Regression Coefficients Research Articles

Social Support as a Correlate of Depression and Quality of Life Among Nigerian Older Adults: a Cross-Sectional Study.

Reduced social support has been associated with presence of depression and reduced quality of life among older adults. The relationships may be better understood by exploring the interactions of individual domains among the constructs. This cross-sectional survey involved a consecutive sample of 206 (116 females and 90 males) older adults living in a Southern Nigeria community. The Multidimensional Scale of Perceived Social Support, Geriatric Depression Scale, and World Health Organization Quality of Life-OLD Questionnaire, were used to measure social support, depression, and quality of life respectively. Data was analyzed using frequency counts, percentages, mean, standard deviation, multiple regression and Spearman rank-order correlation coefficient, at 0.05 alpha level. Prevalence rate of depression among participants was 45.5%. Social support was perceived to be low by 37.4% of participants with the lowest mean social support score coming from friends domain. Participants' quality of life was generally fairly good (> 60%) with the lowest scores coming from the intimacy domain. Significant correlations between social support domains and each of quality of life (p < 0.05) and depression were respectively positive and negative; but weakest for the friend and strongest for significant others domains. All quality of life domains were significantly correlated with social support except the death and dying domain. All the domains of social support (family and significant other) were significant predictors of depression except the friend domain. Significant others around individual older adults particularly those with depression ought to be educated on the importance of their roles. Stakeholders including healthcare providers may create and support programmes for improved social networking for the older adults in order to enhance their general wellbeing and quality of life.

Effects of low-dose magnesium oxide on elevated serum magnesium levels and improved constipation in hemodialysis patients: a single-center retrospective study

BackgroundThe prevention of hypomagnesemia is critical for improving the life expectancy of patients undergoing hemodialysis (HD). The administration of magnesium oxide (MgO) increases serum Mg concentrations; however, dose adjustments must be done carefully owing to the risk of hypermagnesemia in patients undergoing HD. Additionally, the laxative effects of low-dose MgO on constipation in these patients has not been reported. Therefore, in the present study, we investigated the effects of treatment with low-dose MgO on serum Mg concentration changes and the improvement of defecation in patients undergoing HD.MethodsThe present study was a single-center retrospective observational study of 43 patients undergoing maintenance HD at Shirasagi Hospital. The patients’ clinical characteristics, including serum Mg concentration, were obtained from the hospital’s electronic medical records. In the group who received MgO for constipation, the effectiveness of MgO as a laxative was categorized as effective, ineffective, or unknown on the basis of electronic medical records related to defecation.ResultsOf the 43 patients included in the present study, 23 were prescribed supplemental Mg to prevent hypomagnesemia or maintain mild hypermagnesemia and 19 to prevent constipation. All patients received diasylate with an Mg concentration of 1.0 mEq/L. Additionally, 37 patients (86%) were treated with 330 mg/day MgO. The serum Mg concentrations before and 1, 2, and 3 months after the start of MgO were 2.3 ± 0.2, 2.8 ± 0.4, 2.8 ± 0.5, and 2.8 ± 0.4 mg/dL, respectively (P < 0.001). Multiple linear regression analysis showed that dry weight was independently associated with changes in serum Mg concentration from before to 1 month after MgO administration (regression coefficient = −0.027; P = 0.020). Of the 19 patients evaluated for constipation, 8 (42%) had documented effective bowel movements after the initiation of MgO, 6 had no effect, and 5 were unknown; however, 1 patient in the ineffective group and 2 in the effective group used other laxatives prior to starting MgO.ConclusionsThe results of the present study suggest that the administration of low-dose MgO to patients undergoing HD provides a means of increasing serum Mg concentration without causing dangerous hypermagnesemia, that serum Mg concentrations increase relatively easily in lower-weight patients. In addition, this study shows that low-dose MgO may be effective as an initial treatment for constipation in this patient group in a cautious manner, but this study did not provide sufficient data for the usefulness of low-dose MgO for constipation in patients undergoing HD.

Employing consumer knowledge to protect consumer rights

The research aims to measure the level of connection and impact of consumer knowledge in protecting consumer rights, and the sample consisted of (275) consumers in five markets (large retail markets in Baghdad) as they represent the research community of consumers who go to the markets to buy products. The data and hypotheses were analyzed and tested using appropriate statistical tools, including the arithmetic mean and standard deviation to measure the level of descriptive responses of the research sample, correlation coefficients (Pearson) to test the relationships between the research variables, and the simple and multiple linear regression equation to test the effect. The results showed the validity of the research hypotheses, and concluded with a number of Conclusions and recommendations.

228 The effect of temperature-humidity index in different pregnancy stages on litter traits in Taiwan Landrace sows

Abstract Because of climate change, annual average temperatures are gradually rising. Hence, increasing heat stress can impair the litter traits of Taiwanese sows located in tropical and subtropical zones. However, some pregnancy stages may be impacted more by heat stress than other periods. Thus, the purpose of this study was to demonstrate the effect of temperature-humidity index (THI) in different pregnancy stages on total number born (TNB), number born alive (NBA), and stillborn rate (STB). Data were collected in two Taiwanese farms from 2008 to 2021 for TNB, NBA, and STB, while weather data were collected from the closest respective weather station. There were 4,247 and 6,812 pure line Landrace record from farm 1 and farm 2, respectively. Pregnancy stages included 28 d before mating (BEFORE), mating to 30 d of pregnancy (EARLY), 31 to 70 d of pregnancy (MIDDLE), and 71 d of pregnancy to farrowing (LATE). Average THI was calculated in each pregnancy stage and regression coefficients were estimated by linear mixed models within ASReml. A two-trait analysis was used to estimate regression coefficients and genetic correlations among TNB, NBA, and STB. Results showed THI impacted (P &amp;lt; 0.05) TNB and NBA BEFORE and EARLY, while THI influenced (P &amp;lt; 0.05) STB EARLY and MIDDLE. Regression coefficients for TNB were -0.0069 and -0.0228 for BEFORE and EARLY, respectively. For NBA, regression coefficients were 0.0106 and -0.0391 for BEFORE and EARLY, respectively. Regression coefficients for STB were -0.0651 and 0.1332 for EARLY and MIDDLE, respectively. Heritability estimates for TNB, NBA, and STB were 0.168, 0.113, and 0.069, respectively. Genetic correlations between TNB with NBA and STB were 0.913 and 0.539, respectively. While the genetic correlation between NBA and STB was 0.158. In conclusion, THI impacted BEFORE and EARLY stages for TNB and NBA, while the stages of EARLY and MIDDLE were impacted by THI for STB. Hence, control of the environments in these specific stages for sows could improve the performance of litter traits.

225 Genomic diversity of Katahdin sheep and impacts on genomic prediction

Abstract In the late 1950s, Katahdin hair sheep were developed as a composite breed of medium size and moderate prolificacy, with potential to express resistance to gastrointestinal nematodes. With its increasing popularity and the recent adoption of genomic prediction in the Katahdin breeding program, evaluating the genetic diversity in this breed is necessary. Prediction accuracies rely on the strength of genetic relationships. That strength often increases with selection using genomically-enhanced estimated breeding values; however, it carries the risk of decreasing diversity. We aim to characterize the genetic diversity present in the breed and the subsequent impact on the accuracies of genomic predictions. Genotypes on Katahdin sheep from member flocks in the National Sheep Improvement Program were used. Data from two medium density 50k bead chips and one high density 600k bead chip were merged and limited to shared autosomal single nucleotide polymorphisms (SNP). After quality control, there were 9,705 animals and 31,984 SNP remaining. Only for analyses of inbreeding and heterozygosity, linkage disequilibrium (LD) pruning was performed; variants with an LD score exceeding 0.8 were removed with 29,904 SNP remaining. To determine the extent of population structure, principal component (PC) analysis was conducted with PC one and PC two explaining 4.9% and 3.8% of the variation in the population, respectively. When examining subpopulations, a single ancestral population explained 99.9% of the genetic variation among animals. When clustered by identity-by-state, all animals were placed in a single cluster. Inbreeding coefficients were estimated with four methods: method of moments, variance-standardized relationship minus one, excess homozygosity, and correlation between uniting gametes. Across methods, average inbreeding coefficients ranged from 1.14% to 1.20% with Pearson and Spearman correlations ranging from -0.51 to 0.91 (Table 1). Historical effective population sizes (Ne) were estimated for earlier generations, and a linear regression fit to predict more recent Ne. At the founding of the breed, historical Ne was estimated to be 310, and the current Ne was estimated to be 150. Effects of Ne on the accuracy of genomic predictions were examined for reference population sizes ranging from 1k to 25k for traits of low (0.1), moderate (0.3), and high (0.5) heritabilities. The corresponding number of effective chromosomal segments were 2NeL, where L was the length of the genome in morgans (26M). Accuracies of genomic predictions increased as the reference population size grew, with only marginal gains once the population exceeded 15k. Overall, there were no detectable genetic subpopulations in the Katahdin breed. Current levels of inbreeding were low. With a small Ne the breed can achieve high accuracy for genomic predictions by aiming for a reference population of 15k animals. Negative impacts on genetic diversity due to genomic selection are not of immediate concern.

Over the Past Decade, Preoperative Anemia Has Become a Greater Predictor of Transfusions after Total Knee Arthroplasty.

With advancements in perioperative blood management and the use of tranexamic acid, the rate of transfusions after total knee arthroplasty (TKA) has substantially decreased. As these principles are refined, other modifiable risk factors, such as preoperative anemia, may play an increasingly important role in transfusion risk for patients undergoing TKA. A multicenter, national database was utilized to identify patients undergoing TKA from 2010 to 2021. Anemia was defined by World Health Organization (WHO) definitions as < 12 g/dL for women and < 13 g/dL for men. A predictive model was created using backwards elimination logistic regression to predict transfusion risk, controlling for demographic and medical covariates. The coefficient of anemia was then analyzed for each year. The trend over time was fitted with a best-fit linear regression equation. There were 509,117 patients who underwent TKA, and had a mean age of 67 years (range, 18 to 89). There were 57,716 (11%) patients who were anemic preoperatively, and 15,426 (3%) of patients required a transfusion. Rate of transfusion decreased from 10.6% in 2010 to 0.6% in 2021. The OR (odds ratio) associated with anemia as a predictor of transfusion increased from 3.1 (95% CI [confidence interval]: 2.1 to 4.6) in 2010 to 14.0 (95% CI: 8.9 to 24) in 2021. The results of this study demonstrate that the importance of preoperative anemia as a predictor of transfusion has increased over the past decade as rates of transfusion have decreased. As perioperative blood management protocols improve, preoperative anemia should be considered an important focus of intervention to reduce the risk of transfusion prior to TKA.

Chiefs and Pre-Election Violence in Sub-Saharan Africa: The Precolonial Legacy of Centralized States

This article examines how African chiefs shape pre-election violence (PEV) locally. I argue that chiefs with greater capability of voter coordination, which stems from precolonial centralized states, reduce local risk of PEV. Utilizing existing and original data, I find that precolonial centralized states have a negative effect on PEV in Anglophone Africa, where precolonial institutions have been better preserved. This relationship is robust to a series of tests, including two-stage least-squares regressions. The findings contribute to our knowledge of how local political actors shape violent campaign strategies and of the diverse (pre-)colonial legacies in Sub-Saharan Africa.

Postoperative recreational sports and subjective shoulder function: a comprehensive analysis following intramedullary stabilization of displaced midshaft clavicular fractures.

Introduction Sports-related outcomes and the role of recreational sports activities for shoulder function after intramedullary stabilization (IMS) of displaced midshaft clavicular fractures (DMCFs) in the general population are not well known. In this study, we aimed to determine the sport-related outcomes (return-to-sports [RTS] rate, type of sports, time until RTS, and intensity) and to explore the role of sports after IMS of DMCFs. Materials and Methods This single-center, retrospective, cohort study included patients who underwent IMS of DMCFs between 2009 and 2022 at a Level II trauma center in Germany, experienced no major complications, and had completed at least 1 year of follow-up. Propensity score matching was conducted to obtain a balanced sample of patients who did not engage (cases) and engaged (controls) in postoperative sports activities by adjusting for age and fracture complexity. Groups were compared to assess the impact of regular sports activities on subjective shoulder functioning at follow-up, as evaluated using the Disabilities of the Arm, Shoulder, and Hand and Oxford Shoulder Score (OSS) questionnaires, after controlling for the patient- (i.e., sex and smoking) and treatment- (i.e., surgery duration and physical therapy) factors. Results Among the 199 patients included, the RTS rate was 97.5%, and 160 patients practiced regular postoperative activity, mostly in the same sport and intensity. In the matched cohort (39 cases and 39 controls), practicing regular sports activities postoperatively was the only independent factor associated with a higher OSS in the multiple regression analysis (unstandardized regression coefficient = 2.40; Bias-corrected and accelerated 95% confidence interval [0.28, 4.69]). Conclusions The sport-related outcomes after IMS of DMCFs in our cohort were comparable to those achieved after plate osteosynthesis, and IMS reported in the literature. Recreational sports activities benefitted subjective shoulder function, thereby encouraging further research and potentially influencing management policies. Level of evidence Grade IV-a retrospective observational cohort study.

Development and External Validation of a Prediction Model for Patients with Varicose Veins Suitable for Isolated Ambulatory Phlebectomy.

Isolated ambulatory phlebectomy is a potential treatment option for patients with an incompetent great saphenous vein (GSV) or anterior accessory saphenous vein and one or more incompetent tributaries. Being able to determine which patients will most likely benefit from isolated phlebectomy is important. This study aimed to identify predictors for avoidance of secondary axial ablation after isolated phlebectomy and to develop and externally validate a multivariable model for predicting this outcome. For model development, data for patients included in the SAPTAP trial were used. The investigated outcome was avoidance of ablation of the saphenous trunk one year after isolated ambulatory phlebectomy. Pre-defined candidate predictors were analysed with multivariable logistic regression. Predictors were selected using Akaike information criterion backward selection. Discriminative ability was assessed by the concordance index. Bootstrapping was used to correct regression coefficients, and the c-index for overfitting. The model was externally validated using a population of 94 patients with an incompetent GSV and one or more incompetent tributaries who underwent isolated phlebectomy. For model development, 225 patients were used, of which 167 (74.2%) did not undergo additional ablation of the saphenous trunk one year after isolated phlebectomy. The final model consists of three predictors for avoidance of axial ablation: tributary length (< 15 cm vs. > 30 cm: odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02 - 0.40; 15 - 30 cm vs. > 30 cm: OR 0.18, 95% CI 0.09 - 0.38); saphenofemoral junction (SFJ) reflux (absent vs. present: OR 2.53, 95% CI 0.81 - 7.87); and diameter of the saphenous trunk (per millimetre change: OR 0.63, 95% CI 0.41 - 0.96). The discriminative ability of the model was moderate (0.72 at internal validation; 0.73 at external validation). A model was developed for predicting avoidance of secondary ablation of the saphenous trunk one year after isolated ambulatory phlebectomy, which can be helpful in daily practice to determine the suitable treatment strategy in patients with an incompetent saphenous trunk and one or more incompetent tributaries. Patients having a longer tributary, smaller diameter of the saphenous trunk, and absence of terminal valve reflux in the SFJ are more likely to benefit from isolated phlebectomy.

The effectiveness of intervention in hepatitis C patients and improvement in their referral rate

Background To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV). Methods No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate. Results A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18–59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p < .05. One-sided two-ratio test was performed for statistics of pre-intervention referral rate (p1) and post-intervention referral rate (p2). Normal approximation and Fisher’s exact test for the results obtained were 0.000, p < .05, and the alternative hypothesis p1 − p 2 < 0 was accepted. The linear regression equation was referral = 0.1396 × intervention + 0.3743, and the result model p = 8.79e − 09, p < .05. The model was significant, and the coefficient of intervention was 0.1396. Conclusions The interventions of critical value management and push SMS were correlated with the referral rate of patients with positive anti-HCV.

EFFECT OF PRODUCT MARKET MATRIX ON THE PERFORMANCE OF MEDIUM ENTERPRISES IN NORTH CENTRAL, NIGERIA

This research work examined the effect of product market matrix on the performance of medium enterprises in North Central, Nigeria. The researcher used primary data source from a sample of three hundred and eighty four (384) respondents obtained by the use of a structured questionnaire. The data collected was analyzed using descriptive statistics such as frequency, simple percentage and the relationship between the variables of the model were tested using multiple linear regression analysis. The hypotheses of the study were tested using the probability value of the regression estimates. The result of the regression analysis indicates that Market penetration strategy's regression coefficient is 0.401 and significant (p0.05).  Product development strategy is -0.059 and negligible (p0.05). A one-unit increase in product development decreases medium firm performance by 0.059 units. A one-unit increase in market development strategy increases medium firm performance by 0.196 units (p0.05). Product diversification approach has a strong coefficient of 0.319. This means a one-unit improvement in product diversification strategy increases medium firm performance by 0.319 units. It was concluded that businesses must consider the region's market conditions, competitive hurdles, and client behaviors to flourish. It was recommended among others that Market Penetration and Product Diversification Strategies are advised for medium enterprises in North Central Nigeria due to their benefits. Expanding market share and targeting existing clients can increase performance. Diversifying products to fulfill client needs can enhance revenue and performance. Firms should use both methods to optimize profits.

Abstract PO3-22-07: Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used for axillary downstaging in clinically node-positive breast cancer patients, and a considerable proportion achieves axillary pathological complete response (ax-pCR). After NACT, axillary staging can be done by targeted axillary dissection (TAD). In case of metastases at TAD, axillary lymph node dissection (ALND) is offered regardless of metastases size. This contrasts primary surgery, where small sentinel node metastases (ypN0(i) and ypN1mi) and ≤2 positive sentinel nodes do not confer ALND, although a proportion of patients with small metastases have additional metastatic lymph nodes (LNs) in the axilla. So far, the residual metastatic burden in the axilla when TAD LNs are positive after NACT is unknown. If subgroups of patients with low residual metastatic burden in the axilla (non-TAD LNs) could be identified, these subgroups may be offered de-escalated axillary treatment. Therefore, we investigated the risk of residual metastatic burden in the axilla when the TAD LNs harbored metastases. Methods: We retrospectively retrieved DBCG data on patients staged by TAD after NACT in Denmark between 1.1.2016-31.8.2021. We registered: age, breast biopsy date, type of surgery, type of axillary surgery, count of LNs, sentinel nodes, and marked lymph nodes with and without metastases, including metastasis size, breast tumor histology and receptor subtype, breast tumor size at diagnosis and in the surgical specimen, malignancy grade and type of neoadjuvant treatment. We excluded patients with inflammatory breast cancer, &amp;lt; 4/&amp;gt;8 cycles of NACT, or a non-standard NACT regimen. The primary outcome was risk factors for having high ( &amp;gt;3), low (1-3), or no residual metastatic burden in the axilla when the TAD LNs harbored metastases. We modeled risk factors for both high and low residual metastatic burden in the axilla using multivariable logistic regression and constructed risk models based on the regression coefficients. Results: We identified 1626 patients receiving NACT and TAD in the inclusion period. After excluding ineligible patients and patients who achieved ax-pCR with no subsequent ALND (46%), the study included 383 patients with positive LNs at TAD for further analysis: thereof 188, 127, and 68 with 0, 1-3 and &amp;gt;3 positive non-TAD LNs, respectively. In the adjusted logistic regression analysis, we found that breast pCR (OR= 0.06, 95% CI &amp;lt; .01-0.41, p &amp;lt; .001) and a low proportion of positive TAD LNs (0-66% vs &amp;gt;66%) (OR=0.32, 95% CI 0.17-0.58, p = &amp;lt; .001) were associated with low risk of high residual metastatic burden in the axilla. Patients with one or both low-risk factors present had an 8% (14 of 176 patients) risk of high residual metastatic burden in the axilla. The predictive value of the model for having &amp;lt; 3 non-TAD LN metastases was 92%. When analyzing the 315 patients with ≤3 positive non-TAD LNs, the adjusted logistic regression analysis of 1-3 vs 0 positive non-TAD LNs showed that ypN0(i) in the TAD LN (OR=0.14, 95% CI 0.04-0.53, p = 0.002), small tumor size at diagnosis (20-49 mm vs ≥ 50 mm) (OR = 0.29, 95% CI 0.14-0.60, p = 0.002), breast pCR (OR= 0.38, 95% CI 0.15-0.98, p = 0.04) and low proportion of positive TAD LNs (33-66% vs &amp;gt;66%) (OR= 0.46, 95% CI 0.27-0.77, p = 0.01) were associated with no residual metastases in the axilla. Using these risk factors, 19% (11/58) of the patients in the lowest risk quartile had further metastatic spread to the axilla. Conclusion: Based on an extensive breast cancer registry, we find that breast pCR, low proportion of positive TAD LNs, small metastases, and small tumor size are associated with low risk of residual metastatic LNs in the axilla when the TAD LNs are positive after NACT. With these risk factors, we propose two models to identify patients with low non-TAD residual metastatic burden and patients with a high likelihood of no further metastases. The models can guide breast surgeons in de-escalating axillary treatment in these groups. Citation Format: Frederikke Munck, Maj-Britt Jensen, Ilse Vejborg, Maria Gerlach, Maja Maraldo, Niels Kroman, Tove Tvedskov. Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-07.

Abstract PO3-13-08: D17104: Aryl Hydrocarbon Receptor Signaling and Other Biomarkers of Fat Metabolism in Human Mammary Adipose Tissue from Women with Malignant Breast Disease

Abstract Background: Obesity is a recognized risk factor for the development of metabolic disease and breast cancer possibly due to chronic inflammation mediated by cytokines secreted by adipose tissue. Given this, our group examined differential expression of several markers of chronic inflammation in adipose tissue of both benign and malignant breast tissue from patients. The aryl hydrocarbon receptor (AhR) is an important cytosolic, ligand-dependent transcription factor found within hepatocytes and adipocytes that is upregulated in many types of cancer. AhR promotes the initiation, progression, and metastasis of cancer cells allowing certain cancers to evade immune recognition (Xue et al. Front. Immunology 2018). Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that generates kynurenine (KYN) from tryptophan (TRP), which acts as an AhR agonist. We sought to determine expression of IDO1 via immunohistochemistry (IHC) in mammary adipose tissue associated with benign or malignant breast. We hypothesized that adipose tissue adjacent to malignant breast tissue may have heightened expression of IDO1 in addition to Cyp1b1, and SPP1; both of which are also markers of increased aryl-hydrocarbon transcriptional activity, compared to adipose tissue noncontiguous to malignant lesions. KYN affects gene expression for insulin resistance and levels are elevated in plasma of older obese women compared to lean women; however, the relationship to breast malignancy is not known. Methods: IDO1 (Cell Signaling, 1:200), Cyp1b1 (Thermo Fisher, 1:300), and SPP1 (Thermo Fisher, 1:200) IHC was performed according to the manufacturers' protocols. Adipose tissue immediately adjacent to, and &amp;gt;2 mm away from, tumors (three DCIS, 11 invasive carcinomas) was evaluated in 14 patients. Adipose tissue in separate tissue blocks from benign breast tissue (three ipsilateral, 11 contralateral) in the same patients was also evaluated. Human plasma KYN levels were assayed by HPLC in the Dartmouth Clinical Pharmacology Shared Resource as described previously (Rojas et al. Obesity 2021). Results: In this preliminary pilot study, there was no difference in staining pattern for IDO1 in adipose tissue present in malignant and benign samples. Two patients showed increased Cyp1b1 and SPP1 staining immediately adjacent to the invasive carcinoma (Figure 1). Patients with benign breast disease did not show increased Cyp1b1 or SPP1 staining. Results will be confirmed using qPCR for mRNA. Plasma samples from patients with benign disease showed a lower level of KYN expression on average (0.370 ug/mL, N = 8) compared to plasma from patients with malignant disease (0.424, N = 10). Additionally, the ratio of KYN:TRP was lower in the benign group (0.065) compared to the cohort with malignancy (0.080). Univariate linear regression will be used to further assess relationships between continuous variables in the study population (e.g., patient age, BMI, KYN plasma levels, benign vs malignant breast disease). Regression lines and the associated slope estimates (b-value) and p-values for regression models will be provided on scatter plots. Conclusions: While there was no difference in IDO1 staining patterns in adipose tissue of malignant and benign samples in this group, tissue samples from patients with invasive carcinoma demonstrated increased Cyp1b1 and SPP1 staining adjacent to the malignant tumor; while benign tissue samples did not show a positive stain. This suggests increased aryl-hydrocarbon transcriptional activity in invasive breast carcinoma—further linking AhR signaling with adipose tissue immune dysregulation and invasive malignancy. Additionally, KYN plasma levels were higher in patients with malignant disease indicating a possible relationship between insulin resistance and breast malignancy. Additional research may offer new insights relating to this important pathway and ultimately treatments aimed at blunting its nefarious effects. Citation Format: Adam Ephraim, Jonathan Pirruccello, Scott Palisoul, Jonathan Marotti, Mary Chamberlin. D17104: Aryl Hydrocarbon Receptor Signaling and Other Biomarkers of Fat Metabolism in Human Mammary Adipose Tissue from Women with Malignant Breast Disease [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-08.

Abstract PO1-03-03: STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival

Abstract Background: Standardized definitions of efficacy endpoints are needed to improve clinical trial designs, data reporting and interpretation of results, and to allow cross-trial comparisons. STEEP (Standardized Definitions for Efficacy Endpoints) criteria were proposed in 2007 by an expert panel from the National Cancer Institute (NCI) to provide common definitions for clinical trials in early breast cancer (BC). Invasive disease-free survival (IDFS) was selected as a candidate surrogate endpoint for overall survival (OS) in adjuvant trials and has been widely used in the last 15 years. Advances in BC systemic treatment led to review these criteria (STEEP v2.0), with the definition of a new modified endpoint: invasive BC-free survival (IBCFS). IBCFS excludes second primary non-breast invasive cancers from IDFS which may better detect efficacy effects when the toxicity profile of the intervention is well-known and the risk of second primary cancer is small. Methods: We proposed a multi-trial analysis of 8 adjuvant chemotherapy (CT) trials from GEICAM and TRIO to evaluate the different surrogate endpoints defined in the STEEP v2.0. Trial-level surrogacy was assessed through correlation between the ln hazard ratio (HR) of OS and the ln HR of the different studied endpoints across trials. The correlation was estimated by the weighted, by trial size, least squares regression (WLS) line and evaluated comparing the R2 values between OS and the corresponding endpoint tested. Primary analyses evaluated the correlation of OS with IDFS/IBCFS. Secondary analyses evaluated the correlation of OS with other STEEP v2.0 endpoints (distant disease-free survival [DDFS], distant relapse-free survival [DRFS], recurrence-free survival [RFS], recurrence-free interval [RFI] and distant recurrence-free interval [DRFI]) and explored the surrogacy between OS and all endpoints in specific groups of patients (pts) according to their risk of relapse: hormone receptors positive (HR+)/HER2-negative (HER2-) pts with intermediate/high and high-risk and triple negative (TN) pts. Results: A total of 14,473 pts were included. Median age was 50 years (range, 20–82). All were female, and 51.8% were postmenopausal. With a median follow-up of 115 months (range, 0.0–188) we found 2,504 OS events, 4,146 IDFS events (60.9% being distant recurrences) and 3,810 IBCFS events (62.4% being distant recurrences). For each trial, HR of OS, IDFS and IBCFS indicated same conclusions. If HR&amp;lt; 1 for OS, it was also for IDFS and IBCFS and the same was true when HR &amp;gt;1. R2 results of the weighted linear correlations between the ln HR of OS versus (vs) IDFS and OS vs IBCFS were 0.86 and 0.89, respectively. Confidence intervals (CI) at 95% were both overlapping. All other efficacy endpoints showed strong correlation with OS in the overall analysis. R2 values for HR+/HER2- intermediate/high and high-risk pts were 0.89 (OS vs IDFS) and 0.84 (OS vs IBCFS). For TN pts the correlations were weaker, being 0.63 (OS vs IDFS) and 0.73 (OS vs IBCFS). All WLS R2 values are described in the table. Conclusions: All tested STEEP v2.0 endpoints were strongly correlated with OS (R2 close to 1), meaning that their use as surrogate endpoints for adjuvant CT trials is appropriate. Notably, no differences were found between them in this multi-trial analysis. Therefore, none of them is more appropriate than other to discriminate the value of a new intervention vs comparator in adjuvant CT studies with mature data and long-term follow-up. Table: Citation Format: Sara López-Tarruella, Marina Pollan, Ander Urriticoechea, Eva Carrasco, Gonzalo Spera, Miguel Martín, Begoña Bermejo, Linnea Chap, Manuel Ruíz - Borrego, John Crown, Jose Angel García-Sáenz, Arlene Chan, Angel Guerrero, Valerie Bee, Lourdes Calvo, Rodrigo Fresco, Andrea Blasco, Andrés Hernando, Dennis Slamon. STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-03.

Abstract PS18-01: Stage Advancement and The Rate of Growth Associated with Preoperative Delay in Patients Having Breast Cancer

Abstract Introduction: For every delay interval between breast cancer diagnosis and surgery we have previously found a relative decline in disease-specific survival of 26% (60 d) and overall survival of 9-10% (30 d). There is, however, little explanation for this. In our experience, patients focus on the likelihood of cancer growth between diagnosis and surgery, and whether preoperative delay might lead to upstaging, with nodal status of particular concern when they are clinically node-negative. With little published data about delay-associated upstaging and no large-scale national data determining how fast tumors grow, this study was performed to determine these rates. Methods: Patients ≥18 years old having stage 0-III breast cancer who received surgery as first treatment between 2010 and 2020 were reviewed in the National Cancer Database (NCDB), the largest national dataset to contain the needed clinical and pathologic staging. Patients were reviewed for correlation between preoperative delay and cancer upstaging, defined as an increase from cT to pT or cN to pN stages, after assessing baseline clinical stage inaccuracy. Accuracy of clinical staging was determined by comparing clinical stages at presentation to pathologic stages at surgeries ≤15 days of diagnosis, assuming negligible tumor growth in that period. cN3 and cT3 tumors were excluded as there is no higher size-dependent pathologic stage. Upstaging probabilities and odds ratios (ORs) were estimated with logistic regression, adjusted for age, race, Hispanic ethnicity, gender, histology, grade, phenotype, and clinical T or N stage. For patients with delays &amp;gt;15 days, adjusted linear regression coefficients of tumor size on preoperative delay were used to estimate primary invasive tumor growth rates. Results: Among 1,040,197 patients, the median time between diagnosis and surgery was 34 days (IQR 23-49), with 11.6% having primary tumoral and 14.6% having nodal upstaging. In the 10.2% of patients where surgery was performed ≤15 days of diagnosis, 13.9% of DCIS, 11.5% of cT1, and 4.5% of cT2 tumors were upstaged (p &amp;lt; 0.0001). For every 30 days of delay between diagnosis and surgery, the ORs for tumor upstaging, adjusted for covariates, were 1.09 for DCIS (95%CI 1.07-1.10, p&amp;lt; 0.0001), 1.12 for cT1 (95%CI 1.10-1.14, p&amp;lt; 0.0001), and 1.16 for cT2 tumors (95%CI 1.14-1.19, p&amp;lt; 0.0001). For invasive tumors, the adjusted 30-d ORs for upstaging in HR+, HER2+, and TN primaries were 1.12 (95%CI 1.11-1.14), 1.11 (95%CI 1.07-1.15), and 1.19 (95%CI 1.15-1.23), respectively (individual p’s &amp;lt; 0.0001). In the 9.8% of clinically N0 (cN0) patients with a diagnosis-to-surgery interval of ≤15 days, 14.2% were upstaged to node-positive. cN0 patients had an adjusted OR for upstaging to node-positive of 1.06 (95%CI 1.05-1.07, p&amp;lt; 0.0001) for every 30 days of delay. The number of 30-d intervals for cT1mi, cT1a, cT1b, cT1c and cT2 invasive primary tumors to grow 1 mm was 7.8, 7.1, 3.9, 2.8, and 2.0, respectively. Conclusions: Even when accounting for clinical stage inaccuracy, longer delays are associated with a quantifiable increase in upstaging and likelihood of becoming node-positive at surgery. This may explain the higher disease-specific and overall mortality associated with preoperative delay found in prior studies. With larger tumors having a higher delay-associated likelihood of upstaging and faster growth rates, delays become more problematic as tumor size increases. This information reinforces the need to minimize preoperative delays by demonstrating their consequences. It also provides data to address some of breast cancer patients’ most pressing preoperative concerns about how fast breast tumors grow and their upstaging potentials while they await treatment. Citation Format: Richard Bleicher, Karen Ruth, Austin Williams, Eric Ross, Andrea Porpiglia, Allison Aggon, Mary Pronovost, Dennis Holmes. Stage Advancement and The Rate of Growth Associated with Preoperative Delay in Patients Having Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS18-01.

Quaternary branched polyethylenimine‐based nanocomposite for removal of NO3− ions from aqueous solutions

AbstractThis study synthesized a nanocomposite based on quaternary branched polyethyleneimine containing sodium alginate and graphene oxide and characterized by FE‐SEM, EDX‐MAP, XRD, FT‐IR, and TGA and used as an efficient sorbent for the removal of nitrate ions. The maximum ion exchange in optimized conditions was discovered to be 75%. The experimental studies showed that nitrate removal follows the pseudo‐first‐order model due to more consonance. Also, Weber–Morris and Boyd models suggested that the nitrate ions adsorption on the surface of nanocomposite is not controlled only by the intraparticle diffusion step. Moreover, Langmuir, Redlich–Peterson, and Hill models exhibited high regression coefficients of 0.991, 0.993, and 0.992, respectively. Thermodynamic studies confirmed the adsorption system was spontaneous and exothermic. Recovery assay showed that more than 98% of the nitrate ion exchanged by the nanocomposite was regenerated and nanocomposite could be reused seven cycles without efficacy reducing significantly. The nanocomposite showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coli cells, with minimum inhibitory concentrations of 62.5 and 125 μg mL−1, and zone of growth inhibition of 17.5 ± 0.5 and 10.5 ± 0.5 mm, respectively. The results represented that the introduced nanocomposite is a useful material for the removal of nitrate ions from aqueous solution and has antibacterial properties.

Abstract PO4-07-10: Validation of An Ultrasound-Based Scoring System of Axillary Metastasis in Breast Cancer

Abstract Introduction: Ultrasound is the imaging modality of choice in the evaluation of axillary involvement in breast cancer. Our group previously created a scoring method to predict axillary lymph node metastasis (ALNM) based on ultrasound characteristics. In this study we validated the model and tested it among different Memorial Sloan Kettering Breast Cancer Sentinel Lymph Node Metastasis Nomogram1 (MSK) subgroups. Methods: The ultrasound score (table 1) was previously developed using data collected at a single institution from 2019 – 2021 by allocating points based on the regression coefficients of variables found to significantly predict ALNM. Subsequent evaluation of the discrimination of this model found it was robust to different patient demographic and tumor characteristics based on receiver operating characteristic curve analysis2. In this study, we validated the test statistics of our score at an outside institution. We also pooled patients from both institutions and evaluated the score performance in different MSK subgroups by the likelihood for sentinel node metastasis based off of clinical and pathologic data without accounting for imaging findings. Results: Between 2019-2021, 140 patients with breast cancer were analyzed for validation of the axillary ultrasound scoring system and when combined with the dataset of patients from the index institution, 358 pooled patients were stratified by predicted ALNM positivity according to MSK. In the validation cohort, the NPV for low risk (0-1) scores was 87%, while the PPV for high-risk (5+) scores was 71%. Overall in the combined cohort, 241 (67%) patients had low risk (0-1) axillary ultrasound scores and 33 (9%) had high risk (5+) scores. In this combined cohort, NPV was 84% (203/241 low-risk score patients were node negative), while PPV for high-risk scores was 85% (28/33 high risk score patients were node positive). When analyzed according to level of MSK predicted ALNM rates, for patients with &amp;lt; 50% predicted ALNM positivity, the NPV of low-risk scores was 87-89% and the PPV for high-risk axillary scores was 100%. For patients with &amp;gt;50% predicted ALNM positivity, the NPV of low-risk scores was 66% and the PPV of high-risk scores was 82%. Conclusions: A scoring system to predict ALNM among biopsy proven breast cancer patients undergoing upfront surgery was successfully developed from a multivariate model based on axillary ultrasound characteristics. This model was validated at a separate institution. The scoring system shows advantageous negative and positive predictive values for axillary node metastasis, especially among patients with &amp;lt; 50% predicted nodal involvement based on the MSK nomogram. This data may help foster better communication about ALNM risk between radiologists and treating clinicians to inform treatment decisions. Table. Scoring System for Likelihood of ALNM based on Ultrasound Characteristics Citation Format: Spencer Van Decar, Elizabeth Carpenter, Alexandra Adams, Jason Shore, Iulian Dragusin, Erika Davis, Craig Tork, Robert Krell, Troy Graybeal, Katherine Clifton, Arianna Buckley, Guy Clifton. Validation of An Ultrasound-Based Scoring System of Axillary Metastasis in Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-10.

A shelf life prediction method for butter based on the effects of β‐carotene on colour and oxidative stability

This study aimed to examine the impact of β‐carotene, astaxanthin and phytosterol esters on the colour and oxidative stability of butter, as well as to explore a shelf life prediction method based on colour analysis. The results of correlation analysis indicated a significant linear correlation between acidity and whiteness index and yellowness index, with a linear fit coefficient (r2) exceeding 0.9796. In comparison with traditional shelf life prediction models, this method exhibited an average deviation of only 6.9% in its predicted results. The findings may contribute to the rapid evaluation of the shelf lives of commercial butter products.

Levels of melatonin and some indicators of angiogenesis, antioxidant system and lipid peroxidation in blood plasma in women with uterine leiomyoma

Uterine leiomyoma is one of the most common gynaecological diseases, which often leads to loss of fertility. It is known that in this pathology, damage to the tissues of the uterus is accompanied by oxidative stress, and the mechanisms of its compensation play a decisive role in the process of myometrial regeneration, especially when performing organ-preserving operations. The aim of the study was to determine the levels of melatonin, reproductive hormones and state of angiogenesis, antioxidant system and lipid peroxidation in women of reproductive age who were diagnosed with uterine leiomyoma. Material and methods. 60 women of reproductive age with uterine leiomyoma (study group) were examined. The control group consisted of 20 healthy women of the same age group. Melatonin levels in women's blood were determined once, on an empty stomach, at 8 a.m.; the concentrations of estradiol and progesterone in the follicular phase of the menstrual cycle were also measured. The state of the angiogenesis system was studied by examining the levels of vascular endothelial growth factor (VEGF) and the content of the final metabolites of nitric oxide NO in blood plasma. The activity of the antioxidant system was assessed by blood plasma concentrations of reduced glutathione, glutathione peroxidase, and glutathione transferase. Indicators of lipid peroxidation were investigated by the content of malondialdehyde (MDA) in blood plasma and erythrocytes. Results. It was found that in the patients of the study group with leiomyoma, there was a significantly lower level of melatonin in blood plasma (111.1 ± 18.5 ng/mL) compared to the control group (153.5 ± 8.5 ng/mL), while the concentration of estradiol was almost three times higher (107.4 ± 25.3 pg/mL) compared to the control group (36.2 ± 3.2 pg/mL), and the concentration of progesterone was 1.9 times higher (2.1 ± 0.4 ng/mL compared to 1.1 ± 0.5 ng/mL in the control group). The level of VEGF in blood plasma in women with uterine leiomyoma was also higher (90.4 ± 23.6 pg/mL) compared to the control group (35.1 ± 8.3 pg/mL), as well as the concentration of final metabolites of nitric oxide, which reached 25.3 ± 5.9 pg/mL compared to 9.9 ± 3.9 pg/mL in the control group. The reduced glutathione level in the blood plasma of women with uterine leiomyoma was significantly lower (0.77 ± 0.13 µmol/L) compared to healthy women (1.02 ± 0.14 µmol/L) in the control group, while the concentrations of glutathione-S-transferase and glutathione peroxidase enzymes were higher (161.3 ± 22.3 ng/mL and 235.7 ± 35.9 ng/mL, respectively), whereas in the control group these indicators were 118.9 ± 18.0 ng/mL and 105.3 ± 41.2 ng/mL, respectively. The MDA content in women of the study group was higher, measuring 5.2 ± 0.8 nmol/L in plasma and 10.8 ± 1.1 nmol/L in erythrocytes compared to 2.3 ± 0.8 nmol/L and 5.3 ± 0.8 nmol/L in the control group, respectively. Conclusions. The levels of melatonin and reduced glutathione in the blood plasma of women with uterine leiomyoma were significantly lower, while the concentrations of estradiol, progesterone, glutathione-S-transferase, glutathione peroxidase, VEGF, final metabolites of nitric oxide, as well as the average MDA content in plasma and erythrocytes, were significantly higher compared to healthy women. In the study group, the relationship between the level of progesterone in blood plasma and the content of malondialdehyde in erythrocytes was described using a linear regression equation, which, as we suggest, indicates an activating effect of progesterone on oxidative stress mechanisms in the myometrium. In our opinion, oxidative stress in uterine leiomyoma occurs due to inadequate activity of the antioxidant system, an integral part of which is melatonin, leading to enhanced angiogenesis against the background of estrogen-induced myometrial proliferation.

Reactivities of acrylamide warheads toward cysteine targets: a QM/ML approach to covalent inhibitor design.

Covalent inhibition offers many advantages over non-covalent inhibition, but covalent warhead reactivity must be carefully balanced to maintain potency while avoiding unwanted side effects. While warhead reactivities are commonly measured with assays, a computational model to predict warhead reactivities could be useful for several aspects of the covalent inhibitor design process. Studies have shown correlations between covalent warhead reactivities and quantum mechanic (QM) properties that describe important aspects of the covalent reaction mechanism. However, the models from these studies are often linear regression equations and can have limitations associated with their usage. Applications of machine learning (ML) models to predict covalent warhead reactivities with QM descriptors are not extensively seen in the literature. This study uses QM descriptors, calculated at different levels of theory, to train ML models to predict reactivities of covalent acrylamide warheads. The QM/ML models are compared with linear regression models built upon the same QM descriptors and with ML models trained on structure-based features like Morgan fingerprints and RDKit descriptors. Experiments show that the QM/ML models outperform the linear regression models and the structure-based ML models, and literature test sets demonstrate the power of the QM/ML models to predict reactivities of unseen acrylamide warhead scaffolds. Ultimately, these QM/ML models are effective, computationally feasible tools that can expedite the design of new covalent inhibitors.