Minimal Risk Research Articles

Anti-Spike monoclonal antibody monotherapies and immune escape risk minimization strategies.

Anti-Spike monoclonal antibody monotherapies and immune escape risk minimization strategies.

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection.

Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1year. One of them was transiently HBsAg-positive at the age of 7years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.

Combined treatment of postmenopausal patients with pelvic organ prolapse and genitourinary syndrome

Background. Colpoptosis combined with stress urinary incontinence is one of the most common conditions in postmenopausal women. Menopause is also associated with the risk of genitourinary syndrome due to estrogen deficiency. Despite the variety of options for surgical correction of genital prolapse and urinary incontinence, there is no universal technique. The use of vaginal approach in pelvic floor surgery is associated with several controversies regarding the rates of recurrence and mesh-associated complications. Studies of the state of the endothelium in menopause have demonstrated a close relationship between age-related features and the frequency of adverse clinical outcomes, which requires an optimal intervention not only on the hormonal status but also on the microcirculatory system. Aim. To improve the principles of complex treatment of pelvic organ prolapse and genitourinary syndrome in postmenopausal patients. Materials and methods. The study included 48 postmenopausal patients with genital prolapse of stage II and above according to the POP-Q classification. All patients received continuous menopausal hormone therapy (MHT) with a combined estrogen-progestogen agent. The patients in group 1 (n=24) received MHT according to clinical guidelines for managing patients with genitourinary syndrome. The patients in group 2 (n=24), in addition to MHT, received sulodexide containing glucurono-2-amino-2-deoxyglucoglucan sulfate before the intended surgical treatment and for 30 days after surgery. Correction of colpocystocele, proctocele and stress urinary incontinence was performed using anterior and posterior colporrhaphy, perineoplasty, and urethral sling placement in case of stress urinary incontinence. Results. Six months after surgical treatment, signs of genital prolapse recurrence were detected in 3 patients (12.5%) in group 1, and 1 patient (4.2%) showed signs of mesh-associated complications (implant extrusion) after urethral sling placement. In group 2, only 4.2% of patients (n=1) showed signs of recurrence of stage II cystocele. All patients who underwent urethral sling surgery reported improved urinary incontinence (n=10). During complex therapy, 3 months after surgery, a more significant improvement of endothelial dysfunction markers was noted in group 2 patients (homocysteine level in group 1 after treatment was 12.27±0.34, in group 2 – 8.34±0.24). Conclusions. Combination therapy of genitourinary syndrome and genital prolapse using MHT, endotheliotropic drugs and vaginal surgical approach in postmenopausal patients contributes to effective and safe treatment associated with minimal risk of complications and recurrence rate. Endothelial dysfunction correction is an essential step in planning surgical intervention in menopausal patients, which contributes to improving tissue repair in the postoperative period.

Impact of radioactive emissions from the Laguna Verde nuclear power plant using CALPUFF

Monitoring and regulating radioactive emissions from nuclear power plants is important for evaluating and managing the associated radiological risks to humans and the environment. Radioactive emissions can occur during different stages of nuclear power generation, posing concerns about exposure to ionizing radiation. Modeling, particularly using advanced simulation techniques, is a crucial tool for assessing both routine and accidental emissions. This work assesses the potential environmental and radiological impacts of radioactive emissions from the Laguna Verde nuclear power plant (Veracruz, México) using the CALPUFF model for dispersion and the ERICA tool for ecological risk assessment. Normal operations simulations showed that the higher concentrations and ground depositions were observed in Veracruz. The probability of exceeding screening doses was acceptably low (<5%), indicating minimal cancer risk from controlled releases. During nuclear accidents, dispersed plumes were observed with varying directions depending on wind speed. The study identified potential risks to five designated cities as receptor sites, with some plume sweeps diverting pollutants. The most affected receptor site (Veracruz) recorded the highest air concentrations, depositions, and radiation doses. These findings offer valuable insights for regulators, decision-makers, and the public, emphasizing low impacts from controlled releases but highlighting potential risks during nuclear accidents.

Evaluating the efficacy of vermicomposted products in rain-fed wetland rice and predicting potential hazards from metal-contaminated tannery sludge using novel machine learning tactic

The study assessed the ecotoxicity and bioavailability of potential metals (PMs) from tannery waste sludge, alongside addressing the environmental concerns of overuse of chemical fertilizers, by comparing the impacts of organic vermicomposted tannery waste, chemical fertilizers, and sole application of tannery waste on soil and rice (Oryza sativa L.) plants. The results revealed that T3, which received high-quality vermicomposted tannery waste as an amendment, exhibited superior enzymatic characteristics compared to tannery sludge amended (TWS) treatments (T8, T9). After harvesting, vermicomposted tannery waste treatment (T3) showed a more significant decrease in PMs bioavailability. Accumulation of PMs in rice was minimal across all treatments except T8 and T9, where toxic tannery waste was present, resulting in a high-risk classification (class 5 < 0.01) according to the SAMOE risk assessment. Results from Fuzzy-TOPSIS, ANN, and Sobol sensitivity analyses (SSA) further indicated that elevated concentrations of PMs (Ni, Pb, Cr, Cu) adversely impacted soil-plant health synergy, with T3 showing a minimal risk in comparison to T8 and T9. According to SSA, microbial biomass carbon and acid phosphatase activity were the most sensitive factors affected by PMs concentrations in TWS. The results from the ANN assay revealed that the primary contributing factor of toxicity on the TWS was the exchangeable fraction of Cr. Correlation statistics underscored the significant detrimental effect of PMs' bioavailability on microbial and enzymatic parameters. Overall, the findings suggest that vermicomposting of tannery sludge waste shows potential as a viable organic amendment option in the near future.

Estimation of potential health risks on metals and metalloids contaminants in black goby (Gobius niger) consumption in selected niger delta coast, nigeria

IntroductionThe Niger Delta in Nigeria is subject to anthropogenic influences, impacting the quality of its water bodies, including the Sombrero River. This study aims to investigate the concentrations of metals and metalloids in Gobius niger from the Sombrero River, as these contaminants can pose risks to human health through seafood consumption. Specifically, zinc (Zn), iron (Fe), copper (Cu), lead (Pb), arsenic (As), and cadmium (Cd) were analyzed using atomic absorption spectroscopy (AAS). Materials and MethodsSamples were collected from three different stations along the Sombrero River. The concentrations of Zn, Fe, Cu, Pb, As, and Cd were determined using AAS. Hazard Quotients (HQ), Chronic Daily Intake (CDI), Hazard Index (HI), and Individual Lifetime Cancer Risk (ILCR) values were calculated to assess the potential health risks associated with consuming fish contaminated with these metals and metalloids. ResultsStation 1 had the highest Zn concentration, followed by Fe, Cu, Pb, Cd, and As, with Zn reaching 104.8 ± 1.37 mg kg−1. Station 2 exhibited a similar trend, while Station 3 had Zn as the predominant metal and metalloid. Notably, Pb, As, and Cd levels were consistently low at all stations. While Pb was within permissible limits set by FAO/WHO for contaminants in the fish samples, Zn exceeded regulatory guidelines, suggesting a potential source of contamination. Hazard Quotients (HQ) highlighted a significant risk associated with zinc, especially for children. Chronic Daily Intake values showed metals in fish consumed by adults and children were generally within safe limits, except for Zn, which exceeded Maximum Tolerable Daily Intake (MTDI). Hazard Index values pointed to a substantial long-term health risk, particularly for children due to high zinc levels. However, Individual Lifetime Cancer Risk (ILCR) values were generally below 1, indicating relatively low cancer risks from G. niger consumption for both age groups. ConclusionThis study emphasizes the need for monitoring and managing metals and metalloid pollution in the Niger Delta region to ensure safe seafood consumption and community well-being. While certain metals pose minimal health risks, it highlights the necessity of specific interventions to reduce excessive zinc exposure and safeguard long-term health in the region.

Construction of fungicide nano delivery platform through crystal engineering for sustainable fungal control

The adverse effects resulting from off-target pesticide application pose significant risks to both ecosystems and public health. Therefore, developing a pesticide delivery system that is straightforward, effective, and devoid of secondary pollution is crucial for environmental safety. Herein, self-assembled crystalline materials involved pyrimethanil (PYR) and organic acids were constructed by crystal engineering. These materials allowed for direct manipulation of the physicochemical properties and environmental fate of PYR by the building modules. The melting point of PYR was increased from 96.19 °C to 206.69 °C. The photostability and volatile stability were improved by 3.85-fold and 297-fold, respectively. Afterwards, these crystalline materials were prepared as nano cocrystal suspensions (NCSs) in water by the one-pot method. The PYR NCSs exhibited potent bioactivity against Botrytis cinerea and demonstrated slow-release behavior. Upon foliar spraying, the PYR NCSs exhibited desirable foliar wettability with a contact angle lower than 36°. By limiting leaching into the soil and reducing environmental pesticide exposure, PYR NCS ensured the safety of both earthworms and plants. The structure–property relationships of PYR NCSs were elucidated through intermolecular interaction analysis and theoretical calculations. Overall, the NCSs constructed by the supramolecular chemistry strategy are characterized by the simple preparation, high bioactivity, stability, no carrier, slow-release, and minimal environmental risk, which offers insight for improving the utilization and sustainable management of pesticides.

Nutritional insights into broths in relation to elemental composition

AbstractDespite the popular claim that broths are a good source of essential elements, few studies have been devoted to clarifying this narrative. In fact, there is growing concern about the risk of ingesting toxic elements. This study focused on assessing the content of important elements (Ca, Cd, Cu, Fe, K, Mg, Na, and Pb) in various types of broths (beef, fish, poultry, pork, and vegetable). The samples (n = 30) included broths of different origins, including laboratory-prepared broths and broths prepared by professional cooks from Czech school canteens. The broths were evaluated as potential sources of essential elements in relation to their reference daily intake, as well as their potential toxicity risk in relation to Cd and Pb. Although significant variability was observed in the contents of the investigated elements, the results generally contradicted the popular narrative that broths are a good source of Ca, Cu, Fe, and Mg, as their contents did not achieve even 5% of the recommended daily intake. The amount of Ca in the broths was minimal even compared to the amount in tap water. The consumption of broths poses minimal risk regarding the presence of Cd and Pb. Graphic abstract

Advancing Lip Augmentation: State-of-the-Art 2D and 3D Analysis for Assessing Volume Enhancement and Lip Line Redefinition

Over the preceding five decades, there has been a noticeable surge in the pursuit of achieving voluminous and well-defined lips. This trend has prompted an escalating number of individuals to undergo lip augmentation procedures, aiming for a natural three-dimensional enhancement of lip volume and distinct vermilion borders. Despite the proliferation of lip augmentation techniques, there remains a dearth of comprehensive investigations into their precise effects on the three-dimensional structural integrity of the lips. This research endeavors to address this gap by employing stereophotogrammetry as a quantitative tool to scrutinize lip augmentation outcomes and to appraise the efficacy of lip plumpers. The study methodology involves a comparative analysis of lip dimensions among subjects treated with a commercial lip plumper using multi-spectral imaging for lip dimension assessment, coupled with markerless tracking technology and 3D interpolating surface methodology to analyze lip volume and shape. Additionally, the study evaluated lip youth state, including moisture level, softness, firmness, and tissue density. The demand for lip augmentation procedures is driven by perceived advantages such as quick recovery and minimal risk. Therefore, it is crucial to substantiate their efficacy with robust findings. The investigation suggests that both 3D and 2D stereophotogrammetry techniques are reliable for evaluating lip size before and after augmentation, whether through cosmetic or aesthetic approaches. Overall, the study provides a comprehensive analysis of a lip treatment aimed at enhancing volume and redesigning lip lines. It demonstrates that stereophotogrammetry is effective for assessing 3D lip dimensions and their correlation with internal lip structure. This research could be particularly valuable for evaluating the efficacy and duration of various lip enhancement techniques, including dermal fillers, implants, and topical cosmetic formulations, offering quantitative and reproducible assessments over time.

Abnormal Pathology Following Vaginal Hysterectomy for Pelvic Organ Prolapse Repair.

Objective: Uterine-sparing surgery for pelvic organ prolapse (POP) repair has shown good results, but the potential negative implications of leaving the uterus in place are yet to be fully defined. We aimed to assess the risk of unanticipated abnormal gynecological pathology at the time of reconstructive pelvic surgery. Methods: A retrospective consecutive case series including women who underwent vaginal hysterectomy for POP repair at a tertiary medical center in 2006-2020. All patients were offered a free Pap smear test at the age of 65 years as part of a national screening program. Transvaginal ultrasound was routinely performed preoperatively. Standard 3 pedicle hysterectomy was performed with/without bilateral salpingo-oophorectomy (BSO). Results: The study comprised 462 women of mean age 63 ± 9.3 years without previous known malignant or premalignant pathology. Benign pathology was observed in 286 patients (61.9%). Endometrial malignancy was found in three patients (0.7%) and significant premalignant pathology in 15 patients (3.2%), including cervical intraepithelial neoplasia stage 2-3 in seven patients (1.5%) and complex hyperplasia with atypia in eight patients (1.7%). All these pathologies were found in postmenopausal women. None had preoperative clinical symptoms or endometrial thickness of ≥5 mm on preoperative ultrasound. In the 35 patients after BSO, adnexal findings were normal (77.2%) or benign (22.8%). Conclusions: Premenopausal women with uterovaginal prolapse and normal preoperative evaluation have a minimal risk of significant abnormal uterine pathology. In postmenopausal women, the risk of unanticipated malignant uterine pathology is 0.7% and 3.2% for significant premalignancy.

Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials.

Automated insulin delivery (AID) devices have shown to be a promising treatment to improve glycemic control in patients with type 1 diabetes mellitus (T1DM). However, its efficacy in pregnant women with T1DM remains uncertain. PubMed, Scopus, Cochrane Central and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing AID to standard care (SC), defined as use of sensor-augmented pump and multiple daily insulin injections. Outcomes included time in range (TIR), nocturnal TIR, time in hypoglycemic and hyperglycemic ranges, among others. Sensitivity and trial sequential analyses (TSA) were performed. CRD42023474398. We included five RCTs with a total of 236 pregnant women, of whom 117 (50.6%) received AID. There was a significant increase in nocturnal TIR (mean difference [MD] 12.69%; 95% CI 8.74-16.64; p < 0.01; I2 = 0%) and a decrease in glucose variability (standard deviation of glucose; MD -2.91; 95% CI -5.13 to -0.69; p = 0.01; I2 = 0%). No significant differences were observed for TIR, HBGI, LGBI, mean glucose and time spent in hyperglycemia and hypoglycemia. Regarding TSA, the statistical significance obtained in nocturnal TIR was conclusive and with minimal risk of a type I error. Our findings suggest that AID systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with T1DM, with no effect in the risk of hypoglycemia and hyperglycemia compared with current insulin treatments.

ENHANCING ELECTIVE SURGERY MANAGEMENT WITH OPENPREDICTOR: VALIDATION OF A CLINICAL DECISION AID FOR OPTIMIZING ELECTIVE PATHWAYS

OpenPredictor, a machine learning-enabled clinical decision aid, has been developed to manage backlogs in elective surgeries. It aims to optimise the use of high volume, low complexity surgical pathways by accurately stratifying patient risk, thereby facilitating the allocation of patients to the most suitable surgical sites. The tool augments elective surgical pathways by providing automated secondary opinions for perioperative risk assessments, enhancing decision-making. Its primary application is in elective sites utilising lighter pre-assessment methods, identifying patients with minimal complication risks and those high-risk individuals who may benefit from early pre-assessment.The Phase 1 clinical evaluation of OpenPredictor entailed a prospective analysis of 156 patient records from elective hip and knee joint replacement surgeries. Using a polynomial logistic regression model, patients were categorised into high, moderate, and low-risk groups. This categorisation incorporated data from various sources, including patient demographics, co-morbidities, blood tests, and overall health status.In identifying patients at risk of postoperative complications, OpenPredictor demonstrated parity with consultant-led preoperative assessments. It accurately flagged 70% of patients who later experienced complications as moderate or high risk. The tool's efficiency in risk prediction was evidenced by its balanced accuracy (75.6%), sensitivity (70% with a 95% confidence interval of 62.05% to 76.91%), and a high negative predictive value (96.7%).OpenPredictor presents a scalable and consistent solution for managing elective surgery pathways, comparable in performance to secondary consultant opinions. Its integration into pre-assessment workflows assists in efficient patient categorisation, reduces late surgery cancellations, and optimises resource allocation. The Phase 1 evaluation of OpenPredictor underscores its potential for broader clinical application and highlights the need for ongoing data refinement and system integration to enhance its performance.

Pharmacokinetic and Environmental Risk Assessment of Prime-2-CoV, a Non-Replicating Orf Virus-Based Vaccine against SARS-CoV-2

Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV’s theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV’s use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV’s favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine’s safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications.

Abstract PO4-07-09: CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT

Abstract Background BreastScreen Australia, a mammographic population screening program, provides assessment of suspected breast cancer to the point of diagnosis using a combination of conventional imaging and percutaneous biopsy. Comprehensive local staging, not performed at BreastScreen, determines the extent of disease and may identify additional clinically significant breast abnormalities. Local staging options include completion of bilateral mammographic work-up, ultrasound, and/or contrast-based imaging (CBI) (magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)), with biopsy as required. We introduced CBI for local staging after diagnosis of screen-detected cancer at our academic hospital breast service in Melbourne, Australia. We report diagnostic findings for otherwise occult disease and their impact on treatment decisions in women who underwent CEM for local staging. Material and methods Women with screen-detected breast cancer who underwent CEM for local staging between November 2018 to April 2022 were identified retrospectively. The reporting breast-specialised radiologist compared BreastScreen and CEM images to identify additional enhancing abnormalities. Additional abnormalities were further investigated with preoperative percutaneous biopsy, surgical biopsy, or problem-solving CBI. Additional CEM-detected abnormalities were documented, with invasive cancer or DCIS recorded as true positive (TP) and any other findings as false positive (FP). Impact on surgical decisions was assessed. Results 204 patients underwent CEM. 62/204 (30%) patients had 76 additional abnormalities, of which 36 (47%) were TP and 40 (53%) FP. CEM identified otherwise occult malignant lesions in 30/204 (15%) patients. TPs comprised 75% invasive cancers and 25% DCIS. 83% (30/36) of malignant abnormalities were ipsilateral to the index lesion, while 17% (6/36) were contralateral. The majority of additional invasive cancers were Grade 2 (20/27, 74.1%), followed by Grade 1 (4/27, 14.8%) then Grade 3 (3/27, 11.1%). All additional invasive cancers had the same phenotype as the patient’s index cancer (ER+/HER2-), except for one abnormality which was ER+/HER2+ where the index cancer was ER+/HER2-. The FP abnormalities consisted of normal breast tissue (20/40, 50%), benign lesions (16/40, 40%) and atypical proliferative lesions (4/40, 10%). Occult malignancies were more common for patients with higher background parenchymal enhancement (20% for moderate/marked vs 4% for minimal/mild, p=0.0023), with no statistically significant differences found by breast density (BIRADS A or B = 12%, vs BIRADS C or D = 20%, p=0.23) or by age (40-49=38%, 50-59=13%, 60-69=13%, ³70=19%, p=0.88). Additional abnormalities found on CEM resulted in surgical management change in 45/204 (22%) patients, including wider resection (24/45), conversion to mastectomy (8/45), contralateral breast surgery (6/45), additional ipsilateral excision (5/45), and bracketing (2/45). Conclusions The use of CEM for local staging of screen-detected breast cancers identified otherwise occult malignancy in 15% of patients. Age and mammographic density did not identify groups at minimal risk of additional findings. Pathology of additional malignancy suggests it is clinically significant. CEM may improve local staging and direct appropriate management of screen-detected breast cancers. Citation Format: Caroline MacCallum, Kenneth Elder, Carolyn Nickson, Kelly Ruecker, Allan Park, Bruce Mann. CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-09.

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [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 PO4-19-02.

A Dialogues Summarization Algorithm Based on Multi-task Learning

With the continuous advancement of social information, the number of texts in the form of dialogue between individuals has exponentially increased. However, it is very challenging to review the previous dialogue content before initiating a new conversation. In view of the above background, a new dialogue summarization algorithm based on multi-task learning is first proposed in the paper. Specifically, Minimum Risk Training is used as the loss function to alleviate the problem of inconsistent goals between the training phase and the testing phase. Then, in order to deal with the problem that the model cannot effectively distinguish gender pronouns, a gender pronoun discrimination auxiliary task based on contrast learning is designed to help the model learn to distinguish different gender pronouns. Finally, an auxiliary task of reducing exposure bias is introduced, which involves incorporating the summary generated during inference into another round of training to reduce the difference between the decoder inputs during the training and testing stages. Experimental results show that our model outperforms strong baselines on three public dialogue summarization datasets: SAMSUM, DialogSum, and CSDS.

The Prevalence of Prostate Cancer in Organ Donors With Increased Prostate-Specific Antigen

Elevated PSA levels were found in 139 kidney donors out of a total of 472 donors from our Transplant Centre tested between 2009 and 2022, representing 29,4%. We analyzed these kidney donors with elevated prostate specific antigen (PSA) levels, at mean age 47,3 years. PSA values ranged from 2.8 to 160.4 ng/ml, mean 13,9ng/ml), proper range <2.5 ng/ml. Prostate hist-pat examination was performed in 38/139 - 27% donors. 14 cases of prostate cancer (Pca) were found, Gleason 3+3 in 8 cases, 3+4 in four cases (one donor disqualification), one case Gleason 4+3 (donor disqualification), one case Gleason 4+5 (donor disqualification). There were 33 patients who met the criteria, age ≥50 years and PSA level > 10 mg/mL; of these, prostate hist-pat was performed in 24 cases, Pca was found in 10/42% cases. There were no difference between donors ≥ 50 years old, PSA>10 ng/ml with and without pathomorphological diagnosis of Pca in respect of age (mean 60,4 vs. 60,6 years), creatinine clearance according to the Cockroft-Gaulta formula (mean 101,6 vs. 94,8 ml/min) and PSA levels (mean 34,1 vs. 29,3 ng/ml). Among other donors with Pca three were <50 years with PSA >10 ng/ml and one was ≥ 50 years and PSA< 8 ng/ml. Kidneys from donors with prostate cancer were transplanted into 19 recipients, 10 men, nine women, follow-up time 1-10 years. There was no case of prostate cancer transmission. One of the recipients died of neoplasm – breast cancer. ConclusionsDonors ≥ 50 years old, PSA>10 ng/ml have higher risk of Pca. Accepting donors with Pca (Gleason 3+3, and 3+4) possesses minimal risk of transmission. All donors ≥ 50 years and also younger with increased PSA require further diagnostic procedure (e.g. DRE, USG, eventually histological examination).

Role of self-actualization in green production behavior: Evidence from rice smallholders in China

Understanding who adopts green production and why are important issues that need to be addressed in the context of increasingly severe agricultural pollution. Previous studiesh have generally researched smallholder subsistence orientation, typically employing profit maximisation or risk minimisation models. However, Chinese farmers have differentiated, and have unique characteristics. This study collected 960 random rice farmers and their village committee administrators (n=19) and conducted quantitative analysis. The findings revealed that 94.9% of the farmers’ rice-planting area was less than 2 ha, whereas 80.21% of farmers self-reported their rice production purpose as family self-feeding. Furthermore, using the new standard to define smallholders based on whether their production purpose is self-feeding or selling, non-smallholders have an overall advantage and pass the t-test. Even more non-smallholder (76.32% ) intentionally choose green pesticide than smallholders (66.1%), but their decision-making logic is different. Binary logistic regression results show that three aspects of self-actualization (environmental, market, and personal) positively and significantly affects the green production behavior of smallholders, but not significant for non-smallholders. In China, where smallholders are the mainstay of agriculture production, green production by smallholders will greatly improve the ecological environment and provide higher-quality agricultural products.

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.MethodsA confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.DiscussionThis multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.Trial registration: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325.