bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Placebo-Controlled Trial of Topical Capsaicin for Delayed Chemotherapy-Induced Nausea and Vomiting
Authors: Bright Heber Rew , Singh Ashish , Joel Anjana , Georgy Josh Thomas , John Ajoy Oommen , Rajkumar Pradeep , Jiji Hema , Stehno-Bittel Lisa , Samuel Prasanna , Chandy Sujith J. 
Published: June 2024

PURPOSE We examined the efficacy of topical capsaicin in reducing delayed chemotherapy-induced nausea and vomiting (CINV). METHODS Adults on highly emetogenic chemotherapy regimens applied 2 g of capsaicin ointment (0.075%) or matching placebo four times a day to the abdomen for 5 days in addition to standard antiemetic regimen in this blinded randomized controlled trial. Patients were monitored for nausea and vomiting in the immediate (day 1), delayed (days 2-5), and extended phases (days 2-15). Self-reported incidence and daily episodes of CINV were compared between the groups. Onset, severity, need for rescue antiemetics, cumulative vomiting episodes, and safety were also compared. RESULTS In total, 160 patients were enrolled. The final modified intention-to-treat population included 75 patients each in the capsaicin and placebo groups. Fewer patients experienced nausea (36.0% [n = 27] v 53.3% [n = 40]; P = .033) and vomiting (28.0% [n = 21] v 42.7% [n = 32]; P = .060) in the capsaicin arm during the delayed phase. During the extended phase, there was a significantly lower incidence of nausea (44% v 64.0%; P = .014) in the capsaicin arm. No difference in nausea (26.7% v 25.3%) or vomiting (22.7% v 18.7%) was evident in the immediate phase. The average daily episodes of nausea and vomiting were significantly fewer in the capsaicin arm during the delayed and extended phases. With capsaicin, no grade 3 nausea (9.3% v 0.0%; P = .007) was observed, and the time to first nausea and vomiting was significantly prolonged. There were no differences between the groups with respect to rescue antiemetics, unscheduled hospital visits, and adverse events. CONCLUSION Topical capsaicin reduced the incidence of nausea and the average number of vomiting episodes during delayed and extended phases without increasing adverse effects.
Deep immune profiling of intrahepatic cholangiocarcinoma with CODEX multiplexed imaging.
Authors: Shekhar Soumya , Sahai Vaibhav , Howe Kathryn , Zhu Qingfeng , Kondo Aya , Fedor Helen L. , Gunchick Valerie , Assarzadegan Naziheh , Azad Nilofer Saba , Yarchoan Mark , Baretti Marina 
Published: June 2024

4117 Background: Intrahepatic cholangiocarcinoma (iCCA) is subclassified by the presence or absence of potentially actionable molecular alterations, of which IDH1 mutations and FGFR2 fusions and rearrangements are most frequently observed. Little is known about the relationship between molecular features of iCCAs and the tumor immune microenvironment (TME). Methods: We performed a high-parameter immune phenotyping of the TME of FGFR2 fusion/rearrangement positive (FGFR2+), IDH1 mutation positive (IDH1+), and FGFR2/IDH1 wild type iCCA samples at the single-cell level using CO-Detection by indEXing (CODEX). Neighborhood analysis was based on a k-nearest-neighbors approach followed by k-means clustering to identify the spatial location of each cell type and their proximity to one another. Simplified spatial networks specific to molecular subtypes were generated based on the shortest Euclidean distances from any given cell to all other cell types. Results: A total of 24 tumors were examined (n=7 FGFR2+, n=9 IDH1+, n=8 other). Compared to other molecular subtypes, FGFR2+ tumors had an immune-desert phenotype characterized by a reduced abundance of CD8+ T cells (p < 0.05), CD117+ mast cells (p < 0.05), and CD68+/CD163+ macrophages (p < 0.05) but with an increased number of CD11b+/CD15+ granulocytes (p < 0.05). IDH1+ tumors were characterized by a decreased amount of CD11b+/CD15+ granulocytes (p < 0.05) when compared to other subtypes. In terms of spatial analysis, CD4+ T cells were located further from tumor cells in FGFR2+ iCCA compared to IDH1+ iCCA (p < 0.05) and other molecular subtypes (p=0.05). In contrast, CD11b+/CD15+ granulocytes were located closer to tumor cells in FGFR2+ tumors (p < 0.05). Additionally, closer neighbor proximity between CD4+ T cells and CD11b+/CD15+ granulocytes was observed in FGFR2+ tumors compared to both IDH1+ tumors (p < 0.05) and other tumor subtypes (p = 0.05), indicating a stronger lymphoid–myeloid neighboring relationship in the TME of FGFR2+ iCCA. Conclusions: FGFR2+ and IDH1+ iCCAs have distinct immunophenotypes, providing initial evidence that molecular alterations may inform the selection of patients for immunotherapy. Both the quantity of immune cells as well as the spatial relationships between immune cells may influence iCCA prognosis and response to therapy. Tailoring immunotherapeutic approaches to specific molecular subsets may improve outcomes across the divergent molecularly defined iCCA subtypes.
Utilization of tumor-informed circulating tumor DNA in detecting minimal residual disease and guiding adjuvant therapy in liver cancer.
Authors: Guo De-Zhen , Zhang Shi-Yu , Gu Zhu-Jun , Zhou Shuang-Tao , Jin Da-Wei , Yang Shuang , Fan Jia , Zhou Jian , Yang Xin-Rong 
Published: June 2024

4125 Background: Hepatocellular carcinoma (HCC), a prevalent malignancy and a leading cause of cancer-related mortality, often exhibits a grim prognosis due to recurrence post-surgical treatment. Minimal residual disease (MRD) is deemed a crucial factor contributing to early relapse following radical surgery. Previous studies have indicated that circulating tumor DNA (ctDNA) may serve as a promising biomarker for evaluating MRD in various cancers. However, its applicability in liver cancer remains unclear. Methods: We prospective included 136 patients during 2019 to 2021 who underwent curative-intention surgery for HCC in Zhongshan hospital. Plasma samples (n=625) were collected prior to surgery, 1-month post-surgery, and during subsequent surveillance. Patient-specific somatic mutations were identified through whole-exome sequencing of tumor tissue. For each patient, 16 patient-specific somatic mutations were selected and employed to assess ctDNA through ultra-deep sequencing of plasma DNA. Results: The median follow-up period was 24 months. At the last follow-up, 45 (33.1%) patients relapsed. The preoperative ctDNA concentration was elevated in patients who experienced tumor relapse after surgical treatment compared to those didn’t relapse (median: 125 vs.8.4 mean tumor molecules/mL, P<0.001). Most of patients (80.9%) demonstrated a significant decrease in ctDNA concentration to negative levels after curative surgery. Those maintaining a positive postoperative ctDNA status faced a higher recurrence risk (HR=11.5, P<0.001). Throughout longitudinal follow-up, positive longitudinal ctDNA (positive in any point) was significantly associated with a higher recurrence risk (HR=69.3, P<0.001). The area under the curve of longitudinal ctDNA for predicting recurrence was 0.956, boasting a sensitivity of 93.3% and specificity of 97.8%. The median interval from the first positive longitudinal ctDNA to clinical recurrence confirmed by imaging test was 4 months. The predictive performance of longitudinal ctDNA for recurrence surpassed that of alpha-fetoprotein (0.956 vs. 0.680, P<0.001). Patients with positive longitudinal ctDNA experienced benefits from adjuvant therapy (HR=0.4, P=0.019). Moreover, a decrease or stability of ctDNA after adjuvant therapy indicated treatment response and delayed clinical relapse (HR=0.3, P=0.00012). Conclusions: Tumor-informed ctDNA proves to be a reliable indicator for MRD detection after surgical treatment for HCC, enabling the prediction and anticipation of recurrence before clinical manifestation. It plays a crucial role in guiding the application of adjuvant therapy and assessing treatment efficacy, thereby facilitating postoperative management and enhancing the precision of medical interventions.
Bone metastases and skeletal related events in patients with gastrointestinal neuroendocrine tumors.
Authors: Bruges Paula , Schonman Ian , Zahurak Marianna , Laheru Daniel A. , He Jin , Johnston Fabian McCartney , Greer Jonathan , Solnes Lilja , De Jesus-Acosta Ana 
Published: June 2024

4126 Background: The clinical implications and management of bone metastases in patients (pts) with gastrointestinal neuroendocrine tumors (GI-NETs) is poorly characterized. In this study we investigated the frequency of bone metastases and skeletal-related events (SRE) in pts with GI-NETs. Methods: Retrospective review of ptswith GI-NETs seen at our institution between 2010-2022. We collected clinicopathologic data including tumor primary site, tumor differentiation, grade using Ki-67 labeling index (G1, G2, or G3), time of diagnosis of metastatic GI-NET, and development of bone metastases (synchronous or metachronous). Diagnosis of metastatic bone disease was assessed by contrast imaging (CT, MRI) and/or functional imaging studies (FDG or DOTATATE PET). SRE were defined as bone pain, spinal cord compression, pathological fracture or tumor-related hypercalcemia. Bone directed therapy was defined as use of bisphosphonates, radiation therapy, and surgical intervention. Results: We identified a total of 865 pts with metastatic GI-NETs. Of these, 122 pts (14%) had evidence of bone metastases. In pts with bone metastases, median age was 60 y/o and 72 pts (59%) were male. Primary tumor sites included pancreas (n=52, 47%), small bowel (n=50, 45%), rectum (n=4, 4%), colon (n=3, 3%), and gallbladder (n=1, 1%). Tumors were G1 (n=31, 28%), G2 (n=51, 47%), G3 (n=27, 25%). The majority of pts had well-differentiated tumors (n=103, 84%). Imaging for initial diagnosis of bone metastasis included PET (n=65, 53%), MRI (n=29, 24%), and CT (n=28, 23%). Synchronous metastases occurred in 34 pts (28%). Metachronous bone metastasis occurred in 88 pts (72%) with a median time to developing bone metastasis of 38 months. SRE occurred in 46 pts (38%), with 36 pts (30%) experiencing bone pain, 5 pts (4%) experiencing pathological fracture, 5 pts (4%) experiencing spinal cord compression, and 2 pts (2%) experiencing hypercalcemia. Thirty-six pts (30%) received bone-directed therapy, including bisphosphonates (n=25, 20%), radiation (n=19, 16%), or surgical intervention (n=4, 3%). Median overall survival (OS) was 83.3 months. Factors associated with increased probability of SRE included younger age, non-white race, low tumor grade, synchronous presentation, and poorly differentiated tumor. Risk factors for decreased OS included male gender, intermediate or high-grade disease, and spinal cord involvement. Bisphosphonate therapy was the most frequently used bone-directed treatment (n=25, 20%). Conclusions: Bone metastases occurred in 14% of pts with GI-NETs and SRE occurred in 38% of these pts. SRE were more likely to occur in pts with synchronous metastatic bone disease, intermediate/high grade tumors or poorly differentiated tumors. Further studies evaluating interventions to decrease SRE and impact in quality of life in pts with GI-NETs are warranted.
Types of thromboembolic events and their outcomes among patients with active colorectal cancer: A nationwide propensity matched analysis.
Authors: Farooq Faryal , Kumar Manoj , Afzal Muhammad Sohaib , Sultan Muhammad , Nasir Bilal , Byreddi Laxman Yashwant , Devarkonda Vishal , Ali Shafaqat , Atluri Sundeep 
Published: June 2024

e15530 Background: Venous thromboembolic events (VTE) are a major cause of morbidity & mortality in patients with active cancer. We aim to investigate the outcome and incidence of acute DVT and PE in colorectal cancer compared to all other malignancies. Methods: The National Readmission Database (2016-2020) was queried to identify all-cause admissions for patients with active colorectal cancer (CRC). A Propensity Score Matching (PSM) model, matched such patients with cases having any type of other malignancies. Pearson’s x2 test was applied to the PSM-2 matched cohorts to compare outcomes. Results: Among 2.9 million all-cause hospitalizations of CRC patients, about 3.9% suffered a VTE. The majority had acute DVT (1.9%), followed by acute PE (1.3%), followed by DVT with PE (0.7%). After propensity-matching & multivariate analysis, patients with CRC have a lower incidence of acute DVT (2.7% vs 2.8%, aOR: 0.92), acute PE (1.8% vs 2%, aOR: 0.84) & DVT with PE (0.96% vs 1.02%, aOR: 0.90) [p < 0.001] as compared to other malignancies. Among different VTEs, the mortality was highest for acute PE (aOR: 2.66), followed by DVT with PE (aOR: 2.28) & DVT (aOR: 1.89) [p < 0.001]. Resource utilization is also higher in CRC-related hospitalizations complicated by VTE, with patients suffering a DVT having the highest LOS (9 vs 5 days) & total cost of hospitalization ($25,910 vs $17,964) [p < 0.001] followed by DVT with PE and PE respectively. CRC patients had higher readmission rates for DVT as compared to PE at 30 days (18.2% vs 17%, p: 0.029) and subsequently at 90-day intervals. Conclusions: CRC-related hospitalizations had lower rates of DVT and PE compared to other active malignancies. The mortality was highest for PE in this cohort, while healthcare-related burden and readmission rates were higher for DVT.
The treatment outcomes of patients with BRAFV600E–mutated metastatic colorectal cancer (mCRC): The Polish retrospective cohort study.
Authors: Zok Jolanta , Bieńkowski Michał , Radecka Barbara , Kuchar Agata , Borowiec Szymon , Streb Joanna , Jurczyk Michał , Jakieła-Drąg Anna , Gelej Marek , Zając Patryk , Ploch-Glapińska Małgorzata , Duchnowska Renata 
Published: June 2024

e15535 Background: BRAF V600E mutation is found in approximately 6-11% of metastatic colorectal cancer patients (mCRC). According to the international guidelines in BRAFV600E mutated mCRC, the triplet chemotherapy FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with bevacizumab and encorafenib plus cetuximab should be considered in 1st and 2nd line treatment setting, respectively. Methods: This retrospective and multicenter study evaluates clinical practices in BRAFV600Emutated mCRC patients treated between 2011 and 2023 in Poland. All patients were tested for BRAF and RAS mutations before starting the 1st line treatment, using PCR from archival paraffin-embedded tumor tissue. Results: One hundred twenty-six patients (median age 68 years (range 45-85), 55% female and 45% male) from five oncology centers were included. The majority of patients had a right-sided primary tumor 69 (55%). The 1st line of chemotherapy received 100 patients (79,4%). The majority of patients received doublet chemotherapy: FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin), FOLFIRI (folinic acid, 5-fluorouracil, irinotecan), XELOX (capecitabine, oxaliplatin), FOLFIRI and bevacizumab: 30 (30%), 47 (47%), 5 (5%), 3 (3%), respectively. Only three patients (3%) received FOLFOXIRI, and one patient with bevacizumab. The median duration of 1st line treatment for the overall population was 5.26 months (95% CI 2 days - 18.9 months). Subsequently, 50 (50%), 20 (20%), 6 (6%), and 1 (1%), patients received 2nd, 3rd, 4th, and 5th line therapy, respectively. The most frequently used 2nd chemotherapy regimens were FOLFOX ( n = 8; 16%), FOLFOX plus bevacizumab ( n = 13; 26%), FOLFIRI ( n = 13; 26%), and FOLFIRI plus aflibercept ( n = 7; 14%). During the median follow-up period of 38.5 months (range 32.0 – N/A), 96 (79.3%) patients died. Median OS from mCRC diagnosis was 13.7 months (95% CI: 11.3-17.6). Conclusions: This study highlights the unmet need for effective treatment strategies for patients with BRAFV600E mutated mCRC in Poland.
Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer
Authors: Ang Daniel , Chan Johan , Ong Whee Sze , Tan Hui Shan , Ng Quan Sing , Yuen John , Chen Kenneth , Tay Kae Jack , Wong Siew Wei , Saad Marniza , Nagata Masayoshi , Horie Shigeo , Chansriwong Phichai , Ng Chi-Fai , Wong Alvin , Chua Melvin L.K. , Toh Chee Keong , Tan Min-Han , Lim Tony , Bhagat Ali Asgar S. , Kanesvaran Ravindran 
Published: June 2024

PURPOSE Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes. METHODS Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS). RESULTS A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients. CONCLUSION In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.
The Serenade Topic, the Serenade Construction, and the Creation of Amorous Sweetness in Ottocento Opera
Authors: Boyle Matthew L. C. 
Published: June 2024

Abstract
The critical reception of early nineteenth-century Italian opera has long focused on its supposed cloying sweetness. This sweetness, often framed as amorous, shaped the discourse and affective experiences of primo ottocento opera. Stendhal, for instance, likened Gioachino Rossini's music to lusciously ripe fruit and to sexual arousal. Adolf Bernhard Marx found a concert of Mercadante arias to leave the bitter “aftertaste of lots of sugar.” And August Wilhelm Ambros compared Rossini's melodies to gazing into the eyes of a Titian nude. This article proposes that amorous sweetness was associated with the vocal serenade, a genre evocative of sweet melodies and the ardent love of courtship. The musical elements that articulated serenade topics, what Stephen Rumph calls figurae, saturated slow movements of early nineteenth-century Italian opera. These included pizzicato strings, sustained winds, parallel thirds, and modulations to mediant keys. Although these figurae may appear in conjunction with diegetic serenades or topical serenade passages, they also frequently appeared independent of dramatically appropriate amorous situations. This article proposes that a common configuration of serenade figurae acted as a stock orchestral texture. This convention is modeled as a musical construction: the serenade construction. It paired musical structures with the semantic meanings of the serenade. In its evocation of serenading, the serenade construction preserved scripted listening strategies for attending to vocal melodies and their associated affective responses. It consequently regulated the perception of vocal timbre and perceived melodicity.
Perspectives in collective cell migration – moving forward
Authors: Stehbens Samantha J. , Scarpa Elena , White Melanie D. 
Published: June 2024

ABSTRACT
Collective cell migration, where cells move as a cohesive unit, is a vital process underlying morphogenesis and cancer metastasis. Thanks to recent advances in imaging and modelling, we are beginning to understand the intricate relationship between a cell and its microenvironment and how this shapes cell polarity, metabolism and modes of migration. The use of biophysical and mathematical models offers a fresh perspective on how cells migrate collectively, either flowing in a fluid-like state or transitioning to more static states. Continuing to unite researchers in biology, physics and mathematics will enable us to decode more complex biological behaviours that underly collective cell migration; only then can we understand how this coordinated movement of cells influences the formation and organisation of tissues and directs the spread of metastatic cancer. In this Perspective, we highlight exciting discoveries, emerging themes and common challenges that have arisen in recent years, and possible ways forward to bridge the gaps in our current understanding of collective cell migration.
Femoral bone structure and mechanics at the edge and core of an expanding population of the invasive frog Xenopus laevis
Authors: Dumont Maïtena , Herrel Anthony , Courant Julien , Padilla Pablo , Shahar Ron , Milgram Joshua 
Published: June 2024

ABSTRACT
Understanding how living tissues respond to changes in their mechanical environment is a key question in evolutionary biology. Invasive species provide an ideal model for this as they are often transplanted between environments that differ drastically in their ecological and environmental context. Spatial sorting, the name given to the phenomenon driving differences between individuals at the core and edge of an expanding range, has been demonstrated to impact the morphology and physiology of Xenopus laevis from the invasive French population. Here, we combined a structural analysis using micro-CT scanning and a functional analysis by testing the mechanical properties of the femur to test whether the increased dispersal at the range edge drives differences in bone morphology and function. Our results show significant differences in the inner structure of the femur as well as bone material properties, with frogs from the centre of the range having more robust and resistant bones. This is suggestive of an energy allocation trade-off between locomotion and investment in bone formation, or alternatively, may point to selection for fast locomotion at the range edge. Overall, our results provide insights on the growth of the long bones and the formation of trabecular bone in frogs.
Electromagnetic transmission of two-dimensional inhomogeneous plasma photonic crystal
Authors: Liu Zhen , Liu Rubing , Jun Peng , Lin Liguang , Qiu Dianqing , Lin Qi 
Published: June 2024

A 2D tunable plasma photonic crystal (PPC) was constructed and implemented experimentally over a frequency range of 1 GHz–12 GHz within the electromagnetic spectrum. The PPC was simulated using an inhomogeneous model of a plasma tube based on microwave diagnostics and numerical simulations. The simulation results were found to be in good agreement with the experimental results. The data indicates that for TM polarization, localized plasmons will be excited at various positions within the tube, which does not rely on an interface with the medium, resulting in a broad forbidden band due to plasma inhomogeneity. The bandwidth of this band is consistent with the plasma frequency range. Furthermore, a lattice resonance band is observed, which is related to the incident angle. The cutoff effect of inhomogeneous PPC for TE polarization can be predicted by averaging the plasma parameters. The structure or plasma parameters can be adjusted to tune all the bands mentioned above. These findings can be used as a reference for applications in communication and microwave devices, and could potentially be utilized as a diagnostic tool for plasma parameters.