourism Development in Curiak Island Area

Abstract This study was conducted to identify local participation under proboscis monkey conservation-based ecotourism development in Curiak Island Area and the relationship between their socio-demographic characteristics. A total of 20 respondents participated in the study. The data taken included respondents’ profiles and local community participation in proboscis monkey ecotourism development. The data were analyzed by using descriptive statistics analysis and rank Spearman correlation analysis. The results showed that local community participation in proboscis monkey conservation-based ecotourism is at a medium level with an average mean score of 3.34. The correlation coefficient between age and local community participation is −0.223 with a significance value of 0.345 so that it can be said that there is no significant relationship (p&gt;0.05) between age and local community participation and are at a very low category, the correlation coefficient value between gender and local community participation is 0.286 with a significance value of 0.221 so that it can be said that there is no significant relationship (p&gt;0.05) between gender and community participation local and are at a low category, the correlation coefficient value between education and local community participation is 0.296 with a significance value of 0.205 so that it can be said that there is no significant relationship (p&gt;0.05) between education and local community participation and are at a low category, and the correlation coefficient value between income and local community participation is 0.496 with a significance value of 0.026 so that it can be said that there is a real relationship (p&lt;0.05) between income and local community participation and are at a medium category. It can be concluded that local community participation in proboscis monkey conservation-based ecotourism is at a medium level. The socio-demographic characteristic that has a real relationship with local community participation is monthly income. Socio-demographic characteristics that have no significant relationship with local community participation are age, education, and educational background.

Identification of immune biomarkers in treatment-naive patients with metastatic pancreatic cancer treated with the GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.

e16331 Background: Elraglusib (9-ING-41), a potent and selective GSK-3 inhibitor, is a targeted anticancer agent with clinical activity in phase 1 trial and undergoing clinical development for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). Elraglusib (9-ING-41) displayed immune-modulatory activity in preclinical models and modulation of serum cytokine profile in clinical specimens. Here, we investigated the correlation between plasma levels of cytokines/chemokines/soluble cell receptors/growth factors (CCSG) and clinical outcomes of patients with mPDAC treated with elraglusib and gemcitabine/nab-paclitaxel (GnP) in an exploratory study. Methods: CCSGs were evaluated in the pre-dose plasma samples of patients with newly diagnosed mPDAC enrolled in the 1801 phase 2 study (NCT03678883) treated with GnP (n = 13) or elraglusib/GnP (n = 32). Using a Luminex immunoassay, 40 CCSGs were screened as predictive biomarkers of median overall survival (mOS) in the elraglusib/GnP arm using 5-fold cross-validation and maximally selected rank statistic cutpoint determination. A subset of CCSGs (n = 10) was remeasured using an MSD immunoassay with greater sensitivity. Maximally selected rank statistic cutpoint determinations were conducted using MSD results for elraglusib/GnP samples with mOS and median progression free survival (mPFS). P values &lt; 0.05 were considered statistically significant. Results: Luminex screening revealed several CCSGs significantly stratified elraglusib/GnP patients by mOS. IL-6 and IL-8 were identified as top candidates with stable and significant results on cross-validation. Using the MSD assay, both were confirmed to stratify elraglusib/GnP patients by OS and extended to analyze PFS. Low level of IL-8 conferred a better OS prognosis (HR: 0.0919, 95%, CI: 0.0205-0.411, P &lt; 0.001) than low IL-6 (HR: 0.205, 95%, CI: 0.063-0.665, P = 0.005) in the elraglusib/GnP treated patients. Correlations with mPFS were similar in the elraglusib/GnP patients for IL-6 (HR: 0.248, 95% CI: 0.072-0.848, P = 0.02) and IL-8 (HR: 0.297, 95%, CI: 0.111-0.743, P = 0.01). Conclusions: Preliminary results of our exploratory study identified low plasma levels of IL-6 and IL-8 prior to elraglusib/GnP treatment as potential predictive biomarkers associated with improved outcomes in previously untreated patients with mPDAC. The 1801 Part 3 Arm B clinical trial recruitment has been completed. We plan to analyze additional pre-dose plasma samples obtained from approximately 200 patients by April 2024. These will be analyzed using interim OS data available by April 2024 and included in the final presentation. Clinical trial information: NCT03678883 .

Baseline value and longitudinal kinetics of circulating nucleosomes during neo-adjuvant chemotherapy in newly diagnosed ovarian cancer: Results from the randomized phase II trial CHIVA (GINECO).

e15029 Background: Nucleosomes (DNA wound around histone proteins) were reported as potential cancer biomarkers (1). The links between circulating nucleosomes and clinical endpoints in advanced ovarian cancer (OC) patients treated with neo-adjuvant chemotherapy (NACT) +/- interval debulking surgery (IDS) were retrospectively assessed in the randomized phase II CHIVA trial (2). Methods: The diagnostic concentration and the longitudinal kinetics of 2 nucleosomes (H3K27 and H3K36, log-scale) were investigated at baseline, during NACT, after IDS, and at progression. The baseline titer measured with Nu.Q prototype immunoassays (H3K27Me3, H3K36Me3 (Belgian Volition SRL, Belgium)) was compared to those of a cohort of 201 cancer-free subjects. Their prognostic values regarding the probability of obtaining a complete IDS and progression-free survival (PFS) were assessed with respect to the modeled CA-125 KELIM (3), classical clinical covariates and treatment arms. The maximum selected rank statistics was used to determine the optimal cut-off at different disease management times. Results: H3K27 and H3K36 nucleosome concentrations were available for 148/188 patients. H3K36 and H3K27 baseline concentrations were correlated and significantly higher in OC patients compared to cancer-free subjects (H3K36, 2.8 vs 2.4 ng/mL, P&lt;0.0001; H3K27, 3.2 vs 2.1, P&lt;0.0001), without difference according to BRCA status. The baseline titer of H3K36 was an independent predictor of the completeness of IDS (OR=0.33; 95% CI=0.13-0.71, p=0.009). The baseline concentration of H3K27 was independently associated with PFS (&lt; or ≥3.8 ng/mL, HR=1.84, 95%CI=1.11-3.02, p=0.016), complementary to the CA-125 KELIM. Both nucleosome longitudinal kinetics showed a decrease during NACT, but there was no significant statistical association between their kinetics and radiological response rate, completeness of IDS or PFS. Conclusions: Baseline values of H3K36 and H3K27 could represent a non-invasive method for detecting OC, with potential relevant prognostic value of initial titers in newly diagnosed OC patients. 1. McAnena, Cancers 2017. 2. Ferron, Gynecol Oncol 2023. 3. You, CCR 2020.

Construction and validation of a necroptosis-related prognostic signature in acute myeloid leukemia.

Acute myeloid leukemia (AML), an uncommonly low 5-year survival and high mortality rate, is a potentially catastrophic diagnosed subtype of leukemia. The development of new prognostic markers is urgently needed to guide its treatment. Necroptosis is a newly defined biological process for regulating cell death, and previous studies have confirmed that the abnormality of the physical function can lead to multiple malignancies. Here, we performed necroptosis-related genes (NRGs) to build a predictive model in the Cancer Genome Atlas (TCGA)-AML patients, thus exploring the correlation between the NRG prognosis signature (NRG score) of this model and immune infiltration, pathway activity, clinical features, and immunotherapy. Besides, we computed the statistical measure Spearman rank correlation between the NRG score and the Log IC50 values of therapeutic agents. Subsequently, we divided the TCGA-AML cohort into 2 groups, one with high scores and the other with low scores depending on the model score. AML patients with high NRG scores exhibited a lower estimated overall survival (OS) rate than those with low NRG scores, which was confirmed in the validation set. The prognostic value of the constructed NRG signature to the AML, independent of other variables, was demonstrated by uni- and multivariate stepwise regression analysis. When comparing the infiltrating states of specialized cells associated with immune system from the 2 groups, B cells naive, Plasma cells, and monocytes represented significant differences among various subgroups of samples. Moreover, the 30 hallmark-related pathways related to necroptosis characteristics were remarkably different between the high/low NRG score groups. And patients showed remarkable NRG score distribution in clinical features of bone marrow lymphocyte, category, and FAB classifications. Besides, we found that the BIRB0796, VX680, Vorinostat, and Axitinib positively related with NRG score, whereas CI. 1040, PD. 0325901, Z.L LNle. CHO, and AZD6244 negatively correlated with the NRG score. These drugs may provide a reference for subsequent treatment.

Association between C-reactive protein/albumin ratio and all-cause mortality in patients with stroke: Evidence from NHANES cohort study

Background and aimsThe inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. Methods and resultsData were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. ConclusionElevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.