Early Stage Research Articles

Impact of racial disparities in adjuvant treatment of triple negative breast cancer (TNBC) among American Indians/Alaskan Natives (AI/AN) and non-Hispanic Whites (NHW) on overall survival (OS).

e13736 Background: There are significant differences in patient and tumor characteristics among AI/AN and NHW breast cancers (BC) which adversely impact overall survival in AI/AN. Prior studies have also shown higher Mortality: Incidence ratio for BCs in AI/AN as compared to NHW. The aims of this study are to 1) investigate disparities in adjuvant treatment of TNBC between the two races adjusting for age, stage, and year of diagnosis; and 2) Assess differences in OS. Methods: This was a hospital based, retrospective cohort study using the National Cancer Database. AI/AN and NHW women with TNBC, greater than or equal to 18 years of age, diagnosed with BC between the years 2010 through 2019, stages I, II, and III were included. Propensity score matching in a 1:3 ratio was used for age, year, and analytical stage at diagnosis. Primary endpoint was time to first treatment and compliance with recommended treatment. Secondary endpoint was OS. Results: A total of 489 AI/AN and 1465 matched NHW women with TNBC were identified. AI/AN women traveled longer distances for cancer care (p<.01), resided in lower median income zip codes at the time of diagnosis (p<.001), had a higher Charlson-Deyo (CD) comorbidity score (p<.001), and were less likely to have private insurance (p<.001). There was no difference in the rates of chemotherapy, surgery, and radiation therapies that were recommended and received by the two races. Time to first treatment was significantly longer for AI/AN as compared to NHW women (Mean ± SD: 35 ± 27 days vs. 39 ±27 days; p=.005). Multivariable analysis revealed that longer time to first treatment was associated with only higher CD score (p=.013) and non-private insurance (p=.027), but no longer associated with race (p=.324). Compliance with recommended treatment was similar between AI/AN and NHW women (93.5% vs 92.9%, p=.096). Compliance was significantly associated with only insurance status (p < .001) with Medicare/Medicaid having the lowest compliance. OS did not differ by race (p=.299, HR=1.132; 95% CI: 0.90-1.43). Cancer stage, CD score, insurance status, and treatment compliance were associated with worse OS. Conclusions: In patients with TNBC, there was no difference in time to treatment, compliance with recommended treatment or OS among AI/AN in comparison to White women when matched for age, stage, and year of diagnosis. Medicare/Medicaid insurance was associated with prolonged time to treatment, lower compliance with recommended treatment and decreased survival when compared with other insurances. Higher comorbidities adversely impacted time to treatment and overall survival. In order to improve BC mortality, it is important to manage comorbid conditions and improve detection of cancer at earlier stages. Prospective studies comparing outcomes by race are needed to confirm these findings.

Patterns of screening and access to care in women diagnosed with breast cancer in a safety-net system.

1531 Background: Screening mammography reduces breast cancer specific mortality by allowing diagnosis at an earlier stage. Inconsistent guidelines and limitations in access to primary care are among factors that affect screening uptake. In this study, we reviewed patient characteristics, access to care, and uptake of screening mammogram (SMMG) prior to a breast cancer diagnosis at a safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Simmons Comprehensive Cancer Center. Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 and 2019 at PH were reviewed and data on demographics and clinical presentation were collected. Patients were categorized based on SMMG uptake prior to their cancer diagnosis: never-screened, ever-screened (SMMG > 2 years prior to diagnosis) and recent-screened (SMMG within 2 years of diagnosis). Results: A total of 468 new breast cancer cases were identified (48.7% Hispanic; 32.9% Black). Of these, 12.2% were younger than 40 and 27.8% were 40-49. Payer mix included 64.7% uninsured and 34.8% Medicare/Medicaid. Half of the patients (50.6%) never had SMMG. Never-screened rate was higher among younger patients (98.2% in < 40; 53.8% in 40-49; and 39.4% in >50; p < 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged >40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients >40 was 40.1% (165/411), of whom 22 (13.3% of screen-detects) were diagnosed with cancer on their first ever SMMG. Race/ethnicity, insurance status, and positive family history of cancer were not significantly different between never, ever, and recent-screened patients. Screening uptake correlated with nodal status, tumor size and stage at diagnosis. Patients who had a prior encounter at Parkland were more likely to have a SMMG. Patients established with Parkland primary care at diagnosis were more likely to have early-stage disease. In patients < 40, 24.6% presented with stage IV disease at diagnosis and 57.9% did not have a primary care provider. A positive family history of breast/ovarian cancer or any cancer was noted in 38.6% and 57.9% of patients < 40, respectively. Conclusions: In the cohort presented here, 27.8% of patients were between age 40-49, reflecting the impact of a gap in the guideline, which is now addressed in the most recent iteration of USPSTF guidelines. Connecting ED users to primary care, identifying higher risk individuals through family history, and increasing SMMG rate in the primary care setting are among strategies to reduce the rate of late-stage diagnosis of breast cancer, particularly among vulnerable patient populations.

Ipsilateral recurrence and breast cancer outcomes in carriers of BRCA1/2 pathogenic variants according to locoregional treatments.

e12584 Background: Our previous study of 255 breast cancer (BC) patients, carriers of BRCA1/2 pathogenic variants (PV), showed that patients who underwent mastectomy without post-mastectomy radiotherapy (PMRT) had higher rates of local recurrence (LR) than those who underwent PMRT or breast-conserving therapy (BCT). Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data was extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006-12/2022. Data extracted included demographics, tumor characteristics, disease stage, surgical and oncological treatment, use of RT and disease outcomes. Results: Overall, 481 BC patients with BRCA1/2 germline mutations were identified, 20 of them presented with synchronous bilateral disease. Median follow-up time was 75.3 months (range 12.5-211). After excluding 16 patients with metastatic de novo disease and 1 patient not operated for medical reasons, 464 patients with 484 primary tumors were analyzed. Of these, 234 (48.3%) mastectomies (84% were skin- or nipple-sparing, SSM/NSM, 16% total mastectomy) and 250 (51.7%) BCT were performed. In the non-PMRT group (n=153) there was earlier disease stage at diagnosis (77.6% of tumors were Tis and T1N0) compared to the PMRT group (n=81) and BCT group (4.9% and 45%, respectively, p<0.001). All had free surgical margins. LR rate in the study cohorts was 20/153 breasts (13.1%) in the non-PMRT group compared with 1/81 breasts (1.2%) in the PMRT group (p=0.003), and 16/250 (6.4%) in the BCS group (p=0.024). All but one recurrence were invasive. Cumulative incidence of LR at 5 and 10 years was 14.1% and 15.9% in the non-PMRT, compared to 4.4% and 9.4% in BCT group, respectively (p=0.034). No significant difference in overall survival was observed (p=0.39). Conclusions: BRCA1/2 PV carriers treated with mastectomy without PMRT had higher rates of LR than those who underwent mastectomy and PMRT or BCT, despite earlier stage disease. Further studies are needed to compare these outcomes to non- BRCA1/2 carriers and find means to improve local control in these patients.

Novel liquid biopsy assay to distinguish benign from malignant pelvic masses.

e17563 Background: Despite not ranking among the top ten most common cancers in women in the United States, ovarian cancer stands as the fifth leading cause of cancer-related deaths in this population. According to the American Cancer Society, only 20% of ovarian cancers are found at stages I-II, when 94% of patients are expected to live longer than five years after diagnosis. Instead, the majority of ovarian cancers are detected at stages III-IV, when long term survival is 20% or less. Early identification of ovarian cancer is challenging due to the wide range of symptoms with which a patient may present, most of which lack specificity for ovarian cancer. Even in cases where a physician may want to rule in or out ovarian cancer, the available methods for screening have a low positive predictive value. These methods include bimanual exams, transvaginal ultrasounds, and CA-125 blood tests. In a screening capacity, the sensitivity for a bimanual exam finding ovarian cancer is only about 44%, transvaginal ultrasound is approximately 85%, and CA-125 testing registers at 77%. The need for better tools to detect ovarian cancer is clear. Genece Health has developed an assay utilizing a proprietary algorithm that leverages deep learning to analyze cfDNA fragment size, end motif, and coverage patterns, along with other genomic features, to detect the presence of ctDNA in blood originating from ovarian cancer. The data presented herein demonstrate that the Genece Health assay has the ability to detect ctDNA in a single tube of blood using low pass whole genome sequencing in a cost-effective way to distinguish between malignant and benign pelvic masses. Methods: Blood was prospectively collected from 56 females with pelvic masses in advance of removal and histopathology (approximately 32 cancer and 24 benign masses) in Streck cfDNA BCT Devices. Additionally, healthy female donor blood from 50 individuals procured through the San Diego Blood Bank were collected in Streck cfDNA BCT Devices. cfDNA was extracted from double-spun plasma and low-pass whole genome sequencing (2X – 5X coverage) was performed. Data were analyzed with the Genece Health Algorithm. Results: The Genece Health Algorithm demonstrated the ability to distinguish between pelvic masses that were deemed benign versus malignant via histopathology. There was a significant (P<0.01) difference between the classifier assigned to the malignant and benign and presumed normal groups. Conclusions: The investigational assay described herein shows progress toward the ability to use non-invasive molecular testing to identify ovarian cancer in a blood sample. A blood test to differentiate between a benign and malignant pelvic mass will enhance the ability of physicians to detect ovarian cancer at earlier stage, improving clinical outcomes for women. The cost-effective low-pass whole genome sequencing approach taken by Genece will be further explored in expanded cohorts.

Association between antibiotic use and mortality among older persons receiving first-line immune checkpoint inhibitors for non-small cell lung cancer (NSCLC).

e14607 Background: There is biologic plausibility that antibiotics (ABX) may reduce the effectiveness of cancer therapy, most notably immune checkpoint inhibitors (ICI). As ABX are commonly prescribed to older persons and more than a third of US persons with cancer are eligible for ICIs, use of ABX has important population health implications. We assess the association between ABX use and mortality among persons with NSCLC who receive first-line (1L) treatment. Methods: Using SEER-Medicare, we assembled a cohort of persons ≥66 years with NSCLC who received 1L treatment with platinum-based chemotherapy (PLT) or ICI (PLT without ICI, PLT with ICI, and ICI monotherapy) within one year of cancer diagnosis between 2017-2019. We assessed overall ABX exposure from 1 month to 1 year prior to treatment initiation and by ABX class. Primary outcome was all cause deaths within three years of treatment initiation or until 12/31/2020. Multivariable Cox proportional hazard models adjusting for individual-level characteristics (demographics, time-to-treatment, comorbidities, healthcare use, SEER registry, and neighborhood socioeconomic status) and landmark analyses of 1-6 months after cancer treatment were used to assess the association between ABX exposure and mortality. Results: Among 4,182 persons (mean age 75 years, 85% white, 68% chemo-immunotherapy within 2 months of NSCLC diagnosis), 63%, 18%, and 18% received PLT, PLT+ICI, and ICI, respectively. ICI+/-PLT increased in prevalence from 20% of treatments (2017) to 55% (2019). The mean age of persons who received ICI alone (78 years old) was higher than PLT or PLT+ICI. Prior to 1L treatment, 22% and 72% of persons received ABX within 30 days and 1 year prior to cancer treatment, respectively. The three most common ABX classes were fluoroquinolones (48%), penicillins (21%), and macrolides (18%). The cohort was followed for 3,274 person-years and included 2,958 deaths within 1 year and 4,144 deaths within 3 years of follow-up. Compared with persons who did not receive ABX within 3 months of cancer treatment, ABX use was associated with higher risk of death within 3 years for ICI alone [HR 1.24 (1.05-1.46) but not for PLT alone or PLT+ICI. Fluoroquinolones were associated with an elevated risk of mortality among persons who received ICI alone HR 1.41(95%CI: 1.1-1.8) and PLT alone HR 1.18 (95%CI: 1.05-1.32) but not PLT+ICI. Our findings were similar across definitions of ABX exposure (30 days to 1 year prior to treatment) and analytic landmarks after treatment initiation. Conclusions: Among patients with NSCLC who received 1L treatment, we identified an association between ABX exposure prior to treatment and increased mortality among persons who received ICI monotherapy but not PLT+ICI. As ICIs expand to more cancer types and earlier stages, ABX use may have a significant impact on outcomes and population health.

Improving access to palliative care to mitigate multi-dimensional breast cancer suffering.

e24084 Background: The breast cancer (BC) divide persists as a global health and equity challenge. IARC data show that in low human development index (HDI) countries – 1/27 women is diagnosed with BC in their lifetime and 1/48 die from it. In very high HDI countries, BC is more common (1/12), but death is much less so (1/71). Hence, BC generates a substantial burden of serious health-related suffering (SHS) worldwide, and a particularly high and unmet demand for end-of-life care in poorer countries. This research links to three Lancet Commissions (LC): the forthcoming report of LC on BC, follow-up to LC Global Access to Palliative Care (PC), and LC on Cancer and Health Systems. We apply the concept of SHS to delineate and measure PC need for BC. This research is the first to explore disease-specific SHS, building on previous estimates that did not differentiate across cancers. Focusing on BC adds knowledge on: experiences of suffering across the cancer continuum including survivorship; dimensions of suffering specific to women and especially young women; and, differences in symptoms of suffering by stage of diagnosis. Methods: To identify symptoms and dimensions of suffering and to estimate the BC-specific SHS burden, 14 experts, most from the Lancet BC Commission, based in 12 countries of varying HDI, participated in: 1) an online survey on days of SHS and days receiving PC; 2) focus groups to discuss BC need for generalist and specialist PC from time of diagnosis; and 3) structured interviews to refine and deepen data. Results: Stage IV disease and end-of-life account for most PC consultations; no PC consultations were recommended in earlier stages. Experts concluded BC-specific SHS must be differentiated for metastatic disease based on staging, and highlighted symptoms of suffering associated with gender, reproductive age and sexuality ignored in previous work. They estimated an annual average PC need of approximately 175 days for decedents, and over 50 days per year for non-decedents estimated to live 4 years with SHS. Unmet need is high as BC decedents reported receive about 75 days, and non-decedents about 90 days of PC prior to the last year of life. Oncology experts focus on PC being only for final disease stage, yet PC experts stress the need for earlier PC integration into the BC trajectory, including survivorship. Conclusions: With 669,500 deaths in 2023, the burden of BC-specific SHS total is estimated at over 118 million days a year. These numbers represent suffering from pain, dyspnea, fatigue, as well as range of other symptoms that could benefit from PC. Yet, PC is unavailable for the majority in low- and middle-income countries. In addition, some BC symptoms of suffering are under-recognized globally. Health and cancer should prioritize this substantial opportunity to respond to patient, family and caregiver suffering by investing in appropriate PC access and capacity development.

The role of obesity in the clinicopathologic variables and treatment of early stage breast cancer.

e12555 Background: Breast cancer (BC) is the second most common cancer among women in the United States. Studies have found obesity to be a key risk factor for BC, in which obese patients have higher recurrence and mortality. With 40% of the United State population being obese, we studied the differences in clinicopathological variables and treatment of normal-weight (NW) and obese patients with BC in a community-based cancer center within Florida. Methods: In this retrospective study, 535 patients with non-metastatic breast cancer (NMBC) diagnosed between January 1st, 2015 and December 31st, 2021 were identified. A Two Proportion Z test was done to evaluate the association between body mass index (BMI) groups of NW (BMI <25) and obese (BMI >30) patients amongst several independent variables. Variables included are histology, grade, estrogen and progesterone receptor status (ER/PR), human epidermal growth factor receptor 2 (HER2) status, chemotherapy, and surgical modality. Results: Results demonstrated that only Grade 2 histology was statistically more prevalent in NW vs obese patients (p < 0.01). 218 patients underwent mastectomy with 54% in the obese BMI. 317 patients were treated with lumpectomy with 65% in the obese BMI. Of the 211 NW patients, 97% were HER2 negative or low compared to 96% in the obese group. Only 3% and 4% of patients were HER2 positive in NW and obese groups, respectively. Of the obese patients, 40% were treated with neoadjuvant/adjuvant chemotherapy compared to 33% of NW patients (p=0.05). Factors such as mean age, smoking status and other demographic information were not statistically different between the groups. Conclusions: This study demonstrates that obese NMBC patients required chemotherapy more often than NW patients and that histologic characteristics cannot explain this difference in treatment. Factors such as stage at diagnosis or BC prognostic scores may contribute to the increased use of chemotherapy in obese patients. A limitation of this study is that the stage of disease at diagnosis was not abstracted, as a new staging system for BC was implemented in 2018. Furthermore, studies have suggested that, in obese patients, difficulty in identification of a mass in clinical or self -breast exam and poor compliance with screening guidelines may delay diagnosis of BC at an earlier stage. Obesity has many negative health effects, and with the increased use of novel weight loss medications, it will be important in the future to study the impact this may have on breast cancer development, histopathologic features, and treatment of patients with breast cancer. [Table: see text]

Challenges and Potential of Artificial Intelligence in Neuroradiology.

Artificial intelligence (AI) has emerged as atransformative force in medical research and is garnering increased attention in the public consciousness. This represents acritical time period in which medical researchers, healthcare providers, insurers, regulatory agencies, and patients are all developing and shaping their beliefs and policies regarding the use of AI in the healthcare sector. The successful deployment of AI will require support from all these groups. This commentary proposes that widespread support for medical AI must be driven by clear and transparent scientific reporting, beginning at the earliest stages of scientific research. Areview of relevant guidelines and literature describing how scientific reporting plays acentral role at key stages in the life cycle of an AI software product was conducted. To contextualize this principle within aspecific medical domain, we discuss the current state of predictive tissue outcome modeling in acute ischemic stroke and the unique challenges presented therein. Translating AI methods from the research to the clinical domain is complicated by challenges related to model design and validation studies, medical product regulations, and healthcare providers' reservations regarding AI's efficacy and affordability. However, each of these limitations is also an opportunity for high-impact research that will help to accelerate the clinical adoption of state-of-the-art medical AI. In all cases, establishing and adhering to appropriate reporting standards is an important responsibility that is shared by all of the parties involved in the life cycle of aprospective AI software product.

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an...

Early-time γ-ray constraints on cosmic-ray acceleration in the core-collapse SN 2023ixf with the Fermi Large Area Telescope

Context. While supernova remnants (SNRs) have been considered the most relevant Galactic cosmic ray (CR) accelerators for decades, core-collapse supernovae (CCSNe) could accelerate particles during the earliest stages of their evolution and hence contribute to the CR energy budget in the Galaxy. Some SNRs have indeed been associated with TeV γ-rays, yet proton acceleration efficiency during the early stages of an SN expansion remains mostly unconstrained. Aims. The multi-wavelength observation of SN 2023ixf, a Type II supernova (SN) in the nearby galaxy M 101 (at a distance of 6.85 Mpc), opens the possibility to constrain CR acceleration within a few days after the collapse of the red super-giant stellar progenitor. With this work, we intend to provide a phenomenological, quasi-model-independent constraint on the CR acceleration efficiency during this event at photon energies above 100 MeV. Methods. We performed a maximum-likelihood analysis of γ-ray data from the Fermi Large Area Telescope up to one month after the SN explosion. We searched for high-energy, non-thermal emission from its expanding shock, and estimated the underlying hadronic CR energy reservoir assuming a power-law proton distribution consistent with standard diffusive shock acceleration. Results. We do not find significant γ-ray emission from SN 2023ixf. Nonetheless, our non-detection provides the first limit on the energy transferred to the population of hadronic CRs during the very early expansion of a CCSN. Conclusions. Under reasonable assumptions, our limits would imply a maximum efficiency on the CR acceleration of as low as 1%, which is inconsistent with the common estimate of 10% in generic SNe. However, this result is highly dependent on the assumed geometry of the circumstellar medium, and could be relaxed back to 10% by challenging spherical symmetry. Consequently, a more sophisticated, inhomogeneous characterisation of the shock and the progenitor’s environment is required before establishing whether or not Type II SNe are indeed efficient CR accelerators at early times.

The empathetic refutational interview to tackle vaccine misconceptions: Four randomized experiments.

We introduce and report early stage testing of a novel, multicomponent intervention that can be used by healthcare professionals (HCPs) to address false or misleading antivaccination arguments while maintaining empathy for and understanding of people's motivations to believe misinformation: the "Empathetic Refutational Interview" (ERI). We conducted four experiments in 2022 with participants who were predominantly negative or on the fence about vaccination (total n = 2,545) to test four steps for tailoring an HCP's response to a vaccine-hesitant individual: (a) elicit their concerns, (b) affirm their values and beliefs to the extent possible, (c) refute the misinformed beliefs in their reasoning in a way that is tailored to their psychological motivations, and (d) provide factual information about vaccines. Each of the steps was tested against active control conditions, with participants randomized to conditions. Overall, compared to controls, we found that observing steps of the ERI produced small effects on increasing vaccine acceptance and lowering support for antivaccination arguments. Critically, an HCP who affirmed participants' concerns generated significantly more support for their refutations and subsequent information, with large effects compared to controls. In addition, participants found tailored refutations (compared to control responses) more compelling, and displayed more trust and openness toward the HCP giving them. The ERI can potentially be leveraged and tested further as a tailored communication tool for HCPs to refute antivaccination misconceptions while maintaining trust and rapport with patients. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Extremely Large-Scale MIMO: Fundamentals, Challenges, Solutions, and Future Directions

Extremely large-scale multiple-input-multipleoutput (XL-MIMO) is a promising technology to empower the next-generation communications. However, XL-MIMO, which is still in its early stage of research, has been designed with a variety of hardware and performance analysis schemes. To illustrate the differences and similarities among these schemes, we comprehensively review existing XL-MIMO hardware designs and characteristics in this article. Then, we thoroughly discuss the research status of XL-MIMO from "channel modeling", "performance analysis", and "signal processing". Several existing challenges are introduced and respective solutions are provided. We then propose two case studies for the hybrid propagation channel modeling and the effective degrees of freedom (EDoF) computations for practical scenarios. Using our proposed solutions, we perform numerical results to investigate the EDoF performance for the scenarios with unparallel XL-MIMO surfaces and multiple user equipment, respectively. Finally, we discuss several future research directions.

Time-to-diagnosis and peri-diagnostic healthcare utilization between screen- and non-screen detected cancers: Evidence from SEER-Medicare.

11135 Background: Cancer screening programs can improve outcomes and may reduce treatment cost and utilization by shifting cancers to earlier, more curable stages at diagnosis (Dx). Few studies have evaluated the impact of screening on outcomes prior to diagnosis. Such information is needed to better understand the potential impact of newer blood-based multicancer early detection technologies. Methods: We conducted a retrospective cohort study using SEER cancer registry data linked with Medicare claims. Patients with a breast cancer (BC) or colorectal cancer (CRC) Dx between 2010-2019 were included if they were 65-74 years old at Dx, continuously enrolled in Medicare Parts A&B, had a Charlson Comorbidity Index of ≤2, and no cancer for ≥12 months prior to Dx. Those enrolled in an HMO or with high genetic risk for BC (in BC cohort) were excluded. Patients were assigned to screening groups prior to Dx; screening was defined as ≥1 screening procedure in the 6 months prior to Dx using CPT/HCPCS codes. Screening included FIT/FOBT, sigmoidoscopy, colonoscopy, CT colonography, mt-sDNA (CRC), and mammography (BC). Screened and not screened groups were compared for statistical significance using chi-squared for categorical variables, Wilcoxon rank-sum test for continuous variables. Results: Screening procedures were more prevalent in the BC cohort (68%) than the CRC cohort (44%) (table). Both screened subgroups (vs non-screened subgroups) had significantly lower proportions of patients diagnosed at stage 4 (2% vs 10% BC, 16% vs 27% CRC) and shorter times from first screening or imaging procedure to confirmed diagnosis (BC: 33 vs 227 days, CRC: 14 vs 29 days). Screened patients in both cancer cohorts had a similar number of average procedures prior to treatment initiation as non-screened (BC: 4.8 vs 4.2, CRC: 3.3 vs 3.3 respectively, including screening procedures). Conclusions: Individuals diagnosed with BC and CRC through screening exhibit earlier stage diagnoses and shorter intervals to diagnosis. Novel screening technologies such as MCED tests can potentially improve peri-diagnostic outcomes in cancers lacking existing or widely adopted screening methods. [Table: see text]

Strategy to regulate fermentation rate of commercial cut cabbage kimchi by supercooling storage

Kimchi products are often discarded by burst package due to the excessive fermentation during long-term distribution. In this study, supercooling storage was approached to prevent deterioration during distribution by regulating fermentation rate and maintaining quality of products by lowering storage temperature. Herein, cut cabbage kimchi (CCK) products were stored in the supercooling condition by stepwise temperature control algorithm for 12 weeks. During storage, the temperature of CCK was strictly followed the algorithm, maintaining −3.5 °C at the lowest step without ice nucleation. The supercooled CCK were reduced in the LAB growth comparing to the refrigerated CCK, presenting superior quality. Further, heterofermentative LABs were dominant in supercooled CCK after 12 weeks, maintaining the earlier stage of fermentation. Reversely, homofermentative LABs were dominant in refrigerated CCK, meaning the latter stage of fermentation. Freezing suppressed the growth of aerobic bacteria and LAB in CCK and lost the physicochemical qualities by damages from freezing and thawing. Thus, supercooling storage could help maintain the original qualities of CCK to control fermentation rate at −3.5 °C for long-term storage in the static condition. Further studies can be conducted at −3.5 °C reflecting practical conditions.

Ethnicity and health insurance disparities in rectal carcinoma.

e13732 Background: Ethnicity and insurance coverage affect healthcare delivery in rectal carcinoma (RC). RC pts (pts) with Medicaid or no insurance are more likely to present with distant stage RC compared to Medicare/private insurance pts, and have a worse prognosis even when stage is accounted for. To combat such issues, federal law requires that non-profit hospitals, which make up 58% of all community hospitals, to provide charity care, or financial assistance, to those eligible. As insurance status, ethnicity and race have been found to independently affect colon cancer care, we expect similar results for RC in our limited but diverse cohort. Methods: Trinitas Medical Center RWJBH is an urban, community hospital that predominantly treats a minority population and provides financial assistance to eligible underinsured pts. Due to this assistance, or Charity Care, we can provide access to cancer care for many who would not ordinarily have such means. With institutional IRB approval, we completed a retrospective chart review of 59 pts diagnosed with Stage I-IV RC from 2017-2023. We assessed ethnicity, insurance carriers and treatment choices. Results: We reviewed 59 pts with the following ethnic distribution: 22 Hispanic (H), 21 White (W), 11 Black (B) and 5 Asian (A) pts. The median age at diagnosis with RC was 57 in H, 64 in B, 71 in W and 71 in A pts. B pts were found to be diagnosed with more advanced disease: 36% at Stage III and 45% at Stage IV, with none diagnosed at Stage I or II. H pts had comparatively fewer distant stage diagnoses (23% at Stage III, 18% at Stage IV). Neoadjuvant chemotherapy and radiation therapy to 20 of 59 pts treated at our center, 15 of whom subsequently received surgery. Four of five of these declined surgical intervention post neoadjuvant therapy. H pts had the following primary insurance carriers: 36% Medicaid, 36% Medicare, 27% Charity care. 62% of W pts had Medicare and 14% Medicaid. 27% had B pts had Medicare, 27% Medicaid and 9% had Charity care. 50% of the 59 pts had Charity care, with most pts in this group being H. Conclusions: Research suggests that immigrants utilize healthcare facilities less than U.S. citizens and programs like Charity care may be underutilized. In our RC cohort, 38 of 59 (64%) pts were racial minorities, of these 50% received Charity care. Most did not receive screening prior to a diagnosis of rectal cancer and many applied for Charity Care only after their diagnosis. Despite offering significant financial assistance to our pts, we suggest education to immigrants regarding insurance coverage, broader screening efforts and the ability to offer improved subspecialty care to RC pts. In particular, we look to target B and H who present at younger ages and are not Medicare eligible. We believe this will lead to earlier staging of RC, which should lead to improved survival for minority pts.

Rectal cancer: Demographics and healthcare outcomes in a minority-rich community hospital.

e13735 Background: Rectal cancer (RC) has seen a decreasing incidence and mortality due to national screening guidelines, innovative therapies and new technology. In recent years, however, we have noted shifts in its demographics pertaining to variation in stage at diagnosis and mortality rates amongst various ethnic groups. Minority populations, namely Hispanic (H) and Black (B) patients (pts), continue to see higher incidence, diagnosis at more advanced stages and poorer survival than White (W) pts. In B pts, mortality rates are higher with an increased likelihood of distant-stage RC creating a significant survival disparity. Current studies involving H and Asians(A) show similar disparities. Compared to other malignancies, RC has improved survival for pts when diagnosed in a timely fashion and therefore, we seek to identify potential patterns within the diverse population we care for. Methods: Trinitas Medical Center RWJBH is an urban, community hospital that predominantly treats a minority population. With institutional IRB approval, we completed a retrospective chart review of 59 pts diagnosed with Stage I-IV RC from 2017- 2023. Pts were treated at our cancer center. We assessed age and stage at diagnosis and demographics such as age, sex and ethnicity. Results: We reviewed 59 pts with the following ethnic distribution: 22 H, 21 W, 11 B and 5 A pts. The median age at diagnosis with RC was 57 in H, 64 in B, 71 in W 71. More males were diagnosed in all groups except A pts. B pts were found to be diagnosed with more advanced disease: 36% at Stage III, 45% at Stage IV. W pts also saw a similar trend with 33% at Stage III and 24% at Stage IV. Our H pts had comparatively fewer distant stage diagnoses: 23% at Stage III, 18% at Stage IV. Common sites of metastasis in B: liver 27%, lung 27%, locoregional lymph nodes 9%. In W pts: liver 24%, locoregional lymph nodes 24%, lung 10% and brain 5%. In H pts, 10 of 22(45%) were diagnosed without metastatic disease, though of the 10 who did, 2 had brain involvement. Mortality was highest in B pts at 55%, 33% for W, 20% for A and 18% for H pts. Conclusions: In our study, we note H pts being diagnosed at an earlier median age, at earlier stages of disease, with higher survival rates. Our B pts were diagnosed younger than W pts, at later stages of disease, with higher mortality rates. Brain involvement, which usually is rare, was seen in both H and W upon recurrence. Despite having a multi specialized cancer center, we note limitations in our access to screening resources and the availability of colorectal surgical expertise to enhance care for our underserved population. The challenge of disentangling disparities within RC will benefit from improved healthcare access and availability of multimodality resources in this disease state where cure is the ultimate goal.

Ancient stellar populations in the outskirts of nearby grand-design spirals: Investigation of their star formation histories

Context. The main sequence (MS) of star-forming galaxies (SFGs) is the tight relation between the galaxy stellar mass (M⋆) and its star formation rate (SFR) and was observed up to z ∼ 6. The MS relation can be used as a reference for understanding the differences among galaxies, which are characterised by different rates of stellar production (starbursts, SFGs, and passive galaxies), and those inside a galaxy that is made up of different components (bulge, disk, and halo). To investigate peculiar features found in our galaxies sample in more depth, we focus here on their star formation history (SFH). Aims. The SFHs are a fundamental tool for revealing the galaxy path from the earlier stages of formation to the present time. The various phases of galaxy evolution are imprinted on the source spectrum globally and locally. Thus, we are able to interpret the dynamical origin of the spirals quantitatively and distinguish between in situ or ex situ formation processes. Methods. We performed a spectral energy distribution fitting procedure that accounted for the energetic balance between UV (observed) and far-IR (optically obscured) radiation on a sample of eight nearby face-on grand-design spiral galaxies from the DustPedia sample. This approach allowed us to study the spatially resolved MS of the sample and to recover the past SFH by accounting for attenuation due to the presence of dust. By exploiting the BAGPIPES code, we constrained the SFHs for each galaxy with a delayed exponentially declining model to derive their mass-weighted age (tMW). Results. The spiral galaxies in our sample have similar radial tMW trends overall. A central old region (tMW up to ∼7 Gyr, consistent with the presence of a bulge for various systems) is followed by younger regions in which the disks are still forming stars (tMW ∼ 4 Gyr). At larger distances from the centre of the galaxies, tMW increases mildly in general. Strikingly, in two galaxies (NGC4321 and NGC5194), we found a steep increase in tMW that reached levels similar to those of the bulge. These old stellar populations in the very galaxy outskirts, which are also detectable as “quenched rings” below the spatially resolved MS, is unexpected. We discuss their potential origin by considering the different gas phases (HI and H2) of the source with the most prominent quenched ring, NGC4321, and argue for two main possibilities: (1) some environmental effect (e.g. starvation) could affect the outer edge of the galaxies or (2) the circumgalactic medium of sources outside of high-density clusters might have stopped to supply pristine gas to the galaxy (e.g. if its specific angular moment is too high for being accreted).

Electrochemiluminescence aptasensor toward femtomolar detection of alpha synuclein oligomer as parkinson's disease marker using CdTe@ZnS quantum dots as luminescent label and graphdiyne@polyaniline as novel co‐reactant

AbstractParkinson's disease (PD) as a progressive health issue effects on the central nervous system. It is well established that soluble ‐synuclein (−syn) oligomers cause neuronal death in the earliest stages of PD. So, development of sensitive and selective method for a‐syn analysis is a challenge. Here an electrochemiluminescence (ECL) aptasensor designed for selective and ultrasensitive detection of α‐syn oligomer using graphdiyne@polyaniline with N‐doped active sites (GDY@PANI) as novel coreactant agent combined with CdTe@ZnS QD as luminescent lable for amplified self‐enhanced electrochemiluminescence (ECL) response. For the first time a novel ECL sensing platform based on GDY@PANI/CdTe@ZnS QD composite was designed using new co‐reactant based on GDY. Compared to CdTe@ZnS QD, GDY/CdTe@ZnS QD, CdTe@ZnS QD/tri‐propylamine and PANI/CdTe@ZnS QD, the GDY@PANI/CdTe@ZnS QD composite exhibited amplified ECL emissions and ECL efficiency of the proposed system also increased compared to more QDs based ECL systems. Under the optimal conditions, the proposed ECL aptasensor exhibited a wide linear range of 0.2 fM to 8 nM for α‐syn oligomer determination with a low detection limit of 0.02 fM (S/N=3). The fabricated sensor has advantages of good reproducibility, high sensitivity and stability and being capable of detecting α‐syn oligomer in human blood serum and also lysate of dopaminergic nerve cells. The obtained results confirmed that the GDY@PANI can be used as a novel co‐reactant in development of the ECL based bio devices with great potential applicability for biomarkers analysis, diagnosis and management of Parkinson or other diseases.

Differential effects of choline on TLR2/4 mediated signaling through possible regulation of toll-interacting protein in hepatocellular carcinoma cell lines

Abstract Objectives Toll-like receptor (TLR) mediated inflammatory status plays an important role in development and progression of hepatocellular carcinoma (HCC). Toll-interacting protein (TOLLIP) has an inhibitory effect on TLR-mediated inflammatory signalling and expression profile of TOLLIP varies between malignancies including HCC. Cholinergic anti-inflammatory pathway (CAP) is an endogenous mechanism that controls inflammatory status via α7nicotinic acetylcholine receptors (α7nAChR). This study aims to investigate the effect of CAP-acting agent choline on TOLLIP and its related TLR-mediated inflammatory response in HCC cells with distinct differentiation stages. Methods The expression patterns of α7nAChR, TLR2/4, TOLLIP, IL6,NFkB genes were evaluated by RT-PCR and ELISA in the presence of choline, along with the real-time cell proliferation and migration in HEP3B and SNU449 HCC cell lines. The interaction between choline and TOLLIP assessed by using in-silico analyses. Results Choline downregulated TOLLIP in Hep3B and SNU449 cells. However, the expressions of α7nAChR, NF-κB, IL-6, TLR2 and TLR4 showed a decreased pattern in well differentiated HEP3B cells, while an increased pattern in poorly differentiated SNU449 cells. Conclusions Choline might exert differential effects in TLR2/4-dependent signalling based on the differentiation stages of the HCC cells, suggesting its potential therapeutic effects in earlier stages of HCC which might be result of its partial modulation of TOLLIP.

Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review From NAFLD to MAFLD and MASLD.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide, making it the leading cause of liver related morbidity and mortality. Currently, liver biopsy is the gold standard for assessing individuals with steatohepatitis and fibrosis. However, its invasiveness, sampling variability, and impracticality for large-scale screening has driven the search for non-invasive methods for early diagnosis and staging. In this review, we comprehensively summarise the evidence on the diagnostic performance and limitations of existing non-invasive serum biomarkers and scores in the diagnosis and evaluation of steatosis, steatohepatitis, and fibrosis. Several non-invasive serum biomarkers and scores have been developed over the last decade, although none has successfully been able to replace liver biopsy. The introduction of new NAFLD terminology, namely metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently metabolic dysfunction-associated steatotic liver disease (MASLD), has initiated a debate on the interchangeability of these terminologies. Indeed, there is a need for more research on the variability of the performance of non-invasive serum biomarkers and scores across the diagnostic entities of NAFLD, MAFLD and MASLD. There remains a significant need for finding valid and reliable non-invasive methods for early diagnosis and assessment of steatohepatitis and fibrosis to facilitate prompt risk stratification and management to prevent disease progression and complications. Further exploration of the landscape of MASLD under the newly defined disease subtypes is warranted, with the need for more robust evidence to support the use of commonly used serum scores against the new MASLD criteria and validation of previously developed scores.