tbuckley/cabot-search huggingface dataset:
Abstract 22: Poloxamer 188 Protects Mouse Brain Microvascular Endothelial Cells in an in-vitro Traumatic Brain Injury Model
Authors: Felicia P Lotze, Michele M Salzman, Johannes A Pille, Claudius Balzer, Josephine E Hees, William J Cleveland, Matthias L Riess
Journal: Circulation (2019)

Introduction: Traumatic brain injury (TBI), a major cause of severe disability and death, can lead to disruption of the vascular endothelial system and cell membrane integrity, threatening the survival of multiple cell types. Reducing these could improve the clinical outcome of TBI. Poloxamer 188 (P188) has been shown to protect different cell types against ischemia/reperfusion (IR) injury. Hypothesis: P188 protects mouse brain microvascular endothelial cells (MBECs) against injury in an in-vitro compression-type TBI model. Methods: Confluent MBEC cultures were exposed to normoxic (complete media; 21% O 2 , 5% CO 2 , 74% N 2 ; 37°C) or hypoxic (glucose-, serum-free media; 0.01% O 2 , 5% CO 2 , N 2 balance; 37°C) conditions for 5 hrs, with compression (9.81 N / 0.16 cm 2 ) added during the first hour of normoxia/hypoxia. All MBECs then underwent 2 hrs of reoxygenation in normoxic conditions ± P188 (10 μM, 100 μM, 1 mM). Samples were assayed for cell number, cytotoxicity (lactate dehydrogenase [LDH] release), and metabolic activity. Statistics: Data are mean ± SEM. Kruskal-Wallis one-way analysis of variance on Ranks, Dunn’s Method; p &lt;0.05, * vs normoxia, † vs hypoxia, ** vs normoxia + compression, †† vs hypoxia + compression; n = 11-19 experiments/group. Results: Compared to normoxic cells without compression, cell number and metabolic activity decreased and cytotoxicity increased in cells exposed to hypoxic conditions +/- compression followed by reoxygenation. In hypoxic cells, 1 mM P188 increased cell number and metabolic activity and decreased cytotoxicity, while 100 μM only increased metabolic activity and decreased cytotoxicity and 10 μM only increased metabolic activity. In hypoxic compressed cells, no concentration of P188 improved cell number, however, 10 μM and 100 μM P188 increased metabolic activity, while 1 mM increased metabolic activity and decreased cytotoxicity. There was no difference between normoxic compressed and non-compressed cells in any assay, although all concentrations of P188 tested increased metabolic activity in normoxic compressed cells. Conclusion: P188, present during reoxygenation, provides protection to MBECs exposed to simulated IR injury, as well as compression-type TBI.
Phase II Study of Pemetrexed Plus Cisplatin and Cetuximab in Advanced Squamous Cell Carconima of the Head and Neck
Authors: J.B. Vermorken, T.C. Gauler, J. Stoehlmacher-Williams, A. Dietz, J.M. Lopez-Picazo, O. Hamid, A.M. Hossain, T. Burkholder, S. Chang, L. Licitra
Journal: Annals of Oncology (2012)
First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer
Authors: Xingsheng Hu, Xin Zheng, Sheng Yang, Lin Wang, Xuezhi Hao, Xinge Cui, Lieming Ding, Li Mao, Pei Hu, Yuankai Shi
Journal: Journal of Hematology & Oncology (2020)

BPI-9016M is a novel small-molecule inhibitor that simultaneously targets both c-Met and AXL tyrosine kinases. This phase I study aimed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of BPI-9016M in Chinese patients with advanced non-small cell lung cancer (NSCLC).Over the dose range of 100 mg to 800 mg, eligible patients were administered with a single dose of 9016M tablet and received 7 days of pharmacokinetics evaluation, followed by continuous dose administration (QD dosing, 28 days). Standard "3 + 3" dose escalations were performed.Twenty NSCLC patients were treated. All patients experienced at least one adverse event (AE), of which treatment-related adverse events (TRAEs) were reported in 17 (85.0%) patients. The most common TRAEs were alanine transaminase (ALT) elevation (60%), bilirubin increased (40%), dysgeusia (40%), constipation (30%), hypertension (25%), and palmar-plantar erythrodysesthesia syndrome (15%). The TRAEs of grade 3 or higher during treatment were hypertension (15%), pulmonary embolism (5%), and laryngeal pain (5%). No dose-limiting toxicity (DLT) was observed, and the MTD was not reached. The median time to Cmax ranged from 2.0 to 3.5 h, and the plasma concentration of BPI-9016M declined rapidly after Tmax fitting a single-compartment model. The mean AUC0-72 h of M1 and M2-2, main metabolites of BPI-9016M, were 4.8-6.6 folds and 4.1-9.8 folds higher than that of BPI-9016M, respectively. Exposure to BPI-9016M, M1, and M2-2 reached moderate saturation at 600 mg. Among 19 evaluable patients, 1 had a partial response and 10 patients had stable disease.BPI-9016M showed favorable safety and pharmacokinetic profiles, and no DLT was observed at doses up to 800 mg once daily. The promising antitumor activity in Chinese NSCLC patients supports further development of this tyrosine kinase inhibitor.Clinical Trial ID: NCT02478866, registered May 21, 2015.
Prognostic and Predictive Values of KRAS in EGFR-Based Subgroups and Combined With p53 in Completely Resected Non-Small Cell Lung Cancer (NSCLC): A Lace-Bio Study
Authors: P.A. Janne, F.A. Shepherd, C. Domerg, G. Le Teuff, R. Kratzke, P. Hainaut, J. Pignon, R. Rosell, J. Soria, M. Tsao
Journal: Annals of Oncology (2012)
Undergraduate examination and assessment of knowledge and skills is crucial in capacity planning for the future healthcare workforce in physical activity interventions
Authors: Ann Bernadette Gates, Michelle Grace Swainson, Fiona Moffatt, Roger Kerry, George S Metsios, Ian Ritchie
Journal: British Journal of Sports Medicine (2020)

The WHO Global Action Plan on Physical Activity (GAPPA) (#GAPPA)1 highlights the importance of a systems-wide approach to achieving the global goals for reducing physical inactivity at the national, community, individual and patient levels. Within this scope, objective 1.4 of that plan details the vision and strategy for capacity planning for the health workforce and the collaborations required for success. This objective is closely linked to existing global and national efforts to enable the future healthcare professional (HCP) workforce to have the capability and competencies to make every contact count for physical activity support and advice (via brief interventions). A significant part of these goals is to enable the future and current healthcare workforce to meet the challenges of non-communicable diseases (NCDs), sustainable development goals (SDGs) and person-centred healthcare, exemplars of which have been identified in most European countries.2 3 Indeed, a physical activity resource focused approach in undergraduate healthcare courses such as medicine, nursing and allied health is critical in higher education institutes’ (HEIs) strategies2 4 5 to deliver on these directives.

Reaching the potential of knowledge and skill acquisition in physical activity interventions is a challenge in practice.6–8 Yet we know that HCP practice influences healthcare behaviours in patients: this is the basis of ‘making every contact count’ …
Selective Internal Radiation Therapy (SIRT) for Gist Liver Metastases Resistant to Tyrosine Kinase Inhibitors
Authors: P. Hohenberger, N. Rathmann, A. Peschel, J. Schuette, S.O. Schoenberg, D. Dinter, S. Diehl
Journal: Annals of Oncology (2012)
Linking Transcriptomic and Imaging Data Defines Features of a Favorable Tumor Immune Microenvironment and Identifies a Combination Biomarker for Primary Melanoma
Authors: Robyn D. Gartrell-Corrado, Andrew X. Chen, Emanuelle M. Rizk, Douglas K. Marks, Margaret H. Bogardus, Thomas D. Hart, Andrew M. Silverman, Claire-Audrey Y. Bayan, Grace G. Finkel, Luke W. Barker, Kimberly M. Komatsubara, Richard D. Carvajal, Basil A. Horst, Rui Chang, Anthea Monod, Raul Rabadan, Yvonne M. Saenger
Journal: Cancer Research (2020)

Abstract Patients with resected stage II-III melanoma have approximately a 35% chance of death from their disease. A deeper understanding of the tumor immune microenvironment (TIME) is required to stratify patients and identify factors leading to therapy resistance. We previously identified that the melanoma immune profile (MIP), an IFN-based gene signature, and the ratio of CD8+ cytotoxic T lymphocytes (CTL) to CD68+ macrophages both predict disease-specific survival (DSS). Here, we compared primary with metastatic tumors and found that the nuclei of tumor cells were significantly larger in metastases. The CTL/macrophage ratio was significantly different between primary tumors without distant metastatic recurrence (DMR) and metastases. Patients without DMR had higher degrees of clustering between tumor cells and CTLs, and between tumor cells and HLA-DR+ macrophages, but not HLA-DR− macrophages. The HLA-DR− subset coexpressed CD163+CSF1R+ at higher levels than CD68+HLA-DR+ macrophages, consistent with an M2 phenotype. Finally, combined transcriptomic and multiplex data revealed that densities of CD8 and M1 macrophages correlated with their respective cell phenotype signatures. Combination of the MIP signature with the CTL/macrophage ratio stratified patients into three risk groups that were predictive of DSS, highlighting the potential use of combination biomarkers for adjuvant therapy. Significance: These findings provide a deeper understanding of the tumor immune microenvironment by combining multiple modalities to stratify patients into risk groups, a critical step to improving the management of patients with melanoma.
カペシタビンによる手足症候群の予防における,尿素/乳酸ベースの外用角質溶解剤の有効性を明らかにするプラセボ比較対照試験:米国の北中部癌治療グループ (NCCTG)の試験N05C5
Authors: L Wolf Sherry, Qin Rui, P Menon Smitha, Rowland Kendrith M., Thomas Sachdev, Delaune Robert, Christian Diana, Pajon Eduardo R., V Satele Daniel, L Berenberg Jeffrey, L Loprinzi Charles
Journal: Journal of Clinical Oncology (2010)
PD-0030 2-Year Follow-Up of A Phase II Study on Catumaxomab as Part of a Multimodal Approach in Primarily Resectable Gastric Cancer
Authors: Carsten Bokemeyer, Karsten Ridwelski, G. Ramadori, Djordje Atanackovic, Dirk Arnold, Ewald Wöll, Markus Buechler, Christian Krüger, Christoph Schuhmacher
Journal: Annals of Oncology (2012)
Chronic Myelogenous Leukaemia Following S-1 THerapy for Rectal Cancer: A Case report
Authors: M. Manabe, T. Nishii, N. Harada, H. Nakano, T. Takakuwa, S. Okamoto, Y. Aoyama, T. Kumura, A. Mugitani
Journal: Annals of Oncology (2012)
Abstract 292: Accuracy of a Dispatch-Directed Breathing Verification Diagnostic Tool as Assessed by Data From Electronic Patient Care Records and Emergency Dispatch Systems
Authors: Scott T Youngquist, Jonathan Poulson, Daniel Ashwood, Srilakshmi Sangaraju, Hill Stoecklein, Greg Scott, Jeff Clawson, Christopher H Olola
Journal: Circulation (2019)

Introduction: Identification of sudden out-of-hospital cardiac arrest (OHCA) and delivery of bystander emergency medical dispatcher (EMD)-directed pre-arrival instructions are key elements in the chain of survival. In order to provide instructions, dispatchers must formulate a clinical impression (rather than a definitive diagnosis) after an abbreviated history and dispatcher-directed examination of the scene. Thus, fast and accurate identification tools are imperative in the treatment of OHCA. Hypothesis: A dispatch-directed breathing verification diagnostic tool (BVDxT) accurately identifies inadequate breathing from OHCA. Methods: A retrospective design using EMD data matched to electronic patient care records (ePCRs) from the Salt Lake City Fire Department. The BVDxT, an embedded interface within the dispatch system, allows dispatchers to count breaths as reported by callers and record the rate of 4 consecutive patient breaths. OHCA was defined as non-trauma cases that had paramedic primary impression of cardiac arrest, respiratory arrest, or overdose or a Glasgow Coma Score of 3. Results: A total of 45,007 emergency dispatch cases were matched with the paramedic impressions of 38,258 ePCRs. Of the matched cases, 2660 cases included some use of the BVDxT, 1,365 (51.3%) had used the BVDxT to completion (i.e. breathing rate was recorded during the call) and, of those, 1,248 (91.4%) had complete on-scene paramedic primary or secondary impressions to match to the BVDxT outcomes. Median time using the tool was 28 seconds (IQR: 21-39). Overall, BVDxT identified 68.6% (n = 856/1,248) callers with disordered breathing and paramedics recorded 16.4% (205/1,248) cases of OHCA. BVDxT demonstrated a 70.7% (145/205) sensitivity, and 31.8% specificity for OHCA. Conclusions: Preliminary evidence suggest the BVDxT does well in predicting abdominal breathing condition. Although, by design, emergency dispatch tools tend to have high sensitivity, the low specificity of the tool may over-triage the number of abnormal breathing issues in the field - which may result in a substantial proportion of possible false positives. Changes in patient condition between call receipt and EMS arrival may also impact these findings.
Expression Profiling of 21 Biomolecules in Locally Advanced Nasopharyngeal Carcinomas (LA-NPC) of Caucasian Patients Treated with Chemotherapy or Chemo-Radiotherapy (CRT) in the Context of a Hellenic Cooperative Oncology Group Randomized Trial
Authors: M. Bobos, D. Krikelis, G. Karayannopoulou, L. Resiga, S. Chrysafi, E. Samantas, D. Andreopoulos, V. Vasiliou, E. Ciuleanu, G. Fountzilas
Journal: Annals of Oncology (2012)
P-0254 Dealing with Cetuximab in First Line of Metastatic CCR Kras Wild Type: Preliminary Results from a French Prospective Study Premium
Authors: Laurent Mineur, Laurent Miglianico, Louis Dourthe, Denis Smith, Nathalie Bonichon-Lamichhane, Nicolas Mathe, Marie Maurin
Journal: Annals of Oncology (2012)
Shared decision making: doctors have expertise that patients want or need
Authors: Robert Dingwall, Alison Pilnick
Journal: BMJ (2020)

The basic problem with shared decision making is that it has always been a matter of ideology rather than evidence.1 As Gulbrandsen points out in his response,2 shared decision making has paid very little attention to the substantial body of research on doctor-patient interactions that has been generated since the 1970s when audio and later video …
Utilization of Formalin-Fixed, Paraffin-Embedded Archival Tissue for Cytogenetic Analysis of Microarray-Comparative Genomic Hybridization
Authors: M. Oikawa, J. Arai, H. Kondo, M. Nakashima, T. Hayashi, K. Yoshiura, H. Yano, T. Nagayasu
Journal: Annals of Oncology (2012)
A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer
Authors: Paul G. Corn, Miao Zhang, Graciela M. Nogueras-Gonzalez, Lianchun Xiao, Amado J. Zurita, Sumit K. Subudhi, Shi-Ming Tu, Ana M. Aparicio, Cristian Coarfa, Kimal Rajapakshe, Shixia Huang, Nora M. Navone, Sue-Hwa Lin, Guocan Wang, Sumankalai Ramachandran, Mark A. Titus, Theocharis Panaretakis, Gary E. Gallick, Eleni Efstathiou, Patricia Troncoso, Christopher Logothetis
Journal: Clinical Cancer Research (2020)

Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation.Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6-22.7 months), and mOS was not reached. Reductions in PSA ≥ 90%, bone-specific alkaline phosphatase ≥ 50%, and urine N-telopeptides ≥ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1.Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
NICE recommends implantable monitor to identify atrial fibrillation after stroke
Authors: Elisabeth Mahase
Journal: BMJ (2020)

People who have had a stroke with no identified cause could have their heart activity tracked and sent remotely to their doctor, suggests draft guidance of the UK National Institute for Health and Care Excellence.1 The guidance, which is under consultation until 4 February, said that the Reveal LINQ monitor can be used to track heart activity over long periods of time and …
Rosia: A Single-Arm Study in More Than 1000 Patients (PTS) Receiving Front-Line Bevacizumab (BEV) + Chemotherapy (CT) for Ovarian Cancer (OC)
Authors: C. Mendiola, I. Davidenko, N. Colombo, J. Korach, F. Selle, P. Gocze, E. Chmielowska, P. Pautier, D. Bollag, A.M. Oza
Journal: Annals of Oncology (2012)
Hepatitis E virus finds its path through the gut
Authors: Noémie Oechslin, Darius Moradpour, Jérôme Gouttenoire
Journal: Gut (2020)

Hepatitis E virus (HEV) infection is a major cause of acute hepatitis and jaundice worldwide.1 HEV genotypes (gt) 1 and 2 are transmitted through the faecal-oral route and cause primarily waterborne epidemics, whereas the zoonotic gt 3 and 4 are transmitted via the consumption of undercooked or raw pork or game meat. Infection of immunocompromised patients with HEV gt 3 may result in chronic hepatitis E and the development of cirrhosis. Beyond liver disease, HEV can cause a number of extrahepatic manifestations, including neurological complications such as neuralgic amyotrophy and Guillain-Barre syndrome. Very similar to hepatitis A virus (HAV), HEV harbours a positive-strand RNA genome, and both are found as so-called quasi-enveloped virions in blood and as naked virions in bile and faeces.2 

Although HEV is known to be enterically transmitted, there was limited evidence for infection of the gastrointestinal tract. In a study published in this journal, Marion et al addressed this question by the development of different cell culture systems, including primary human small intestinal epithelial cells, polarised primary enterocytes and intestinal tissue specimens obtained from small bowel resections.3 Using primary HEV gt 1 and 3 isolates from stool samples of patients with hepatitis E as well as virus derived from the gt 3 Kernow-C1 p6 clone, the …
A Prospective Randomized Trial Evaluating Gene Expression Arrays to Select Neoadjuvant Chemotherapy Regimen for Operable Breast Cancer: First Report of the Remagus04 Trial
Authors: J. Pierga, B. Asselain, S. Alsafadi, E. Brain, F. Lerebours, S. Delaloge, D. Gentien, N. Servant, B. Sigal-Zafrani, F. André
Journal: Annals of Oncology (2012)
Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50%
Authors: J.F. Gainor, H. Rizvi, E. Jimenez Aguilar, F. Skoulidis, B.Y. Yeap, J. Naidoo, S. Khosrowjerdi, M. Mooradian, C. Lydon, P. Illei, J. Zhang, R. Peterson, B. Ricciuti, M. Nishino, J. Zhang, J.A. Roth, J. Grishman, D. Anderson, B.P. Little, B.W. Carter, K. Arbour, J.L. Sauter, M. Mino-Kenudson, J.V. Heymach, S. Digumarthy, A.T. Shaw, M.M. Awad, M.D. Hellmann
Journal: Annals of Oncology (2020)

Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. Tumor mutation burden (TMB) also predicts response to ICIs but is often not available in real time for decision making in the first-line setting. Smoking exposure can be a proxy for TMB in NSCLC. The impact of smoking status on efficacy of PD-1 blockade in NSCLC patients with PD-L1 TPS ≥50% has not been well defined.To investigate the relationship between smoking and activity of ICIs in NSCLC, we retrospectively studied 315 patients with NSCLC and PD-L1 TPS ≥50% at five USA academic medical centers. Objective response rates (ORRs), progression-free survival (PFS), and duration of response (DOR) were compared between never (<100 lifetime cigarettes), light (≤10 pack-years), and heavy (>10 pack-years) smokers. A subset of patients underwent next-generation sequencing to estimate TMB.We identified 36 (11%) never, 42 (13%) light, and 237 (75%) heavy smokers with NSCLC and PD-L1 TPS ≥50% treated with ICIs. Objective responses were observed in 27%, 40%, and 40% of never, light, and heavy smokers, respectively (P = 0.180 never versus heavy; P = 1.000 light versus heavy). Median PFS and median DOR were numerically shorter in never and light smokers compared with heavy smokers (PFS 3.0 versus 4.0 versus 5.4 months; median DOR 6.9 versus 10.8 versus 17.8 months), but were not statistically different [PFS: hazard ratio (HR) 1.37, P = 0.135 and HR 1.24, P = 0.272; DOR: HR 1.92, P = 0.217 and HR 1.79, P = 0.141].PD-(L)1 inhibitors are associated with antitumor activity in NSCLC with PD-L1 TPS ≥50% regardless of smoking status. Nevertheless, there is a signal of potentially decreased durability among never and light smokers that should be further evaluated. Distinct immunobiologic features may affect initial response versus durability of antitumor immunity to programmed cell death 1 (PD-1) blockade.
Her Signaling Effects on the NK Cell-Mediated Cytotoxicity via Regulation of MHC Class I-Related Chain A/B in Cancer Cells
Authors: R. Okita, D. Mougiakakos, K. Yasuda, A. Maeda, T. Yukawa, S. Saisho, Y. Hirami, K. Shimizu, M. Nakata, R. Kiessling
Journal: Annals of Oncology (2012)
Trimodality Treatment of Locally Advanced, Resectable Esophageal Squamous Cell Carcinoma: A Single Institute Experience in Southern Taiwan
Authors: Y.-H. Chen, H.-I Lu, C.-H. Huang, K.-M. Rau, Y.-C. Chiu, Y.-M. Wang, Y.-Y. Chen, C.-T. Liu, S.-H. Li
Journal: Annals of Oncology (2012)
P2.23 First-Line Gefitinib in Epidermal Growth Factor Receptor Mutation-Positive (EGFR+) Non-Small Cell Lung Cancer (NSCLC) in an Israeli Cohort
Authors: S. Ben-Arieh, D. Urban, N. Maimon, R. Leibowitz-Amit, D. Keizman, H. Biran, M. Mishaeli, A. Onn, M. Gottfried
Journal: Annals of Oncology (2012)
P3.09 Sheba Medical Center's Breast Repository
Authors: Y. Cohen, A. Onn, A. Lax, A. Yosepovich, S. Litz, S. Kalish, R. Felemovicius, G. Hout-Silony, M. Gutman, M. Shabtai, D. Rosin, A. Valeanu, E. Winkler, M. Sklair-Levy, B. Kaufman, I. Barshack
Journal: Annals of Oncology (2012)