Biologic Factors Research Articles

Active ingredient identification and purification of organosilicon spray adjuvant and its uptake and translocation in rice (Oryza sativa L.).

The assessment of residue, absorption, conduction, and degradation of agricultural organosilicon surfactants in the environment is hindered by the lack of information on active ingredients and corresponding quantitative standards for organosilicon spray adjuvants. The spray adjuvant 'Jiexiaoli,' a primary organosilicon spray agent in China, was identified as hydroxy (polyethylene) propyl-heptamethyl trisiloxane (TSS-H) with 3-15 ethoxy (EO) groups. Purification of TSS-H was achieved through semi-preparative separation using high-performance liquid chromatography (HPLC), resulting in TSS-H purity exceeding 96%. An accurate residual detection method for nine oligomers (4-12 EO) of TSS-H in rice roots, stems, leaves, and culture solution samples was developed using HPLC tandem high-resolution mass spectrometry (HPLC-HRMS). Recoveries for nine oligomers of TSS-H in the four matrices ranged from 80.22% to 104.01%. Foliar application experiments demonstrated that TSS-H did not transfer from the upper to the lower parts of the rice plant. The half-lives of each oligomer (4-12 EO) in leaves were less than 3.21 days. Root application experiments revealed a root concentration factor (RCF) ranging from 0.20 to 0.56, a biological enrichment factor (BCF) ranging from 0.36 to 0.68, a transpiration factor (TSCF) ranging from 0.069 to 0.086, and a transport factor (TF) ranging from 0.08 to 0.43. These results indicated that TSS-H could be absorbed by rice roots and conducted to the above-ground parts of rice plants. This study fills the data gap in the environmental risk and food safety assessment of agricultural silicone spray adjuvants. © 2024 Society of Chemical Industry.

Cardiovascular Disease in Women Challenges and Differences in Diagnosis and Management

Cardiovascular Disease (CVD) is a leading cause of morbidity and mortality in women worldwide. Biologic and sociocultural factors account for the variation in presentation and natural history of CVD in women. Research in the last two decades focusing on CVD in women has led to an improved understanding of conventional and novel risk factors, sex specific pathophysiology of Ischemic heart disease (IHD). The salient features of IHD in women are a higher prevalence of risk factors, angina, lower burden of obstructive coronary artery disease and a poorer prognosis in comparison with men. Evaluation and management of disease with higher prevalence in women including myocardial infarction with non obstructive coronary arteries (MINOCA), stress induced cardiomyopathy (Takotsubo syndrome) and spontaneous coronary artery dissection (SCAD) are discussed.

Crop rotation as a biological factor of weed control in spring barley crop in the Sonkovsky district of the Tver region

Spring barley is widely used for fodder and food purposes. Modern farming systems involve the use of short crop rotations, which leads to a deterioration in the phytosanitary condition of the fields, so improving the structure of the fields is a priority. The potential of the crop will not be fully exploited if local resources are used irrationally. Weed components, in turn, inhibit crop growth and reduce the amount of product obtained. Successful weed control is based on a systematic approach involving agrotechnical, biological and chemical measures. The pursuit of yield without the optimization of technological processes leads to low profitability of agricultural production, so a properly selected predecessor is the key to profit for agricultural producers. The aim of the study is to regulate barley weeds in the Tver region using biological methods. Crop rotation is the cheapest method without material costs. Predecessors have a different effect on the species and quantitative composition of weeds. The maximum clogging in the sum of weed vegetation, including biological groups, was found for the oat predecessor (62 pcs/m2 of juvenile weeds and 53 pcs/m2 of perennial weeds). The best predecessor for spring barley in the experiment is corn for silage, after which the number of Erysimum cheiranthoides decreased to 3 pcs/m2, which caused an increase in the yield of the studied crop from 4.5 to 7.4 t/ha.

Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta

Mesenchymal stem cells (MSCs) have tremendous potential in cell therapy and regenerative medicine. The placenta-derived MSCs (PMSCs) are becoming favorable sources as they are ethically preferable and rich in MSCs. Although several subgroups of PMSCs have been identified from human term placenta, optimal sources for specific clinical applications remain to be elucidated. This study aimed to isolate MSCs from various components of the placenta, and compare their biological characteristics, including morphology, proliferation, immunophenotype, differentiation potential, growth factor and cytokine secretion, and immunomodulatory properties. Finally, four distinct groups of PMSCs were isolated from the placenta: amniotic membrane-derived MSCs (AM-MSCs), chorionic membrane-derived MSCs (CM-MSCs), chorionic plate-derived MSCs (CP-MSCs), and chorionic villi-derived MSCs (CV-MSCs). The results showed that CV-MSCs had good proliferation ability, and were easier to induce osteogenic and chondrogenic differentiation; CP-MSCs exhibited the strongest inhibitory effect on the proliferation of activated T cells, secreted high levels of EGF and IL-6, and could well differentiate into osteoblasts, adipocytes, and chondroblasts; AM-MSCs showed good growth dynamics in the early generations, were able to grow at high density, and tended to induce differentiation into osteogenic and neural lineages. These findings may provide novel evidence for the selection of seed cells in clinical application.

Salicylic acid and jasmonic acid-mediated different fate of nickel phytoremediation in two populations of Alyssum inflatum Nyár.

This study investigates Ni phytoremediation and accumulation potential in the presence of salicylic acid (SA) (0, 50 and 200 μM) and jasmonic acid (JA) (0, 5 and 10 μM) in two populations of Alyssum inflatum under various nickel (Ni) doses (0, 100 and 400 μM). By measuring Ni levels in the shoots and roots, values of bioaccumulation coefficient (BAC), biological concentration factor (BCF) and translocation factor (TF) were calculated to quantify Ni accumulation and translocation between plant organs. Additionally, the amounts of histidine (His), citric acid (CA) and malic acid (MA) were explored. The results showed that plant dry weight (DW) [in shoot (29.8%, 8.74%) and in root (21.6%, 24.4%)] and chlorophyll [a (17.1%, 32.5%), b (10.1%, 30.9%)] declined in M and NM populations respectively, when exposed to Ni (400 μM). Conversely, the levels of MA [in shoot (37.0%, 32.0%) and in root (25.5%, 21.2%)], CA [in shoot (17.0%, 10.0%) and in root (47.9%, 37.2%)] and His [in shoot (by 1.59- and 1.34-fold) and in root (by 1.24- and 1.18-fold)] increased. Also, in the presence 400 μM Ni, the highest accumulation of Ni was observed in shoots of M (1392 μg/g DW) and NM (1382 μg/g DW). However, the application of SA and JA (especially in Ni 400 μM + SA 200 μM + JA 5 and 10 μM treatments) mitigated the harmful impact of Ni on physiological parameters. Also, a decreasing trend was observed in the contents of MA, CA, and His. The reduction of these compounds as important chelators of Ni caused a decrease in root-to-shoot Ni transfer and reducing accumulation in the shoots of both populations. The values of phytoremediation indices in both populations exposed to Ni (400 μM) were above one. In presence of the SA and JA, these indices showed a decreasing trend, although the values remained above one (BAC, BCF and TF > 1). Overall, the results indicated that SA and JA can reduce phytoremediation potential of the two populations through different mechanisms.

Effects of Platelet-Rich Plasma and Concentrated Growth Factor on Viability of Ultra-Diced Cartilage Grafts in a Rabbit Model

Although rhinoplastic surgery has progressed considerably in recent years, nasal dorsal irregularities still cause postoperative distress for both surgeons and patients. The aim of this study was to measure the association between two biologic graft adjuncts, platelet-rich plasma (PRP) and concentrated growth factor (CGF), and ultra-diced cartilage viability in an animal model. This study was designed as a randomized in-vivo study using a rabbit model. Fourteen rabbits were utilized in this investigation. The ultra-diced cartilage was obtained from auricular cartilage. The graft biologic adjunct is the predictor variable. There were three treatment groups: graft mixed with PRP or CGF or untreated (control). The grafts were placed in three separate pockets opened on the same rabbit. Grafts were harvested 3months after insertion for analysis. The primary outcome variable was histopathological and regenerative scores obtained from multiple histopathological parameters indicating the viability of the cartilage. Histopathological score parameters were chondrocyte loss, inflammation, fibrosis, cartilage fragmentation, and calcified area formations in the lacunae. Regenerative score parameters were peripheral cell proliferation in the cartilage tissue, vascularization in the connective tissue, proteoglycan increase in the matrix, and the amount of connective tissue. The variables were age, sex, and weight. Statistical analysis employed the analysis of variance test, with a significance level of P<.05. The sample was composed of 14 rabbits and 42 samples. The histopathologic scores were 11.93 (±2.49), 8.78 (±2.19), and 6.85 (±1.46) for the control, PRP, and CGF groups, respectively. A statistically significant difference was found in the PRP (P<.0275) and CGF (P<.0001) groups compared to the control group. The regenerative scores were 6.21 (±0.97), 8.85 (±1.70), and 12.07 (±1.26) for the control, PRP and CGF groups, respectively. A statistically significant difference was found in the PRP (P<.0159) and CGF (P<.0001) groups compared to the control group. This is the first study investigating the ultra-diced cartilage graft in an experimental animal model. Histopathological examination has shown that mixing ultra-diced cartilage with CGF or PRP increases viability by reducing the histopathological score and increasing the regenerative score.

Using inductive machine learning to identify risk factors for healthcare workers to get infected with highly contagious viruses (based on COVID-19 model)

Epidemic and pandemic spread of highly contagious viruses (SARS-CoV, influenza A virus, Ebola virus, MERS-CoV, and SARS-CoV-2) has been a trend observed in the first two decades of the 21st century. The predominant impact made by the biological occupational factor on healthcare workers determines their high occupational risk of infection, a severe disease course and a fatal outcome. Epidemiological data mining based on machine learning algorithms is successfully used in epidemiological practice to identify factors (predictors) contributing to infection in various risk populations. In this study, the database generated from a survey of 1312 healthcare workers was analyzed intelligently. A total of 6912 machine learning models were implemented. SARS-CoV-2 infection was found to be facilitated by providing medical care to a COVID-19 patient, using a full set of PPE after direct contact with a COVID-19 patient, direct contact with items in the external (hospital) environment, vaccination against COVID-19 after direct contact with a COVID-19 patient, acting as nursing staff (cleaners) and being present during aerosol-generating procedures. The study identified four groups of predictors determining SARS-CoV-2 infection in healthcare workers: contact with a COVID-19 patient and environmental items, PPE quality and complexity, occupational affiliation of healthcare workers and their BMI values. One predictor was found in 56.2 % of healthcare workers; two, in 19.2 %; three, in 16.4 %; four, in 5.5 %; and five predictors, in 2.7 %. Thus, epidemiological data mining is a modern stage in epidemiological analysis. The use of machine learning methods allows for multifactorial assessment of SARS-CoV-2 infection risks in healthcare workers and enables identifying and reliably estimating the most significant predictors. Intelligent data analysis has flexible architecture, which allows adjusting the model under study and supplementing new data to the existing database, detecting changes in an epidemiological situation and accomplishing relevant preventive and anti-epidemic activities.

Использование индуктивного типа машинного обучения для выявления факторов риска инфицирования медицинских работников высоко-контагиозными вирусами (на модели COVID-19)

Epidemic and pandemic spread of highly contagious viruses (SARS-CoV, influenza A virus, Ebola virus, MERS-CoV, and SARS-CoV-2) has been a trend observed in the first two decades of the 21st century. The predominant impact made by the biological occupational factor on healthcare workers determines their high occupational risk of infection, a severe disease course and a fatal outcome. Epidemiological data mining based on machine learning algorithms is successfully used in epidemiological practice to identify factors (predictors) contributing to infection in various risk populations. In this study, the database generated from a survey of 1312 healthcare workers was analyzed intelligently. A total of 6912 machine learning models were implemented. SARS-CoV-2 infection was found to be facilitated by providing medical care to a COVID-19 patient, using a full set of PPE after direct contact with a COVID-19 patient, direct contact with items in the external (hospital) environment, vaccination against COVID-19 after direct contact with a COVID-19 patient, acting as nursing staff (cleaners) and being present during aerosol-generating procedures. The study identified four groups of predictors determining SARS-CoV-2 infection in healthcare workers: contact with a COVID-19 patient and environmental items, PPE quality and complexity, occupational affiliation of healthcare workers and their BMI values. One predictor was found in 56.2 % of healthcare workers; two, in 19.2 %; three, in 16.4 %; four, in 5.5 %; and five predictors, in 2.7 %. Thus, epidemiological data mining is a modern stage in epidemiological analysis. The use of machine learning methods allows for multifactorial assessment of SARS-CoV-2 infection risks in healthcare workers and enables identifying and reliably estimating the most significant predictors. Intelligent data analysis has flexible architecture, which allows adjusting the model under study and supplementing new data to the existing database, detecting changes in an epidemiological situation and accomplishing relevant preventive and anti-epidemic activities.

The Correlation of Education, Employment, Parental Income and Social Emotional Development with the Nutritional Status of Preschool Children Living in Flood Areas

Nutrition is a biological factor that influences children's growth and development. In 2022, the World Health Organization stated that around 148.1 million children under five years old have a height that is not appropriate for their age or stunting, 45 million children are too thin compared to their height or wasting, and 37 million children are too heavy for their height or overweight..This study aims to determine the nutritional status of preschool children in flood areas and looking at the correlation of education, employment, parental income and children's social emotional development with the nutritional status of preschool children. The sample in this study was 114 preschool children aged 3 - 6 years who lived in flood areas. Sampling technique with cluster sampling. There are 9.6% of children who are very underweight, 29.8% are underweight, 15.8% are at risk of being overweight according to weight per age. According to height per age, there are 22% of children who are malnourished and 0.9% obese. According to BMI, there are 22.8% malnutrition and 18.4% malnutrition. There were 13.2% of children in the short category and 4.4% of very short children. There is a social emotional relationship between children and nutritional status according to BMIA. However, stunting and undernutrition or underweight are important findings in this study. These findings relevant for nursing to design and implement treatment or prevention interventions in overcoming nutritional problems in children. Future studies require surveys with larger samples and with more varied characteristics.

Water Quality River Estuary of Batang Hari, Musi Banyuasin District, the Province of South Sumatera

This study aims to determine the water quality of the estuary of the Batangharileko River based on factors of physics, chemistry and biology. The results showed that the water quality of the estuary of the Batangharileko River by physical factors already meets the criteria of raw water for class I, II , III and IV. While chemical parameters already meet the criteria class III water quality standards. Water Appropriation Category I is for the raw water of drinking water, class II for facilities/infrastructure recreation and freshwater fish breeding, class III for fishery cultivation and watering the plants, the Group IV for watering plants. Biological parameters in this case is the abundance, diversity index and dominance index, Batangharileko River estuary has undergone minor contamination although physiologically not appear on macrozoobenthos life

Kartogenin Induces Chondrogenesis in Cartilage Progenitor Cells and Attenuates Cell Hypertrophy in Marrow-Derived Stromal Cells.

Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to use in patients. This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration. Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs. KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human marrow-derived stromal cells (BM-MSCs); however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment. In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

CircCUL3 drives malignant progression of cervical cancer by activating autophagy through sponge miR-223-3p upregulation of ATG7

Circular RNA (circRNA) has emerged as a pivotal regulatory factor in cancer biology, yet its exact role in cervical cancer remains incompletely understood. In this study, we investigated the functional role of circCUL3 in cervical cancer and explored its potential as a therapeutic target. Functional gain and loss experiments were conducted in Hela and Siha cell lines to elucidate the biological functions of circCUL3 in cervical cancer. The results revealed that circCUL3 overexpression significantly enhanced cell viability, migration, and invasion while suppressing apoptosis, while circCUL3 knockout displayed the opposite effects. Mechanistically, we identified hsa-miR-223-3p as a target of circCUL3, with its expression being negatively regulated by circCUL3. Furthermore, we discovered that circCUL3 could sequester miR-223-3p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in cervical cancer cells. In vivo validation using a xenograft mouse model further supported our in vitro findings. Notably, we found that chloroquine (CQ), an autophagy inhibitor, restored miR-223-3p expression and counteracted the oncogenic effect of circCUL3 overexpression. In conclusion, circCUL3 potentially contributes to the malignant progression of cervical cancer by acting as a sponge for miR-223-3p, resulting in the upregulation of ATG7 and the activation of autophagy.

Expression profiling of cochlear genes uncovers sex-based cellular function in mouse cochleae

Sex is a pivotal biological factor that significantly impacts tissue homeostasis and disease susceptibility. In the auditory system, sex differences have been observed in cochlear physiology and responses to pathological conditions. However, the underlying molecular mechanisms responsible for these differences remain elusive. The current research explores the differences in gene expression profiles in the cochlea between male and female mice, aiming to understand the functional implication of sex-biased gene expression in each sex. Using RNA-sequencing analysis on cochlear tissues obtained from male and female mice, we identified a significant number of genes exhibiting sex-biased expression differences. While some of these differentially expressed genes are located on sex chromosomes, most are found on autosomal chromosomes. Further bioinformatic analysis revealed that these genes are involved in several key cellular functions. In males, these genes are notably linked to oxidative phosphorylation and RNA synthesis and processing, suggesting their involvement in mitochondrial energy production and regulatory control of gene expression. In contrast, sex-biased genes are associated with mechano-transduction and synaptic transmission within female cochleae. Collectively, our study provides valuable insights into the molecular differences between the sexes and emphasizes the need for future research to uncover their functional implications and relevance to auditory health and disease development.

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is a multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed to estimate the connection between relative leucocyte telomere lengths (rLTL) - biomarker of cellular ageing with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both sexes. The results suggested that rLTL are significantly shorter in obese, compared with lean group (P < 0·01). Negative correlation of rLTL with total oxidant status (TOS) (Spearman's ρ = -0·365, P < 0·001) as well as with C-reactive protein (Spearman's ρ = -0·363, P < 0·001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35 % of total variability; antioxidant factor with 30 % of total variability and lipid antioxidant - biological ageing factor with 12 % of the total variability. The most important predictor of BMI > 30 kg/m2 according to logistic regression analysis was PCA-derived antioxidant factor's score (OR: 1·66, 95th Cl 1·05-2·6, P = 0·029). PCA analysis confirmed that oxidative stress importance in biological ageing is caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homoeostasis deepness, even before any overt disease occurrence.

Investigation of heavy metals uptake in root-shoot of native plant species adjoining wastewater channels.

Metal pollution in water, soil, and vegetation is an emerging environmental issue. Therefore, this study investigated the abundance of heavy metals (HMs) within roots and shoots of native plant species i.e., Bromus pectinatus, Cynodon dactylon, Poa annua, Euphorbia heliscopa, Anagallis arvensis, and Stellaria media grown in the adjoining area of municipal wastewater channels of a Pakistani city of Abbottabad. HMs concentrations (mg L-1) in municipal wastewater were: chromium (Cr) (0.55) > nickel (Ni) (0.09) > lead (Pb) (0.07) > cadmium (Cd) (0.03). Accumulation of HMs in both roots and shoots of plant species varied as B. pectinatus > C. dactylon > P. annua > E. heliscopa > A. arvensis > S. media. Irrespective of the plant species, roots exhibited higher concentrations of HMs than shoots. Higher amount of Cr (131.70 mg kg-1) was detected in the roots of B. pectinatus and the lowest amount (81 mg kg-1) in A. arvensis, Highest Cd concentration was found in the shoot of B. pectinatus and the lowest in the E. heliscopa. The highest concentration of Ni was found in the roots of S. media (37.40 mg kg-1) and the shoot of C. dactylon (15.70 mg kg-1) whereas the lowest Ni concentration was achieved in the roots of A. arvensis (12.10 mg kg-1) and the shoot of E. heliscopa (5.90 mg kg-1). The concentration of HMs in individual plant species was less than 1000 mg kg-1. Considering the higher values (> 1) of biological concentration factor (BCF), biological accumulation co-efficient (BAC), and translocation factor (TF), B. pectinatus and S. media species showed greater potential for HMs accumulation than other species. Therefore, these plants might be helpful for the remediation of HM-contaminated soil.

Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Association between blood urea nitrogen levels and diabetic retinopathy in diabetic adults in the United States (NHANES 2005-2018).

To investigate the association between blood urea nitrogen (BUN) levels and diabetic retinopathy (DR) in adults with diabetes mellitus (DM). Seven cycles of cross-sectional population information acquired from NHANES(national health and nutrition examination surveys) 2005-2018 were collected, from which a sample of diabetic adults was screened and separated into two groups based on whether or not they had DR, followed by weighted multivariate regression analysis. This study collected a complete set of demographic, biological, and sociological risk factor indicators for DR. Demographic risk factors comprised age, gender, and ethnicity, while biological risk factors included blood count, blood pressure, BMI, waist circumference, and glycated hemoglobin. Sociological risk factors included education level, deprivation index, smoking status, and alcohol consumption. The multiple regression model revealed a significant connection between BUN levels and DR [odds ratio =1.04, 95% confidence interval (1.03-1.05), p-value <0.0001],accounting for numerous variables. After equating BUN levels into four groups, multiple regression modeling showed the highest quartile (BUN>20 mg/dl) was 2.22 times more likely to develop DR than the lowest quartile [odds ratio =2.22, 95% confidence interval (1.69-2.93), p- value <0.0001]. Subgroup analyses revealed that gender, race, diabetes subtype, and duration of diabetes had a regulating effect on the relationship between BUN and DR. BUN levels were related with an increased prevalence of DR, particularly in individuals with BUN >20 mg/dl. These findings highlight the significance of BUN level in assessing the risk of DR.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown. In this study, we utilized human dermal lymphatic endothelial cells (HDLECs) and an inducible, lymphatic endothelial cell (LEC)-specific Zmiz1 knockout mouse model to investigate the role of Zmiz1 in LECs. Transcriptional profiling of ZMIZ1-deficient HDLECs revealed downregulation of genes crucial for lymphatic vessel development. Additionally, our findings demonstrated that loss of Zmiz1 results in reduced expression of proliferation and migration genes in HDLECs and reduced proliferation and migration in vitro. We also presented evidence that Zmiz1 regulates Prox1 expression in vitro and in vivo by modulating chromatin accessibility at Prox1 regulatory regions. Furthermore, we observed that loss of Zmiz1 in mesenteric lymphatic vessels significantly reduced valve density. Collectively, our results highlight a novel role of Zmiz1 in LECs and as a transcriptional regulator of Prox1, shedding light on a previously unknown regulatory factor in lymphatic vascular biology.

Abstract PO3-04-04: Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy

Abstract Introduction A small proportion of women with human epidermal growth receptor 2 (HER2) positive metastatic breast cancer (mBC) achieve “no evidence of disease” (NED) status with HER2 monoclonal antibody therapy. Patients who achieve NED status have excellent long term outcomes with overall (OS) and progression free survival (PFS) rates greater than 95%. Presently there are no reliable biologic or clinical factors which are predictive of NED. It is also unclear in NED patients when it would be safe to discontinue therapy. Therefore, even in HER2+ mBC NED patients, HER2 therapy is often continued indefinitely. In this study, we characterize clinical outcomes in HER2+ mBC patients who achieved NED status and received HER2 antibody therapy for 5+ years. Methods We conducted a retrospective analysis of patients at a U.S. academic medical center. Patients with HER2+ mBC who had received at least 5 years of either trastuzumab or trastuzumab/pertuzumab (from 2014- 2023) were identified for our NED cohort. For a non-NED comparator group, we identified women with stage IV HER2+ mBC from the tumor registry (from 2012-2021). Descriptive statistics were used to describe the demographic information and clinical characteristics. Kaplan-Meier method with log-rank test was used to analyze OS and PFS between both patient cohorts. Results 102 patients were identified that received trastuzumab or trastuzumab/pertuzumab for 5+ years. From this group, 33 patients were identified as NED based on clinical documentation and imaging. From our tumor registry data, there were 58 stage IV HER2+ patients. 34 patients met inclusion criteria for our non-NED cohort. The median follow-up time was 132 (range: 39 - 296) months for the NED cohort and 26 (range: 1-99) months for the non-NED cohort. The average diagnosis age was significantly older for the NED cohort (61 vs. 52 years, P=0.001). No other significant differences with respect to hormone receptor expression, race, or the presence of brain metastases were observed between groups. With respect to HER2 therapy, 61% of NED patients had received trastuzumab alone, and 39% trastuzumab/pertuzumab. By contrast in the non-NED cohort most received trastuzumab/pertuzumab (59%). The median time on HER2 therapy for the NED group was 125 months—70% of patients in the NED cohort were still receiving therapy vs, 12% for the non-NED cohort. As expected, the median OS (NR vs. 25.5 months; P&amp;lt; 0.0001) and PFS (NR vs. 7.9 months; P&amp;lt; 0.0001) were significantly longer in the NED cohort. 5 and 10 year OS rates for the NED cohort were 90.5% (95% confidence interval (CI): 80.8-100%) and 87% (95% CI: 75.9-99.8%), respectively. By contrast, for the non-NED cohort 5 and 10 year OS rates were only 21.3% (95% CI: 11.06-41.1%) and 0% (95% CI: 0-0%), respectively. 5 and 10 year PFS rates were 84.1% (95% CI: 72.2-97.9%) and 76.6% (95% CI: 67.7-93.6%), respectively for the NED cohort, and both were 0% for the non-NED cohort. The presence of brain metastases in the NED cohort was associated with reduced 5 and 10 year OS rates: 60% (95% CI: 29.3-100%) and 40% (95% CI: 13.7-100%), respectively. We observed in the NED cohort was associated with a drop in ejection fraction and clinically significant heart failure in 24% of patients while on HER2 therapy. Conclusions HER2+ mBC patients who achieve NED status have an excellent prognosis with starkly different clinical outcomes compared to HER2+ mBC patients who do not. We observed that 10 year OS rates in HER2+ NED patients was approximately 90%, which did not differ from 5 year OS rates. This suggests that HER2 therapy could be potentially discontinued after 5 years in mBC patients who achieve NED. More studies are needed to develop robust predictive markers for patients likely to achieve NED with HER2 targeted therapy. Citation Format: Alexis Bennett, Zhengyi Chen, James Martin, Naji Mallat, Pingfu Fu, Alberto Montero. Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy [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 PO3-04-04.

Abstract PO4-09-07: Overall Survival According to Race and Socioeconomic Status Among Women Treated for BreastCancer at Ascension Health Hospitals in Metropolitan Detroit

Abstract Background: Despite increasing public awareness and education regarding racial inequality, African American (AA) patients continue to carry higher likelihood of death from breast cancer due to both cancer phenotype and remediable factors of access to care and socioeconomic status. Patients and Methods: We identified 3,241 patients treated for breast cancer between 2006 and 2015 at Ascension St John Hospital (Detroit MI), Ascension Macomb Oakland Hospital (Warren MI) and Ascension Providence Hospital (Southfield MI). Of these, 2530 (78.1%) were categorized as White (W), 658 (20.3%) as African American (AA), and 53 (1.6%) as Other. We considered known risk factors of race and zip code as well as marital status and having any Medicaid insurance (7.4%). 58.55% of patients were married, 15.88% never married, 13.9% widowed, and 11.6% divorced or separated. There were 632 (19.5%) cases represented from the 50 most affluent zip codes in Michigan (median income $83,125 to $140,372), 400 (12.3%) from the 50 least affluent zip codes (median income $14,909 to $33,500), 2199 (67.8%) from the intermediate zip codes, and 10 (0.31%) unknown or out of state. Tumors subtypes were 62% Luminal A (HR+/HER2-), 9.5% Basal (HR-/HER2-), 3.74% Her2 Enriched (HR-/HER2+), and 8% Triple Positive (HR+/HER2+). There were 279 Stage T0 Receptor positive DCIS and 64 Receptor Negative DCIS. 57.3% had lumpectomy or partial mastectomy as the first course of surgery, 27.9% had some form of mastectomy and 14.7 percent mastectomy with reconstruction. SAS for Windows 9.4, Cary, NC and Tableau 2023.1 was used for descriptive and crude analysis. Results: As expected overall survival was highly statistically associated (p&amp;lt; 0.0001) with the variables: age, race, subtype, node positivity and AJCC pathologic stage. Socioeconomic risk factors including zip code (p&amp;lt; 0.0001), marital status (p=0.0006), and carrying Medicaid insurance (p&amp;lt; 0.0001) statistically influenced overall survival. When considering the 50 most affluent zip codes, just 3.79% were African American (AA), with a greater proportion diagnosed at Stage I (49.85%) as compared to the 50 least affluent zip codes (81.97% AA; 37.74% Stage I, p= 0.022). Conclusions: As expected, breast cancer survival was influenced by race, tumor, and patient characteristics. This analysis allows for evaluation of the relative influence of biologic factors (e.g.tumor subtype and cancer stage) and socioeconomic indicators including zip code (stratified by median income) and insurance status. Citation Format: Shaveena Sivapalan, Khalid Berdi, Ali Shamsa, Maria Vlachaki, Aye Thet, Jeffrey Falk, Carrie Dul, Paul Chuba. Overall Survival According to Race and Socioeconomic Status Among Women Treated for BreastCancer at Ascension Health Hospitals in Metropolitan Detroit [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 PO4-09-07.