tbuckley/cabot-search huggingface dataset:
Teleoncology: Assessing online communication skills of millennial medical students.
Authors: Ernesto Gil Deza, Lourdes Gil Deza, Mariana Abal, Marta Dragosky, Claudia Lorena Acuna, Alba Marin Ordoñez, Monica Montiel, Flavio A Tognelli, Leonel Smolje, Cesar Gonzalez, Maximiliano Brandon, Carlos Garcia Gerardi, Gaston Martin Reinas, Sandra L. Ares, Daniela Gercovich, Edgardo G. J. Rivarola, Eduardo L. Morgenfeld, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2021)

e13616 Background: COVID-19 posed new challenges in patient care and led to an increase in teleoncology. This paper analyzes telemedicine communication skills of millennial medical students of the postgraduate program of Clinical Oncology at Universidad del Salvador, Buenos Aires. Methods: Student assessment was based on a video call interaction with simulated patients in two stations (30 minutes each) of the Virtual Observational Standard Clinical Examination (V-OSCE), implemented in November 2020. Students received virtual communication guidelines and participated in training sessions to use the video call platform. All interactions were recorded. Assessment items (Table). Results: A total of 25 students were evaluated: 1 (4%) was ineligible due to network connection issues; 24 (96%) participated in both interactions. We analyzed 48 interactions in total. Opening: 6/48 interactions completed all five required items. Most recurring problems: not checking for patient’s previous experience with teleoncology (37/48) and not providing an alternative communication channel in case of technical difficulties (40/48). Middle: the results were similar to in-person interaction observed in previous exams, 35/48 interactions completed all required items. End: 16/48 interactions completed both items. In 32/48 the student did not check for patient understanding of the information provided. Only 3/48 interactions completed all 12 items. Conclusions: A) The V-OSCE is a useful tool to practice and evaluate teleoncology communication skills. B) The Middle Moment of the interactions was similar to an in-person interaction. However, the Opening and End of the interview were more challenging. The most critical struggles being: checking for patient’s previous experience in teleoncology, providing an alternative communication channel in case of technical difficulties and checking for patient understanding. C) COVID-19 established new forms of communication that are likely to remain even after the pandemic has ended. It is important to address this demand for online communication skills in medical education curricula.[Table: see text]
Application value of plasma exosomal long RNA in SCLC diagnosis and prognosis.
Authors: Chang Liu, Jialei Wang, Shenglin Huang, Hui Yu, Zhengfei Zhu, Min Fan
Journal: Journal of Clinical Oncology (2021)

8566 Background: Little research has focused on blood exosomal transcription profile in small cell lung cancer (SCLC). The aim of this study is to identify plasma exosomal specific transcriptional profile in SCLC and explore the application value of plasma exosomal long RNA (exLR) in SCLC diagnosis and prognosis. Methods: This study included 81 healthy people and 40 SCLC patients receiving standard first-line chemotherapy with etoposide and carboplatin/cisplatin. The efficacy was evaluated by progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). 19 Patients who achieved complete response (CR) or partial response (PR) as best response during the first-line therapy and had not progressed within the following 90 days after the end of first-line therapy were defined as chemosensitive. 21 Patients who achieved stable disease (SD) as best response or received progressive disease during the first-line therapy or within the following 90 days after the end of first-line therapy were defined as chemoresistant. Baseline plasma samples were collected from 40 SCLC patients (17 patients’ samples after 2 courses were collected) and 81 healthy people. Plasma exosomes were isolated and purified; exosomal RNA were extracted for high-throughout sequencing analysis. Results: We obtained plasma exLRs profiles from 81 healthy control samples and 57 SCLC samples (baseline samples from 40 patients plus samples collected by 17 patients after 2 courses). Bioinformatics analysis found that exLRs were significantly different between the SCLC and the healthy control group; between the chemosensitive and the chemoresistant group; between the baseline samples and the paired samples after 2 courses. For 40 SCLC patients receiving first-line chemotherapy, ORR was 65.0%, DCR was 90.0% and mPFS was 6.0 months (95% CI, 4.3-7.7 months). Multivariate analysis showed that baseline brain metastases and baseline bone metastases were independent predictors of poor PFS; and 223 genes were independent predictors of PFS. There were 10 genes (AC107954.1, H2AFZP2, CALB2, IFITM9P, GFPT2, PLA1A, CHST10, AC021231.2, SETP20, HILPDA) intersected in differentially expressed genes between the SCLC and the healthy control group, differentially expressed genes between the chemosensitive and the chemoresistant group and independent predictors of PFS. These 10 genes were highly expressed in both the SCLC group and the chemoresistant group, and their high expression was an independent risk factor for poor PFS. Conclusions: This study firstly identified the plasma exLRs profiles in SCLC patients, verified the feasibility and value of identifying biomarkers based on exLRs profiles in SCLC diagnosis and prognosis.
Clinical characteristics and risk factors for death among hospitalised children and adolescents with COVID-19 in Brazil: an analysis of a nationwide database
Authors: Eduardo A Oliveira, Enrico A Colosimo, Ana Cristina Simões e Silva, Robert H Mak, Daniella B Martelli, Ludmila R Silva, Hercílio Martelli-Júnior, Maria Christina L Oliveira
Journal: The Lancet Child & Adolescent Health (2021)
A phase III multicenter randomized controlled trial of postsurgical stereotactic radiotherapy versus surgically targeted radiation therapy (STaRT) for the treatment of large (&gt;2.5cm) newly diagnosed brain metastases: Trial in progress.
Authors: Jeffrey Weinberg, Mary Frances McAleer, Jason Michael Johnson, Rajat Kudchadker, Jeffrey Scott Wefel, Ying Yuan, Heather Y. Lin
Journal: Journal of Clinical Oncology (2021)

TPS2067 Background: Resection (R) followed by single or multi-fraction stereotactic radiosurgery (SRT) of brain metastases lowers resection bed recurrence compared to R alone. Nevertheless, for larger (&gt;2.5cm) brain metastasis, 12-month recurrence rates after R+SRT can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy device (GammaTile or GT, GT Medical Technologies, Tempe, AZ) utilizing Cs-131 seeds embedded within a bioresorbable collagen tile was developed and is described as Surgically Targeted Radiation Therapy (STaRT) to distinguish it from external beam radiation therapy. It is hypothesized that immediate adjuvant radiotherapy (RT) and/or RT dose intensification could improve outcomes. The device is FDA-cleared for this indication and early commercial use is demonstrating favorable safety and efficacy outcomes. STaRT allows rapid dose delivery of radiation therapy directly to the tumor bed with predictable dosimetry immediately at the time of resection, and an intense but localized radiation treatment, which may confer a reduced risk for radiation necrosis compared to other therapies. The device is easily placed with minimal additional operative time and limited staff radiation exposure. It is hypothesized that R+ STaRT will increase the surgical bed recurrence-free survival, while reducing the impact on functional and neurocognitive status compared to R+SRT. Methods: Multicenter, randomized, comparison trial of patients with resectable, previously untreated “index” brain metastases measuring ≥2.5–5 cm, and 0–3 other tumors, will be preoperatively randomized 1:1 to undergo either R+ SRT or R+STaRT to the index lesion; unresected tumors in both groups will receive SRT. Planned sample size is 180 from 13 sites. Enrollment will open in Q1. Primary endpoint is surgical bed-recurrence free survival. Secondary endpoints include overall survival, quality of life (Functional Assessment of Cancer Therapy-Brain, Linear Analog Self-Assessment), neurocognition (Hopkins Verbal Learning Test, Trail Making Tests, Controlled Oral Word Association), functional status (Karnofsky Performance Scale, Barthel-ADL), and adverse events. Follow-up will be at 1,3,6,9, and 12 months, then every 6 months through 24 months. This will be the first randomized trial comparing R+SRT versus R+STaRT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures will be captured to elucidate the potential risks and benefits of these two differing post-operative RT delivery methods in the setting of newly diagnosed metastatic brain tumors. Clinical trial information: NCT04365374.
Trends in breast cancer mortality according to molecular subtypes: A population-based study.
Authors: Yunan Han, Shuai Xu, Graham A. Colditz, Adetunji T. Toriola
Journal: Journal of Clinical Oncology (2021)

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p&lt;0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p&lt;0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p&lt;0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.
The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages
Authors: Yanping Wu, Xiang Luo, Qingqing Zhou, Haibiao Gong, Huaying Gao, Tongzheng Liu, Jiaxu Chen, Lei Liang, Hiroshi Kurihara, Yi-Fang Li, Rong-Rong He
Journal: Acta Pharmaceutica Sinica B (2021)

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.
Impact of dietary carbohydrate type and protein–carbohydrate interaction on metabolic health
Authors: Jibran A. Wali, Annabelle J. Milner, Alison W. S. Luk, Tamara J. Pulpitel, Tim Dodgson, Harrison J. W. Facey, Devin Wahl, Melkam A. Kebede, Alistair M. Senior, Mitchell A. Sullivan, Amanda E. Brandon, Belinda Yau, Glen P. Lockwood, Yen Chin Koay, Rosilene Ribeiro, Samantha M. Solon-Biet, Kim S. Bell-Anderson, John F. O’Sullivan, Laurence Macia, Josephine M. Forbes, Gregory J. Cooney, Victoria C. Cogger, Andrew Holmes, David Raubenheimer, David G. Le Couteur, Stephen J. Simpson
Journal: Nature Metabolism (2021)
MSIFinder: A python package for detecting MSI status using random forest classifier.
Authors: Tao Zhou, Libin Chen, Jing Guo, Mengmeng Zhang, Huanhuan Liu, Yanrui Zhang, Huina Wang, Shanbo Cao, Haijun Wang, Feng Lou
Journal: Journal of Clinical Oncology (2021)

2601 Background: Microsatellite instability (MSI) is a common genomic alteration in several tumors, such as colorectal cancer, endometrial carcinoma, and stomach, which is characterized as microsatellite instability-high (MSI-H) and microsatellite stable (MSS) based on a high degree of polymorphism in microsatellite lengths. MSI is a predictive biomarker for immunotherapy efficacy in advanced/metastatic solid tumors, especially in colorectal cancer (CRC) patients. Several computational approaches based on target panel sequencing data have been used to detect MSI; However, they are considerably affected by the sequencing depth and panel size. Methods: We developed MSIFinder, a python package for automatic MSI classification, using random forest classifier (RFC)-based genome sequencing, which is a machine learning technology. We included 19 MSI-H and 25 MSS samples as training sets. First, RFC model were built by 54 feature markers from the training sets. Second. The software was validated the classifier using a test set comprising 21 MSI-H and 379 MSS samples. Results: With this test set, MSIFinder achieved a sensitivity (recall) of 0.997, a specificity of 1, an accuracy of 0.998, a positive predictive value (PPV) of 0.954, an F1 score of 0.977, and an area under curve (AUC) of 0.999. We discovered that MSIFinder is less affected by low sequencing depth and can achieve a concordance of 0.993, while exhibiting a sequencing depth of 100×. Furthermore, we realized that MSIFinder is less affected by the panel size and can achieve a concordance of 0.99 when the panel size is 0.5 m (million base). Conclusions: These results indicated that MSIFinder is a robust MSI classification tool and not affected by the panel size and sequencing depth. Furthermore, MSIFinder can provide reliable MSI detection for scientific and clinical purposes.[Table: see text]
Changes in neutrophil /lymphocyte ratio and platelet count after chemotherapy correlate with cheomtherapy response and predicition of prognosis in patients with advanced gastric cancer.
Authors: Yibing Liu, Qingju Meng, Zhiguo Zhou, Li Jing
Journal: Journal of Clinical Oncology (2021)

e16030 Background: The aim of the study was to investigate the predictive value of neutrophil to lymphocyte ratio(NLR) and platelet count(PLT) in the prediction of chemotherapy response and prognosis in patients with advanced gastric cancer. Methods: In this retrospective study, a total of 260 advanced gastric cancer patients were analyzed and the correlation between NLR, PLT and overall survival (OS) were investigated. The receiver operating curve (ROC) was drawn to determine the optimal critical value of NLR. These cases were included and separated into different groups according to the median values of NLR or PLT. Results: Low baseline NLR level correlated with improved clinicopathological characteristics, including organ-free metastasis, Borramn type I and II, tubular adenocarcinoma and papillary carcinoma. Low baseline PLT level also associated with Borramn classification. Alterations in the NLR and PLT levels were associated with therapeutic efficacy and prognosis. The patients who remained in or switched to the low NLR level had an improved objective response rate(ORR), disease control rate(DCR) and survival ratios. The patients who remained in or switched to the low PLT level had an improved DCR. Univariate analyses showed that pathological type, Borramn typing, changes of NLR, and efficacy of chemotherapy were significant predictors of OS. Multivariate analyses showed that pathological type and efficacy evaluation were independent prognostic factor. Conclusions: This study demonstrated that the changes of NLR and PLT following chemotherapy can predict the chemotherapy results in patients with advanced gastric cancer. But, baseline NLR and PLT level haven’t prognostic value in patients with advanced gastric cancer. However, pathological types and the results of the first therapeutic evaluation could have prognostic value in patients with advanced gastric cancer.
Discovery of a novel, dual mechanism anti-angiogenic and anti-proliferative agent with oral anti-tumor activity
Authors: Robert Tuman, Jay Mei, Chih Ho, Robert Galemmo, Donald Ludovici, Judith Baker, Candace Burns, Ann Devine, Umar Maharoof, Jan Sechler, Eric Strobel, Rose Tominovich, Stacy Skrzat, Sandra Voina, Dana Johnson
Journal: Cancer Research (2004)

4558  Angiogenesis, the growth of new microvessels, is considered critical for the growth of most solid tumors and their metastatic spread. Agents that inhibit tumor-induced angiogenesis generally either target processes involved in activating endothelial cell (EC) and/or smooth muscle cell (SMC) proliferation (typically growth factors such as VEGF, PDGF, bFGF) or block other functional steps in the angiogenesis process (e.g. EC migration, adhesion, alignment and tube formation), but without directly affecting tumor cell growth. While pure angiogenesis inhibitors have been demonstrated pre-clinically and clinically to produce anti-tumor activity when administered as monotherapy, the current thinking is that the more effective anti-cancer therapy might be anti-angiogenic therapeutics used in combination with cytotoxic or directed cytostatic agents that also target the proliferating tumor cells. An agent that simultaneously targets both the angiogenic process and the tumor cell compartment by combining both anti-angiogenic and tumor cell anti-proliferative activites into a single molecule would be highly desirable and would represent a novel class of oncology therapeutics. By cross-screening potent anti-angiogenic PDGFR-kinase inhibitors for tumor cell anti-proliferative activity, dual mechanism compounds with novel properties were identified. Using this strategy, we identified ATP-competitive inhibitors of PDGF receptor tyrosine kinase that exhibit both anti-angiogenic and tumor cell anti-proliferative activities. One such compound potently inhibits PDGFR-β kinase with an IC50 of 0.002 μM and displays relatively good selectivity versus a large panel of serine/threonine and other tyrosine kinases. In cell-based assays, the compound exhibits potent, concentration-dependent inhibition of PDGF-BB-stimulated SMC proliferation (IC50 = 0.003 μM) and it directly inhibits the in vitro growth of 9 of 11 human tumor cell lines in culture (IC50s= 0.007 –0.033 μM). The selected compound exhibits potent anti-angiogenic activity in vitro in the rat aortic ring assay of microvessel outgrowth (IC50 = 0.015 μM) and is active in vivo following oral dosing at 30 mg/kg in the matrigel mouse model of PDGF-BB-stimulated angiogenesis. When administered orally as a single agent to nude mice bearing human tumor xenografts, the compound produces significant, dose-dependent (25-100 mg/kg, BID) growth inhibition against four different human tumors (LoVo colon, A375 melanoma, H460 lung and MDA-MB-231 breast) suggesting broad anti-tumor activity. The primary pharmacology of this interesting dual mechanism compound will be presented.