Main Cause Research Articles

Analysis of Neshani Andreas's The Purple Violet of Oshaantu as a Presentation of the Writer's Liberal African Feminist Thought to the Inequalities of Rural Namibian Women

ABSTRACT: This study examines the plight of women's rights in a Namibian Oshiwambo traditional male-dominated society, a concept that has not been fully explored in Namibian literature. The article uses the liberal African feminist theoretical framework, whose main argument is that men and women are not different and they should be treated equally. These feminists identify the main cause of female oppression as male domination. The aim of this research is to enable the reader to understand the impact of male dominance as the source of gender inequality and injustice against rural women and to erode the belief that women are inferior to men, highlighting Namibian rural women's capability of owning property and becoming self-reliant. Hence, the study uses Neshani Andreas's work to express this concern and seeks to pave the way to challenge all forms of male domination in an attempt for women to regain their voice, identity, and rights.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Botanical Extracts and Compounds of Castanea Plants and Methods of Use: US20190125818A1 - The United States Patent Evaluation.

Bacterial infections are increasingly difficult to combat, which makes them a threat to public health on a global level. Staphylococcus aureus is considered one of the main causes of infections in hospitals, as it has a variety of virulence factors, as well as is able to produce bacterial biofilms, which, consequently, bring numerous damages to public health as a result of increased resistance to conventional antibiotics and a longer hospital stay. Therefore, the use of compounds extracted from medicinal plants is a potential pharmaceutically acceptable target, as they do not have toxicity and the potential to disrupt biofilms produced by Staphylococcus aureus already evidenced, thus revealing their relevance to our study. The objective of this work was to perform a critical analysis of a patent with natural extracts against bacterial biofilms found in the United States Patent and Trademark Office (USPTO) database, to map the possible bioactive compounds that may serve as potential future antimicrobial drugs. A technological survey was carried out to verify existing patents using natural extracts with anti-biofilm potential. For this, it was searched with the keywords: Botanical extracts AND biofilms; which were performed in the United States Patent and Trademark Office (USPTO) database. Thus, the selected patent used a non-aqueous extract partitioned and vacuum-contracted, subsequently lyophilized for assays with antimicrobial potential. Because of this, a patent was analyzed regarding its chemistry, and biological activity, followed by a critical analysis of the technology proposed in the invention. When using the keywords Botanical extracts AND biofilms in the USPTO, it was possible to find twenty-two inventions; however, only four patents in the USPTO were in agreement with the proposal of the natural extract having antimicrobial activity and an anti-biofilm potential, of which two belonged to the same applicant with similar proposals. The key point of this invention was to enable the compounds of the Castanea sativa plant and its methods of obtaining the extract to present a significant antimicrobial action associated or not with antibiotics, promoting the development of new therapies against bacterial infections capable of disrupting biofilms. The invention developed a methodology for extracting Castanea sativa, in which pentacyclic triterpene compounds were found mostly in its leaves. Whereas for the extraction, the crude methanol extracts called extracts 224 from the ground leaves were made by maceration, filtered, combined, concentrated under pressure in rotary evaporators, and lyophilized. After that, they were resuspended in water and partitioned in succession with hexane, ethyl acetate, and butanol. The most active refined partition was the 224C extract with the solvent ethyl acetate, which was subjected to further fractionation using silica column chromatography. Resulting in the most refined extract, which was 224C-F2, capable of acting directly on the quorum sensing of bacteria, mainly Staphylococcus aureus, blocking the translation of RNAIII, including a series of exotoxins. Regarding the antimicrobial capacity against Staphylococcus aureus, it presented Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of 1.56 μg/mL-1 and > 100 μg/mL -1, respectively. Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact of bacterial biofilms, which causes damage to industries in general and to health. From this, the invention analyzed has a promising proposal with antimicrobial potential focusing on the great impact of bacterial biofilms. Therefore, natural extracts with antibiofilmic potential can help to minimize the economic losses caused to health due to these multidrug-resistant microorganisms with different virulence mechanisms.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency

Abstract: Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) – if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the ‘impending HTN-E’ group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. ‘Impending HMOD’ means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Interleukin-38 and Insulin Resistance.

Insulin resistance, i.e., decreased biological response to insulin, is a risk factor for many diseases, such as obesity, type 2 diabetes (T2DM), cardiovascular disease, polycystic ovary syndrome, some forms of cancer and neurodegenerative diseases. One of its main causes is chronic low-grade inflammation, mediated by the proinflammatory pathways, such as the c-Jun N-terminal kinase (JNK) pathway and the nuclear factor kappa B (NFκB) pathway. Interleukin (IL)-38 (IL-38) is a newly discovered cytokine that belongs to the IL-1 family. There are three hypothetical pathways through which IL-38 may bind to the specific receptors and inhibit their proinflammatory activity. Those pathways are associated with IL-36 receptor (IL-36R), IL-1 receptor accessory protein-like 1 (IL1RAPL1) and IL-1 receptor 1 (IL1R1). There are studies linking IL-38 to improve insulin sensitivity through the difference in serum IL-38 in patients with insulin resistance or the correlation of IL-38 concentrations with insulin resistance indexes. However, many questions still remain regarding the biological activity of IL-38 itself and its role in the pathogenesis of insulin resistance. The goal of this study is to showcase IL-38, its biological activity, hypothesized signaling pathways, connection with insulin resistance and future perspectives of research on IL-38. We present that IL-38 associated signaling can be a potential target for the treatment of insulin resistance and associated diseases.

Cognitive and brain connectivity trajectories in critically ill COVID-19 patients.

Multiple Organ failure (MOF) is one of the main causes of admission to the Intensive Care Unit (ICU) of patients infected with COVID-19 and can cause short- and long-term neurological deficits. To compare the cognitive functioning and functional brain connectivity at 6-12 months after discharge in two groups of individuals with MOF, one due to COVID-19 and the other due to another cause (MOF-group), with a group of Healthy Controls (HC). Thirty-six participants, 12 from each group, underwent a neuropsychological and neuroimaging assessment at both time-points. Functional connectivity of the resting state networks was compared between COVID-19 and HC while controlling for the effect of MOF. The association between functional connectivity and neuropsychological performance was also investigated. Compared to the HC, COVID-19 group demonstrated hypoconnectivity between the Default Mode Network and Salience Network. This pattern was associated with worse performance on tests of attention and information processing speed, at both time-points. The study of the association between cognitive function and brain functional connectivity in COVID-19 allows the understanding of the short- and long-term neurological alterations of this disease and promotes the development of intervention programs to improve the quality of life for this understudied population.

Parkinson's Disease Is Predominantly an Environmental Disease.

Parkinson's disease is the world's fastest growing brain disorder, and exposure to environmental toxicants is the principal reason. In this paper, we consider alternative, but unsatisfactory, explanations for its rise, including improved diagnostic skills, aging populations, and genetic causes. We then detail three environmental toxicants that are likely among the main causes of Parkinson's disease- certain pesticides, the solvent trichloroethylene, and air pollution. All three environmental toxicants are ubiquitous, many affect mitochondrial functioning, and all can access humans via various routes, including inhalation and ingestion. We reach the hopeful conclusion that most of Parkinson's disease is thus preventable and that we can help to create a world where Parkinson's disease is increasingly rare.

Few-Shot Object Detection With Self-Supervising and Cooperative Classifier.

Few-shot object detection (FSOD), which detects novel objects with only a few training instances, has recently attracted more attention. Previous works focus on making the most use of label information of objects. Still, they fail to consider the structural and semantic information of the image itself and solve the misclassification between data-abundant base classes and data-scarce novel classes efficiently. In this article, we propose FSOD with Self-Supervising and Cooperative Classifier ( [Formula: see text]) approach to deal with those concerns. Specifically, we analyze the underlying performance degradation of novel classes in FSOD and discover that false-positive samples are the main reason. By looking into these false-positive samples, we further notice that misclassifying novel classes as base classes are the main cause. Thus, we introduce double RoI heads into the existing Fast-RCNN to learn more specific features for novel classes. We also consider using self-supervised learning (SSL) to learn more structural and semantic information. Finally, we propose a cooperative classifier (CC) with the base-novel regularization to maximize the interclass variance between base and novel classes. In the experiment, [Formula: see text] outperforms all the latest baselines in most cases on PASCAL VOC and COCO.

Lightweight AC Arc Fault Detection Method by Integration of Event-Based Load Classification

As the main cause of electrical fires, arc fault detection attracts lots of attention in recent years. However, with the growing complexity of electric loads, arc fault detection becomes more difficult. This paper proposes a lightweight arc fault detection method that integrates load classification into fault detection. Firstly, according to the turn-on patterns, we divide loads into resistive, inductive and switchable loads. Load classification is developed using an event-based method. Then, arc detection method is developed for each load category, which is achieved through sequential forward floating selection. Its performance is validated by the experiment data and comparison with other reported methods. Meanwhile, the selection of classifiers, sampling rate, and sampling periods for arc fault detection are also discussed in detail. The results show that the proposed method not only achieves a high fault detection performance but also keeps a relatively low sampling rate and short sampling period. Thus, it is beneficial for practical arc fault interrupter development.

Clinical application of split liver transplantation: a single center report of 203 cases

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

A cross-sectional analysis of the association between sleep disorders and cancer using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014.

Cancer is one of the main causes of death in the world, and sleep disorders are a serious public health problem, especially in large cities; of these, insomnia and obstructive sleep apnea (OSA) are the most common. In the last decade, studies have pointed to a possible association between sleep disorders and cancer. The aim of this study is to evaluate whether there is any association between sleep disorders and cancer. Five National Health and Nutrition Examination Surveys (NHANES) (2005-2014) from the United States were combined in order to obtain the sample. Two main sleep variables were assessed: having trouble sleeping and/or ever telling a doctor one had a sleep problem. The odds ratio of ever having a cancer diagnosis was the main outcome. Data were analyzed by binary logistic regression models in Jamovi. The final sample comprised 26,821 participants. Individuals who reported having trouble sleeping had an odds ratio of 1.48 (95% confidence interval = [1.336-1.646]; P < .001) of having been diagnosed with cancer, and those who had already been diagnosed with a sleep disorder had an odds ratio of 1.21 (95% confidence interval = [1.046-1.415]; P = .011), showing an increased chance of having been diagnosed with cancer. In men, these values were even greater, with an odds ratio of 1.56 (95% confidence interval = [1.321-1.843]; P < .001) and an odds ratio of 1.26 (95% confidence interval = [1.013-1.582]; P = .037), respectively, for having trouble sleeping and for having been diagnosed with a sleep disorder, in relation to having been diagnosed with cancer. Individuals who had trouble sleeping or who had been diagnosed with a sleep disorder at any time in their life were more likely to have been diagnosed with cancer. Porcacchia AS, Pires GN, Andersen ML, Tufik S. A cross-sectional analysis of the association between sleep disorders and cancer using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014. J Clin Sleep Med. 2024;20(4):515-520.

Salvia officinalis Improves Glycemia and Suppresses Pro-inflammatory Features in Obese Rats with Metabolic Syndrome

Obesity is regarded as the main cause of metabolic diseases and a core factor for all-cause mortality in the general population, notably from cardiovascular disease. The majority of people with type 2 diabetes have obesity and insulin resistance. Some evidence indicates that an individual with obesity is approximately 10 times more likely to develop type 2 diabetes than someone with moderate body weight. One of the most significant therapeutic herbs, Salvia officinalis (Lamiaceae) (SAGE), possesses potent medicinal importance. The aim of this article was to evaluate the anti-diabetic and antiobesity activity of SAGEAE against HFD-induced obesity in rats. Thirty adult albino rats were randomly divided into five equal groups: control, High-fat Diet (HFD) administrated rats, HFD + Salvia officinalis Aqueous Extract (SAGEAE) (150 mg/kg.bw.), HFD + SAGEAE (300 mg/kg.bw.) and HFD + metformin (500 mg/kg.bw.). Body weight, plasma biochemical parameters, oxidative stress, inflammatory indicators, hepatic Phosphoenolpyruvate Carboxykinase 1 (PCK1), Glucokinase (GK), brain Leptin Receptor (LepRb), Glucose Transporter-4 (GLUT4), Sirtuin 1 (SIRT1) and mRNA33-5P gene signalling mRNA levels were all assessed after 8 weeks. A histological examination of the liver was also performed to check for lipid accumulation. The administration of HFD resulted in increased body weight, glucose, insulin, leptin, Total Cholesterol (TC), Triglycerides (TG), Thiobarbaturic Acid Reactive Substances (TBARS), Monocyte Chemoattractant Protein-1 (MCP1), Interleukine-6 (IL-6) and tumor necrosis factor-α (TNF- α) as well as hepatic PCK1, brain LepRb and adipose tissue mRNA33-5P gene expression. However, our findings revealed a significant reduction in adiponectin, High-density Lipoproteincholesterol (HDL-C), reduced glutathione (GSH) and Superoxide Dismutase (SOD) levels as well as the expression of hepatic GK and adipose tissue SIRT1 and GLUT4 genes. Also, administration of SAGEAE significantly normalized body weight, glucose, insulin, leptin, adiponectin, TC, TG, HDL-C, TBARs, SOD, IL-6, MCP-1 and TNF-α in plasma and liver tissue of HFD-treated rats. On the other hand, PCK1, GK, LepRb, SIRT1, GLUT4 and mRNA33-5P gene expression was enhanced in obese rats when administrated with SAGEAE. Histological and US studies support the biochemical, PCR and electrophoretic results. The findings imply that SAGEAE could be used as a new pharmaceutical formula in the treatment of obesity.

Effects of planetary day-night temperature gradients on He 1083 nm transit spectra

A notable fraction of helium observations probing the evaporating atmospheres of short-period gas giants at 1083 nm exhibit a blueshift during transit, which might be indicative of a day-to-night side flow. In this study, we explore the gas dynamic effects of day-to-night temperature contrasts on the escaping atmosphere of a tidally locked planet. Using a combination of 3D hydrodynamic simulations and radiative transfer post-processing, we modeled the transmission spectra of the metastable helium triplet. Our key findings are as follows: (1) Increasing the day-night anisotropy leads to a narrowing of the helium line and an increase in the blueshift of the line centroid of a few km s−1. (2) The velocity shift of the line depends on the line-forming altitude, with higher planetary mass-loss rates causing the line to form at higher altitudes, resulting in a more pronounced velocity shift. (3) A critical point of day-night anisotropy comes about when the blueshift saturates, due to turbulent flows generated by outflow material falling back onto the planet’s night side. (4) A strong stellar wind and the presence of turbulent flows may induce time variations in the velocity shift. Assuming that the day-night temperature gradient is the main cause of the observed blueshifts in the He-1083 nm triplet, the correlation between the velocity shift and day-night anisotropy provides an opportunity to constrain the temperature gradient of the line-forming region.

Investigations of an increased incidence of non-Aspergillus invasive mould infections in an onco-haematology unit.

Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillusmould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillusmould infections in the onco-haematology unit of a Swiss tertiary care hospital. All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillusmould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated. A significant increase of the incidence of non-Aspergillusmould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillusmould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillusmould infections. However, novel diagnostic procedures may have improved their detection. We report a significant increase in non-Aspergillusmould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.

The Effect of Ozone Therapy Stimulation on Diabetes Wound Healing Process

&lt;p&gt;Health problems that are currently developing include diabetes mellitus (DM) with various complications including diabetic ulcers. Diabetic ulcers are the main cause of prolonged pain and even amputation in DM patients. Diabetic wounds are a complication of diabetes that often occurs in the extremities, increasing morbidity and lessens the patient's personal satisfaction. Ozone therapy is one method used to speed up the healing process for diabetic ulcers. This study plans to examine the impact of ozone treatment feeling on diabetic injury mending. The exploration strategy utilizes a semi exploratory technique with a pretest and posttest non-identical benchmark group plan. The testing strategy is a non-likelihood inspecting method.The population in this study were all patients suffering from diabetic wounds who received wound care at the Edwcare clinic in Langsa city. The respondents of this study were patients suffering from diabetic wounds who received wound care at the Edwacare wound care center in Langsa City, Indonesia consisting of 28 respondents who received modern wound care dressings and 28 respondents received wound care combined with modern dressings and ozone therapy. The research instrument for assessing wound severity used the Bates-Jensen Wound Assessment Tool. Data analysis used the Friedman and Kruskal Wallis tests. Based on the research results, it was found that there was a more significant effect between wound care using a combination of modern dressings and ozone therapy with a Mean Rank value of 39.75 compared to wound care that only received modern dressing wound care with a Mean Rank value of 17.25 with a value of p -value &amp;lt;0.05. The conclusion is that the effect of ozone stimulation significantly influences the healing process of diabetic wounds and is recommended as a nursing intervention that can be applied in treating diabetic wounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Keywords: Diabetes mellitus, diabetic wounds, ozone therapy, stimulation&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt;

Abstract 6837: Prolonged effects of hypoxia in luminal breast cancer cells

Abstract Metastasis is the main cause of tumor-related mortality in breast cancer patients. Improving our understanding of the metastatic cascade is imperative to improve patient outcomes. Prior research indicates cancer cells with increased metastatic potential have acquired adaptive properties induced by factors in the tumor microenvironment (TME), including hypoxia. However, previous hypoxia research has primarily focused on signaling changes that occur when cancer cells are in the hypoxic TME and does not account for long-term changes that may occur once cancer cells re-enter normoxia, such as when they metastasize. Our research in patient-derived circulating tumor cell (CTCs) lines and breast cancer cell lines indicates that certain transcriptional changes are maintained after cells leave hypoxia, and that these post-hypoxic cells maintain a higher metastatic potential compared to cells not exposed to hypoxia. Taking an un-biased approach to define changes in hypoxia-exposed breast cancer cells upon reoxygenation, we performed bulk RNA-Seq on post-hypoxic luminal breast cancer cell lines compared to normoxic controls cultured either in adherent or suspension conditions, the latter to mimic the physiological context of CTCs. We found that a subset of genes that were differentially expressed in hypoxic conditions were maintained as up- or down-regulated after cells were reoxygenated, indicating a “hypoxic memory”. Additionally, a subset of differentially expressed genes were unique to the post-hypoxic cells, demonstrating both prolonged and novel gene expression changes induced by hypoxia exposure. We also performed functional assays and observed that this post-hypoxic state is associated with a more aggressive phenotype. Current research in our lab is on-going to understand the epigenetic changes that may be responsible for this hypoxic memory. Overall, this research will improve our understanding of the prolonged consequences of hypoxia on CTC biology and metastasis. Citation Format: Aidan Moriarty, Oihana Iriondo, Yonatan Amzaleg, Remi Klotz, Min Yu. Prolonged effects of hypoxia in luminal breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6837.

Mechanism of scour around two piers

AbstractScour around the bridge piers is the main cause of bridge failure below any bridge pier placed within the waterways. It is more than hundred years back a number of researchers described the vortex shedding phenomenon and the resulting Aeolian tones from a circular cylinder. Since then there have been a large number of investigations dealing with various aspects of this phenomenon. In many practical works and situations, flow takes place around more than one obstruction and objects in close proximity. Invariably in all these cases, interference effects occur and the forces on the obstructions are much influenced by these effects. These effects play a key role in the structures like flow-induced vibration of TV and transmission towers, and in many other practical situations. In this research paper the changes in the flow field that occur due to the interference effects are shown, analysed and the results as given in literature are compared with the present experimental work. The features have been brought out in this paper mainly make use of stand and geometry of circular cylinders in close proximity and the flow part of geometry in side by side arrangement.

Current concepts in postpartum anemia management.

Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

Abstract 1260: Collapse of cancer cell micronuclei from oxidative damage

Abstract Chromosomal instability, a hallmark of aggressive cancers, disrupts genome integrity through multiple hits by ongoing missegregation of chromosomes. These chromosomes, inherited only by one daughter cell, are subsequently encapsulated in micronuclei (MNi). Micronucleation is detrimental for replication fidelity not only because it sustains chromosomal missegregation, but also because MNi frequently undergo irreversible collapse during interphase exposing their enclosed chromatin to the cytosol. This exposure catalyzes chromosomal rearrangements and heritable epigenetic abnormalities that have been shown to further bolster cancer evolution and therapeutic resistance. Moreover, MNi collapse is known to promote distant metastasis and poor prognosis through eliciting a non-canonical response of otherwise inflammatory signaling pathways. Despite the fundamental role played by MNi catastrophe in compromising genome integrity and sustaining cancer progression, and the subsequent therapeutic potential of targeting this process, the mechanisms underlying MNi collapse are poorly understood. Here, we identify mitochondria-derived reactive oxygen species (ROS) as the main cause of MNi rupture. Notably, we observe that MNi that locate closer to mitochondria are more prone to rupture. Accordingly, increasing ROS chemically and by H2O2 addition increment rupture in a panel of 5 different tumor cell lines, while decreasing ROS using pan-cellular or mitochondrial specific scavengers reduce the frequency of ruptured MNi. By using a combination of advanced super-resolution microscopy, proteomics, transcriptomics, in vitro biochemistry assays, and extensive mutagenesis, we reveal the exact pathway leading to MNi collapse. We demonstrate that ROS promote a noncanonical function of the membrane repair ESCRT-III complex scaffolding protein, CHMP7. ROS reduce CHMP7 interaction with ESCRT-III promoting CHMP7 oligomerization and its binding to the inner nuclear membrane protein, LEMD2. CHMP7, while aggregating, physically pulls the micronuclear envelope together with the LEMD2-associated lamina, thereby disrupting MNi integrity. Finally, we show that hypoxic conditions promote ROS-dependent CHMP7-LEMD2 interaction, inducing MNi rupture and inflammatory signaling. Thus, we observe that human tumors characterized by hypoxia have a significantly increased predominance of ruptured MNi, providing a mechanistic link between tumor hypoxia and downstream processes that drive cancer progression. Citation Format: Melody Di Bona, Yanyang Chen, Albert Agustinus, Matthew Deyell, Mercedes A. Duran, Christy Hong, James Hickling, Daniel Bronder, Sara Martin, Nadeem Riaz, Bill Diplas, Manisha Jalan, Nancy Lee, Alban Ordureau, Benjamin Izar, Ashley Laughney, Simon Powell, Stefano Santaguida, John Maciejowski, Thomas Jeitner, Samuel Bakhoum. Collapse of cancer cell micronuclei from oxidative damage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1260.

Abstract 4665: USP18 promotes anlotinib resistance in medullary thyroid carcinoma by stabilizing aurora B kinase

Abstract Targeted therapy resistance is the main cause of disease progression in advanced medullary thyroid carcinoma (MTC). However, the key molecules and mechanisms remain unclear. We previously performed a genome-wide in vitro screen of Anlotinib resistance-related genes in human MTC cell line TT using CRISPR-dCas9-SAM system and identified ubiquitin-specific protease 18 (USP18) as a key molecule mediating Anlotinib resistance in MTC. However, its downstream mechanism needs further clarification. Based on the high-throughput DNA sequencing results of the control group and the Anlotinib screening group, a group of key genes related to Anlotinib resistance in MTC was screened through the MAGeCK algorithm and the enrichment ratio of sgRNA in the Anlotinib screening group. Among them, USP18 ranked first in the enrichment results. Analysis of the correlation between the expression level of USP18 in MTC patient specimens and survival revealed that patients with high USP18 expression in tumor cells had poorer prognosis. Overexpression of USP18 in MTC tumor cells significantly promoted the growth of subcutaneous xenograft tumors in NOD/SCID mice treated with Anlotinib. In vitro cell experiments also showed that overexpression of USP18 promoted the proliferation of MTC tumor cells and significantly inhibited the proportion of cell apoptosis after Anlotinib treatment. Further research found that USP18, as a deubiquitinating enzyme that can specifically remove ISG15-like ubiquitin-like proteins from substrate proteins, can improve the kinase stability of Aurora B by removing ISG15-like ubiquitin modification and promote MTC tumor cell proliferation through the activation of PI3K-Akt signaling regulated by Aurora B kinase. Application of Aurora B kinase inhibitor in Anlotinib-resistant MTC cell lines significantly inhibited tumor cell proliferation, and Aurora B kinase inhibitor significantly increased the proportion of cell apoptosis in MTC tumor cells overexpressing USP18. In the subcutaneous xenograft tumor model of MTC in NOD/SCID mice, the growth of xenograft tumors in the Anlotinib combined with Aurora B kinase inhibitor treatment group was also significantly inhibited. In summary, overexpressed USP18 can activate PI3K-Akt signaling and promote tumor cell proliferation by increasing the stability of Aurora B kinase, ultimately leading to the formation of Anlotinib resistance in MTC patients. Combined use of Aurora B kinase inhibitor is a potentially effective combined treatment strategy for Anlotinib-resistant MTC patients. Citation Format: Xuan Qin, Xing Wan, Dapeng Li, Yimeng Liu, Xianhui Ruan, Fangkun Luan, Kejia Xu, Jia Li, Rong Xiang, Yongjun Piao, Yi Shi, Xiangqian Zheng. USP18 promotes anlotinib resistance in medullary thyroid carcinoma by stabilizing aurora B kinase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4665.