tbuckley/cabot-search huggingface dataset:
Association between temperature variability and daily hospital admissions for cause-specific cardiovascular disease in urban China: A national time-series study
Authors: Yaohua Tian, Hui Liu, Yaqin Si, Yaying Cao, Jing Song, Man Li, Yao Wu, Xiaowen Wang, Xiao Xiang, Juan Juan, Libo Chen, Chen Wei, Pei Gao, Yonghua Hu
Journal: PLoS Medicine (2019)

Background Epidemiological studies have provided compelling evidence of associations between ambient temperature and cardiovascular disease. However, evidence of effects of daily temperature variability on cardiovascular disease is scarce and mixed. We aimed to examine short-term associations between temperature variability and hospital admissions for cause-specific cardiovascular disease in urban China. Methods and findings We conducted a national time-series analysis in 184 cities in China between 2014 and 2017. Data on daily hospital admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and ischemic stroke were obtained from the database of Urban Employee Basic Medical Insurance (UEBMI) including 0.28 billion enrollees. Temperature data were acquired from the China Meteorological Data Sharing Service Center. Temperature variability was calculated from the standard deviation (SD) of daily minimum and maximum temperatures over exposure days. City-specific associations between temperature variability and cardiovascular disease were examined with overdispersed Poisson models controlling for calendar time, day of the week, public holiday, and daily mean temperature and relative humidity. Random-effects meta-analyses were performed to obtain national and regional average associations. We also plotted exposure-response relationship curve using a natural cubic spline of temperature variability. There were 8.0 million hospital admissions for cardiovascular disease during the study period. At the national-average level, a 1-°C increase in temperature variability at 0–1 days (TV0–1) was associated with a 0.44% (0.32%–0.55%), 0.31% (0.20%–0.43%), 0.48% (0.01%–0.96%), 0.34% (0.01%–0.67%), and 0.82% (0.59%–1.05%) increase in hospital admissions for cardiovascular disease, ischemic heart disease, heart failure, heart rhythm disturbances, and ischemic stroke, respectively. The estimates decreased but remained significant when controlling for ambient fine particulate matter (PM2.5), NO2, and SO2 pollution. The main limitation of the present study was the unavailability of data on individual exposure to temperature variability. Conclusions Our findings suggested that short-term temperature variability exposure could increase the risk of cardiovascular disease, which may provide new insights into the health effects of climate change.
The relationship between tumor budding, tumor microenvironment, and survival in patients with primary operable colorectal cancer.
Authors: Hester Catharina Van Wyk, Antonia K. Roseweir, Ditte Anderson, Elizabeth Sutton, Paul G. Horgan, Donald C McMillan, Joanne Edwards
Journal: Journal of Clinical Oncology (2019)

581 Background: Tumour budding is an independent prognostic factor in colorectal cancer and has recently been defined by the International Consensus Conference on Tumour Budding. The aim was to use the ITBCC budding evaluation method to examine relationships between tumour budding, tumour factors, tumour microenvironment, gene expression profiles and survival in patients with primary operable CRC. Methods: Hematoxylin and Eosin (H&amp;E) stained slides of 953 CRC patients, diagnosed between 1997 and 2007 were evaluated for tumour budding according to the ITBCC-criteria. The tumour microenvironment was evaluated using tumour stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumour inflammatory cell infiltrate. Differential gene expression was assessed using TempO-Seq gene expression profiling (BioSpyder Technologies Inc., CA, USA) using the Surrogate+Tox targeted panel (2,733 genes selected for biological diversity, maximal information content, and widespread pathway coverage). Results: High budding (n = 269/ 28%) was significantly associated with TNM stage (P &lt; 0.001), venous invasion (P &lt; 0.001), weak KM grade (P &lt; 0.001), high TSP (P &lt; 0.001) and reduced cancer specific survival (CSS) (HR = 5.04; 95% confidence interval [CI], 3.50-9.51; P &lt; 0.001) and was independent of venous invasion, KM grade, and Ki67 proliferation index. RNA expression analysis was employed using TempO-Seq to determine differential gene expression between tumours with (n = 8) and without budding (n = 18). Three genes were identified as significantly differentially expressed: S100A2 (S100 calcium binding protein A2) was upregulated by 2.9 fold (padj &lt; 0.00001); REG1A (regenerating family member 1 alpha) was downregulated by 4.7 fold (padj &lt; 0.01) and LCN2 (lipocalin 2) was downregulated by 2.2 fold (padj &lt; 0.01). Conclusions: Tumour budding stratifies patients’ survival in primary operable colorectal cancer and associates with differing gene expression profiles and factors of the tumour. Therefore, the ITBCC budding evaluation method should be used to assess tumour budding as supplement the TNM staging system and can help to further subdivide colorectal cancer into new prognostic groups.
Oncologic Therapy for Solid Tumors Alters the Risk of Clonal Hematopoiesis
Authors: Kelly Bolton, Ryan Ptashkin, Lior Braunstein, Daniel Kelly, Sean M Devlin, Catherine C. Coombs, Matahi Moarii, Minal Patel, Elsa Bernard, Antonin Berthon, Dominik Glodzik, Michael Francis Walsh, Diana Mandelker, Akshar Patel, Jessica Schulman, Gunes Gundem, Choonsik Lee, Montserrat García-Closas, Stuart Gardos, Jose Baselga, David M. Hyman, Martin S. Tallman, Howard Scher, Dean Bajorin, Mariko Yabe, Virginia M. Klimek, Luis Alberto Diaz, Nilanjan Chatterjee, Michael F. Berger, Lindsay M. Morton, Ross L. Levine, Ahmet Zehir, Elli Papaemmanuil
Journal: Blood (2018)
Embryonal Tumors
Authors: Roger J. Packer
Journal: Neuro-Oncology (2012)

Embryonal tumors are a diverse group of primitive tumors occurring predominantly in children, but also arising in young adults. Medulloblastoma is the most common tumor type within this categorization and molecular data increasingly demonstrates that medulloblastoma is not a single entity, but is actually comprised of multiple tumor types with different molecular signatures and probably prognoses. The atypical teratoid/rhabdoid tumor has been diagnosed primarily in children less than 2 years of age and carries a very poor prognosis. Management of embryonal tumors is similar across tumor types, is usually patterned after studies performed in older children with medulloblastoma, and is comprised of total to near-total surgical resections, staging studies, separation into risk stratification groupings, and postoperative treatments with varying doses of radiation and chemotherapy. Because of the concern over sequelae, young children are treated initially with chemotherapy in attempts to obviate or delay the need for radiation therapy. Survivors remain at a major risk for long-term neurologic, neurocognitive, psychologic, and endocrinologic sequelae.
Transcript profiling of neuroendocrine tumors (NETs) to identify new targets and mechanism of progression.
Authors: Emily Walzer, Suraj Peri, Karthik Devarajan, Jianming Pei, Kathy Q. Cai, Yulan Gong, Steven J. Cohen, Igor A. Astsaturov, Paul F. Engstrom, Namrata Vijayvergia
Journal: Journal of Clinical Oncology (2019)

292 Background: Few studies have characterized the molecular drivers of NET growth and mechanisms differentiating poorly differentiated (PD) and well differentiated (WD) NETs. We explored the role of dysregulated transcriptome as the principal molecular mechanism of NETs with the goal to identify novel targets and biomarkers of differentiation. Methods: With IRB approval, de-identified, formalin fixed NET samples were used to extract total RNA for transcriptome analysis. All pathology specimens were centrally reviewed. Gene expression profiles of 774 genes were obtained using nCounter platform (PanCancer pathway panel, Nanostring TechnologiesTM). The resulting count data was voom normalized and differentially expressed genes between PD and WD NETs were identified using linear modeling methods available in R-Bioconductor LIMMA package. Candidate genes with potential therapeutic implications were validated in tissue microarrays by immunohistochemistry (IHC). Results: Analysis of gene count data between 16 PD and 23 WD NETs resulted in 154 differentially expressed genes on the 774 gene panel (FDR &lt; 10% and 2 fold change (FC) up- or down-regulated), some of which may be potential drug targets (Figure 1). E.g. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for transcriptional repression, and CHK1, a G2/M cell cycle regulator, were upregulated in PD compared to WD NETs (2.7 and 3.1 FC, respectively) and serine/threonine-protein kinase PAK 3, involved in cytoskeleton reorganization, was upregulated in WD NETs (3.4 FC). IHC staining also suggested overexpression of EZH2 and its enzymatic substrate H3K27me in PD NETs (p &lt; 0.001). PAK 3, another novel therapeutic candidate overexpressed in WD NETs (p &lt; 0.001) was confirmed using IHC, validating the transcriptome analysis at protein level. Conclusions: These findings, combined with previously reported pathway analysis (Vijayvergia et.al 2017)], highlight biological differences between PD and WD NETs and serve as a platform for future research. They also support investigation of novel drugs that inhibit activity of EZH2 (e.g. EPZ6438) in PD NETs and PAK3 (e.g FRAX597) in WD NETs.
SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mfolfirinox versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma.
Authors: Davendra Sohal, Shannon McDonough, Syed A. Ahmad, Namita Gandhi, Muhammad Shaalan Beg, Andrea Wang-Gillam, James Lloyd Wade, Katherine A Guthrie, Andrew M. Lowy, Philip Agop Philip, Howard S. Hochster
Journal: Journal of Clinical Oncology (2019)

414 Background: Clinical outcomes after curative therapy of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. For early control of systemic disease with aggressive perioperative chemotherapy (CTx), we conducted a prospective trial in the National Clinical Trials Network (NCTN) setting. Methods: S1505 was a randomized phase II trial of periop (12 weeks pre-, 12 weeks post-op) CTx with either mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin; Arm 1), or gemcitabine/nab-paclitaxel (Arm 2). Eligibility required adult patients with ECOG PS 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); &lt; 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Primary outcome is 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients, accrual up to 150 patients was planned, to account for cases deemed ineligible at central radiology review. Results: From 2015 to 2018, 147 patients were enrolled; 74 to Arm 1; 73 to Arm 2. At central radiology review, 42/147 (29%) were ineligible; of these, 15 (36%) had venous involvement ≥ 180°, 22 (52%) had arterial involvement, 28 (67%) had distant disease. One patient had distal cholangiocarcinoma (ineligible); one withdrew consent after randomization. Eligible patients (n = 103) had median age 64 years; males 58%; whites 89%; PS 0 64%. Of 103, 99 (96%) started and 86 (83%) completed preop CTx. There was one death due to sepsis and 61 additional patients experienced grade 3/4 toxicities. To date, 76 of 99 (77%) patients went to surgery and 72 (73%) underwent resection. Conclusions: This is the first-ever NCTN study of periop CTx for resectable PDA. Accrual was brisk, establishing feasibility. Ineligible cases after central radiology review highlight quality control and physician education imperatives for neoadjuvant PDA trials. Preop CTx safety and resection rates are encouraging. Follow up for OS is ongoing. Clinical trial information: NCT02562716.
Spatial Network Mapping of Pulmonary Multidrug-Resistant Tuberculosis Cavities Using RNA Sequencing
Authors: Keertan Dheda, Laura Lenders, Shashikant Srivastava, Gesham Magombedze, Helen Wainwright, Prithvi Raj, Stephen J. Bush, Gabriele Pollara, Rachelle Steyn, Malika Davids, Anil Pooran, Timothy Pennel, Anthony Linegar, Ruth McNerney, Loven Moodley, Jotam G. Pasipanodya, Carolin T. Turner, Mahdad Noursadeghi, Robin M. Warren, Edward Wakeland, Tawanda Gumbo
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection (n = 14) and healthy lung tissue from control subjects without tuberculosis (n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways.Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm3 (15–389 cm3). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation "sink" in the central caseum–fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid–mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden (r > 0.6), whereas T-helper effector systems did not.Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis–related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions.
Abstract 14871: Examining Lay Provider Response to an Unannounced Simulated Sudden Cardiac Arrest Using an Immersive Virtual Reality System
Authors: Alfredo Almodovar, David G Buckler, Benjamin S Abella, Audrey L Blewer, Marion Leary
Journal: Circulation (2017)

Introduction: Due to the sudden nature of a sudden cardiac arrest (SCA) event, capturing actual bystander response data is difficult. Current technologies such as virtual reality (VR) wearable devices allow us to create high stress scenarios programmed for heightened realism. No studies have examined the use of an immersive VR wearable designed specifically to capture lay bystander response to an unannounced SCA event. Objectives: We sought to characterize lay bystander response to an unannounced SCA event during an immersive, multisensory (audio, visual, tactile) VR scenario. Methods: Using our VR SCA system integrated with a CPR recording manikin, subjects interacted with simulated bystanders and were able to give vocal commands such as “call 911” or “get an AED”. Subjects performed CPR on the simulated victim in the virtual environment while also performing CPR on the manikin (Figure). Subjects were unaware of the nature of the event but were told to respond however they would to an emergency situation...
Abstract 14697: Significance of First-degree Atrioventricular Block on Lethal Ventricular Arrhythmias of Adult Patients With Total Correction of Tetralogy of Fallot
Authors: Yoshitaka Kimura, Koji Fukuda, Makoto Nakano, Yuhi Hasebe, Kyoshiro Fukasawa, Takahiko Chiba, Keita Miki, Shunsuke Tatebe, Hideki Ota, Masato Kimura, Osamu Adachi, Yoshikatsu Saiki, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Several studies have demonstrated the importance of mechanoelectrical interaction in patients with surgically corrected tetralogy of Fallot (ToF). However, significance of PR interval p...
Progression-free survival (PFS) and subgroups analyses of lenvatinib in patients (pts) with G1/G2 advanced pancreatic (panNETs) and gastrointestinal (giNETs) neuroendocrine tumors (NETs): Updated results from the phase II TALENT trial (GETNE 1509).
Authors: Jaume Capdevila, Nicola Fazio, Carlos López-López, Alexandre Teule, Juan W. Valle, Salvatore Tafuto, Ana B. Custodio, Nicholas Reed, Markus Raderer, Enrique Grande, Rocio Garcia-Carbonero, Paula Jiménez-Fonseca, Vicente Alonso, Lorenzo Antonuzzo, Andrea Spallanzani, Alfredo Berruti, Isabel Sevilla, Adelaida La Casta Munoa, Jorge Hernando, Toni Ibrahim
Journal: Journal of Clinical Oncology (2019)

332 Background: Pts with advanced G1/G2 NETs have limited treatment options with overall response rates (ORR) with targeted agents (TA) &lt; 10%. Benefit on PFS after TA therapy has not been demonstrated. The mechanism of action of lenvatinib (VEGFR1-3 &amp; FGFR1-4 inhibitor) may increase efficacy and revert primary and acquired resistance to TA. We report the updated results on PFS, safety and subgroups. Methods: This prospective phase II study had two cohorts: G1/G2 panNETs and giNETs. All pts had baseline documented disease progression (PD) by RECIST. For panNETs, PD to TA was mandatory, regardless prior therapy with somatostatin analogs (SSAs) or chemotherapy (CHT), and for giNETs, PD on SSAs. Pts were treated with lenvatinib at 24 mg qd until PD or intolerable toxicity. The primary endpoint was ORR by central radiology review. PFS was calculated by investigator assessment. Biochemical responses were defined as reduction from baseline &gt; 50%. With 55 pts per arm our study was powered to identify an ORR ≥ 25% (90% power, 5% α-error). Results: We recruited 111 pts (55 panNETs/56 giNETs). Prior therapies were CHT 32%, SSAs 87%, everolimus (E) 70% and sunitinib (S) 30% for panNETs. ORR was 29%, 40% for panNETs and 18.5% for giNETs. With a median follow-up of 17 months (m), PFS for panNETs was 15.8 m (95% CI 11.4-NR) and 15.4 m (95% CI 11.5-19.5) for giNETs. Dose reductions/interruptions were needed in 91.8% with a median dose of 20 mg qd. In the subgroups analyses, all pts obtained the same benefit in PFS and ORR, including grade and prior therapy with S (PFS: 16.4 m, ORR: 43.7%) or E (PFS: 15 m, ORR: 37.1%) (p = ns). A significant correlation of chromogranin A decrease and prolonged PFS in giNETs (17.6 m vs NR, p = 0.032) was observed. The most frequent G3-4 adverse events were hypertension (20.7%), asthenia (13.5%), diarrhea (7.2%) and abdominal pain (5.4%). Conclusions: Lenvatinib showed the highest reported ORR with a TA by central radiology assessment in panNETs and giNETs with promising PFS in a pretreated population. The benefit was observed across subgroups analyses, including pretreated pts with TA. Clinical trial information: NCT02678780.
Knowledge, attitudes and beliefs about vaccination in primary healthcare workers involved in the administration of systematic childhood vaccines, Barcelona, 2016/17
Authors: Camila Andrea Picchio, Mireia Garcia Carrasco, Maria Sagué-Vilavella, Cristina Rius
Journal: Eurosurveillance (2019)

Background Healthcare professionals are a reliable and impactful source of information on vaccination for parents and children. Objectives We aimed to describe the knowledge, attitudes and beliefs primary care professionals involved in administration of childhood vaccines in Barcelona have about vaccines and vaccination. Methods In 2016/17, surveys were administered in person to every public primary care centre (PCC) with a paediatrics department (n = 41). Paediatricians and paediatric nurses responded to questions about disease susceptibility, severity, vaccine effectiveness, vaccine safety, confidence in organisations, key immunisation beliefs, and how they vaccinate or would vaccinate their own children. We used standard descriptive analysis to examine the distribution of key outcome and predictor variables and performed bivariate and multivariate analysis. Results Completed surveys were returned by 277 (81%) of 342 eligible participants. A quarter of the respondents reported doubts about at least one vaccine in the recommended childhood vaccination calendar. Those with vaccine doubts chose the response option ‘vaccine-hesitant’ for every single key vaccine belief, knowledge and social norm. Specific vaccine knowledge was lacking in up to 40% of respondents and responses regarding the human papilloma virus vaccine were associated with the highest degree of doubt. Being a nurse a risk factor for having vaccine doubts (adjusted odds ratio (ORa) = 2.0; 95% confidence interval (95% CI): 1.1–3.7) and having children was a predictor of lower risk (ORa = 0.5; 95% CI: 0.2–0.9). Conclusions Despite high reported childhood immunisation rates in Barcelona, paediatricians and paediatric nurses in PCC had vaccine doubts, especially regarding the HPV vaccine.
A Phase 1, Single-Dose, Open-Label, 5-Treatment, Crossover, Pharmacokinetic Study of Comparative Bioavailability of Epinephrine Nasal Spray and EpiPen® in Healthy Adults With Seasonal Allergies
Authors: Jun Chen, Shivani Chilampalli, Giovanni DeCastro, Eshwaran Narayanan, Rajesh R. Wakaskar, George J. Atiee
Journal: Journal of Allergy and Clinical Immunology (2019)
Stratification for Age in Non-Transfusion-Dependent Thalassemia: Data from a National Italian Networking
Authors: Alessia Pepe, Laura Pistoia, Nicola Romano, Giuseppe Colaci, Aurelio Maggio, Antonella Carollo, Saveria Campisi, Maria Caterina Putti, Ilaria Fotzi, Domenico D'Ascola, Emanuele Grassedonio, Vincenzo Positano, Antonella Meloni
Journal: Blood (2018)
Case 5-2019: A 48-Year-Old Woman with Delusional Thinking and Paresthesia of the Right Hand
Authors: Charlotte Hogan, Brent P. Little, Jonathan C.T. Carlson, Oliver Freudenreich, Ana Ivkovic, Jason M. Baron
Journal: New England Journal of Medicine (2019)

A 48-year-old woman presented with tingling of the right hand and was found to have disorganized and delusional thinking. Laboratory evaluation revealed normocytic anemia and an elevated prolactin level. MRI of the head was normal. Results of additional diagnostic tests were received.
Short Diagnosis to Treatment Interval (DTI) Is Associated with Inferior Outcome in Newly Diagnosed Patients with Mantle Cell Lymphoma, a MER/LEO and Alliance Collaboration
Authors: Matthew J Maurer, Amy S. Ruppert, Brian K. Link, Lawrence D Kaplan, David J Inwards, Andrew L. Feldman, Eric D. Hsi, Adam Pettinger, Jonathon B. Cohen, Peter Martin, Brad S Kahl, Nancy L. Bartlett, James R. Cerhan, John P. Leonard, Thomas M. Habermann
Journal: Blood (2018)
The Effect of omalizumab in Mastocytosis Patients. Prospective double-blind, placebo-controlled multicentre study
Authors: Meike Distler, Tatjana Maul, Urs Steiner, Peter Jandus, Carla Murer, Nicole Graf, Tatjana Petkvic, Joerg Sebach, Alexander Navarini, Lars French, Arthur Helbling, Peter Schmid-Grendelmeier
Journal: Journal of Allergy and Clinical Immunology (2019)