tbuckley/cabot-search huggingface dataset:
Ambient Temperature and External Causes of Death in Japan from 1979 to 2015: A Time-Stratified Case-Crossover Analysis
Authors: Rui Pan, Yasushi Honda, Emiko Minakuchi, Satbyul Estella Kim, Masahiro Hashizume, Yoonhee Kim
Journal: Environmental Health Perspectives (2022)

Background: Although substantial evidence suggests that high and low temperatures are adversely associated with nonaccidental mortality, few studies have focused on exploring the risks of temperature on external causes of death. Objectives: We investigated the short-term associations between temperature and external causes of death and four specific categories (suicide, transport, falls, and drowning) in 47 prefectures of Japan from 1979 to 2015. Methods: We conducted a two-stage meta-regression analysis. First, we performed time-stratified case-crossover analyses with a distributed lag nonlinear model to examine the association between temperature and mortality due to external causes for each prefecture. We then used a multivariate meta-regression model to combine the association estimates across all prefectures in Japan. In addition, we performed stratified analyses for the associations by sex and age. Results: A total of 2,416,707 external causes of death were included in the study. We found a J-shaped exposure–response curve for all external causes of death, in which the risks increased for mild cold temperatures [20th percentile; relative risk (RR)=1.09 (95% confidence interval [CI]: 1.05,1.12)] and extreme heat [99th percentile; RR=1.24 (95% CI: 1.20, 1.29)] compared with those for minimum mortality temperature (MMT). However, the shapes of the exposure–response curves varied according to four subcategories. The risks of suicide and transport monotonically increased as temperature increased, with RRs of 1.35 (95% CI: 1.26, 1.45) and 1.60 (95% CI: 1.35, 1.90), respectively, for heat, whereas J- and U-shaped curves were observed for falls and drowning, with RRs of 1.14 (95% CI: 1.03, 1.26) and 1.95 (95% CI: 1.70, 2.23) for heat and 1.13 (95% CI: 1.02, 1.26) and 2.33 (95% CI: 1.89, 2.88) for cold, respectively, compared with those for cause-specific MMTs. The sex- and age-specific associations varied considerably depending on the specific causes. Discussion: Both low and high temperatures may be important drivers of increased risk of external causes of death. We suggest that preventive measures against external causes of death should be considered in adaptation policies. https://doi.org/10.1289/EHP9943
Abstract EP11: Long-term Outcomes Of Transcatheter Aortic Valve Replacement Compared With Surgical Aortic Valve Replacement: A Retrospective Cohort Study With Overlap Propensity Score Weighting
Authors: Zhe Li, Jodi Edwards
Journal: Circulation (2022)

Objectives: This longitudinal observational study utilized surgical procedure data from Ontario, Canada to compare mid- and long-term clinical outcomes in a representative real-world cohort of patients (2007-2019) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Methods: A novel overlap weighting propensity score method was used to match patients on the date of TAVR or SAVR, conditional on baseline patient characteristics. Primary outcomes were all-cause and cardiovascular mortality either in-hospital or at 1, 3 and 5 years post-discharge. Secondary outcomes included ischemic stroke, hemorrhagic stroke, myocardial infarction, acute kidney injury, vascular complications, atrial fibrillation, endocarditis, permanent pacemaker implantation, defibrillator, reintervention, and cause-specific readmission at 1, 3 and 5 years post-discharge. In-hospital outcomes were compared using multivariable logistic regression. Long-term primary and secondary outcomes for patients undergoing TAVR vs. SAVR were compared using an overlap propensity score-weighted competing risks sub-distribution proportional hazards model. Results: The study included 9,355 SAVR and 2,641 TAVR patients. Hazards of all-cause mortality at 1 year (Hazard Ratio [HR], 1.25; 95% CI, 1.06-1.48), 3 years (HR, 1.48; 95% CI, 1.31-1.68) and 5 years (HR, 1.51; 95% CI, 1.36-1.69) were significantly higher in the TAVR compared to SAVR group. Cardiovascular mortality was significantly higher in the TAVR group at 3 (HR, 1.40; 95% CI, 1.08-1.80) and 5 years (HR, 1.41; 95% CI, 1.13-1.77). Non-cardiovascular mortality was also significantly higher in the TAVR group at 1 year (HR, 1.46; 95% CI, 1.03-2.06), 3 years (HR, 1.48; 95% CI, 1.17-1.88), and 5 years (HR, 1.41; 95% CI, 1.16-1.72). Hazards of myocardial infarction were significantly greater in the TAVR at 1 year (HR, 1.72; 95% CI, 1.08-2.74), 3 years (HR, 1.86; 95% CI, 1.35-2.57), and 5 years (HR, 1.82; 95% CI, 1.37-2.42). Hazards of angina readmission were significantly greater in the TAVR at 3 years (HR, 1.94; 95% CI, 1.26-3.00) and 5 years (HR, 1.87; 95% CI, 1.26-2.78). Conclusions: In real-life patients who underwent a TAVR experienced an excess cardiac and non-cardiac mortality compared to SAVR. More studies with long-term follow-up are needed to confirm the long-term clinical benefits of TAVR and effort to improve patient selection are warranted.
Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer
Authors: Annika Fendler, Scott T.C. Shepherd, Lewis Au, Katalin A. Wilkinson, Mary Wu, Andreas M. Schmitt, Zayd Tippu, Sheima Farag, Aljosja Rogiers, Ruth Harvey, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Benjamin Shum, Camille L. Gerard, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe Queval, Caitlin Kavanagh, Emma C. Wall, Edward J. Carr, Sina Namjou, Simon Caidan, Mike Gavrielides, James I. MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O’Flaherty, Robyn L. Shea, Gail Gardner, Darren Murray, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Nicholas Van As, Kate Young, Andrew J.S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L.V. Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, Robert J. Wilkinson, James Larkin, Samra Turajlic
Journal: Cancer Cell (2022)
94P Preliminary outcome data for deep inspiratory breath hold guided stereotactic radiotherapy (SBRT) with robotic couch correction for early stage non-small cell lung cancers (NSCLC)
Authors: T. Basu, M.R. Senapati, J.M. Priyadharshni, R. Nair, U. Saxena, S. Rajurkar
Journal: Annals of Oncology (2022)
A Stromal Tumor Presenting as a Pseudoaneurysmal Dilation of the Small Bowel Mimicking a Lymphoma on FDG PET/CT
Authors: Liu Xiao, Yueqi Wang, Lin Li
Journal: Clinical Nuclear Medicine (2021)

An 84-year-old woman visited our hospital with hematochezia for 1 month. Abdominal CT and FDG PET/CT showed local thickening of the small intestine, resembling an intestinal aneurysmal dilatation. Thus, a lymphoma was suspected, and surgical resection was performed. The final pathology revealed an exophytic small bowel stromal tumor with perforation, causing pseudoaneurysmal dilation of the small bowel. This case emphasized the importance of considering a small bowel stromal tumor when faced with similar FDG PET/CT findings.
From description to generalization, or there and back again
Authors: Kelsey L. West, Kasey C. Soska, Whitney G. Cole, Danyang Han, Justine E. Hoch, Christina M. Hospodar, Brianna E. Kaplan
Journal: Behavioral and Brain Sciences (2022)

In his target article, Yarkoni prescribes descriptive research as a potential antidote for the generalizability crisis. In our commentary, we offer four guiding principles for conducting descriptive research that is generalizable and enduring: (1) prioritize context over control; (2) let naturalistic observations contextualize structured tasks; (3) operationalize the target phenomena rigorously and transparently; and (4) attend to individual data.
Evaluating a polygenic hazard score to predict risk of developing metastatic or fatal prostate cancer in the multi-ancestry Million Veteran Program cohort.
Authors: Meghana Pagadala, Julie Ann Lynch, Roshan Karunamuni, Patrick Alba, Kyung Min Lee, Fatai Agiri, Tori Anglin-Foote, Hannah Carter, J. Michael Gaziano, Guneet Kaur Jasuja, Rishi Deka, Brent S. Rose, Matthew Panizzon, Richard Hauger, Tyler Seibert
Journal: Journal of Clinical Oncology (2022)

155 Background: Early detection of prostate cancer to reduce mortality remains controversial because there is often also overdiagnosis of low-risk disease and unnecessary treatment. Genetic scores may provide an objective measure of a man’s risk of dying from prostate cancer and thus inform screening decisions. This might be especially useful in men of African ancestry, who have a higher average risk of prostate cancer death but are often treated as a homogeneous group. Our object was to determine whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with risk of metastatic or fatal prostate cancer in a racially and ethnically diverse population. Methods: We analyzed the Million Veteran Program (MVP), a multi-ancestry population of over 500,000 individuals participating in the VA healthcare system. Genotype data were used to calculate the genetic score, PHS290. Family history of prostate cancer (first-degree relative) and ancestry group (harmonized genetic ancestry and self-reported race/ethnicity: European, African, Hispanic, or Asian) were also studied. The primary outcome studied was age at death from prostate cancer. The key secondary outcome was age at diagnosis of prostate cancer metastases. Cox regression was used to test associations. Results: 513,997 MVP participants were included. Median age at last follow-up: 69 years. PHS290 was associated with age at death from prostate cancer in the full cohort and for each ancestry group ( p &lt;10 -16 ). Comparing men in the highest 20% of PHS290 to those in the lowest 20%, the hazard ratio (HR 80/20 ) for death from prostate cancer was 4.41 [95% CI: 3.9-5.02]. Corresponding hazard ratios for European, African, Hispanic, and Asian subsets were 4.26 [3.66-4.9], 2.4 [1.77-3.23], 4.72 [2.68-8.87], and 10.46 [2.01-101.0]. When accounting for family history and ancestry group, PHS290 remained a strong independent predictor of fatal prostate cancer (Table). PHS290 was also associated with metastasis. PHS290 was higher, on average, among men with African ancestry. Conclusions: PHS290 stratified US veterans of diverse ancestry for lifetime risk of metastatic or fatal prostate cancer. Predicting genetic risk of lethal prostate cancer with PHS290 might inform individualized decisions about prostate cancer screening.[Table: see text]
Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1
Authors: Sant P. Chawla, Brian A. Van Tine, Seth M. Pollack, Kristen N. Ganjoo, Anthony D. Elias, Richard F. Riedel, Steven Attia, Edwin Choy, Scott H. Okuno, Mark Agulnik, Margaret von Mehren, Michael B. Livingston, Vicki L. Keedy, Claire F. Verschraegen, Tony Philip, G. Chet Bohac, Sergey Yurasov, Adam Yakovich, Hailing Lu, Michael Chen, Robert G. Maki
Journal: Journal of Clinical Oncology (2021)

CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma.Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed.A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02).Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.
171P Detection of NTRK1/2/3 rearrangements by PCR test for 5’/3’-end unbalanced expression
Authors: E. Imyanitov, A. Romanko, V. Tiurin, N.V. Mitiushkina, A. Venina, E. Preobrazhenskaya, R. Mulkidjan, A.O. Ivantsov, S. Orlov, A. Togo
Journal: Annals of Oncology (2022)
Abstract 10867: Two-Phase Nurse Navigator-Directed Transition-of-Care for Advanced Heart Failure During Index Hospitalization Reduces 30-Day Readmission Rates
Authors: Hayley Mitchel, Alaxandra Kozerski, Robert Valenzuela, Paul Patalinghug, Christine Davidson, Radha Gopalan
Journal: Circulation (2021)

Introduction: Heart failure (HF) is a leading cause of death in the US. Its management costs over $30 billion annually, and 65% is due to HF hospitalizations. In 2012 the Centers for Medicare and Medicaid Services instituted the Hospital Readmissions Reduction Program, designed to reduce cost burden by penalizing hospitals with readmission rates &gt;20%. Current average 30-day readmission rates are estimated to be approximately 20-23%. We conducted a retrospective analysis of 30-day readmission rates of HF patients at a quaternary medical center, under management of a novel RN navigator (RNN) transition-of-care strategy. Methods: Transition-of-care was conducted in two phases: inpatient education and outpatient rapid follow-up (Table 1). Education focused on essential HF knowledge and its significance to the patient’s morbidity/mortality. Notes were recorded on a white board in the patient’s room during phase 1 to allow for daily review throughout the hospitalization. Phase 2 follow-up call was made within 48hrs of discharge. Data was collected on patients hospitalized at Banner University Medical Center Phoenix from 4/2020-12/2020 with a primary diagnosis of decompensated HF, excluding those with durable mechanical circulatory support. The average time spent educating patients during phase I was adaptive based on patients’ comprehension of the material, and 30-day all-cause readmission was recorded. Results: A total of 233 patients were analyzed, and each patient received an estimated average of 90 minutes of inpatient education. Re-hospitalization within 30 days of discharge occurred in 12 patients (5.15%). Conclusions: In this analysis we report a 30-day readmission rate in HF patients from a single center that is remarkably lower than the national average. This was achieved via a 2-phase RNN transition-of-care strategy during index hospitalization. Primary limitation is the retrospective nature of the analysis in a single-center cohort.
Reasons to Consider the COVID-19 Vaccination Status of Patients With Cancer When Analyzing Their COVID-19 Outcomes
Authors: Kazuki Takada, Shinkichi Takamori, Naoko Miura, Yasunori Shikada, Mototsugu Shimokawa
Journal: Journal of Clinical Oncology (2021)

In the recent article by Sharafeldin et al 1 published by the Journal of Clinical Oncology, the authors constructed the National COVID Cohort Collaborative, a centralized data resource representing the largest multicenter cohort of COVID-19 cases, and identified risk factors for allcause mortality from COVID-19 in patients with cancer.They stated that COVID-19 was significantly associated with an increased risk of all-cause mortality in patients with cancer (hazard ratio, 1.20; 95% CI, 1.15 to 1.24) and that age $ 65 years, male sex, Southern or Western US residence, higher number of comorbidities, hematologic malignancy, multisite tumors, and recent cytotoxic therapy were associated with an increased risk of all-cause mortality among patients with COVID-19. 1 The results of their study are extremely informative for not only health care workers, especially those involved in the treatment of patients with cancer, but also the patients and their families.However, we are interested in the COVID-19 vaccine uptake in the cohort of this study, the data of which were not shown in the original paper.
Tumor-specific interendothelial adhesion mediated by FLRT2 facilitates cancer aggressiveness
Authors: Tomofumi Ando, Ikue Tai-Nagara, Yuki Sugiura, Dai Kusumoto, Koji Okabayashi, Yasuaki Kido, Kohji Sato, Hideyuki Saya, Sutip Navankasattusas, Dean Y. Li, Makoto Suematsu, Yuko Kitagawa, Elena Seiradake, Satoru Yamagishi, Yoshiaki Kubota
Journal: Journal of Clinical Investigation (2022)

Blood vessel abnormalization alters cancer cell metabolism and promotes cancer dissemination and metastasis. However, the biological features of the abnormalized blood vessels that facilitate cancer progression and whether they can be targeted therapeutically have not been fully investigated. Here, we found that an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), is expressed preferentially in abnormalized vessels of advanced colorectal cancers in humans and that its expression correlates negatively with long-term survival. Endothelial cell–specific deletion of Flrt2 in mice selectively pruned abnormalized vessels, resulting in a unique metabolic state termed "oxygen-glucose uncoupling," which suppressed tumor metastasis. Moreover, Flrt2 deletion caused an increase in the number of mature vessels, resulting in a significant increase in the antitumor effects of immune checkpoint blockers. Mechanistically, we found that FLRT2 forms noncanonical interendothelial adhesions that safeguard against oxidative stress through homophilic binding. Together, our results demonstrated the existence of tumor-specific interendothelial adhesions that enable abnormalized vessels to facilitate cancer aggressiveness. Targeting this type of adhesion complex could be a safe and effective therapeutic option to suppress cancer progression.
Phase II Study of Ramucirumab in Advanced Biliary Tract Cancer Previously Treated By Gemcitabine-Based Chemotherapy
Authors: Sunyoung Lee, Rachna T. Shroff, Shalini Makawita, Lianchun Xiao, Anaemy Danner De Armas, Priya Bhosale, Kavitha Reddy, Ahmed Shalaby, Kanwal Raghav, Shubham Pant, Robert A. Wolff, Milind Javle
Journal: Clinical Cancer Research (2022)

VEGF receptor-2 (VEGFR-2)-mediated angiogenesis contributes to pathogenesis of biliary tract cancers (BTC). We investigated ramucirumab, a mAb targeting VEGFR-2 for treatment of advanced, chemorefractory BTC.This is a phase II, single-arm trial for advanced, unresectable, pre-treated patients with BTC with ECOG 0/1, adequate liver, renal, and marrow functions. Ramucirumab was administered at 8 mg/kg, 2 weekly with restaging performed 8 weekly. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Exploratory endpoints included correlation of tumor mutational status with PFS and OS.61 patients were enrolled: the median age was 58.5 years; 59 with stage IV disease; 62%, intrahepatic cholangiocarcinoma; 22%, gallbladder cancer; and 16%, extrahepatic cholangiocarcinoma. All received prior chemotherapy: 52% had 1 prior, and rest ≥2 prior lines. Median treatment duration was 10.1 weeks (range, 2.1-86). Median PFS was 3.2 months [95% confidence interval (CI), 2.1-4.8]; median OS, 9.5 months (95% CI, 5.8-13.6). One (1.7%) patient achieved partial response; 26 (43.3%), stable disease; and 25 (41.7%), disease progression; DCR, 45%. Median 6-month PFS and OS rates were 32% (95% CI, 0.22-0.46) and 58% (95% CI, 0.47-0.72). The majority of toxicities were grade 1 or 2; grade 3 proteinuria (1, 2%), hypertension (13, 22%), and pulmonary embolism (1, 2%), and grade 4 gastrointestinal bleeding (1, 2%) occurred.Ramucirumab was well tolerated and resulted in PFS similar to that achieved with other chemotherapy regimens used historically for chemorefractory BTC.
Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mechanism of Cetuximab Resistance in Metastatic Colorectal Cancer
Authors: Raquel Cruz-Duarte, Cátia Rebelo de Almeida, Magda Negrão, Afonso Fernandes, Paula Borralho, Daniel Sobral, Lina M. Gallego-Paez, Daniel Machado, João Gramaça, José Vílchez, Ana T. Xavier, Miguel Godinho Ferreira, Ana R. Miranda, Helder Mansinho, Maria J. Brito, Teresa R. Pacheco, Catarina Abreu, Ana Lucia-Costa, André Mansinho, Rita Fior, Luís Costa, Marta Martins
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance. Experimental Design: We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab. Results: In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanistically, PLCγ1 expression was found to bypass cetuximab-dependent EGFR inhibition by activating ERK and AKT pathways. This novel resistance mechanism involves a noncatalytic role of PLCγ1 SH2 tandem domains in the propagation of downstream signaling via SH2-containing protein tyrosine phosphatase 2 (SHP2). Accordingly, SHP2 inhibition sensitizes PLCγ1-resistant cells to cetuximab. Conclusions: Our discoveries reveal the potential of PLCγ1 as a predictive biomarker for cetuximab responses and suggest an alternative therapeutic approach to circumvent PLCγ1-mediated resistance to cetuximab in patients with RAS WT mCRC. In this way, this work contributes to the development of novel strategies in the medical management and treatment of patients with mCRC.