bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined impact of primary tumor molecular profile and location in the relapse pattern of early-stage, microsatellite stable colorectal cancer.
Authors: Manca Paolo , Kris Ayush , Walch Henry S. , Fong Christopher , Jee Justin , Pichotta Karl , Schultz Nikolaus , Chatila Walid Khaled , Sanchez-Vega Francisco , Yaeger Rona
Published: June 2024

3603

Background: The primary tumor location (PTL) and the genetic profile of colorectal cancer (CRC) impact the risk, localization and timing of metastases. We investigated the PTL-specific impact of genomic alterations in a large cohort of patients (pts) with localized, MSS CRC through the automatic data mining of radiology reports and comprehensive genome profiling (CGP). Methods: Eligible CRC cases consisted of consecutive early-stage primary tumor samples from pts seen at a single institution (Memorial Sloan Kettering, MSK). All tumors were MSS, without pathogenic POLE mutations, and diagnosed after Jan 1st 2015, when MSK-IMPACT testing was standard in the clinic. MSK-IMPACT sequencing provided CGP of 341-505 genes. All pts underwent at least 1 surveillance scan at MSK comprising at least chest, abdomen and pelvis, had a minimum follow-up (FUP) of 1 year and developed metastatic disease at least 6 months after initial diagnosis. Time to metastasis (TTM) for each anatomic site was retrieved from radiology reports using validated natural language processing methods. TTM was defined for each organ as the interval from the diagnosis until the first radiologic evidence of metastasis or last scan. TTMs and OS were modeled with univariate cox regression, using competitive risk of death for TTMs. FDR was used to account for multiple comparisons, with a threshold of <0.1. Results: The final cohort comprised 1442 pts, with a median FUP of 42.3 months (IQR 39.5-44.5) and a median number of 6 scans (IQR 4-10) per pt. The PTL was right colon, left colon and rectum in 305, 498 and 639 pts. Expected PTL-specific metastatic patterns were observed, comprising higher risk of peritoneal metastases for right-sided PTL (HR=1.41, p=0.050) and higher risk of lung metastases for rectal tumors (HR=1.45; p=0.004); rectal cancer had the highest risk of metastatic relapse (HR=1.42, p<0.001). The impact of genetic alterations on the risk of developing metastatic disease varied by PTL and the metastatic site. Ten, eight and one pathway-metastatic site significant associations were observed, respectively, in the left-sided, right-sided and rectal PTL cohorts; the most relevant are reported in the table. Conclusions: The metastatic patterns and prognostic stratification of pts with early-stage MSS CRC are affected by the interplay of PTL and genetic profile. Genomic alterations are less impactful on outcomes of pts with rectal cancers. [Table: see text]
Tumor microbiota, consensus molecular subtype and survival in colon adenocarcinoma.
Authors: Rodriguez Salas Nuria , Trilla-Fuertes Lucía , Gámez-Pozo Angelo , Lalanda-Delgado Pedro , Matamala-Luengo Daniel , Lopez Vacas Rocio , Dittmann Antje , Custodio Ana , Ghanem Ismael , Martinez-Perez Daniel , Fresno-Vara Juan Angel , Feliú Jaime
Published: June 2024

3607

Background: Microbiota can contribute to inflammation and tumor initiation and progression of colorectal cancer. The aim of this study was the characterization of microbiota proteins in colon adenocarcinoma paraffin samples and the study of the differential microbiota abundances according to survival and Consensus Molecular Subtypes (CMS). Methods: 158 patients with high-risk stage II and stage III colon cancer and treated with surgery and adjuvant chemotherapy were included into the study. Microbiota was studied in the tumor paraffin samples using mass-spectrometry proteomics. Protein isolations were prepared in SDS 2% and digested with trypsin. Then, an analysis of each sample was done using a data-independent acquisition (DIA) mode on an Orbitrap Fusion (Thermo Scientific). Proteomics identification and quantification was done in Spectronaut using Microbiome Database and SwissProt human database as references. Survival analyses were done using BRB Array Tools. Comparisons between CMS were performed using a Kruskal-Wallis test. Results: 158 colon cancer patients (mean age: 67 years, 41% women, 49(31%)-109(63%) stage II-III, 59(37%)-99(63%) right-left colon), were analyzed. Nineteen microbiota proteins and 2,696 human proteins were quantified. After applying quality criteria, 13 microbiota and 1,940 human proteins were used for subsequent analyses. Kaplan-Meier analyses determined three microbiota proteins related to DFS: 1. Firmicutes, Faecalibacterium, p=0.0038; 2. Fusobacteria, Fusobacterium, p=0.0066; 3. Bacteroidetes, Bacteroides, p=0.0099. A microbiota signature combining these three proteins was built, capable to distinguish between patients with low (5 years DFS 80%) and high-risk of relapse (5 years DFS 55%) (p=0.0021, HR= 2.62, 95%CI=(1.45-5.31)). AUC = 0.88. Multivariate analysis showed that the microbiota signature added prognostic value to tumor stage . Additionally, microbiota profiles were different between CMS. CMS1 had a higher expression of proteins from Bacteroidetes. CMS2 showed an enrichment in Prevotella and CMS4 had higher levels of Fusobacterium. Conclusions: Metaproteomics in colon adenocarcinoma paraffin samples were performed, identifying thirteen microbiota proteins after applying quality criteria. The presence of three specific microbiota proteins seems to be related to DFS in colon cancer and a prognostic signature combining them was built. Moreover, CMS had differential microbiota protein profiles, having CMS1 the higher expression of Bacteroidetes proteins, CMS2 had higher levels of Prevotella, and CMS4 presented higher levels of Fusobacterium.
A phase III trial comparing 5-FU plus cisplatin (CF) versus CF plus docetaxel or radiotherapy as neoadjuvant treatment for locally advanced esophageal cancer: 5-year follow-up from JCOG1109.
Authors: Kato Ken , Ito Yoshinori , Daiko Hiroyuki , Ozawa Soji , Ogata Takashi , Hara Hiroki , Kojima Takashi , Abe Tetsuya , Bamba Takeo , Watanabe Masaya , Kawakubo Hirofumi , Shibuya Yuichi , Tsubosa Yasuhiro , Takegawa Naoki , Kajiwara Takeshi , Baba Hideo , Ueno Masaki , Machida Ryunosuke , Nakamura Kenichi , Kitagawa Yuko
Published: June 2024

4082

Background: Triplet chemotherapy with CF plus docetaxel (DCF) improved survival compared to CF as a neoadjuvant treatment for locally advanced esophageal squamous cell cancer (ESCC) based on the result from JCOG1109 (jRCTs031180202). Here we report results with 5 years minimum follow-up. Methods: Eligible patients (pts) with ESCC of clinical stage IB, II, III (excluding T4) (UICC 7th) from 44 institutions were randomized 1:1:1 to neoadjuvant CF (cisplatin 80 mg/m2 on day1 plus 5-FU 800 mg/m2 on days 1-5 Q3W/2 course), DCF (docetaxel 70 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus 5-FU 750 mg/m2 on days 1-5 Q3W/3 course), or CF-RT (cisplatin 75 mg/m2 on day 1 plus 5-FU 1000 mg/m2 on days 1-4 Q4W/2 course, radiation 41.4 Gy/23 fr). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), and safety. Differences in OS was assessed in the ITT using the stratified log-rank test. The data cutoff date for the analysis was July 20, 2023. Results: Of 601 pts 199 CF, 202 DCF, and 200 CF-RT were enrolled from December 5, 2012 to July 20, 2018. Among 601 pts, 88.2% were male, median (range) age was 65 (30-75), clinical stage III (nonT4) pts were 62.6%. Median follow-up time (range) was 5.5 years (y) (0-10.6). Median OS in CF, DCF, and CF-RT arm were 5.8 y, 10.2 y, and 8.2 y, and 5-year OS was 51.9%, 65.1%, and 60.2%, respectively (stratified log-rank test: one-sided p = 0.004 for CF vs. DCF and one-sided p = 0.15 for CF vs. CF-RT). By the stratified Cox regression analysis for OS, hazard ratios (HR) [95% CI] with DCF vs. CF was 0.68 [0.51–0.91] and that with CF-RT vs. CF was 0.86 [0.66–1.13]. The HR for OS in exploratory comparison between DCF vs. CF-RT was 0.78 [0.59-1.05]. Median PFS in CF, DCF, and CF-RT arm were 2.7 y, 9.5 y, and 5.8 y, and 5-year PFS was 42.6%, 55.7%, and 53.5%, respectively. In the CF arm, there were initially 4 treatment-related and 15 other deaths, with 1 additional treatment-related and 2 other deaths over two more years. The DCF arm reported 4 and 10 deaths respectively, with 3 additional deaths from other causes. In the CF-RT arm, there were 4 treatment-related and 27 other deaths, followed by 2 more treatment-related and 4 other deaths in the extended period. Conclusions: After 5 years follow-up, neoadjuvant DCF continued to demonstrate clinically meaningful improvements in OS and PFS compared to CF in patients with locally advanced ESCC. Clinical trial information: jRCTs031180202 .
Neoadjuvant chemotherapy with albumin-bound paclitaxel plus cisplatin and capecitabine for locally advanced esophageal squamous cell carcinoma: A prospective phase II trial.
Authors: Zhang Wen , Li Yong , Xue Liyan , Qu Dong , Jiang Zhichao , Gao Shugeng , Zhou Aiping
Published: June 2024

4087

Background: Surgery-based combination therapy is the current primary treatment for nonmetastatic esophageal squamous cell carcinoma (ESCC). An increasing number of results indicate that neoadjuvant chemotherapy alone might be a choice for perioperative treatment. Previously, a retrospective study we conducted showed that neoadjuvant chemotherapy with albumin-bound paclitaxel plus cisplatin and capecitabine (referred to as the APCC regimen) for locally advanced ESCC had achieved promising results. To further confirm the efficacy of this regimen, we conducted this prospective phase II clinical study. Methods: Patients (pts) with locally advanced ESCC (cT2N+M0, cT3-4aNanyM0) received preoperative chemotherapy with the APCC regimen (albumin-bound paclitaxel 125 mg/m2 iv, day 1/8, cisplatin 60 mg/m2 iv day 1, and capecitabine 1750 mg/m2 po bid day 1-14, repeated every 21 days for 4 cycles). The primary endpoint was pathological complete response (pCR), and the secondary endpoints were major pathological response (MPR), the R0 resection rate, disease free survival (DFS), overall survival (OS), and safety. Results: A total of 82 pts were enrolled and all received 4 cycles of preoperative APCC regimen. Of the 80 (97.6%) pts who underwent surgery, the R0 resection rate was 100%, pCR was observed in 23 (28.7%) pts and 50 (62.5%) pts had an MPR. Postoperative pathology revealed that 42 (52.5%) pts had stage I (ypT0-2N0M0). The most common grade 3/4 adverse events of chemotherapy included neutropenia (25%), leukopenia (14.5%), nausea (7.5%) and peripheral neurotoxicity (5.5%). No neoadjuvant chemotherapy related, or perioperative death occurred. As of December 1, 2023, with a median follow-up time of 36.8 months, 16(19.5%) patients had recurrent disease, among which 8 (8.5%) pts had local recurrence, 10 (12.2%) pts had distant metastasis. The 3-year DFS rate was 79.4%. As of the last follow-up, eight pts died, and the 3-year survival rate was 88.8%. Conclusions: The results meet our initial aim that preoperative chemotherapy with albumin-bound paclitaxel, cisplatin and capecitabine is highly active and resulted in a considerable pCR and MPR rate with promising 3-year survival rate in pts with locally advanced ESCC, while well-tolerated. This triplet regimen could be another effective neoadjuvant treatment strategy for locally advanced ESCC. Clinical trial information: NCT04390958 .
A prospective phase 2 single-arm study to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (Keypoint-1).
Authors: Xu Peiran , Su Polan , Wang Weiwei , He Jia , Zhao Luo , Zhou Weixun , Merritt Robert , Li Li , He Kai
Published: June 2024

4088

Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent esophageal cancer type worldwide with poor prognosis and limited treatment options. Combination immunotherapy and chemotherapy improved the outcomes in patients (pts) with metastatic esophageal cancer. However, the benefit of neoadjuvant immuno-chemotherapy in pts with locally advanced ESCC is unknown. We evaluated the efficacy and safety of neoadjuvant treatment with pembrolizumab plus chemotherapy in pts with locally advanced ESCC. Methods: Eligible pts who were aged 18-80 years with untreated, locally advanced ESCC were enrolled in this single-arm, phase 2 trial at Peking Union Medical College Hospital (China) from July 2020 to April 2022. Pts received neoadjuvant treatment with docetaxel 75 mg/m2, carboplatin area under the curve (AUC) 4-5 (or cisplatin 75 mg/m2), and pembrolizumab 200 mg via IV every 3 weeks. Within 4-8 weeks of completion of neoadjuvant treatment, pts underwent surgery. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints were treatment-related adverse events and R0 resection rate. The study is registered at ClinicalTrials.gov (NCT05302011). Results: Thirty pts were enrolled (Table). As of December 1, 2023, median follow-up time was 27.9 months. Twenty-eight pts received 4 cycles and 2 received 3 cycles of the neoadjuvant treatment. Six pts did not proceed with surgery because of disease progression (3/6) and personal choice (3/6). Twenty-four pts (24/30, 80%) underwent minimally invasive esophagectomy (MIE). The R0 resection rate was 100%. Perioperative complications were manageable, including anastomotic leakage (2/24, 8.3%) and nerve injury (1/24, 4.2%). Of these 24 pts, 7 (29.2%) achieved pCR and 5 (20.8%) were CAP1 (near complete response, College of American Pathologists protocol). The median disease-free survival (DFS) was 30.6 months. Median overall survival data is not yet available. Grade 3/4 treatment-related adverse events include leukopenia (10, 33.3%), alopecia (3, 10.0%), and pneumonitis (1, 3.3%). One patient died of Stevens-Johnson syndrome. We are conducting molecular and immunological correlative studies to explore potential biomarkers related to the treatment. Conclusions: Neoadjuvant treatment with combination pembrolizumab and chemotherapy demonstrated encouraging anti-tumor activities, good surgical outcomes and a manageable safety profile in pts with locally advanced ESCC, supporting further evaluation in a prospective randomized phase 3 trial. Clinical trial information: NCT05302011 . [Table: see text]
CLDN18/CLDN18.2 IHC assay comparison (SP455, 43-14A, EPR19202) and co-prevalence expression with other biomarkers in gastric carcinoma.
Authors: Clements Miranda E , Willis Sophie E , Korade Martin , Ortiz Lorenzo , Zalesak-Kravec Stephanie , Lombard Cam , Richardson Chris , Chambers Andrew , Kim Yeoun Jin , Tsao Tsu-Shuen , Robida Mark , Zaucha Jan , Berry Deborah , Jones Gemma N , Barrett Allison , Durham Nick , Rebelatto Marlon , Broggi Maria , Thress Kenneth S. , Giraldo Nicolas
Published: June 2024

4089

Background: Despite recent advances in treatment, gastric cancer (GC) remains the fourth leading cause of cancer-related mortality worldwide. Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target as its expression is mostly restricted to the gastric epithelium and persists in a significant fraction of GC and other upper gastrointestinal tumors (e.g. pancreatic ductal adenocarcinoma). The goal of this study was to compare the analytical performance of multiple CLDN18/CLDN18.2 IHC assays and understand the prevalence of CLDN18.2 with other GC-relevant biomarkers (PD-L1, HER2) and the tumor immune microenvironment. Methods: Cell lines (n=11) and primary resection specimens from patients with GC (n=91) were studied. To compare the analytical performance of three CLDN18/CLDN18.2 IHC assays, FFPE samples were stained with pan-CLDN18 (43-14A) and CLDN18.2-specific (SP455 and EPR19202) clones. Staining results were validated using orthogonal methods i.e., flow cytometry and mass spectrometry. The relationship of CLDN18.2 expression with PD-L1 (SP263) and HER2 (HercepTest) as well as T cell contexture (CD3/CD8/PanCK; CD3/PD-L1/Ki67) were explored by IHC and chromogenic multiplex IHC. Association of these markers with clinicopathological features was also investigated. Results: Comparison of the three CLDN18/CLDN18.2 IHC assays showed similar analytical performance across cell lines and GC samples. Using orthogonal methods, we determined that the limit of detection and linear range was comparable amongst assays. In GC, samples classified as CLDN18/CLDN18.2 positive at a cutoff of 75% with 2-3+ intensity included 22% (SP455), 22% (43-14A), and 15% (EPR19202) of samples. Classification at other CLDN18/CLDN18.2 cutoffs were also explored and will be presented. Only one case (1%) showed significantly discrepant staining patterns between pan-CLDN18 and CLDN18.2-specific assays (H score 235 vs. 105, respectively). CLDN18.2 positivity did not correlate with HER2 expression, PD-L1 expression, T cell densities (cells/mm2), or any of the tested clinicopathological characteristics i.e., tumor grade, histologic subtype, or TNM stage. Conclusions: We demonstrated a concordant analytical performance between the tested CLDN18/CLDN18.2 IHC assays in GC. Their implementation in the clinical setting might help identify patient candidates that could benefit from treatment with CLDN18.2 targeted therapies. Additional research is needed to confirm similar analytical performance between the three IHC assays in other indications.
Atezolizumab + bevacizumab versus lenvatinib as first-line systemic therapy for treatment of hepatocellular carcinoma in a real-world population: Outcomes from the HCC CHORD database.
Authors: Freeman Mark , Krishnan Tharani , LEE Cha Len , Dibajnia Pooya , Ramjeesingh Ravi , Solar Vasconcelos Joao Paulo , Lyubetska Hanna , Ding Philip Q. , Lim Howard J , Knox Jennifer J. , Meyers Brandon M. , Gordon Vallerie Lynn , Cheung Winson Y. , Tam Vincent C.
Published: June 2024

4111

Background: Lenvatinib (LEN) and the combination of atezolizumab with bevacizumab (AB) are widely considered first-line systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC), but have never been compared directly in a randomized clinical trial. Cross-trial comparisons between IMbrave150 and LEAP-002 appear to show similar survival outcomes for AB compared to LEN, respectively, while survival with LEN was shorter in the REFLECT trial. Methods: Patients treated with AB or LEN first-line for HCC from August 2018 to August 2022 in the Canadian provinces of British Columbia, Alberta, Manitoba, Nova Scotia and two centers in Ontario were included in this study. Demographic and clinical outcomes data were gathered. Statistical analysis identified the median OS, PFS, and physician-assess response rate (RR) associated with each treatment. Results: We identified 453 patients treated with first-line AB (n = 159) or LEN (n = 294). 85% were male, 14% had HBV, 32% HCV, 70% cirrhosis, 27% BCLC B disease, 69% BCLC C,37% distant metastasis, 88% Child-Pugh A, 87% ECOG 0-1 performance status and 55% had previous locoregional treatment. The two cohorts were balanced with respect to most demographic factors, but patients in the LEN cohort had higher incidence of ECOG Performance Status ≥ 2 (11% vs 5%; p = 0.047), lower incidence of HBV (12% vs 19%; p=0.047) and higher incidence of HCV (36% vs 25%; p=0.03). Median follow-up time of the AB cohort was 9.9 months (mos) compared to 11.8 mos for LEN. Median overall survival (mOS) of this HCC population was 15.4 mos. mOS was 19.7 mos (95% CI: 14.5-NR) in the AB cohort and 14.4 mos (95% CI: 12.2-17.1) in the LEN cohort (HR 0.72; 95% CI: 0.54-0.95; p=0.021). Median progression-free survival (mPFS) was 6.9 mos in the overall population, 8.3 mos for AB and 6.3 mos for LEN (HR 0.85; 95% CI: 0.68-1.06; p=0.20). RR was 29% overall, 31% for AB and 28% for LEN (p=0.50). LEN was the most common second-line treatment after AB (86%), while after LEN 46% of patients received regorafenib and only 21% received second-line AB. Conclusions: This study provided real-world efficacy outcomes for AB directly compared to LEN in the first-line treatment of HCC in a Western country. AB was correlated with superior OS compared to LEN, but PFS and RR appear to be similar.
Association of BRCA1/2 pathogenic variants with primary tumor location and metastatic organotropism in pancreatic adenocarcinoma.
Authors: Hood Ryan , Rathore Srishti , Seewald Nicholas J. , Reiss Kim Anna
Published: June 2024

4151

Background: Pancreatic cancers (PDACs) with BRCA1/2 pathogenic variants (PVs) are prognostically favorable and predict response to platinum-based treatment. Recent data suggest that these mutations may be more strongly associated with cancers arising from the body/tail (B/T) compared to the head of the pancreas (HOP). Primary tumors of the B/T are known to frequently metastasize to the peritoneum, which is thought to be largely due to anatomic location. We hypothesized that BRCA1/2 PVs may interact with tumor location in determining sites of metastatic spread. Methods: We conducted a retrospective study using a database of patients with BRCA1/2 PVs and PDAC as well as wildtype (WT) control patients matched for age, sex, year and stage at diagnosis. Demographic and clinical data were compared by Fisher’s exact test. Adjusted odds ratios for each site of metastasis or somatic variant were estimated using logistic regression with backwards stepwise AIC minimization. Cases with diagnosed metastases and available next generation somatic sequencing were included in the respective logistic regression models. Results: Patients with BRCA1/2 PVs were more likely to have masses in the B/T compared to control patients [51.6% vs 31.0%; p-value < 0.001]. After adjusting for age, sex, platinum-based chemotherapy, curative-intent surgical resection, and primary location, patients with BRCA1/2 PVs were less likely to develop peritoneal metastases compared to control patients (see table, row 3). Additionally, for patients with B/T masses, the rate of peritoneal spread was significantly lower in those with BRCA1/2PVs compared to those without (OR: 0.41 [0.20, 0.83]). We did not observe a significant association between BRCA1/2 PV and peritoneal spread in patients with HOP masses (OR: 1.09 [0.48, 2.5]). Furthermore, patients with BR CA1/2PVs were significantly less likely to have a TP53 mutation compared to controls (51% vs 71%; p = 0.038). This association persisted after adjusting for the variables described above (see table, row 3). No significant differences were found for mutations in KRAS (83% vs 86%; p = 0.60), SMAD4 (16% vs 13%; p = 0.59), or CDKN2A (19% vs 29%; p = 0.13). Conclusions: Our data suggest that patients with BRCA1/2-related PDAC are more likely to present with B/T masses compared to WT patients, are less likely to have TP53 mutations and are less likely to have peritoneal spread of disease. These data support that the prognostic benefit of BRCA-related PDAC may be linked to a favorable somatic mutation profile. [Table: see text]
Integrated genomic and transcriptomic analysis to predict FOLFIRINOX response in metastatic pancreatic ductal adenocarcinoma.
Authors: Lansbergen Marjolein Francisca , Dings Mark Pui Gien , Koster Jan , Wilmink Johanna , Van Laarhoven Hanneke W.M. , Bijlsma Maarten F.
Published: June 2024

4153

Background: Given the lack of benefit of first-line chemotherapy (FOLFIRINOX) for a large proportion of metastatic pancreatic ductal adenocarcinoma (mPDAC) patients, predictive markers for treatment outcome are urgently needed. Previous studies showed that transcriptome-based classifiers and homologous recombination deficiency (HRD) associate with outcome in this patient group. Here, we aimed to validate the benefit of RNA and whole genome sequencing (WGS) in predicting treatment outcome in a Dutch mPDAC FOLFIRINOX-treated cohort. Methods: Patients with mPDAC who intended to start FOLFIRINOX were included in the CPCT-02 cohort. 108 patients started FOLFIRINOX and had successful WGS and RNA sequencing of their pretreatment biopsies. 51 mPDAC samples of non-FOLFIRINOX treated patients were also included in the cohort in order to explore the relation between transcriptome-based subtype and somatic mutational status with more power. Transcriptomic subtypes were established according to literature. HRD labels were derived from the previously published CHORD algorithm. Results: 88 percent of the included samples had a KRAS mutation and 82 percent had mutated TP53. The KRAS wild-type patients showed MYC amplifications, gene fusions in NTRK1, NTRK3, BRAF, NRG1, ALK, FGFR2 and RAF1, and mutations in mismatch repair proteins. Patients with a KRAS wild-type tumor had a better survival following FOLFIRINOX treatment (p = 0.009) compared to KRAS mutated tumors. No other mutations were found to be prognostic. As described before, transcriptome-based classification according to Moffitt revealed a cluster of tumors with a “Moffitt-negative” subtype, showing low expression of classical and basal-like signature genes. We found that KRAS wild-type tumors were enriched for this Moffitt negative subtype (p < 0.0001), while they did not have lower tumor cellularity. The gene expression of these Moffitt negative tumors correlated with neural-like and neuroendocrine gene sets. In contrast to previous studies, we did not observe a better response to FOLFIRINOX for patients with an HRD-tumor (OS: p = 0.21, PFS: p = 0.054). We noted an increased expression for the alternative non-homologous end joining pathways in HRD samples (p = 0.049) that might have countered the advantageous effect of HRD. Conclusions: We found that KRAS wild-type tumors do not fit in the classical – basal-like classification schemes. We could not prove a significant prognostic effect for HRD. Both KRAS status and transcriptome-based subgroup were prognostic for FOLFIRINOX treatment response and should therefore be further validated for incorporation in diagnostic practice.
Patient factors related to the real-world adoption of 3 months of adjuvant chemotherapy (ACT) in patients with stage III colorectal cancer (CRC).
Authors: Krishnan Tharani , Leung Emily , Solar Vasconcelos Joao Paulo , Lim Howard J , Loree Jonathan M. , Davies Janine Marie , Gill Karamjit , Gill Sharlene
Published: June 2024

e15609

Background: Based on the IDEA analysis, 3 months (mos) of ACT with CAPOX is an option for both low-risk and high-risk stage III CRC, with potential resource utilization, cost and toxicity benefits. This study examined the patterns of uptake of CAPOX vs FOLFOX and duration of ACT, focussing on patient factors, in a contemporary post-COVID real-world cohort of patients (pts) in British Columbia, Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX from January 2021 to December 2022. Demographic, tumor, and treatment information was collected. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher’s exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, age > 70y (P = 0.039), low/intermediate grade (P = 0.005) and low-risk disease (P < 0.0001) were significantly associated with 3 mos of CAPOX. There was no difference in ACT choice with regards to ECOG status, ileostomy or pre-existing neuropathy. 29% of pts planned for 6 mos of ACT had low-risk disease, with 52% of these receiving CAPOX. Patients who received 6mos of ACT were significantly more likely to report neuropathy (68 vs 36%, P < 0.0001) and to stop oxaliplatin early (54 vs 31%, P < 0.0001). The most likely reason for early discontinuation of ACT was neuropathy in the 6mos group and gastrointestinal toxicity in the 3mos group (P < 0.0001). Irrespective of duration, mean time from consult to ACT was longer for FOLFOX vs CAPOX (24 vs 19 days, P = 0.007). Conclusions: In this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low. 6 mos of oxaliplatin is still being offered to pts with low-risk disease, and is associated with more neuropathy warranting early oxaliplatin cessation. Exploration of patient preferences and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. [Table: see text]
The Fate of “Essential Religious Practices” in India's Constitutional Courts
Authors: Verma Pranav
Published: June 2024

It has been nearly seven decades since the Indian Supreme Court laid down the “essential religious practices” test to determine which religious practices are granted constitutional protection against state regulation. This article surveys the forty-three cases in which the essentiality plea has been raised since its formulation in 1954 until August 2022. Although the essentiality plea has a staggeringly high failure rate of 84 percent before India's constitutional courts, judicial decisions show a shift in legal rationale. The article shows that many of these decisions invariably reflected the socioreligious context of their time. An increase in anti-Muslim religious polarization meant that the fate of the essentiality plea differed depending on the religion of litigants. This judicial treatment of cases stands in stark contrast to the cases decided during the initial decades of the Constitution, when the government was avowedly secular.
“Freedom Is Not Free from Colonialism”
Authors: Kim Sung Eun
Published: June 2024

This article analyzes the augmentation of local Korean men to the US Army and UN Command during the Korean War. Scholars have conventionally interpreted Korean augmentee soldiers as having been vital to solving dire manpower needs and “rescuing” the Republic of Korea. Offering an alternative to such positive appraisals, this article dissects the UN Command and analyzes how the colonial techniques of the US and French militaries facilitated the subordination of Korean soldiers. The author demonstrates how the United States borrowed military practices pioneered by the French at their colonial outposts and implemented them on the Korean Peninsula. This scaffolding of transcolonial practices enabled the US Army to maximize Korean augmentee soldiers as dispensable necropolitical labor. By addressing the transcolonial origins of Korean Augmentation Troops to the US Army, this study reconsiders the Korean War as a historic site for consolidating colonial hierarchies between nations during an ostensibly postcolonial period.
The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression
Authors: Young Katherine A. , Wojdyla Katarzyna , Lai Tiffany , Mulholland Katie E. , Aldaz Casanova Silvia , Antrobus Robin , Andrews Simon R. , Biggins Laura , Mahler-Araujo Betania , Barton Philippa R. , Anderson Keith R. , Fearnley Gareth W. , Sharpe Hayley J.
Published: June 2024

PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell–cell contact. PTPRK regulates cell–cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.
Are You Ready to Recommend Physical Activity for Pregnant People?
Authors: Davenport Margie H. , Mottola Michelle F. , May Linda E. , Tinius Rachel , McDonald Samantha , Nagpal Taniya S. , Shaw Janet M.
Published: June 2024

Apply It!

• Prenatal physical activity is associated with approximately a 40% reduction in the odds of developing major pregnancy complications (e.g., preeclampsia, gestational hypertension, gestational diabetes) without increasing the risk of miscarriage, preterm birth, or a small-for-gestational age baby.

• All pregnant individuals who do not have exercise contraindications are encouraged to accumulate 150 minutes of moderate-intensity physical activity each week.

• The Get Active Questionnaire for Pregnancy was developed as a self-administered exercise preparticipation screening tool to identify the small number of individuals who may have a contraindication to prenatal exercise. This document can be used with the Health Care Provider Consultation form for Prenatal Physical Activity to improve communication between the health-care provider, the pregnant individual, and the fitness professional.
Harmozica ravergiensis (Gastropoda: Hygromiidae) in Western Ukraine as part of anthropogenic expansion of its range
Authors: Gural-Sverlova Nina , Gural Roman
Published: June 2024

In September 2023, a large population of the Caucasian snail Harmozica ravergiensis was discovered in a newly built residential complex in Lviv. This is its second record in Western Ukraine, with an interval of almost 20 years, as well as the westernmost known locality of the species. Adults of H. ravergiensis from Lviv had larger shells compared to samples from other introduced Eastern European populations of this species, measured by us personally or described in the literature. Another 16 species of land molluscs, mostly alien to Ukraine or its western part, were found in Lviv together with H. ravergiensis. The latter includes a snail of Crimean origin, Monacha fruticola, which is still rarely recorded north of the steppe zone of Ukraine. In the studied area of Lviv, H. ravergiensis and M. fruticola often formed joint aggregations, which had never been observed before in Ukraine. Possible ways of penetration of H. ravergiensis and some other introduced molluscs into the studied area are discussed. Now H. ravergiensis is most often found in Eastern Ukraine, especially in the Donetsk region (the earliest known record dates back to 1990). There are also a few reliable finds in Western (since 2006) and Central (since 2015) Ukraine. In general, in the late 20th and early 21st centuries, the range of H. ravergiensis expanded significantly, reaching the Tver region of Russia in the north, the southern Ural in the northeast, Central Asia in the southeast, and Western Ukraine in the west. Here, we analyse for the first time the extent of this expansion based on personally studied material, published data, and images in two citizen science databases.
A Study on the Prediction Method of English Performance in Universities based on the Stacking Integrated Model
Authors: Si Tongsheng
Published: June 2024

Students’ performance in higher education reflects their overall quality in higher education. By predicting the performance, students with greater learning problems can be screened out early and given appropriate guidance. To predict students’ performance in English, the knowledge information of courses, examination papers, and historical examination records are used to build a feature project of students’ examinations. Meanwhile, the features strongly correlated with their performance are filtered out. Then the next step of performance prediction is carried out. The results showed that a neural network long and short-term memory performance prediction model incorporating an attention mechanism was more effective than other models in predicting English performance in higher education. Further experiments found that the model reduced the error by 1.04% on the MAE metric, 0.53% on the RMSE metric, and increased its value by 4.12% on the R2 metric. Adding the new feature dataset led to better forecasting by the Att-LSTM model in all metrics. This indicated that the enhanced dataset temporality could improve the effectiveness of the Att-LSTM model in predicting English grades in higher education. The stacked integrated prediction model, by integrating multiple strong regressors, can avoid poor prediction and excessive overall bias due to one regressor and increase the soundness and prediction precision of the mode.
The Impact of Similarity Fusion based Travel Interest Point Recommendation Algorithm in Youth Users’ Study Tours
Authors: Xing Xinli , Wang Daojun
Published: June 2024

Study tours for adolescent users are somewhat contemporary and traditional methods, such as questionnaires cannot meet their psychological expectations. To bring a better experience to teenagers’ study tour, a Latent Dirichlet Allocation (LDA) theme model was used to mine teenage users and their interest points, and then the similarity between LDA and the check-in matrix was calculated and fused. Based on this, an RT-CNN model was built for deep feature extraction of review information, and point-of-interest recommendation was performed by fusing similarity, check-in behavior, and geographic location. The RT-CNN model had an accuracy of 92.7%, a recall of 87.1%, a Mean Absolute Error (MAE) value of 4.2%, a Root Mean Square Error (RMSE) of 4.8%, and F1 values of 89.2% and 88.7% in the two datasets. The new model in this experiment has high accuracy in making interest point recommendations and has a good overall performance.
Spatial and Temporal Characteristic Analysis based Long Short-Term Memory for Detection of Sensor Fault in Autonomous Vehicles
Authors: Zhang Hongwei , Gao Yanan , Liu Huanxue , Chen Yi
Published: June 2024

The artificial intelligence required to create self-directed automobiles relies heavily on the capability of precisely perceiving the environment around oneself. Most self-driving automobiles include several detectors, which work together to form a multi-source perception of the surroundings. Extended use of a system that drives  autonomously will introduce a variety of worldwide and local failure indications due to the extreme sensitivity of the instruments involved to ambient or environmental situations. These failure indications pose significant risks to the technique’s security. The paper presents a real-time information synthesis system incorporating techniques for identifying flaws and accepting faults. The compact connection can be recognized if the qualities mentioned above are provided, and the input information properties may be retrieved in real-time. One way to use the newly introduced method for assessing device reliability is to compute the detectors’ worldwide and local degrees of trustworthiness. In order to ensure the precision and dependability of information combination, problem data is filtered out, and monitor duplication is used to assess both the worldwide and local assurance levels of data from sensors at the moment. The chronological and geographic association of data from sensors allows for this. Experimental findings show that the network’s algorithms can outperform current techniques in terms of both rapidity and precision and can pinpoint the object’s location even when specific sensors are blurry or broken. This research established that the proposed hybrid structure benefits autonomous vehicles’ real-time reliability and speed.
Application of Deep Learning Algorithm in Visual Optimization of Industrial Design
Authors: Zhang Chunju
Published: June 2024

In order to understand the application of degree learning algorithms in industrial design visual optimization, the author proposes an application research based on deep learning algorithms in industrial design visual optimization. The author first starts with the basic principles of deep learning algorithms and provides a detailed explanation of the basic structure of the single-layer network of deep learning algorithms, as well as the restricted Boltzmann machine and its training process. Finally, an example of the performance improvement brought by the application of deep learning technology in handwritten digit recognition was given through an automatic encoder, and a simple summary of deep learning technology was made. Secondly, the NCI matching algorithm is used to match industrial design products and reconstruct the point cloud of industrial products to accurately detect their features. On this basis, deep learning algorithms are applied to construct a visual optimization model for industrial design, determine the output format of the model scene and the output situation of industrial design, and process the model according to the changing characteristics of the industrial design model to comprehensively edit the data of the model. Finally, targeted optimization of the industrial design visual optimization model is carried out based on the technical characteristics of deep learning algorithms, in order to complete the industrial design visual optimization. The experimental comparison results show that the industrial design visual optimization method optimized in this design has higher visual clarity than the traditional industrial design method, reaching 98%. Greatly improves the visual clarity of industrial design.
The Relationship Between Family Functioning and Academic Burnout of College Students: The Mediating Role of Core Self-evaluation and Coping Style
Authors: Yu Haixiang
Published: June 2024

Family is of paramount importance in individual growth and has significant impact on individual academic burnout. Despite of the importance of family functioning, the impact mechanism of overall family functioning on students academic burnout remains unclear. Therefore, this paper examined the mediating role of core self-evaluation and coping style between family functioning and academic burnout. In this study, 314 Chinese college students from different universities were investigated with the family functioning evaluation scale, core self-evaluations scale, simplified coping style scale, and academic burnout scale. The findings showed that family functioning, core self-evaluation, and coping style were significantly and positively correlated with each other. All three variables were significantly and negatively correlated with academic burnout. As expected, core self-evaluation and coping style play a full mediating role between family functioning and academic burnout. This research reveals the impactmechanism between family functioning and academic burnout among Chinese college students, providing effective intervention strategies focusing on students’ core self-evaluation and coping style.
Speckle Noise Detection and Removing by Machine Learning Algorithms in Multisensory Images for 5G Transmission
Authors: Dharani M. , Nagendranath M.V.V.S. , Rafee Shaik Mohammad , Naveen Kishore G. , Venkata T. Krishna Moorthy
Published: June 2024

The multispectral satellite sensor images have multibands, which have some typical noise. There is difficult to detect this tipical noise with low resolution image. The satellite local or gloval pixel information and quantificationare degraded due to this noise. Many standard transformations and filtering operations are developed for detection and removing of non-gaussion noise, which are not given sophisticated results with existing methods. These statistical characteristics are applied to those samples to identify and quantify present tipical noise. The higher-order statistical based machine learning algorithm is developing to remove the speckle noise from satellite image. In this proposed algorithm, implemented the higher order statistical approache such as skewness, kurtosis based adaptive curvelet methods are implemented for the detection and suppression of speckle noise with retrieve of spectral and spectral values. The proposed algorithm preserves smooth and sharp details and maintains the tradeoff level in multispectral bands is suitable for advanced high speed 5G communication with the effective rate of transmission. The proposed results are verified with suitable statistical parameters such as PSNR, Entropy and ERGAS values.
Residual Life Prediction of Rotating Machinery Guided by Quantum Deep Neural Network
Authors: Ye Ganghong , Shi Ningxuan
Published: June 2024

In order to avoid the low prediction rate and high evaluation rate in estimating the service balance life of rotating machinery, this paper presents a quantum gene chain encoded bidirectional neural network (QGCCBNN) for estimating the service balance life of rotating machinery. In QGCCBNN, quantum bidirectional transmission mechanism has been developed. In order to improve the global optimization ability and convergence speed, we have developed a quantum gene chain encoding method to transform the gradient descent into the data transmission and updating. Because of the advantages of QGCCBNN in nonlinear estimation ability and convergence speed, the proposed QGCCBNN for predicting the remaining service life of rotating machinery can achieve higher prediction precision and optimization.The predicted value of the proposed method for the remaining service life of double row roller bearings is 6.33h (actual value is 7.17h), with a prediction error of only 0.84h and a relative prediction error of only 11.72%. The experimental results demonstrate the effectiveness of the proposed method.
Stability Evaluation Method of High Fill Loess Foundation Based on Numerical Simulation
Authors: Wu Wenli , Wang Lei , Cheng Jiheng , Hao Renzhuo
Published: June 2024

In order to understand the stability evaluation method of high fill loess foundation, the author proposes a study on the stability evaluation method of high fill loess foundation based on numerical simulation. The author first established a three-dimensional finite element model of a multi-level high fill slope using PLAXIS 3D software  based on a loess high fill slope engineering project in a certain section of northwest China. The study investigated the effects of changes in fill materials, fill boundaries, slopes, and unloading platforms on slope stability. Secondly, based on the vertical and horizontal displacement of the top and foot of each level of slope under step-by-step filling, the distribution pattern of the most dangerous points of each level of slope and the overall deformation trend of the slope were analyzed. The results indicate that the cohesion and internal friction angle of the filling material are key factors affecting the stability of high fill slopes. Reducing the height of the steps at the boundary between the filling and the undisturbed soil, deepening the width of the steps, reducing the slope, and widening the unloading platform can all improve the stability of the slope. During the construction of lower slopes, there is a significant vertical displacement mutation, while the horizontal displacement mutation is relatively slow; After the construction is completed, the deformation situation is good, and the vertical and horizontal displacement of the higher slope during construction changes greatly, with uneven distribution; After the completion of construction, the consolidation settlement period is long and the deformation is large; Emphasis should be placed on strengthening deformation monitoring at high altitudes after construction is completed. Finally, the platform width can be selected within this range based on the actual engineering situation. After the platform width is greater than 3.6m, as sufficient platform width has been reached at this point, further increasing the platform width has little impact on the safety factor, and the curve gradually flattens out. The research results have determined the stability influencing factors, deformation trends, and development laws of loess high fill slopes in the northwest region, providing a scientific basis for further research on deformation control of loess high fill slopes.