Early Stage Research Articles

Analysis of Research Publications on Leprosy Drugs Related Adverse Drug Reactions – A Scinetometric Study

Abstract: Leprosy is curable and can be treated with multidrug therapy in the early stages. As a result, we chose a Scientometrics evaluation of leprosy research guides on adverse drug reactions to better grasp the current popularity of drug-related responses. During the 2010-2021 a study with a total of 48 publications was selected. This study aims to analyze scientometric tools such as frequency distribution, percentage analysis, double-related growth rate, and interaction rate. During the study period, 7 (14.58%) study publications were submitted in 2018. The related growth rate is identified by decreasing trend and the double time is growing from 2010 to 2021. The 11 published study sizes (22.92%) were provided by top writers, the average Degree of Collaboration is 0.96, and 19 (39.58%) published research articles by headers. India is the largest supplier of 21 leprosy research publications (43.75%). As India is the most productive country in leprosy research, hence there are four out of the top five institutions that are from the Indian center that is listed among the most productive institutions.

Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: A SEER population-based study

BackgroundCombined small cell lung cancer (C-SCLC) is a rare type of small cell lung cancer (SCLC), and it is controversial whether to choose the same treatment regimen as SCLC due to its multiple histologic components. Study methods and resultsRecords of patients with small cell lung cancer diagnosed between 2010 and 2020 were extracted using the SEER database. The OS of patients with different histological types under the same staging and treatment regimen was analyzed. It was found that early-stage (stage IA-IIA) surgical treatment, systemic chemotherapy alone, and chemoradiotherapy were more efficacious than C-SCLC and P-SCLC in patients with limited-stage (P = 0.054, P = 0.001, P = 0.019). In patients with extensive staging, the OS of patients with systemic chemotherapy regimens differed (P = 0.045) and was better in C-SCLC than in P-SCLC. We further explored the treatment strategy for patients with C-SCLC, which was shown by a COX regression model based on prognostic factors screened by Random Forest and LASSO regression models. Surgery, radiotherapy, and chemotherapy would be beneficial for survival. In a subgroup analysis based on stage and treatment regimen, it was shown that patients with early staging (stage IA-IIA) had a better prognosis with surgery (P < 0.001); in patients with extensive staging, chemoradiotherapy was favorable to the patient's prognosis (P = 0.022). ConclusionBoth limited-stage and extensive-stage C-SCLC patients are more sensitive to chemotherapy than P-SCLC patients. Patients with C-SCLC who have access to surgery should undergo surgery as early as possible, while chemoradiotherapy is recommended for patients with extensive staging. Patient age, gender, tumor size, surgery, chemotherapy, radiotherapy, and metastasis may individually affect patient prognosis.

An Updated Review on Molecular Biomarkers in Diagnosis and Therapy of Colorectal Cancer.

Colorectal cancer is one of the most common cancer types worldwide. Since colorectal cancer takes time to develop, its incidence and mortality can be treated effectively if it is detected in its early stages. As a result, non-invasive or invasive biomarkers play an essential role in the early diagnosis of colorectal cancer. Many experimental studies have been carried out to assess genetic, epigenetic, or protein markers in feces, serum, and tissue. It may be possible to find biomarkers that will help with the diagnosis of colorectal cancer by identifying the genes, RNAs, and/or proteins indicative of cancer growth. Recent advancements in the molecular subtypes of colorectal cancer, DNA methylation, microRNAs, long noncoding RNAs, exosomes, and their involvement in colorectal cancer have led to the discovery of novel biomarkers. In small-scale investigations, most biomarkers appear promising. However, large-scale clinical trials are required to validate their effectiveness before routine clinical implementation. Hence, this review focuses on small-scale investigations and results of big data analysis that may provide an overview of the biomarkers for the diagnosis, therapy, and prognosis of colorectal cancer.

Representativeness of race, ethnicity and social determinants of health in patients with advanced non-small cell lung cancer via linkage of real-world electronic health records, administrative claims, and consumer financial data.

e13559 Background: Social determinants of health (SDOH) are both drivers of health disparities and barriers to clinical research participation, particularly among historically underserved or marginalized populations. Using real-world data (RWD), diversity plans in cancer clinical trials frequently aim to reduce disparities and improve representation. Our aim was to describe the representativeness of patients with advanced non-small cell lung cancer (aNSCLC) with respect to race, ethnicity and person-level SDOH in a curated electronic health record (EHR) database. Methods: This was a retrospective cohort study of individuals diagnosed with aNSCLC between 2016–2022 in a US-based oncology EHR database (ConcertAI). Information on person-level SDOH was derived from linkage of curated EHR data to administrative claims and consumer financial data. These data were also compared to a sample of patients diagnosed with first primary NSCLC from the Surveillance, Epidemiology, and End Results (SEER) Program and American Community Survey (ACS), where possible. The Kaplan-Meier product limit estimator was used to compare time from advanced diagnosis to treatment initiation. Results: From an overall sample of 17,772 patients with aNSCLC, a total of 10,390 patients had 1 or more SDOH characteristics of interest documented. Compared with patients without linked SDOH data, a higher proportion of patients with linked person-level SDOH data were non-Hispanic (NH) White patients (79% vs 71%) and lower proportions were NH Black (10% vs 13%), NH Asian/Pacific Islander (2% vs 4%) and Hispanic patients (2% vs 4%). Patients with linked SDOH were also more likely to have aNSCLC progressed from an earlier stage and received biomarker testing for targetable alterations. Overall, 54% of patients were married, 38% completed a bachelor’s degree or higher, 14% worked in a blue-collar occupation, and 61% had an individual income of ≤$35,000. All 4 of these SDOH characteristics differed significantly by race/ethnicity. Differences in time-to-treatment initiation were statistically significant by marital status (median of 50 [married] vs 55 [not married] days; P=0.02) and individual income (median of 50 [&gt;$60,000] vs 55 [≤$30,000] days; P=0.04). Patients with aNSCLC in these data differed from patients in SEER and ACS estimates with respect to greater representation of patients who are NH White, have lower levels of education, and lower individual income. Conclusions: This analysis demonstrated the feasibility of measuring person-level SDOH using EHR from patients with aNSCLC treated at oncology clinics across the US. RWD with linked SDOH characteristics should be used cautiously to address the representativeness gap in evidence from oncology trials given their potential inherent selection biases.

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&lt;.01), resided in lower median income zip codes at the time of diagnosis (p&lt;.001), had a higher Charlson-Deyo (CD) comorbidity score (p&lt;.001), and were less likely to have private insurance (p&lt;.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 &lt; .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 &gt; 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 &lt; 40; 53.8% in 40-49; and 39.4% in &gt;50; p &lt; 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged &gt;40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients &gt;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 &lt; 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 &lt; 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&lt;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.

Impact of video vector analysis of ankle foot orthoses in children with physical disability: A 10-year clinical review

BackgroundAnkle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown. Research questionTo investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability. MethodsAll children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively. Results141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39 %, n=55), unilateral cerebral palsy (38 %, n=54), spina bifida (9 %, n=13), hereditary spastic paraparesis (2 %, n=3) and other (11 %, n=16). No changes were made in 52 % of cases (n=74), tuning in 22 % of cases (n=31), the AFO was recast in 13 % of cases (n=19) and discontinued in 10 % of cases (n=14). A prescription change was recommended in 3 % of cases (n=4). SignificanceOur findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage.

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&lt;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.

Impact of cancer screening results on patient-reported outcomes (PRO) and behavioral intentions.

10608 Background: Cancer is one of the most feared diseases. Multi-cancer early detection (MCED) tests have the potential to expand the number of cancers that are detected at earlier stages, which could result in better clinical outcomes. However, behavioral impacts based on MCED test results could affect the utility and value of these tests. Methods: Two independent data sources evaluated the impact of MCED test results on behavioral intentions and perceptions: a survey of the general population and PRO in an MCED clinical trial. A web-based, 30-minute survey of the US general population was used to ascertain attitudes toward a hypothetical MCED test. Eligible respondents were adults aged 40-80 years without a cancer diagnosis in the previous 5 years. The survey assessed the perceived value of negative results (ie, no cancer signal detected [NCSD]) and the projected impact on post-test behaviors. The prospective PATHFINDER study (NCT04241796) of adults aged ≥50 years who underwent MCED cancer screening included PRO assessments. Post-test assessments included: "I am feeling relieved about my test result" from the adapted MICRA and “How likely are you to follow your healthcare provider’s cancer screening recommendations.” The consistency of sentiment after an NCSD MCED result from the online survey and clinical study was assessed. Results: Of the 1073 online survey respondents, 53% were female, 77% White, 14% Black/African American, and 13% Hispanic. Mean age was 58 years. The most common anticipated emotional impacts were relief (84%), happiness (72%), and confidence (69%). Respondents (66-70%) reported they would expect less worry, fear, stress, and anxiety after an NCSD MCED result. The majority (73%) reported they would maintain or improve health behaviors after an NCSD result. NCSD results were projected to lead to an increase in health-related behaviors, including adherence to recommended cancer screening (98%; 68% increase, 30% maintain current level) and regular doctor visits (46%). Of the 6529 PATHFINDER study participants who received NCSD results, 64% were female, 92% White. Mean age was 63 years. 80% of participants (n = 4685/5865) with NCSD felt relief "sometimes" or "often" after their MCED test result. Over 95% of participants (n = 5637/5863) with NCSD indicated they were "likely" or "very likely" to adhere to cancer screening recommendations in the future. Conclusions: Results from a general population survey and a prospective clinical study indicate that an NCSD result may be associated with positive cancer screening intentions and other preventive healthcare behaviors. An NCSD result may also positively impact psychological and emotional health. While these findings suggest that an NCSD result may provide additional value beyond traditional clinical benefits associated with cancer screening, future research is needed to delineate the behavioral impact following MCED screening. Clinical trial information: NCT04241796 .

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 &lt;25) and obese (BMI &gt;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 &lt; 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]

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.

European beech (Fagus sylvatica L.): A promising candidate for future forest ecosystems in Central Europe amid climate change

Abstract On the one hand, the European beech (Fagus sylvatica L.) is the tree of the future due to ongoing climate changes, on the other hand, there are questions about its expansion and economic use as a replacement for the declining Norway spruce (Picea abies [L.] Karst.). This literature review examines 140 studies summarizing basic research on beech in the context of climate change. As a climax tree species, beech is becoming dominant again in parts of its original range at the middle and higher altitudes of Central Europe, following spruce. It is a shade-loving species that can thrive in various types of mixed forest stands. To cultivate beech, close-to-nature methods, shelterwood, or selection management are optimal. The occurrence of the beech seed year is influenced by factors such as precipitation, temperature, drought, and air pollution. Although beech is generally considered resistant to abiotic and biotic factors, it often needs protection against hoofed game browsing in the earliest stages of development. As climate change progresses, it is essential to cultivate beech in areas rich in precipitation and nutrients where it can thrive even under more extreme conditions. In optimal conditions, beech has shown intensive regeneration in recent years, aggressively displacing other tree species. However, with insufficient precipitation and prolonged periods of drought, beech loses its vigor, production, and ability to compete. For adaptation to climate change, it is recommended to select appropriate beech provenance, promote natural regeneration, and cultivate structurally differentiated stands through positive-selection thinning from above.

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&amp;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.