tbuckley/cabot-search huggingface dataset:
SEX-RELATED DIFFERENCES IN SHEAR STRESS AND ITS INFLUENCE ON ATHEROSCLEROTIC PLAQUE DISTRIBUTION AND PROGRESSION IN HUMAN CORONARY ARTERIES
Authors: Jolanda Wentzel, Michail Papafaklis, Antonios Antoniadis, Saeko Takahashi, Nicholas V. Cefalo, Michelle Cormier, Shigeru Saito, Ahmet U. Coskun, Peter Howard Stone
Journal: Journal of the American College of Cardiology (2020)
A MULTI-MODAL COMPUTER MODEL OF THE HEART CAN PREDICT THERAPY OUTCOME IN CARDIAC RESYNCHRONIZATION THERAPY (CRT)
Authors: Eric Lluch Alvarez, Elham Kayvanpour, Tiziano Passerini, Farbod Sedaghat-Hamedani, Hugo Katus, Benjamin Meder, Tommaso Mansi
Journal: Journal of the American College of Cardiology (2020)
Randomized trial of sequence vs. combination of capecitabine (X) and docetaxel (T): XT vs. T followed by X after progression as first-line therapy for patients (pts) with metastatic breast cancer (MBC)
Authors: S. Beslija, N. Obralic, H. Basic, A. Tatarevic, M. Naila, M. Banjin, A. Cardzic, A. Sosevic, A. Pasic, T. Ceric, B. Salkic
Journal: Journal of Clinical Oncology (2006)

571 Background: Capecitabine (Xeloda [X]) and docetaxel (Taxotere [T]) are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-preatreated MBC [O’Shaughnessy et al. J Clin Oncol 2002], although only one third of pts in the T group received X after progression. We designed this study to determine whether XT is better than sequential T→X in first-line MBC. Methods: 100 pts with measurable MBC, prior adjuvant anthracyclines (100%) but no prior chemotherapy for MBC and KPS ≥70 received 3-weekly cycles of either XT (X 1250mg/m 2 bid d1–14 + T 75mg/m 2 d1) or T→X (T 100mg/m 2 d1 followed after progression by X 1250mg/m 2 bid d1–14). X monotherapy data were not considered in the RR or TTP analyses but were included for OS and safety. Results: The XT and T→X arms were well balanced for prognostic factors: median age 48 (29–59) vs. 51 (31–64) years; median KPS 100 (70–100) in both arms; hormone-responsive disease 20 vs. 16%; dominant metastatic sites (liver 42 vs. 44%, lymph nodes 34 vs. 36%, lung 28 vs 24%, bone 20 vs 18%); number of involved organs (1 = 58 vs. 52%, &gt;1 = 42 vs. 48%); median interval since prior adjuvant anthracyclines (18.5 vs. 17.0 months). Efficacy findings are shown in the table . 74% of the pts in the T→X arm crossed-over to X on progression. The post-study treatment rate was similar in both arms. The most common grade 3/4 adverse events (&gt;5% of pts) with XT vs. T→X were: hand-foot syndrome 18 vs. 4%; stomatitis 16 vs. 8%; neutropenia 12 vs. 14%; neutropenic fever 12 vs. 14%; diarrhea 12 vs. 8%; fatigue 8 vs. 12%; alopecia 6 vs. 8%; edema 4 vs. 8%. Dose reductions were necessary for 52% of pts on XT and 36% of pts on T→X. Conclusions: XT provides significant RR, TTP and OS advantages over T→X. XT should be the standard therapy in fit poor-prognosis pts with aggressive disease. [Table: see text] No significant financial relationships to disclose.
Flexible working: all trainees will be able to work less than full time by 2022
Authors: Abi Rimmer
Journal: BMJ (2020)

Trainees in England will no longer need to meet specific criteria to be able to work less than full time (LTFT), the BMA has announced.

The agreement between the BMA, Health Education England, and NHS Employers means trainees across all medical specialties will be able to work LTFT on the basis of personal choice by the end of 2022.

Previously, access to LTFT working …
SAFETY AND EFFICACY OF ELECTIVE ELECTRIC CARDIOVERSION IN ATRIAL FIBRILLATION WITHOUT THE USE OF TRANSESOPHAGEAL ECHOCARDIOGRAM THE ECARTE STUDY
Authors: Annamaria Iorio, Roberta Rossini, Elona Collaku, Isabelle Piazza, Alberto Ferrari, Alessandra Carobbio, Paolo De Filippo, Michele Senni, Antonello Gavazzi
Journal: Journal of the American College of Cardiology (2020)
Fear of disease progression in patients with gastrointestinal stromal tumors (GIST).
Authors: Ronald Tielen, Jose A.E. Custers, Judith Prins, Johannes HW de Wilt, Marieke F.M. Gielissen, Winette T.A. Van Der Graaf
Journal: Journal of Clinical Oncology (2013)

10549 Background: GIST are rare tumors and before 2000 patients had a dismal prognosis when metastasized. Since the introduction of imatinib and other tyrosine kinase inhibitors overall survival has increased from less than 1 year before 2001 to more than 5 years now. Research on psychosocial consequences for this particular cancer type is scarce. This study focuses on quality of life and fear of disease progression in GIST patients. Methods: Eighty patients with locally advanced or metastatic GIST, being treated with imatinib or sunitinib, from the Radboud University Nijmegen Medical Centre in the Netherlands were asked to participate. Patients completed self-report questionnaires including the EORTC-QLQ-C30, the Cancer Worry Scale, and the Fear of Cancer Recurrence Inventory. Results: Fifty two patients (median age 64.2; range 22-84 years) completed the questionnaires. Two subgroups were identified: patients with locally advanced (n= 27) and metastatic GIST (n= 25). Overall, GIST patients demonstrate a good global quality of life (EORTC-QLQ-C30 mean global health 76.1). However, 50% of them (n= 26) experienced high levels of fear of cancer progression (CWS cut-off point ≥ 14). High levels of fear were not associated with age, gender or between patients with locally advanced or metastatic GIST. Subgroup analyses revealed that patients with high levels of fear of disease progression showed significantly higher levels of psychological distress related to fear of cancer progression and more functional impairments including domains that can be disturbed by fear of cancer progression (e.g. work, daily and social activities, the ability to make future plans or set life goals). Conclusions: Despite a good overall quality of life, a substantial percentage of GIST patients experience high levels of fear of cancer progression, experiencing more psychological distress and more functional impairments compared to patients with low levels of fear. No relation was found with demographic variables nor with stage of disease. This research demonstrates that it is necessary to focus on more specific rather than general quality of life of GIST patients.
Annexin A6 Is Critical to Maintain Glucose Homeostasis and Survival During Liver Regeneration in Mice
Authors: Anna Alvarez‐Guaita, Patricia Blanco‐Muñoz, Elsa Meneses‐Salas, Mohamed Wahba, Abigail H. Pollock, Jaimy Jose, Mercedes Casado, Marta Bosch, Rafael Artuch, Katharina Gaus, Albert Lu, Albert Pol, Francesc Tebar, Stephen E. Moss, Thomas Grewal, Carlos Enrich, Carles Rentero
Journal: Hepatology (2020)

Liver regeneration requires the organized and sequential activation of events that lead to restoration of hepatic mass. During this process, other vital liver functions need to be preserved, such as maintenance of blood glucose homeostasis, balancing the degradation of hepatic glycogen stores, and gluconeogenesis (GNG). Under metabolic stress, alanine is the main hepatic gluconeogenic substrate, and its availability is the rate-limiting step in this pathway. Na+ -coupled neutral amino acid transporters (SNATs) 2 and 4 are believed to facilitate hepatic alanine uptake. In previous studies, we demonstrated that a member of the Ca2+ -dependent phospholipid binding annexins, Annexin A6 (AnxA6), regulates membrane trafficking along endo- and exocytic pathways. Yet, although AnxA6 is abundantly expressed in the liver, its function in hepatic physiology remains unknown. In this study, we investigated the potential contribution of AnxA6 in liver regeneration.Utilizing AnxA6 knockout mice (AnxA6-/- ), we challenged liver function after partial hepatectomy (PHx), inducing acute proliferative and metabolic stress. Biochemical and immunofluorescent approaches were used to dissect AnxA6-/- mice liver proliferation and energetic metabolism. Most strikingly, AnxA6-/- mice exhibited low survival after PHx. This was associated with an irreversible and progressive drop of blood glucose levels. Whereas exogenous glucose administration or restoration of hepatic AnxA6 expression rescued AnxA6-/- mice survival after PHx, the sustained hypoglycemia in partially hepatectomized AnxA6-/- mice was the consequence of an impaired alanine-dependent GNG in AnxA6-/- hepatocytes. Mechanistically, cytoplasmic SNAT4 failed to recycle to the sinusoidal plasma membrane of AnxA6-/- hepatocytes 48 hours after PHx, impairing alanine uptake and, consequently, glucose production.We conclude that the lack of AnxA6 compromises alanine-dependent GNG and liver regeneration in mice.
Deep Convolutional Neural Network-Aided Detection of Portal Hypertension in Patients With Cirrhosis
Authors: Yanna Liu, Zhenyuan Ning, Necati Örmeci, Weimin An, Qian Yu, Kangfu Han, Yifei Huang, Dengxiang Liu, Fuquan Liu, Zhiwei Li, Huiguo Ding, Hongwu Luo, Changzeng Zuo, Changchun Liu, Jitao Wang, Chunqing Zhang, Jiansong Ji, Wenhui Wang, Zhiwei Wang, Weidong Wang, Min Yuan, Lei Li, Zhongwei Zhao, Guangchuan Wang, Mingxing Li, Qingbo Liu, Junqiang Lei, Chuan Liu, Tianyu Tang, Seray Akçalar, Emrecan Çelebioğlu, Evren Üstüner, Sadık Bilgiç, Zeynep Ellik, Özgün Ömer Asiller, Zaiyi Liu, Gaojun Teng, Yaolong Chen, Jinlin Hou, Xun Li, Xiaoshun He, Jiahong Dong, Jie Tian, Ping Liang, Shenghong Ju, Yu Zhang, Xiaolong Qi
Journal: Clinical Gastroenterology and Hepatology (2020)
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol
Authors: Kausik K. Ray, R. Scott Wright, David Kallend, Wolfgang Koenig, Lawrence A. Leiter, Frederick J. Raal, Jenna A. Bisch, Tara Richardson, Mark Jaros, Peter L.J. Wijngaard, John J.P. Kastelein
Journal: New England Journal of Medicine (2020)

Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing.We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent.Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).
Bone and cardiac status in 10-year survivors of breast cancer
Authors: M. E. Trudeau, H. L. Lickley, L. Zhang, G. Hawker, S. Narod, C. Sawka
Journal: Journal of Clinical Oncology (2006)

681 Background: A prospective case-control study was carried out on 425 women treated for breast cancer who survived for 10 years without evidence of recurrence (cases) matched for age, race and length of follow-up from diagnosis to 425 women with benign breast disease followed for 10 or more years (controls). For cases, only 23% received chemotherapy and 33% hormone therapy. Methods: We examined multiple indicators of physical and emotional well-being and report here the results pertaining to cardiac and bone health. Bone mineral density (BMD) was assessed using DXA at the lumbar spine and hip, expressed as gm/cm 2 , and classified as normal/low bone mass/osteoporosis. Cardiac health was assessed using 10 year cardiovascular risk, calculated as low, moderate or high based on age, cholesterol and triglyceride levels, smoking history and blood pressure (according to the calculation published by Genest J et al. CMAJ 2003). Treatment received for both bone and cardiac disease was evaluated. The comparison of cases and controls was assessed using the Wilcoxon non-parametric or Chi-squared tests. Results: Body mass index (BMI) was significantly greater for cases versus controls (27.5 ± 2.4 vs 26.7 ± 4.9; p = 0.034). The mean BMD (corrected for weight) was 1.08 ± 0.05 g/cm 2 at the spine for cases, compared with 1.11 ± 0.06 g/cm 2 for controls (p &lt;0.0001). Among those with osteoporosis at follow-up, 30% of cases compared with 35% of controls had been treated with bisphosphonates; 10% cases and 55% of controls with osteoporosis had received HRT. There were no significant differences in 10-year cardiovascular risk between the cases and controls. Overall, 78% were low, 18% moderate, and 4% high risk. Cholesterol-lowering medications were prescribed to only ≤23% of the moderate and high risk groups in both cases and controls. Conclusions: Despite greater BMI, cases had lower BMD and were less likely to have received treatment for osteoporosis than were controls. 10 year cardiovascular risk was not significantly different in the cases versus controls despite the greater use of HRT in the controls. Both groups appear to be undertreated with cholesterol-lowering medications by today’s standards of care. These findings can help to inform the content of survivorship programs. No significant financial relationships to disclose.
IT-002. AUTOLOGOUS DENDRITIC CELL VACCINE TO COMBAT BRAIN TUMORS IN DOGS AND MICE
Authors: Ratan Bhardwaj, Madhavi Chakravadhanula, Victor Ozols, Joey Georges, Elizabeth Carlson, Chris Hampton, William Decker
Journal: Neuro-Oncology (2013)

A patient's immune system can be instructed to recognize and attack malignant lesions more efficiently. Hence, immunotherapy based on immunization with tumor antigen (Ag)-loaded dendritic cells (DCs) as Ag-presenting cells represents a promising strategy in the multimodal treatment for different can
Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders
Authors: Shahid Mohammad, Stephen J. Page, Li Wang, Seiji Ishii, Peijun Li, Toru Sasaki, Aiesha Basha, Anna Salzberg, Zenaide Quezado, Fumiaki Imamura, Hirotaka Nishi, Keiichi Isaka, Joshua G. Corbin, Judy S. Liu, Yuka Imamura Kawasawa, Masaaki Torii, Kazue Hashimoto-Torii
Journal: Nature Neuroscience (2020)
USE OF ANTIBIOTIC ENVELOPES TO PREVENT CARDIAC IMPLANTABLE ELECTRONIC DEVICE RELATED INFECTIONS: A META-ANALYSIS
Authors: Ghulam Murtaza, Mohit Turagam, Krishna Akella, Domenico Della Rocca, Donita Atkins, Jeffrey Winterfield, Sandeep Gautam, Michael Robert Gold, Rakesh Gopinathannair, Dhanunjaya R. Lakkireddy, Scott Koerber
Journal: Journal of the American College of Cardiology (2020)
Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal
Authors: Masumi Ueda, Renato Martins, Paul C. Hendrie, Terry McDonnell, Jennie R. Crews, Tracy L. Wong, Brittany McCreery, Barbara Jagels, Aaron Crane, David R. Byrd, Steven A. Pergam, Nancy E. Davidson, Catherine Liu, F. Marc Stewart
Journal: Journal of the National Comprehensive Cancer Network (2020)

The first confirmed case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020, in Snohomish County, Washington. At the epicenter of COVID-19 in the United States, the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, and University of Washington are at the forefront of delivering care to patients with cancer during this public health crisis. This Special Feature highlights the unique circumstances and challenges of cancer treatment amidst this global pandemic, and the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.
Correlation of single nucleotide polymorphisms in NER pathway genes with toxicity in advanced non-small cell lung cancer patients treated with chemotherapy.
Authors: Ling Zhang
Journal: Journal of Clinical Oncology (2012)

e18115 Background: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. We assessed whether polymorphisms in genes of NER pathway, such as ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in advanced NSCLC pts. Methods: Eligible pts had histological or cytological confirmed stage IV or IIIB (with malignant pleural effusion) chemo-naïve NSCLC, ECOG PS of 0 to 2 and adequate organ function. Pts received vinorelbine 25 mg/m 2 or gemcitabine 1000 mg/m 2 on day 1 and 8, or docetaxel 75 mg/m 2 or taxel 175 mg/m 2 on day 1 plus cisplatin 75 mg/m 2 or carboplatin AUC=5 on day 1, every 21 days per cycle, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. Hematology and biochemistry analyses were repeated every cycle or before chemotherapy for d8 treatment. Toxicity was classified according to CTC AE 3.0. Venous blood was collected and genomic DNA was isolated. Polymorphisms were assessed. SNPs in ERCC6 (A/G 1413, A/G 1213 and A/G 1097), XPC (T/C 500 and A/C 940), ERCC5 (G/C 1104), RRM1 (−37C/A), CCNH (T/C 270) and MMS19L (G811A) were assessed. Results: Totally 388 pts were included prospectively from Oct 2005 to Mar 2009. Median age was 61 years; 68.8% were male, 36.2% were ECOG PS 1, 33.2% had stage IIIB. The median follow-up time was 18 months (range 8–66 months). Hematological toxicity was the most common AE. SNPs of MMS19L and ERCC6 can predict the AE of chemotherapy in NSCLC,leucopenia (P=0.020), jaundice (P=0.039) by MMS19L. In terms of grade 3-4 AE, SNPs of MMS19L and RRM1 -37C/A have much more predictive effect. SNPs of MMS19L were good at total AE (P=0.042), thrombopenia (P=0.035), SNPs of RRM1 -37C/A were for vomiting (P=0.046) and jaundice (P=0.014). Conclusions: Polymorphisms in ERCC6, MMS19L, RRM1, can predict the tolerability of platinum-based chemotherapy in advanced NSCLC patients. Polymorphisms in other genes of NER pathway, such as ERCC5, CCNH, XPC, have no predictive effect.
Phase I dose escalation study of pemetrexed and carboplatin in chemotherapy-naive elderly patients with advanced nonsquamous non-small cell lung cancer.
Authors: Kazuhiko Yamada, Hiroaki Takeoka, Yoshiaki Zaizen, Fumie Shimamatsu, Koichi Azuma, Tomoaki Hoshino
Journal: Journal of Clinical Oncology (2013)

e19137 Background: The subgroup analyses in several phase III trials have suggested that overall survival after platinum-doublet chemotherapy in elderly patients with non-small cell lung cancer (NSCLC) can be similar to those in younger patients. The combination of carboplatin (CBDCA) with pemetrexed (PEM) is expected as a suitable treatment for carefully selected elderly patients with advanced non-squamous (non-Sq) NSCLC. Methods: Patients with ≥75 years, PS of 0-1, chemotherapy-naïve advanced non-Sq NSCLC were enrolled in this study. They received escalated doses of CBDCA at AUC 4 (cohort 1) or AUC 5 (cohort 2) and PEM 500 mg/m 2 every 3 weeks for six cycles. Dose escalation was decided by dose-limiting toxicity (DLT) occurred in the first cycle of chemotherapy. Study protocol stipulated that additional number of patients, up to maximum of 20 patients, was enrolled to receive the recommended dose of study treatment. The primary objectives were to evaluate feasibility and determine the recommended dose of this combination. Results: A total of 20 patients (6 patients in cohort 1, 14 patients in cohort 2) were enrolled in this study. Median age was 77 (range 75-83). No DLTs were observed in the patients with cohort 1 and the first 6 patients of cohort 2 during the first cycle of chemotherapy, thus the combination of PEM 500 mg/m 2 plus CBDCA at AUC 5 was determined as the recommended dose. Median number of cycles was 4 (range 1-6). The major toxicities were neutropenia, thrombocytopenia, anemia. During the entire period of study, 2 and 5 patients needed to have platelet transfusion and RBC transfusion, respectively. Liver dysfunction, fatigue and anorexia were also common, but these were generally manageable. Six partial responses and 9 stable diseases were observed, giving an overall response rate of 30% and a disease control rate of 75%. Median progression-free survival time was 4.8 months (95% CI, 4.1 – 5.4 months). Conclusions: The combination of PEM 500 mg/m 2 plus CBDCA at AUC 5 was determined as the recommended dose. This combination therapy is generally tolerable, and may have encouraging antitumor activity in chemotherapy-naïve elderly patients with advanced non-Sq NSCLC. Clinical trial information: UMIN000003231.