HR Group Research Articles

DISP-19. ETHNIC DISPARITIES IN METASTASIS PATTERNS AND TREATMENT UTILIZATION AMONG METASTATIC BREAST CANCER PATIENTS WITH BRAIN METASTASIS: A RETROSPECTIVE ANALYSIS OF US HEALTH SYSTEMS DATA (2019-2023)

Abstract INTRODUCTION The treatment landscape for metastatic breast cancer (MBC) with brain metastasis (BM) has evolved due to novel therapies. However, outcomes remain poor and vary among groups. This study investigated ethnic disparities in metastasis (mets) patterns and treatment use among MBCBM patients (pts). METHODS We analyzed deidentified data from seven US health systems in the Guardian Research Network from December 2019 to December 2023. Pts with MBC were categorized by IHC scores: hormone receptor+/HER2-, HER2-low (IHC 1+ or 2+ with negative FISH), HER2 positive, and Triple Negative (TNBC). We used descriptive and comparative statistical analysis. RESULTS Of 421 MBC pts, 200 (47.5%) had HER2+, 167 (39.7%) had HR+/HER2-, and 54 (12.8%) had TNBC. 159 (37.7%) were reclassified as HER2-low, primarily from HR+/HER2- (127; 76.0%) and TNBC (32; 59.3%). Bone mets developed in 29.6% of pts, more prevalent in HER2+ (39.5%), TNBC (25.9%), and HR+/HER2- (19.1%) groups. Non-Hispanics showed higher BM prevalence (74.4% vs. 25.6%). HR+/HER2- BM pts had higher bone mets (71.88%) than HER2+ BM (65.82%). TNBC BM pts had the highest rate of liver mets (57.1%). HER2-low BM pts showed mets across liver (40%), lung (34.29%), and bone (68.57%). In the HER2+ BM group, non-Hispanics had higher liver (40.13% vs. 32.35%) and bone mets (69.08% vs. 52.94%) than Hispanics. In TNBC BM group, Hispanics had higher liver mets (66.67% vs. 35%), while non-Hispanics had higher lung mets (32.5% vs. 11.11%). Both ethnic groups in HR+/HER2- category had high bone mets (78.95% vs. 73.33%). There were disparities in the use of CDK4/6 inhibitors, ICIs, and mTOR inhibitors, with Hispanics frequently using them. CONCLUSION HR+/HER2- BM pts were most affected by bone mets, followed by HER2+ BM. TNBC BM pts predominantly had liver mets. Non-Hispanics had higher BM prevalence. Hispanics frequently used ICIs, CDK4/6 and mTOR inhibitors, which were more frequently used by Hispanics. Further research should explore these disparities in mets patterns, treatment choices, and responses.

Effects of high α-linolenic acid transgenic rapeseed oil diet on growth performance, fat deposition, flesh quality, antioxidant capacity, and immunity of juvenile largemouth bass (Micropterus salmoides).

Omega-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) increases in aquatic products contributes to improving meat quality, thereby positively impacting human health. Different from marine fish which primarily obtain n-3 LC-PUFAs directly from zooplankton and algae, freshwater fish mainly utilize dietary linolenic acid (ALA) as a substrate to synthesize n-3 LC-PUFAs. Our team has successfully created a transgenic rapeseed oil (TRO) with high ALA content. Therefore, we here assessed the impacts of four different diets (LR, low-fat rapeseed oil (RO) diet; HR, high-fat RO diet; LTR, low-fat TRO diet; HTR, high-fat TRO diet) on growth performance, lipid accumulation, fatty acid composition, antioxidant capacity, immunity and serum biochemical indexes of juvenile largemouth bass (Micropterus salmoides), an economically valuable freshwater fish. The results showed no significant difference in survival rate among the four dietary groups. No significant differences in body weight gain and final weight were found between the LR and LTR groups, as well as between HR and HTR groups. No matter if it was a high-fat or low-fat diet, compared with the RO diet, TRO diets significantly increased the content of n-3 LC-PUFA, improved meat quality, effectively alleviated lipid accumulation in livers and muscles of juvenile largemouth bass. In addition, using high-fat diets, TRO diet improved the antioxidant capacity and immune ability of juvenile largemouth bass, thereby promoting the overall health of fish. This study provides novel insights for fish feed formulation optimization from the perspective of genetically modified feed ingredients, and high-quality aquatic products for human consumption.

Abstract A045: Pan-viral serological characterization in African Americans and European Americans with Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is often diagnosed at late-stages, particularly among African Americans (AA). Poor screening and diagnosis are key factors that contribute to worse prognoses and disproportionately high mortality rates. We propose investigating viral exposure history as a potential useful screening method. Additionally, by accounting for neighborhood deprivation index (NDI), a metric for differences in socio-economic statuses, we can potentially mitigate this disparity. With NDI and viral exposure history, our study aims to assess HCC prognoses in racially disparate populations. We used a technique called VirScan, which conjugates Phage-Immunoprecipitation (PhIP) and DNA-sequencing, to profile the antibody repertoire against a viral epitope library. Analyzing serum and plasma samples from population controls (PC), individuals at high-risk for developing HCC (HR), and HCC cases, we performed VirScan on 524 AA (272 PC, 205 HR, and 47 HCC) and 342 European Americans (EA) (141 PC, 130 HR, and 71 HCC) participants from the NCI-UMD cohort between 2009-2020 from the greater Baltimore area (NCT00913757; clinicaltrials.gov). We used XGBoost, a machine- learning model, to classify viral features that can discriminate HCC cases from PC group. XGBoost predicted 31 important viral features which distinguish HCC from PC. Of the 31 viral features, 6 viruses were different between AA and EA (FDR < 0.05). To determine the extent to which socio-economic factors contribute to the cancer disparities, we gathered variables from the 1999 census tract as contributors to deprivation. We used Principal Component Analysis (PCA) to determine loadings of these contributor variables; composite of the final variables is derived as NDI. Comparing across groups, we find that average NDI is highest in HR group (x = 0.33), followed by HCC group (x = 0.21), then PC group (x = 0.19). We find that NDI for AA is significantly higher in HCC group (p = 1.3e-09), HR group (p < 2.2e-16), and PC group (p = 5.0e-10) when compared to that of EA. Thus, we demonstrate that both the viral exposure history and NDI of an individual might be useful in prognoses of HCC. This approach could be used to examine the disparities we see in both incidence and mortality of HCC between AA and EA. Citation Format: Theressa Ewa, Whitney Leet, Limin Wang, Marshonna Forgues, Xin Wei Wang. Pan-viral serological characterization in African Americans and European Americans with Hepatocellular Carcinoma [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A045.

21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer.

To assess the predictive value of the 21-gene recurrence score (RS) on the survival outcomes of postoperative radiotherapy (PORT) in elderly patients with T1N0 luminal breast cancer after breast-conserving surgery. We retrospectively included patients aged ≥ 70years and diagnosed with T1N0 luminal BC between 2004 and 2015 using the data from the Surveillance, Epidemiology, and End Results. The RS groups were categorized using the TAILORx criteria as follows: low risk (RS < 11) (LR), intermediate risk (RS 11-25) (IR), and high risk (RS > 25) (HR). Kaplan-Meier analysis, propensity score matching (PSM), and Cox proportional hazards analysis were used for statistical analysis. We included 5901 patients in the analysis. Of the patients, 4492 (76.1%) underwent PORT, while 1409 (23.9%) did not receive PORT. There were 1588 (26.9%), 3613 (61.2%), and 700 (12.0%) patients classified as LR, IR, and HR, respectively. There were 1182 (74.4%), 2773 (76.8%), and 537 (76.7%) patients in the LR, IR, and HR groups receiving PORT, respectively (P = 0.182). A total of 1353 pairs of patients were completely matched using PSM. PORT was independently associated with better overall survival (OS) (P < 0.001) and breast cancer-specific survival (BCSS) (P = 0.015) in the entire cohort. The sensitivity analyses showed that the receipt of PORT was not associated with OS (P = 0.887) and BCSS (P = 0.861) in the LR group. However, the receipt of PORT was associated with OS (P < 0.001) and BCSS in the IRHR group (P = 0.026). Our study highlights the possible role of the 21-gene RS in predicting the survival outcomes of PORT following BCS in elderly patients with T1N0 luminal breast cancer.

Application of Machine Learning Algorithms for Risk Stratification and Efficacy Evaluation in Cervical Cancer Screening Among the ASCUS/LSIL Population: Evidence from the Korean HPV Cohort Study.

We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL). Between 2010 and 2021, we monitored 1,237 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types a) 16 and 18; b) 31, 33, and 45; and c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates. Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p<0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p<0.001), followed by Hr1-b (9.26, p<0.001) and Hr1-c (7.21, p<0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination. In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Potential Probiotic Properties and Complete Genome Analysis of Limosilactobacillus reuteri LRA7 from Dogs.

This study aimed to isolate and screen canine-derived probiotics with excellent probiotic properties. Strain characterization was conducted using a combination of in vitro and in vivo probiotic characterization and safety assessments, as well as complete genome analysis. The results showed that Limosilactobacillus reuteri LRA7 exhibited excellent bacteriostatic and antioxidant activities. The survival rate at pH 2.5 was 79.98%, and the viable counts after exposure to gastrointestinal fluid and 0.5% bile salts were 7.77 log CFU/mL and 5.29 log CFU/mL, respectively. The bacterium also exhibited high hydrophobicity, self-coagulation, and high temperature tolerance, was negative for hemolysis, and was sensitive to clindamycin. In vivo studies in mice showed that the serum superoxide dismutase activity level was 53.69 U/mL higher in the MR group of mice compared to that of the control group, the malondialdehyde content was 0.53 nmol/mL lower in the HR group, and the highest jejunal V/C value was 4.11 ± 1.05 in the HR group (p < 0.05). The L. reuteri LRA7 gene is 2.021 megabases in size, contains one chromosome and one plasmid, and is annotated with 1978 functional genes. In conclusion, L. reuteri LRA7 has good probiotic potential and is safe. It can be used as an ideal probiotic candidate strain of canine origin.

Prognostic risk model under the immune-associated long chain non-coding ribonucleic acid and its application in survival prognosis assessment of patients with breast cancer

This study aimed to develop a prognostic risk model based on immune-related long non-coding RNAs (lncRNAs). By analyzing the expression profiles of specific long non-coding RNAs, the objective was to construct a predictive model to accurately assess the survival prognosis of breast cancer (BC) patients. This effort seeks to provide personalized treatment strategies for patients and improve clinical outcomes. Based on the median risk value, 300 samples of triple-negative BC (TNBC) patients were rolled into a high-risk group (HR group, n = 140) and a low-risk group (LR group, n = 160). Multivariate Cox (MVC) analysis was performed by combining the patient risk score and clinical information to evaluate the prognostic value of the prognostic risk (PR) model. A total of 371 immune-related lncRNAs associated with the prognosis of TNBC were obtained from 300 TNBC samples. Nine associated with prognosis were obtained by univariate Cox (UVC) analysis, and 3 (AC090181.2, LINC01235, and LINC01943) were selected by MVC analysis for the construction of TNBC PR model. Survival analysis showed a great difference in TNBC patients in different groups (P < 0.001). The receiver operator characteristic (ROC) curve showed the model possessed a good area under ROC curve (AUC), which was 0.928. The patient RS jointing with clinical information as well as the MVC analysis revealed that RS was an independent risk factor (IRF) for prognosis of TNBC (P < 0.05, HR = 1.033286). Therefore, the lncRNAs associated with TNBC immunity can be screened by bioinformatics analysis, and the established PR model of TNBC could better predict the prognosis of patients with TNBC, exhibiting a high application value in clinic.

Comparing the Hemodynamic Effects of Intravenous and Volatile Anesthesia in Patients with End Stage Renal Disease Undergoing Laparoscopic Implantation of Peritoneal Dialysis Catheter in a Randomized Double-Blind Clinical Trial

Background: Due to the associated hypertension and cardiovascular disease in patients with ESRD hemodynamic changes during operations are detrimental and may be life-threatening. Therefore, hemodynamic stability is an important criterion in selecting the anesthetic approach. Methods: 72 ASA class III/IV, ESRD Patients were studied in randomized double blind clinical trial. They were divided into two groups by four-block randomization. A group of patients were induced and maintained by etomidate and second of patients were induced by Na thiopental and maintained by isoflurane. Systolic, diastolic and mean arterial blood pressure and heart rate were measured at interval of pre and post induction, postintubation, pre and post abdominal insufflation during and at the end of surgery and in recovery. The total BP modulators were recorded and postoperative nausea and vomiting was registered in the recovery. Data were analyzed by STATA version 12. Results: There was no significant difference in physical characteristics between two groups. There was no statistical difference between the groups in SBP and HR (P&gt;0.05), although DBP fluctuation&gt;20% at interval postinduction and prior to abdominal insufflation during surgery and at the end of surgery, was significantly higher in the isoflurane group of patients. (P=0.004, 0.001, 0.003 and 0.009, respectively). Also, the MAP fluctuation at interval of post induction, preinsufflation and at the end of surgery was significantly higher in isoflurane of patients. (P=0.04, 0.001, and 0.02, respectively). Conclusion: The group anesthetized with isoflurane had a higher hemodynamic fluctuation, compared to the group anesthetized with etomidate. As hemodynamic changes are critical in patients with ESRD, etomidate is a more appropriate anesthetic choice for implantation of peritoneal dialysis catheter by laparoscopic approach.

Elucidation of the Role of L-Arginine and Nω-Nitro-L-Arginine in the Treatment of Rats with Different Levels of Hypoxic Tolerance and Exposure to Lead Nitrate

Background/Aims: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. Methods: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. Results: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. Conclusion: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.

Comparison of Post-Operative Analgesia of Caudal versus Dorsal Penile Nerve Blocks for Pediatric Patients Undergoing Hypospadias Repair

Abstract Background Hypospadias is the second most common congenital disorder in males after cryptorchidism, but it is the most common penile congenital malformation. It is an abnormality of anterior urethral and penile development in which the urethral opening is ectopically located on the ventral aspect of the penis proximal to the tip of the glans penis, which, in this condition, is splayed open. The urethral opening may be located as far down as in the scrotum or perineum. The penis is more likely to have associated ventral shortening and curvature, called chordee, with more proximal urethral defects. Aim of the Work The aim of this study is to compare the effectiveness of penile block versus caudal block using bupivacaine on the quality of analgesia after hypospadias repair in pediatrics. Methodology This prospective randomized comparative clinical study was conducted in Ain Shams University Hospitals; Pediatric Surgery Unit. It included 30 male patient aged (1–8) years, ASA I or II patients undergoing hypospadias (distal penile and mid penile) repair. They were divided into two groups: Group P: Penile block (n = 15) received dorsal penile nerve block by using the subpubic approach technique. Group C: Caudal block (n = 15) received caudal epidural block using a 22-G needle in the lateral decubitus position. Results There was statistically high significant difference between the two groups in postoperative MAP and HR (p value &amp;lt;0.001) but no statistically significant difference between them in Spo2. FLACC pain scores were significantly lower in group C compared with group P at PACU and 3 hours postoperative (p value &amp;lt;0.001) but no statistically significant difference between them at 6, 9 and 12 hours postoperative. Also, The time for first rescue analgesia was significantly longer in caudal group compared with penile group (P &amp;lt; 0.001) and the total analgesia consumption was also significantly lower (P &amp;lt; 0.001) in group C compared with group P. Postoperative time of ambulation was significantly lower (P &amp;lt; 0.001) in group P compared with group C. Conclusion The current study revealed that Caudal block provided significantly prolonged postoperative analgesia, reduced the postoperative analgesic requirements and prolonged time of ambulation as compared with Penile block in pediatric patients undergoing hypospadias repair.

Potential association between suicide risk, aggression, impulsivity, and the somatosensory system.

Aggression and impulsivity are linked to suicidal behaviors, but their relationship to the suicidal crisis remains unclear. This magnetoencephalography (MEG) study investigated the link between aggression, impulsivity, and resting-state MEG power and connectivity. Four risk groups were enrolled: high-risk (HR; n = 14), who had a recent suicidal crisis; lower-risk (LR; n = 41), who had a history of suicide attempts but no suicide attempt or ideation in the past year; clinical control (CC; n = 38), who had anxiety/mood disorders but no suicidal history; and minimal risk (MR; n = 28), who had no psychiatric/suicidal history. No difference in resting-state MEG power was observed between the groups. Individuals in the HR group with high self-reported aggression and impulsivity scores had reduced MEG power in regions responsible for sensory/emotion regulation vs. those in the HR group with low scores. The HR group also showed downregulated bidirectional glutamatergic feedback between the precuneus (PRE) and insula (INS) compared to the LR, CC, and MR groups. High self-reported impulsivity was linked to reduced PRE to INS feedback, whereas high risk-taking impulsivity was linked to upregulated INS to postcentral gyrus (PCG) and PCG to INS feedback. These preliminary findings suggest that glutamatergic-mediated sensory and emotion-regulation processes may function as potential suicide risk markers.

Combined analysis of the effects of hypoxia and oxidative stress on DNA methylation and the transcriptome in HTR-8/SVneo trophoblast cells.

The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.

Metagenomic insights into the relationship between intestinal flora and residual feed intake of meat ducks

In this study, we sought to determine the effects of intestinal flora on the feed efficiency of meat ducks by evaluating the correlation between intestinal flora and residual feed intake. The F2 generation of Cherry Valley ducks × Runzhou Crested White ducks was used as the study subjects, and feed consumption being recorded from d 21 to 42. RFI was calculated based on growth performance, and 20 low RFI and 20 high RFI ducks were randomly selected to characterize the effect of RFI on growth performance. To analyze the intestinal flora affecting RFI, 16s rDNA sequencing was performed on the contents of 5 intestinal segments from the HR and LR groups, and macrogenomic sequencing was performed on the cecal contents. Feed intake, average daily feed intake, feed conversion ratio, and residual feed intake were lower in low RFI. Analysis of the intestinal flora revealed the cecum to be more highly enriched in the carbohydrate metabolism pathway and less enriched with potentially pathogenic taxa than the other assessed intestinal regions. Further analysis of the cecal microbiota identified nine significantly differentially enriched intestinal flora. In this study, we accordingly identified a basis for the mechanisms underlying the effects of the intestinal flora on meat duck feed efficiency.

Risk prediction of advanced colorectal neoplasia among diabetic patients: A derivation and validation study.

Colorectal cancer (CRC) is the third most common cancer in the world. This study devises and validates a clinical scoring system for risk prediction of advanced colorectal neoplasia (ACN) to guide colonoscopy evaluation among diabetic patients. We identified 55 964 diabetic patients who received colonoscopies from a large database in a Chinese population (2008-2018). We recruited a derivation cohort based on random sampling. The risk factors of CRC evaluated by univariate analysis were examined for ACN, defined as advanced adenoma, CRC, or any combination thereof using binary logistic regression analysis. We used the adjusted odds ratios (aORs) for independent risk factors to devise a risk score, ranging from 0 to 6: 0-4 "average risk" (AR) and 5-6 "high risk" (HR). The other subjects acted as an independent validation cohort. The prevalence of ACN in both the derivation and validation cohorts was 2.0%. Using the scoring system constructed, 78.5% and 21.5% of patients in the validation cohort were classified as AR and HR, respectively. The prevalence of ACN in the AR and HR groups was 1.5% and 4.1%, respectively. Individuals in the HR group had a 2.78-fold increased prevalence of ACN than the AR group. The concordance (c-) statistics was 0.70, implying a good discriminatory capability of the risk score to stratify high-risk individuals who should consider colonoscopy. The clinical risk scoring system based on age, gender, smoking, presence of hypertension, and use of aspirin is useful for ACN risk prediction among diabetic patients.

The Protective Role of Resilience on Cardiovascular Health in Young Adults Exposed to Adverse Childhood Experiences

Background: Adverse childhood experiences (ACEs) are strong emotional or physical stressors that occur during sensitive developmental periods and are associated with reduced cardiovascular health (CVH). Resilience, or the psychological capacity of individuals to cope with adversity, has been recently shown to have a positive influence on CVH. Despite the dose-dependent detrimental impact of ACEs on CVH, it is unknown whether resilience exerts a protective cardiovascular effect against early stress. Thus, the purpose of this study was to investigate the impact that resilience may have on CVH in young adults who experienced ACEs. Methods: Eighteen young and apparently healthy adults (22±3 yo) with a history of severe ACE exposure (≥4) participated in this study and provided self-reported data about resilience. CVH was assessed non-invasively through transcutaneous arterial tonometry to evaluate arterial stiffness (pulse-wave velocity, PWV), myocardial oxygen demand (Systolic Pressure Time Index, SPTI), myocardial oxygen supply (Diastolic Pressure Time Index, DPTI) and myocardial perfusion (Subendocardial Viability Ratio, SEVR). Circulating biomarkers related to CVH were also evaluated (high-sensitive C-reactive protein, hsCRP). Results: Eleven participants reported high resilience (HR: resilience score≥95), while seven reported low resilience (LR: resilience score&lt;95). Young adults with high resilience presented with a significantly lower myocardial oxygen demand (SPTI; HR: 1866±111 vs. LR: 2227±117mmHg·s/min, p=0.047) and higher myocardial perfusion (SEVR; HR: 168±13 vs.LR: 127 ±9% , p=0.034) than those with low resilience and a positive association between SEVR and resilience was identified ( r=0.492; p=0.045). No differences in myocardial oxygen supply ( p=0.225) or arterial stiffness ( p=0.614) were observed between groups. However, circulating hsCRP was also significantly lower in the HR group than the LR (0.89±0.3 vs. 2.96±1 mg/dL, p=0.041) and negatively associated with resilience ( r=-0.511; p=0.051). Conclusions: Our data suggests that, among young and apparently healthy adults exposed to childhood adversity, those who are psychologically more resilient exhibit higher myocardial perfusion and overall better CVH than those less resilient despite a history of severe ACEs. These findings suggest that resilience may protect, at least partially, against the early impact of ACEs on CVH. Future studies are thus warranted to further explore the relationship between resilience and CVH. Supported in part by the Child Health Research Institute at VCU. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats.

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.

First ray mobility in hallux rigidus, hallux valgus, and normal feet based on weightbearing computed tomography and three-dimensional analysis: A case-control study.

BackgroundHallux valgus and hallux rigidus are disorders affecting the first ray and are associated with hypermobility of this structure. This study aimed to investigate the three-dimensional mobility of each joint of the first ray between feet with hallux valgus or hallux rigidus and healthy feet using weightbearing and nonweightbearing computed tomography (CT). MethodsThis case-control study analyzed 17 feet of 11 healthy volunteers (control group), 16 feet of 16 patients with hallux valgus (HV group), and 16 feet of 11 patients with hallux rigidus (HR group). First, nonweightbearing foot CT imaging was performed in the supine position on a loading device with no load applied, with the legs extended and the ankle in the neutral position. Next, a load equivalent to body weight was applied for weightbearing CT imaging. Distal bone displacement relative to the proximal bone was quantified three-dimensionally under both conditions. ResultsIn the HV group, the talonavicular joint showed significantly greater eversion (P=.011) compared with the control group and significantly greater dorsiflexion (P=.027) and eversion (P<.01) compared with the HR group. In the medial cuneiform joint, the HV group showed significantly greater eversion (P<.01) and abduction (P=.011) than the control group. For the first tarsometatarsal joint, the HV group showed significantly greater dorsiflexion (P=.014), inversion (P=.028), and adduction (P<.01) than the control group, and greater inversion (P<.01) and adduction (P<.01) than the HR group. Dorsiflexion of the first tarsometatarsal joint was significantly greater in the HR group compared with the control group (P=.026). ConclusionHypermobility of the first ray appears to be three-dimensional: in hallux valgus, it is centered at the first tarsometatarsal joint, while in hallux rigidus it is mainly in the sagittal plane at the first tarsometatarsal joint only. This difference may explain the different deformities ultimately observed in each condition.

Evaluation of FOXP3 and IL10 as immunosuppressant markers in pediatric acute lymphocytic leukemia patients in Iraq

Background. Increased FOXP3+ Treg levels in the TME were positively correlated with a worse prognosis in certain cancer patients. FOXP3 was significantly overexpressed in pediatric B-ALL patients, and this overexpression was associated with a worse prognosis and increased risk of disease relapse. It is unknown if children that have the condition would have different prenatal immune development. This study investigates the relationship between IL10, and immunological development in pediatric ALL. Methods. The 70 blood samples from children between the ages of 2 and 14 for both sexes were obtained from patients with Acute lymphoblastic leukemia. Furthermore, this study comprised 54 healthy controls. Included in this study, FOXP3 expression on leukemic blast cells were assessed using flow cytometry. And IL10 were assessed using ELISA test. Results. Increase of FOXP3 cells was noticed in children with ALL compared to healthy individuals with significant increase of FOXP3 (mean ± SD, 91.156 ± 12.255 vs. 14.88 ± 7.897pg/ml (p &lt;0.05). In light of these findings, significant differences in the levels of FOXP3, which was higher in induction than consolidation stage of chemotherapy (mean ± SD, 91.24± 11.078vs. 86.35±5. 16.66) pg/ml (p &lt;0.05). Additionally, it was found that the prevalence of lymphoblast that express FOXP3 was notably higher in the HR group in contrast to the SR group (mean ± SD, 95.52± 5.79 vs. 42.88± 31.38) pg/ml (p &lt;0.05). Following these findings, significant differences in the levels of FOXP3 was higher in relapse than new diagnosis chemotherapy stage (mean ± SD, 95.66± 5.167 vs. 91.035±5. 13.177) pg/ml (p&lt;0.05). On the other hand, children with ALL were also found to have significantly higher levels of IL10 in the current study when compared to healthy controls (mean ± SD, 0.146 ± 0.145 vs. 0.076 ± 0.10 pg/ml (P &lt;0.05). Following these findings, significant differences in the levels of IL10 was higher in consolidation than induction chemotherapy stage (mean ± SD, 0.165± 0.084 vs.0 .0720±.018) pg/ml (p &lt;0.05), the serum levels of IL-10 were evaluated in the two groups: new diagnosis and relapse cases. As in the description profile, serum levels are higher in the relapse group with a highly significant difference. For the parameter IL10 (P ≤0.05). As for he mean level, it was as follows: of IL10 (0.130) pg/ml and (0.216) pg/ml, with (P-value =0.0001) in new diagnosis and relapse receptivity. Conclusions. According to our findings, B-ALL patients have significant amounts of both FOXP3 and IL10. This pilot study provides a novel way to look into the process mediating the appearance of these markers in a greater number of B-ALL patients at various stages of their treatment.

Resting heart rate associations with violence exposure and posttraumatic stress symptoms: sex differences in children

BackgroundTraumatic events experienced in childhood can lead to increased risk of cardiovascular disorders in adulthood. Black Americans are disproportionately affected, as they are at increased risk for experiencing childhood trauma and cardiovascular diseases in adulthood. One of the hypothesized mechanisms of this association is through long-lasting dysregulation of the autonomic nervous system, a hallmark physiological biomarker of posttraumatic stress disorder (PTSD), which is twice as prevalent in women compared to men.MethodsNinety-one, majority Black American children, aged 9 were recruited to be a part of our longitudinal study of child development at research centers in Atlanta, GA and Detroit, MI. Resting HR was measured through a electrocardiogram (ECG) recording using the Biopac MP150. Self-report measures of violence exposure and PTSD symptoms were administered by research staff.ResultsChildren with more violence exposure reported increased PTSS as well as lower resting HR. Regression analysis showed evidence of sex modifying this relationship, (B = -0.64, p < 0.05), such that the association between resting HR and PTSS was stronger in girls than in boys. In our exploratory analysis with standard clinical cutoffs of resting HR, the normative HR group was found to significantly moderate the relationship between violence exposure and PTSS in boys, (B = -2.14, p < 0.01), but not girls (B = -0.94, p = 0.27).ConclusionIn our sample of primarily Black urban children, we found that violence exposure was associated with slower, more adult-like HR, that girls showed greater PTSS associated with slower HR while boys did not, and that girls with lower than normative HR showed significantly higher PTSS compared to girls with normative HR. Our sample’s demonstration of psychological consequences in addition to the physiological implications could provide new information about a psychobiological sequelae of violence exposure.

A new model using deep learning to predict recurrence after surgical resection of lung adenocarcinoma

This study aimed to develop a deep learning (DL) model for predicting the recurrence risk of lung adenocarcinoma (LUAD) based on its histopathological features. Clinicopathological data and whole slide images from 164 LUAD cases were collected and used to train DL models with an ImageNet pre-trained efficientnet-b2 architecture, densenet201, and resnet152. The models were trained to classify each image patch into high-risk or low-risk groups, and the case-level result was determined by multiple instance learning with final FC layer’s features from a model from all patches. Analysis of the clinicopathological and genetic characteristics of the model-based risk group was performed. For predicting recurrence, the model had an area under the curve score of 0.763 with 0.750, 0.633 and 0.680 of sensitivity, specificity, and accuracy in the test set, respectively. High-risk cases for recurrence predicted by the model (HR group) were significantly associated with shorter recurrence-free survival and a higher stage (both, p < 0.001). The HR group was associated with specific histopathological features such as poorly differentiated components, complex glandular pattern components, tumor spread through air spaces, and a higher grade. In the HR group, pleural invasion, necrosis, and lymphatic invasion were more frequent, and the size of the invasion was larger (all, p < 0.001). Several genetic mutations, including TP53 (p = 0.007) mutations, were more frequently found in the HR group. The results of stages I-II were similar to those of the general cohort. DL-based model can predict the recurrence risk of LUAD and identify the presence of the TP53 gene mutation by analyzing histopathologic features.