bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant S-1 plus cisplatin-based chemoradiotherapy compared with surgery alone for locally advanced gastric cancer: Randomized, phase II trial.
Authors: Hong Moonki , Yun Kum-Hee , Jung Minkyu , Rha Sun Young , Kim Hyoung-Il , Park Jun Chul , Lee Sang Kil , Choi Seo Hee , Jung Inkyung , Lim Joon Seok , Hyung Woo Jin , Koom Woong Sub , Kim Hyo Song 
Published: June 2024

4076 Background: Patients with locally advanced gastric cancer (LAGC), are known to have a high risk of recurrence even after surgery. This study was designed to delineate whether neoadjuvant concurrent chemoradiotherapy (CCRT) using the S-1/Cisplatin (SP) regimen can effectively downstage the T stage in patients with clinically T4 stage compared with surgery alone (OP). Methods: This is a randomized phase II open label trial and gastric cancer patients with initial clinical T4 were enrolled. Patients were randomized into neoadjuvant CCRT or OP. For the CCRT group, S-1 (20 mg/m2 twice daily, 2 weeks on and 1 week off) and cisplatin (30 mg/m2/day, first day of week 1, 2, 4, and 5) were administered concurrent with radiotherapy (day 1-5 for 5 weeks, total 45 Gy/25 fractions,). Surgery was performed within 3 to 6 weeks after the completion of CCRT. For the OP group, curative surgery was performed within 3 weeks after randomization. Post-operative adjuvant chemotherapy was chosen as S-1 monotherapy or combination of Capecitabine, and Oxaliplatin according to the physician’s choice. The primary objective of this study was to compare the downstaging rates between the groups (65% and 40% for the CCRT and OP group). Using a type I error rate of 0.10 and a power of 0.80, the planned sample size was 51 patients per group but the study was closed prematurely. Results: Between November 2016 and August 2021, 49 patients with T4 were enrolled. Of those, 26 (CCRT) and 23 (OP) patients were randomized but diagnostic laparoscopy for preoperative screening revealed peritoneal seeding in some patients. Finally, 23 (CCRT) and 17 (OP) patients were evaluable and clinicopathologic characteristics were well balanced between the two groups in per protocol analysis. For CCRT, 19 out of 23 (82.61%) patients satisfied downstage, while among 8 out of 17 (47.06%) patients in OP group satisfied downstage ( P=0.038). The median disease-free survival (DFS) was 27.91 months in CCRT group, and 45.96 months in OP group ( P=0.985). The median overall survival (OS) was not reached in CCRT group, and 51.2 months in OR group ( P=0.335). There were no statistically significant differences between neoadjuvant CCRT and surgery group in the aspect of both hematologic and non-hematologic adverse events. Conclusions: In this study, neoadjuvant SP based CCRT significantly increased downstaging in T stage compared than OP alone. The prespecified genomic analysis with transcriptomic sequencing will be available at the meeting. Clinical trial information: NCT03814759 .
Extracellular (EC) Mucin5AC (MUC5AC) detection after neoadjuvant therapy (NAT) and the risk of recurrence in resected pancreatic ductal adenocarcinoma (R-PDA).
Authors: Manne Ashish , Esnakula Ashwini K. , Sheel Ankur , Sara Amir , He Kai , Cloyd Jordan M. , Noonan Anne M. , Hays John L. , Roychowdhury Sameek , Mittra Arjun , Malalur Pannaga G. , Jin Ning , Rahman Shafia , Tsai Susan , Dillhoff Mary , Yang Wancai , Yu Lianbo 
Published: June 2024

4171 Background: The clinical significance of MUC5AC glycoforms is unclear to date. Our earlier study showed the association of lower mature (MM) and immature (IM) MUC5AC in R-PDA with pathological treatment response and EC detection of MM (EC-MM). Here, we have the significance of EC-MM detection in the tissue of R-PDA post-NAT. Methods: Formalin-fixed paraffin-embedded tissue blocks of R-PDA from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Using monoclonal antibodies for 45M1 (MM) and CLH2 (IM), immunohistochemistry was performed to study the cellular expression of MM and IM, and H-scores were calculated. Also, the presence or absence of EC expression of MM is noted. progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Univariate and multivariate Cox regression models were used to model PFS and OS, and clinical and pathological variables were adjusted in the multivariate models. We performed univariate logistic regression analysis to examine the impact of MUC5AC expression on pathological features in resected specimens. Results: Among 100 R-PDA patients, 43 received NAT and 57 had upfront surgery (UpS)). In NAT-group (36-FOLFIRINOX, 2-FOLFOX, and 5-gemcitabine/nab-paclitaxel), EC-MM detection in the resected specimens was associated with worse PFS on multivariate analysis (MVA) (Hazard Ratio (HR) 0.2, 95 % CI: 0.059-0.766, p = 0.01). In the FOLFIRINOX-treated group, the EC-MM detection had a similar impact (HR 0.2, 95 % CI: 0.052-0.847, p = 0.02) on PFS. Cellular MM and IM expression were significant (p < 0.05) on MVA for OS in both groups, but the HRs were not clinically significant (NAT-group, MM - 0.9 & IM - 1.04, FOLFIRNIOX-group, MM - 0.8 & IM -1.02). Expression levels of cellular MM and IM in FOLFIRINOX group and MM alone in NAT-group significantly (p < 0.05) correlated with incomplete resection (R1/R2 vs R0) and perineural invasion. In the UpS group, MUC5AC glycoforms did not significantly correlate with survival or pathological features. Conclusions: Post NAT EC-MM detection and cellular MUC5AC (MM and IM) expression levels are associated with worse PFS and pathological features. Their role in the treatment of naïve patients is still unclear. MUC5AC can be a clinically useful predictive biomarker. Future research should focus examining its importance in advanced tumors and manipulating it for therapeutic purposes.
Effect of tocotrienol and tocopherol regulation by the microbiome on colitis-associated cancer.
Authors: Stafford Amanda , Lam Jie (James) Min , Basgaran Amedra , Lymberopoulos Eva , Tanweer Mohammad , Hobbs Michael , Arney James , Korovilas Dionisios , Delanoue David , Moore Stephen , Alomari Muhannad , Sharma Nikhil 
Published: June 2024

e15512 Background: The association between inflammatory bowel disease (IBD) and a higher risk of colorectal cancer (CRC) has been well established, and is commonly attributed to chronic inflammation and a predisposition to genomic instability ( Feagins et al., 2009 ). Independently, an altered gut microbiome has been evidenced in both IBD ( Halfvarson et al., 2017 ) and CRC ( Marchesi et al., 2011 ). It is unknown whether the altered the IBD-associated microbiome is able to directly influence carcinogenesis via an inflammation-independent mechanisms. Methods: Microbiome analysis was performed using BioCorteX’s industry-leading knowledge graph and integrated proprietary engines v20240126_153156. 2,081 stool samples from adults with IBD and 2,000 stool samples from healthy adults were included. Shannon’s Diversity Index was used to consider within-sample diversity, and PERMANOVA and dimensional scaling based (MDS) on Bray-Curtis diversity was used to consider between-sample diversity. Differential abundance analysis was used to identify species significantly associated with IBD, and a database built on existing literature was used to consider their metabolic products and interactions with known human oncogenes and tumour suppressor genes. Results: Our results show a clearly separation of the IBD microbiome from the healthy population (PERMANOVA p = 0.01), as well as a collapse in Shannon diversity (p < 2.2e-16). Compared to the healthy microbiome, 79 species were significantly (FDR < 0.01) enriched in the IBD stool microbiome, including: Bacteroides fragilis, Bacteroides vulgatus, Bacteroides uniformis, Escherichia coli, Veillonella parvula, Enterococcus faecalis, Fusobacterium mortiferum, and Fusobacterium ulcerans, all of which have previously been evidenced to be enriched in CRC ( Randa et al., 2023 , Bi et al., 2022 , Du et al., 2022 ). Conversely, 115 species were enriched in healthy subjects, including several bacteria with probiotic and anti-tumourigeneic potential such as: Segatella copri, Roseburia inulinivorans, Lactobacillus rogosae, and Coprococcus comes ( Sarah et al., 2022 , Kang et al., 2023 , Campisciano et al., 2020 , Yang et al., 2019 ) Two of the bacteria enriched in the healthy group are producers of both delta-tocotrienol and gamma-tocopherol. These vitamin E isoforms have been implicated in suppression of cancer invasion and proliferation ( Ya et al., 2008 ), in part through NFkB signalling ( Ling et al., 2012 ). Conclusions: This work suggests that that IBD-associated microbiome may contribute to colorectal cancer risk via the suppression of vitamin E isoform signalling, a mechanism that is independent from inflammation. This could present a highly targetable way of mediating CRC-risk in the IBD population.
Exploring young-onset colorectal cancer sex difference incidence rates by race and ethnicity: A SEER database analysis (2000-2020).
Authors: Hechter Sharon , Appiah Jennifer , Kanukuntla Anish Kumar , Alnaser Ibrahim , Eliachevsky Christina , Ji Sophia , Nair Ambica , Greenberg David B. 
Published: June 2024

e15529 Background: Since 1994, there has been a 51% increase in young onset colorectal cancer incidence rates, as reported by the National Cancer Institute. Recently, the U.S. Preventative Task Force revised its guidelines, recommending colorectal cancer screening to commence at age 45 rather than 50. This study aimed to explore sex differences in cancer incidence across various race and ethnicities, aiming to discern whether these differences are rooted in biological factors or environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology and End Result (SEER) program (2000-2020) was used to calculate male-to-female incidence rate ratios (MF IRR) for colon and rectal cancer, stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic), and age-standardized to the 2000 U.S. population for individuals under the age of 50 diagnosed with colon or rectal cancer. Results: A total of 82,238 patients with colorectal cancer under the age of 50 were identified in the study period. Of these, 43,255 (52.6%) were males and 38,983 (47.4%) were females. The incidence trends over the years were analyzed, revealing a steady increase, with the highest incidence found in 2019 (4,819, 5.8%) and the lowest in 2000 (3,189, 3.8%). Non-Hispanic Whites comprised 57.2% of the cases, while the second and third largest groups were Non-Hispanic Black (13.2%) and Hispanic (17.9%). Incidence rates were highest among the non-Hispanic American Indian/Alaskan Native population (8.6 per 100,000 cases), followed by the non-Hispanic Black population (8.4 per 100,000 cases), and lowest in the Hispanic population (5.7 per 100,000 cases). Young-onset colorectal cancer incidence rates exhibited a male predominance, with the MF IRR consistently > 1 every year across race and ethnicity. Non-Hispanic Asian/Pacific Islander had the highest MF IRRs (7 per 100,000 cases in males vs. 5.8 per 100,000 cases in females), while Non-Hispanic American Indian/Alaskan Native had the lowest MF IRRs throughout the years, with the lowest being in 2019 (5.1 per 100,000 cases in males vs. 12.6 per 100,000 cases in females). Conclusions: The MF IRR for young onset colorectal cancer showed no significant variation by race, implying a potential influence of biological factors. Notably, disparities in incidence rates were observed among different racial and ethnic groups, with the highest rates among non-Hispanic Black and non-Hispanic American Indian/Alaskan Native populations. Further research is warranted to pinpoint specific factors driving young onset colorectal cancer, facilitating targeted interventions for at-risk populations.
Study of ELU001, a C’Dot drug conjugate (CDC) targeting folate receptor α (FRα) overexpressing solid tumors.
Authors: Ma Wen Wee , Tolcher Anthony W. , Perez Cesar Augusto , Wahner Hendrickson Andrea Elisabeth , Orr Douglas W. , Murciano-Goroff Yonina R. , Anders Carey K. , Hamilton Erika P. , Swisher Elizabeth M. , Mathews Cara Amanda , Bashir Babar , Rojas-Espaillat Luis Alexander , Colon-Otero Gerardo , Adams Gregory Paul , Reddick Catherine W. , Bayever Eliel 
Published: June 2024

TPS3173 Background: ELU001, pasifolate exatecan, is an ultra-small nanoparticle drug conjugate, known as a CDC (~6 nm), designed to target and penetrate into solid tumors. Due to its size, ELU001 exhibits rapid renal elimination which is expected to reduce or eliminate the toxicities associated with many antibody drug conjugates. ELU001 has ~13 folic acid targeting moieties and ~21 cathepsin-B cleavable exatecan topoisomerase-1 inhibitor payloads covalently bound to short polyethylene glycol chains surrounding a silica core, the C’Dot. ELU001 binds to cancer cells expressing FRα and is internalized into the lysosome where it releases the exatecan payload. ELU001’s dose escalation study reported at ESMO Congress 2023 (1), examined weekly, bi-weekly (Q2W), and tri-weekly schedules over a range of doses in 42 patients. The study revealed that ELU001 could be administered safely and identified a dose level and schedule for the Expansion Studies described below. 22 of the patients with ovarian or endometrial cancers had >1 post-baseline scan(s), of these 2 had a PR and 19 had SD by RECIST v1.1 criteria. ELU001 demonstrated activity against tumors across a range of FRα expression levels, from low to high, retrospectively assessed using the VENTANA FOLR1 RxDx assay and the PS2+ scoring system. Methods: The current multicenter, Tumor Group Expansion open-label phase 1/2 clinical trial investigates ELU001 in patients with ovarian and endometrial cancers and is enrolling three cohorts; 1) ovarian cancer with high FRα expression, 2) ovarian cancer with moderate and low expression and 3) endometrial cancer with low to high expression with assessments based upon the PS2+ scoring system (high = ≥ 75%, moderate = ≥ 50% to < 75%, low = 25% to < 50%, negative = <25% of tumor cells with 2+ or 3+ staining intensity). An initial exploratory dose of 2.0 mg/m2 Q2W was employed in all three cohorts and a second dose of 1.7 mg/m2 Q2W will be studied in the ovarian cancer cohorts. Patients will ultimately be randomized to one of two or more doses to optimize dosing for registration. Primary endpoint: Objective Response Rate (ORR); secondary endpoints include DOR, PFS, TFST, PFS2, OS, adverse events, PK, and ADA assessments. Approximately 20 patients per tumor group will be recruited in the U.S. 1. Ann. Oncol. (2023) 34 (suppl_2): S458-S497. Clinical trial information: NCT05001282 .
Total neoadjuvant therapy with split-course hypofraction radiotherapy combined with CAPOX and envafolimab followed by local excision for locally advanced very low rectal cancer (TRACE-LE): An open-label, single-arm, multicenter, phase II trial.
Authors: Jiang Weizhong , Chi Pan , Tao Kaixiong , Xu Dongbo , Yang Chunkang , Zheng Rong , Xu Benhua , Huang Ying , Chen Zhifen , Huang Shenghui , Xu Zongbin 
Published: June 2024

TPS3647 Background: In the treatment of patients with locally advanced very low rectal cancer, neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is considered a standard therapeutic approach. Short-course hypofractionated radiotherapy, in combination with subsequent chemotherapy, has been shown to be comparable to long-term chemoradiotherapy in terms of neoadjuvant therapy effects in rectal cancer. Additionally, it has been observed that hypofractionated radiotherapy, when combined with programmed death L-1 (PD-L1) blockade, can enhance the immune response. This study aims to investigate efficacy and safety of organ preservation in patients with locally advanced very low rectal cancer by utilizing total neoadjuvant therapy involving split-course hypofraction radiotherapy in conjunction with CAPOX and Envafolimab (a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment). Methods: TheTRACE-LE trail is an open-label, single-arm, multicenter, phase II trial. The target sample is 72 participants. Key eligibility criteria include individuals aged 18-75, confirmed rectal adenocarcinoma, cT3-4N0/cT1-4N1-2 with lower margin ≤ 2cm from anorectal ring's upper edge (MRI) and ECOG performance status of 0-2. The treatment protocol include preoperative split-course hypofractionated radiotherapy (5×7Gy), in conjunction with 6 cycles of CAPOX chemotherapy and Enverolimab (300 mg subcutaneous injections) administered in a 3-week treatment cycle. The primary outcome measure is organ preservation, specifically the rectum intact, owing to no radical total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes). The secondary outcome measures encompass ypT0-1 rate, pathological complete response (pCR) rate, acute and late toxicity as per NCICTCAE V.5.0, local recurrence rate, local regional recurrence rate, disease-free survival, quality of life, and anorectal function. Clinical trial information: NCT05970900 .
Financial Toxicity and Willingness-to-Pay for Cancer Treatment Among People With Multiple Myeloma
Authors: Fiala Mark A. 
Published: June 2024

PURPOSE This study used willingness-to-pay (WTP) exercises to explore the relationships between race, financial toxicity, and treatment decision making among people with cancer. METHODS A convenience sample of people with multiple myeloma who attended an academic medical center in 2022 was surveyed. Financial toxicity was assessed by the Comprehensive Score for financial Toxicity, with scores <26 indicating financial toxicity. WTP was assessed with (1) a discrete choice experiment (DCE), (2) fixed-choice tasks, and (3) a bidding game. RESULTS In total, 156 people were approached, and 130 completed the survey. The majority of the sample was White (n = 99), whereas 24% (n = 31) was African American or Black. Forty-six percent (n = 60) of the sample were experiencing financial toxicity. In the DCE, the relative importance of cost was twice as high for those with financial toxicity (30% compared with 14%; P < .001). In the fixed-choice tasks, they were twice as likely to accept a treatment with shorter progression-free survival but lower costs (adjusted odds ratio [aOR], 2.47; P = .049). In the bidding game, the median monthly WTP of those with financial toxicity was half that of those without ($100 in US dollars [USD] compared with $200 USD; P < .001). Only in the bidding game was race statistically associated with WTP; after controlling for financial toxicity, African American or Black participants were three times as likely (aOR, 3.06; P = .007) to report a lower WTP. CONCLUSION Across all three exercises, participants with financial toxicity reported lower WTP than those without. As financial toxicity disproportionally affects some segments of patients, it is possible that financial toxicity contributes to cancer disparities.
The Association of Adiposity and RAAS With Incident Diabetes in African Americans: The Jackson Heart Study
Authors: Nedungadi Divya , Ayodele Adesanya Timothy M , Rayan Melanie Natasha , Zhao Songzhu , Williams Amaris , Brock Guy , Joseph Joshua J 
Published: June 2024

Abstract

Background
The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American adults. However, studies have not examined the combined interaction between RAAS and adiposity measures in relation to diabetes risk in African American adults.

Objective
We examined the longitudinal association of combined RAAS and adiposity measures with incident diabetes among African American adults in the Jackson Heart Study.

Methods
African American adults were assessed at baseline (2000-2004) and over 12 years of follow-up. RAAS, anthropometric (waist circumference [WC], body mass index), and adipokine (adiponectin, leptin, leptin to adiponectin ratio [LAR]) measures were collected at baseline. Aldosterone, WC, and LAR were chosen as the best predictor variables. The final model, adjusting for age, sex, education, occupation, systolic blood pressure, smoking, physical activity and RAAS-altering medications, incorporated these variables and their interactions (WC*aldosterone + LAR*aldosterone) to explore their impact on incident diabetes.

Results
Among 3219 participants without diabetes at baseline, there were 554 incident cases over a median follow-up period of 7.5 years. Aldosterone, WC, and LAR were positively associated with incident diabetes (all P &lt; .05). A significant interaction was found between WC and aldosterone, with a greater association among individuals with lower WC. This interaction was significant in participants with prediabetes but not in those with normoglycemia. No significant interaction was found between log-LAR and aldosterone with risk of incident diabetes.

Conclusion
Higher aldosterone in participants is associated with greater risk of diabetes, particularly among individuals with prediabetes and lower WC.
An Irak1-Mecp2 tandem duplication mouse model for the study of MECP2 duplication syndrome
Authors: Maino Eleonora , Scott Ori , Rizvi Samar Z. , Chan Wing Suen , Visuvanathan Shagana , Zablah Youssif Ben , Li Hongbin , Sengar Ameet S. , Salter Michael W. , Jia Zhengping , Rossant Janet , Cohn Ronald D. , Gu Bin , Ivakine Evgueni A. 
Published: June 2024

ABSTRACT
MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1. Current MDS mouse models involve transgenic expression of MECP2 only, limiting their applicability to the study of the disease. Herein, we show that an efficient and precise CRISPR/Cas9 fusion proximity-based approach can be utilized to generate an Irak1-Mecp2 tandem duplication mouse model (‘Mecp2 Dup’). The Mecp2 Dup mouse model recapitulates the genomic landscape of human MDS by harboring a 160 kb tandem duplication encompassing Mecp2 and Irak1, representing the minimal disease-causing duplication, and the neighboring genes Opn1mw and Tex28. The Mecp2 Dup model exhibits neuro-behavioral abnormalities, and an abnormal immune response to infection not previously observed in other mouse models, possibly owing to Irak1 overexpression. The Mecp2 Dup model thus provides a tool to investigate MDS disease mechanisms and develop potential therapies applicable to patients.
c-Src-induced vascular malformations require localised matrix degradation at focal adhesions
Authors: Essebier Patricia , Keyser Mikaela , Yordanov Teodor , Hill Brittany , Yu Alexander , Noordstra Ivar , Yap Alpha S. , Stehbens Samantha J. , Lagendijk Anne K. , Schimmel Lilian , Gordon Emma J. 
Published: June 2024

ABSTRACT
Endothelial cells lining the blood vessel wall communicate intricately with the surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require the capability to enzymatically degrade the matrix surrounding them, to facilitate vascular expansion. c-Src plays a key role in blood vessel growth, with its loss in the endothelium reducing vessel sprouting and focal adhesion signalling. Here, we show that constitutive activation of c-Src in endothelial cells results in rapid vascular expansion, operating independently of growth factor stimulation or fluid shear stress forces. This is driven by an increase in focal adhesion signalling and size, with enhancement of localised secretion of matrix metalloproteinases responsible for extracellular matrix remodelling. Inhibition of matrix metalloproteinase activity results in a robust rescue of the vascular expansion elicited by heightened c-Src activity. This supports the premise that moderating focal adhesion-related events and matrix degradation can counteract abnormal vascular expansion, with implications for pathologies driven by unusual vascular morphologies.