bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival results from the phase 2 NIVOFGFR2 study of first-line nivolumab plus CAPOX in patients with FGFR2-positive, PD-L1-positive metastatic gastric cancer.
Authors: Tsimafeyeu Ilya , Musayeva Gunel , Samira Mahmudova , Otkhozoria Nana , Abbasov Bahadur , Kahharov Alisher 
Published: June 2024

4042 Background: The interim analysis of the NIVOFGFR2 phase 2 study showed a 1-year PFS rate of 30.4% in patients with FGFR2-positive, PD-L1-positive metastatic gastric cancer treated with the combination of nivolumab and CAPOX in the first-line setting (GI ASCO 2024). Here, we present data on overall survival (OS) and second-line PFS (PFS2). Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma, and their PD-L1 expression (CPS≥5; DAKO 28-8) and FGFR2 status (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418) were centrally confirmed by IHC. Patients were treated with nivolumab 360 mg in combination with capecitabine and oxaliplatin every 3 weeks till disease progression or unacceptable toxicity. Following progression, the planned treatment regimen included ramucirumab at a dose of 8 mg/kg with paclitaxel. The primary endpoint was the 1-year PFS rate and secondary endpoints included median PFS, PFS2, OS, objective response rate (ORR), and the Grade ≥3 adverse events (AEs) rate. Results: Twenty-three patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with ≥2 metastases 78%; CPS (5-9) 22%, (≥10) 78%, previous surgery 61%, adjuvant/neoadjuvant therapy 17%, time to metastatic disease <1 year 48%). Two (8.7%) patients remain on first-line therapy, 19 (82.6%) have received second-line ramucirumab and paclitaxel, and 10 (43.5%) have received 3 or more lines of therapy. The median follow-up for OS was 17.3 months, with 7 patients still alive. We present the updated efficacy and toxicity results (Table). Conclusions: Despite the modest efficacy of nivolumab with CAPOX in the first-line setting, a favorable median OS was observed, possibly attributable to the incorporation of ramucirumab with paclitaxel in the second-line treatment of FGFR2-positive, PD-L1-positive metastatic gastric cancer. Clinical trial information: NCT05859477 . [Table: see text]
Impact of CTNNB1 alterations on outcomes in patients with hepatocellular carcinoma (HCC).
Authors: Pai Jonathan , Baca Yasmine , Ganguly Rituparna , Akce Mehmet , Algaze Sandra , Chow Lydia D. , Misirian Ani , Hanna Diana L. , Lenz Heinz-Josef , Marshall John , Iqbal Syma , Shroff Rachna T. , Borad Mitesh J. , El-Khoueiry Anthony B. 
Published: June 2024

4106 Background: The WNT/beta catenin (CTNNB1) pathway plays an integral role in the development of HCC. CTNNB1 has been implicated in HCC progression, metastasis, and drug resistance. We examined associations between CTNNB1 mutations and mRNA expression and clinical outcomes in a real-world cohort of patients with HCC. Methods: 1652 HCC tumors were tested at Caris Life Sciences (Phoenix, AZ) and analyzed with Whole Transcriptome Sequencing (WTS; Illumina Novaseq), Whole Exome Sequencing (NovaSeq,WES) and NextGen DNA sequencing (NextSeq, 592 genes). mRNA expression (transcripts per million) was further stratified into top (Q4) and bottom quartiles (Q1). Kaplan Meier estimates were calculated for overall survival (OS) in the molecularly defined cohorts and estimated from time of tissue collection to last contact. Significance was determined to be p <0.05. Chi-square and Mann-Whitney tests determined molecular differences between subgroups and adjusted for multiple comparisons (q<0.05). Results: Pathogenic CTNNB1 mutations were present in 32% of HCC and mutation status was not associated with CTNNB1 expression level. Pts whose tumors had lower CTNNB1 expression had significantly improved OS, 17.9 vs 12.4 months, Q1 vs Q4, HR 0.72, CI: 0.58-0.89 p=0.002. This association remained significant in patients who received first-line IO (Q1 vs Q4: OS 16.7 vs 10.6 mo, HR 0.54, CI: 0.32-0.94, p=0.025) or TKI (Q1 vs Q4: OS 27.1 vs 17.6 mo, HR 0.60, CI: 0.38-0.94, p=0.025). Low CTNNB1-expressing tumors (Q1) had more frequent ARID1A mutations (15% vs 8%); less frequent TP53 mutations (31% vs 42%); lower VEGFA, EPHB4, EPHA2, HIF1A, TGFB1/2/3 expression, lower MAPK activation and lower T-cell inflamed scores vs Q4 tumors (all q < 0.05). All tumors were MSS. CTNNB1 mutation status (MT vs WT) did not impact survival (OS 17.6 vs 15.3 mo, CTNNB1-MT vs CTNNB1-WT, HR 1.05, CI: 0.91-1.20, p=0.55). Similarly, CTNNB1 mutation status (MT vs WT) did not impact OS in pts treated with IO (19.8 vs 19.6 mo, HR 0.99, p=0.94) or TKI (23.0 vs 22.0 mo, HR 0.86, p=0.33). Conclusions: CTNNB1 mRNA expression, but not CTNNB1 mutation status, is associated with survival in HCC. Patients whose tumors had lower CTNNB1 expression appeared to derive more benefit from immune checkpoint inhibitors and TKI therapy in first line. CTNNB1 expression is associated with DNA repair, immune, neuronal and angiogenic pathways which may pave the way for potential therapeutic opportunities. Further studies are needed to prospectively evaluate CTNNB1 as a biomarker for treatment selection in HCC.
A study on classifying tumor neoantigens to enhance the accuracy of liquid biopsy in CRC cancer.
Authors: Guo Fenghua , Liao Wenting , Li Jun , Chen Yaru 
Published: June 2024

e15507 Background: Personalized neoantigen vaccines are a promising therapeutic approach in colorectal cancer (CRC). These vaccines are designed based on the identification of specific gene mutations, aiming to evoke an immune response. However, a major challenge arises from the need to distinguish true mutated sites from numerous false positives, particularly in samples of liquid biopsy, where detection rates may be relatively low. To address this issue, we have developed a robust pipeline to enhance the precision and efficiency of detecting target gene mutations, which is crucial during the neoantigen design process. Methods: In this study, an extensive analysis was conducted using tissue and blood samples from a cohort of 859 CRC patients. We identified mutations in the top third most frequently mutated genes (APC, TP53, and KRAS). To design antigenic sequences, the mutations at these gene sites were concatenated with 14 amino acids from both up and down flanking regions. Subsequently, we utilized a similarity scoring algorithm (pairwise2.align from Biopython) to assess the mutation correlation between oncogenes (APC and KRAS) and the suppressor gene TP53. Results: This study observed that mutations within a specific gene tend to generate distinct patterns of new antigens. The majority of APC mutations (90.04%) in the vicinity of the mutation sites led to premature stop codons. Regarding KRAS, the mutation sites with the highest frequency were in the vicinity of the c.35 and c.182 positions, sharing identical neoantigens with NRAS. In contrast, TP53 mutations appeared to be more influenced by other mutations. Neoantigens derived from TP53 were identified, and it was observed that 82.27% of the sequences exhibited more than 40% similarity with other mutations in the same sample.This may be indicative of a co-occurrence mechanism. Conclusions: The classification of neoantigens appears to be similar to the classification of oncogenes and tumor suppressor genes, which may contribute to adjust the minimum detection threshold of liquid biopsy from the perspective of neoantigens. [Table: see text]
Delineating histomorphological signatures of iCMS subtypes in colorectal cancer using multiplexed fluorescence-in-situ hybridization.
Authors: Joanito Ignasius , Bo Li , Yeo Grace Hui Ting , Lakshmanan Vairavan , Laurensia Yurike , Tan Iain BeeHaut , Prabhakar Shyam 
Published: June 2024

e15603 Background: Our recent single-cell transcriptomic data indicate that colorectal cancer (CRC) can be classified into two major epithelial subtypes: iCMS2 and iCMS31. iCMS3 CRC includes MSI-H and one-third of MSS tumors. The latter are enriched in KRAS, PIK3CA, and BRAF mutations. The iCMS2 subtype often exhibits chromosome instability, including copy number changes in specific chromosome regions. These genomic alterations may be associated with distinct histomorphological features, which can be assessed using hematoxylin and eosin (H&E) staining. Methods: To test this hypothesis, we acquired and analyzed multiplexed Fluorescence in situ Hybridization (mFISH) and immunofluorescence (IF) staining data from 84 samples from 32 patients. For the mFISH data, we targeted 464 genes, encompassing major cell lineage markers and genes differentially expressed between iCMS2 and iCMS3 patient subtypes. Images were acquired over 31 hybridization rounds. Following the acquisition of the mFISH data, the same tissue section was stained with anti-EPCAM, anti-CD45 and anti-Vimentin antibodies to delineate cell boundaries and distinguish between the major cell lineages. Subsequently, all crypts were segmented based on their EPCAM and VIM stains, and parameters such as crypt size (number of pixels), crypt depth (distance to the nearest VIM signal), and fractal dimension were calculated for each crypt. The output of crypt segmentation was then integrated with mFISH RNA data to elucidate cell type proportions and gene expression profiles across and within individual segmented crypts. Results: Here, we found that iCMS2 crypts, in contrast to iCMS3 crypts, are significantly larger, deeper, and have higher fractal dimension. Additionally, our mFISH data demonstrated that iCMS2 tumors contain a higher proportion of undifferentiated (stem-like) cells, while iCMS3 tumors have a higher proportion of goblet (terminally differentiated) cells. The presence of larger and deeper crypts in iCMS2 may suggest a distinct cell state. Indeed, we identified specific genes whose expression was correlated with crypt depth. Conclusions: Our preliminary results suggest that these two iCMS subtypes exhibit distinct histomorphological features, which can be employed as practical and cost-effective companion diagnostics to assist in the pathological discrimination of these subtypes. References: 1Joanito, I., Wirapati, P., Zhao, N. et al. Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer. Nat Genet 54, 963–975 (2022).
Short course versus long course neoadjuvant radiation for patients with locally advanced rectal cancer (LARC): National Cancer Database (NCDB) analysis of the years 2004-2020.
Authors: Sharma Gaurav , Ray Gannon James , Mulekar Madhuri S , Lund Alexander , Huddleston Adam , Aref Amr M. , Abdalla Ahmed 
Published: June 2024

e15606 Background: The two preoperative radiation approaches for LARC are long-course chemoradiotherapy (LC-CRT) and short-course radiation (SC-RT). While previous research suggested similar efficacy, the five-year follow-up of the RAPIDO trial revealed a significant increase in local recurrence rates with SC-RT. We aim to assess the outcomes and utilization patterns of both approaches in the United States of America (USA) using data NCDB. Methods: NCDB data for stage 2B, 2C, and 3 rectal cancer patients were obtained. SC-RT was defined as a total of 25 Gy in 5 fractions, and LC-CRT was defined as 45-60 Gy given over 5 to 6 weeks (with chemotherapy). Data was analyzed using JMP Pro V16. Results were considered significant at α = 0.05. Categorical data were compared using Fisher's or Chi-square test. Numerical data were compared using t-test or ANOVA. Post hoc analysis was conducted using Tukey's HSD. Survival rates were compared using the Kaplan-Meier method. Logistic regression was used to study outcomes' dependence on different factors. Firth adjusted maximum likelihood method was used to model likelihood of unstable outcomes due to biased estimates. Results: Out of the total 39,527 patients, 38,365 (97.06%) received LC-CRT, whereas only 1,162 (2.94%) received SC-RT. Only about 5% of patients received total radiation above 50.4 Gy. SC-RT was significantly more common among Hispanic patients (p = 0.0001), those with lower median income ( < $30,000) (p = 0.01), individuals with more comorbidities (p < 0.0001), and those treated at academic facilities (p < 0.0001). In comparison to SC-RT, LC-CRT demonstrated lower 30 and 90-day mortality after surgery, a higher pathological complete response (pCR) rate, and improved overall survival (OS) (Table). Upon subgroup analysis by stage, significant OS improvement with LC-CRT compared to SC-RT for stage 3 (p = 0.02), whereas no difference in OS was found in stage 2B, C. Detailed analysis will be presented. Conclusions: SC-RT is used by less than 3% of US patients and mainly in academic centers. LC-CRT is more effective, improving pCR and OS. Favorable outcomes with LC-CRT may be due to poor baseline performance status in SC-RT group. Prospective trials are needed to validate these findings. [Table: see text]
Mortality and equitability of radiation treatment in locally advanced rectal cancer: A review from a national cohort.
Authors: Zweigle Joshua Walter , Hebishy Ahmed , Valasapalli Srijan , Mohamed Rana , Muzaffar Mahvish , Burke Aidan Michael 
Published: June 2024

e15608 Background: The treatment paradigm for locally advanced rectal cancer has evolved significantly over the last two decades regarding the timing (neoadjuvant vs. adjuvant) and even the necessity of radiation (RT) or surgery in the curative approach. While these paradigm shifts were evolving, the overall survival (OS) of patients with and without RT and the inclusion of minority populations in these shifts has not previously been well described. Methods: A retrospective cohort study was performed using the NCI SEER database. Survival was calculated with IBM SPSS software using the Kaplan-Meier method and hazard ratios (HR) were calculated using the Cox-regression model with 95% confidence intervals (CI). Patients treated between 2000 – 2020 were included with the cause of death separating OS from cancer-specific survival (CSS). The 5-year survival after 2015 was unreliable and excluded. Patients were separated by whether they had received RT and by the timing of RT (neoadjuvant vs. adjuvant). Additionally, the patients were separated into ‘Non-Hispanic White’ (NHW) and ‘Other’. They were analyzed using a Chi-squared algorithm for an association between race and origin and receipt of RT. This same analysis was done on patients separated by race identified as ‘Black’ or ‘Not Black.’ These Chi-squared analyses were calculated for patients diagnosed before and after January 1, 2016. Results: Of those diagnosed with stage II or III rectal cancer from 2000-2015 who received chemotherapy and surgical intervention with known survival times, the receipt of RT, specifically neoadjuvant RT, improved OS and CSS. There was no evidence that NHW patients received RT at different rates from others. However, they did receive adjuvant RT at higher rates from 2000-2015 and neoadjuvant RT from 2016-2020. For Black patients, from 2000-2015 there was a trend towards lower rates of RT utilization and from 2016-2020 they were less likely to receive RT. Black race did not have a significant association with the timing of RT. Conclusions: Stage II and III rectal cancer patients diagnosed from 2000-2015 who received chemotherapy, surgery, and RT, specifically, neoadjuvant RT had improved OS and CSS. Black patients were less likely to receive RT and, as the standard of care was changing towards total neoadjuvant RT after 2015, NHW patients were more likely than others to be treated with this regimen. [Table: see text]
Tonality and Racism
Authors: Yust Jason 
Published: June 2024

AbstractTonality is one of the most important concepts in music theory, determining how music theorists organize music institutionally (in curricula, conferences, etc.) and conceptually. For François-Joseph Fétis, who first popularized the term in the nineteenth century, it was a central component of his biologically racist, white-supremacist music theory. This essay argues that the term as it is used today perpetuates this racism by associating a mix of musical features and human perceptual capacities with a Eurocentric historical classification, and by maintaining a teleological evolution narrative based on the European classical music tradition. It argues, furthermore, that scholarship can do away with the terms tonality and tonal music and would profit from instead using more specific terminology for musical features like tonics, major and minor keys, scale degrees, consonance, and functional harmony.
Conducting Online Fitness Assessments in Exercise Oncology
Authors: Daun Julia T. , Wagoner Chad W. , Dreger Julianna , Williamson Tanya , Danyluk Jessica , Capozzi Lauren C. , Culos-Reed S. Nicole 
Published: June 2024

Apply It!By reading this article, health and fitness professionals will gain knowledge in:• How to conduct safe online fitness assessments.• How to tailor online fitness assessment protocols based on population needs.• Technology considerations for more inclusive and efficient implementation of online fitness assessments.
Ultrastructural changes of hemocapillaries of the lungs in the late development of experimental acute pancreatitis
Authors: Zaiats Liubomyr , Pasichnyk Olga , Zukow Walery 
Published: June 2024

Background. Today, acute pancreatitis is a common form of acute abdomen in the clinic, the incidence of which has been increasing in recent years. The aim of the work was to study the dynamics of ultrastructural changes of the hemocapillaries of the alveolar wall of the lungs in the late stages of experimental acute pancreatitis. Material and methods. The experiments were carried out on 54 white Wistar male rats weighing 180–220 g. The animals were divided into three groups: first — intact, second — control, third — experimental with a model of acute pancreatitis, which was reproduced by intraperitoneal administration of a 20% solution of L-arginine at a total dose of 5 g/kg at one-hour interval. The control group of animals was intraperitoneally injected with an equivalent dose of isotonic sodium chloride solution. All research were performed under sodium thiopental anesthesia at the rate of 60 mg/kg body weight. Lung tissue for electron microscopic examination was collected from the lower lobe of the left lung at 3–5 and 7 days. Pieces of lung tissue measuring 1×1×1 mm were fixed in a 2.5% glutaraldehyde solution, followed by additional fixation in a 1% osmium tetroxide solution. After dehydration, the material was poured into Epon-Araldite. Sections with a thickness of 20–50 nm obtained on “Tesla BS-490” ultramicrotome were studied in a PEM-125K electron microscope. Results. The ultrastructural analysis showed that already 3 days after the study, dystrophic-destructive changes, as well as adhesion and aggregation of leukocytes, were detected in the endothelial cells. As the study period increased (5–7 days), the intensity of changes in the hemocapillaries of the alveolar wall increased significantly. In the lumen erythrocyte sludge, thromboleukocyte adhesion and aggregation are determined in hemocapillaries. Conclusion. Acute experimental pancreatitis is accompanied by marked changes in the ultrastructural structure of hemocapillaries of the alveolar wall. The nature and severity of structural changes in the hemocapillaries of the alveolar wall depends on the duration of the course of arginine-induced acute pancreatitis.
Incidence, demographics, characteristics and management of acute Achilles tendon rupture: An epidemiological study
Authors: Briggs-Price Samuel , Mangwani Jitendra , Houchen-Wolloff Linzy , Modha Gayatri , Fitzpatrick Emma , Faizi Murtaza , Shepherd Jenna , O’Neill Seth 
Published: June 2024

Background
Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients’ quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK.

Methods
Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records.

Results
ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR.

Conclusion
The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR.
Feasibility of the “Preventing functional decline in acutely hospitalized older patients (PREV_FUNC)” study—A three-armed randomized controlled pilot trial
Authors: Sandberg Linda , Boström Anne-Marie , Hagströmer Maria , Lindgren Charlotte , Kivipelto Miia , Sandlund Christina , Welmer Anna-Karin 
Published: June 2024

Background
Recent studies indicate that in-hospital exercise can mitigate the risk of functional decline in acutely hospitalized older adults. However, there is a lack of studies that compare different types of exercise interventions. This feasibility study was conducted in preparation for a three-armed randomized controlled trial. The aim was to examine the process feasibility (in terms of recruitment and retention rate, intervention compliance and acceptability), and scientific feasibility (in terms of presence of adverse events, and trends with 95% confidence intervals of the outcome measures) of the trial.

Methods
Patients aged ≥75 years, were included from geriatric medical wards at three hospitals in Stockholm, Sweden. Participants in two groups received a specialized intervention program, i.e., Simple or Comprehensive exercise program, respectively and one group received usual care. Assessments were conducted at hospital admission and discharge, and data were analyzed with descriptive statistics.

Results
In the spring 2022, 63 patients met the inclusion criteria and 39 accepted to participate (recruitment rate: 61.9%). COVID-19 affected the inclusion period. A total of 33 participants completed the study (i.e., were assessed at baseline and discharge, retention rate: 84.6%). Participants in the Simple and the Comprehensive exercise programs performed 88.9% and 80% of the possible training sessions, respectively. Both interventions were accepted by the participants and no adverse events were reported. The intervention groups showed a higher median change from admission to discharge than the control group on the Short Physical Performance Battery, the main outcome measure of the trial.

Conclusion
The result of this pilot study suggests that the trial design is feasible and potentially useful for preventing functional decline in acutely hospitalized older adults. A full-scale trial will, however, require some considerations with respect to routines and logistics. The trial was registered at ClinicalTrials.gov, 4 May 2022, registration number NCT05366075.