tbuckley/cabot-search huggingface dataset:
Autologous cytokine-induced killer and dentritic cells in treatment of advanced and unresectable lung cancer.
Authors: Lei Zhang, Baoping Li
Journal: Journal of Clinical Oncology (2012)

e13069 Background: Both experimental and clinical studies showed cytokine-induced killer (CIK) cells have been shown capable of efficiently lysing target tumor cells, which activity can be enhanced by dendritic cell (DC) stimulation. This study demonstrated that co-cultured autologous CIK and tumor antigen-pulsed DC are effective in in treatment of advanced and unresectable lung cancer Methods: Sixteen patients having stage III-IV lung cancer with a malignant pleural effusion, 9 females and 7 males with an average age of 54.3 years old, were included in this study. Autologous CIK and DC were prepared from isolated peripheral blood mononuclear cells and were induced by multiple cytokines. Generated DCs were pulsed by the antigen generated from tumor tissues and co-cultured with CIK. Those patients received 4-6 times of CIK-DC intravenous infusion, 2-3 ×10 9 cells each time. Results: Eleven (68.8%) patients achieved a partial remission. The pleural effusion decreased in all those patients, and in 9 of them the effusion decreased over 50%. The clinical symptoms were relieved in all the patients. There were no significant adverse effects were found. Those patients are still followed for long-term survival outcome. Conclusions: CIK-DCs immunotherapy provides a new and effective treatment for the late stage lung cancer.
Duration of Hybrid Closed-Loop Insulin Therapy to Achieve Representative Glycemic Outcomes in Adults With Type 1 Diabetes
Authors: Lalantha Leelarathna, Hood Thabit, Malgorzata E. Willinska, Lia Bally, Julia K. Mader, Sabine Arnolds, Carsten Benesch, Thomas R. Pieber, Viral N. Shah, Anders L. Carlson, Richard M. Bergenstal, Mark L. Evans, Roman Hovorka
Journal: Diabetes Care (2020)

Closed-loop insulin therapy increases the time spent in target glucose range (70–180 mg/dL) while reducing the time spent in hypoglycemia ( 180 mg/dL) (1), and it is being progressively applied in clinical practice. Randomized clinical trials of closed-loop insulin delivery have been performed over a single day to several months, but the time required to achieve representative glucose outcomes, including control algorithm individualization and behavioral adaptation, is currently unknown. To address this issue we analyzed retrospectively data collected during closed-loop clinical trials in adults with type 1 diabetes and A1C ≥58 mmol/mol (≥7.5%) as such information may be useful in determining the optimal duration of future closed-loop studies as well as follow-up assessments under routine care conditions.

We combined data collected in adults aged 21 years and older during two multinational (U.K., U.S., Austria, and Germany), randomized, day-and-night, hybrid closed-loop studies (2,3) (AP@home04 and APCam11) of 12 weeks’ duration ( N = 56, mean ± SD A1C 68 ± 7 mmol/mol \[8.4 ± 0.6%\] \[range 58–83 mmol/mol (7.5–9.7%)\], age 39 ± 10 years [range 21 to 65 years], diabetes duration 21 ± 9 years [range 6 to 49 years]). The AP@home04 study (2) utilized Dana Diabecare R insulin pump (Sooil, Seoul, South Korea) and FreeStyle Navigator II glucose sensor (Abbott Diabetes Care, Alameda, CA), while the APCam11 study (3) used a modified Medtronic 640G insulin pump and Guardian 3 glucose sensor (Medtronic, Northridge, CA). Both studies used an identical individually adapting, treat-to-target, model-predictive control algorithm residing on a smartphone. Participants were required to deliver a premeal bolus based on carbohydrate content, were not remotely monitored or supervised, …
シロスタゾールによる末梢インターベンションの十分治療(STOP‐IC)研究においてシロスタゾールは大腿膝か病変に対する血管内治療後の血管造影的再狭窄を縮小する
Authors: Yokoi Hiroyoshi, Iida Osamu, Soga Yoshimistu, Nanto Shinsuke
Journal: Circulation (2013)
Abstract 13136: First-Pass Isolation is Associated With Durability of Pulmonary Vein Isolation and Has Impact on Atrial Fibrillation Ablation Outcomes
Authors: Yuichi Ninomiya, Koichi Inoue, Hitoshi Ichiki, Yasuhisa Iriki, Koji Tanaka, Toshinari Onishi, Yuko Hirao, Takafumi Oka, Nobuaki Tanaka, Masato Okada, Hiroyuki Inoue, Yasushi Koyama, Atsunori Okamura, Katsuomi Iwakura, Kenshi Fujii, Mitsuru Ohishi
Journal: Circulation (2019)

Introduction: Durable pulmonary vein (PV) isolation is important to reduce the recurrence of atrial fibrillation (AF). Hypothesis: We investigated the impact of first-pass PV isolation (PVI) (i.e. ...
Physician Time Spent Using the Electronic Health Record During Outpatient Encounters
Authors: J. Marc Overhage, David McCallie
Journal: Annals of Internal Medicine (2020)

Background: The amount of time that providers spend using electronic health records (EHRs) to support the care delivery process is a concern for the U.S. health care system. Given the potential effect on patient care and the high costs related to this time, particularly for medical specialists whose work is largely cognitive, these findings warrant more precise documentation of the time physicians invest in these clinically focused EHR functions. Objective: To describe how much time ambulatory medical subspecialists and primary care physicians across several U.S. care delivery systems spend on various EHR functions. Design: Descriptive study. Setting: U.S.-based, adult, nonsurgical, ambulatory practices using the Cerner Millennium EHR. Participants: 155 000 U.S. physicians. Measurements: Data were extracted from software log files in the Lights On Network (Cerner) during 2018 that totaled the time spent on each of the 13 clinically focused EHR functions. Averages per encounter by specialty were computed. Results: This study included data from approximately 100 million patient encounters with about 155 000 physicians from 417 health systems. Physicians spent an average of 16 minutes and 14 seconds per encounter using EHRs, with chart review (33%), documentation (24%), and ordering (17%) functions accounting for most of the time. The distribution of time spent by providers using EHRs varies greatly within specialty. The proportion of time spent on various clinically focused functions was similar across specialties. Limitation: Variation by health system could not be examined, and all providers used the same software. Conclusion: The time spent using EHRs to support care delivery constitutes a large portion of the physicians' day, and wide variation suggests opportunities to optimize systems and processes. Primary Funding Source: None.
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Authors: Akimasa Hayashi, Jun Fan, Ruoyao Chen, Yu-jui Ho, Alvin P. Makohon-Moore, Nicolas Lecomte, Yi Zhong, Jungeui Hong, Jinlong Huang, Hitomi Sakamoto, Marc A. Attiyeh, Zachary A. Kohutek, Lance Zhang, Aida Boumiza, Rajya Kappagantula, Priscilla Baez, Jessica Bai, Marta Lisi, Kalyani Chadalavada, Jerry P. Melchor, Winston Wong, Gouri J. Nanjangud, Olca Basturk, Eileen M. O’Reilly, David S. Klimstra, Ralph H. Hruban, Laura D. Wood, Michael Overholtzer, Christine A. Iacobuzio-Donahue
Journal: Nature Cancer (2020)
Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance
Authors: Eugene Park, Jingyu Chen, Andrew Moore, Maurizio Mangolini, Antonella Santoro, Joseph R. Boyd, Hilde Schjerven, Veronika Ecker, Maike Buchner, James C. Williamson, Paul J. Lehner, Luca Gasparoli, Owen Williams, Johannes Bloehdorn, Stephan Stilgenbauer, Michael Leitges, Alexander Egle, Marc Schmidt-Supprian, Seth Frietze, Ingo Ringshausen
Journal: Science Translational Medicine (2020)

Inhibition of stromal cell PKC-β mitigates environment-mediated drug resistance in B cell malignancies.
Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in malnourished children.
Authors: R K Chandra
Journal: BMJ (1975)

Serum and nasopharyngeal IgA antibody levels were estimated in 20 malnourished children and 20 matched healthy controls after immunization with a single dose of live attenuated measles or poliovirus vaccine. Seroconversion and serum neutralizing antibody titres were comparable in the two groups. Secretory IgA antibody was detected significantly less often in undernourished children; the time of its first appearance was delayed-and its maximum level was significantly lower. Impaired secretory antibody response in malnourished children may contribute to slow inadequate recovery from viral and enterobacterial infections and predispose to lifethreatening complications.
Biomarker (BM) Analyses of a Phase II Study of Neoadjuvant Pertuzumab and Trastuzumab With and Without Anthracycline (ATC)-Containing Chemotherapy for Treatment of HER2-Positive Early Breast Cancer (BC) (Tryphaena)
Authors: A. Schneeweiss, S. Chia, R. Hegg, C. Tausch, R. Deb, J. Ratnayake, A. Kiermaier, V. McNally, G. Ross, J. Cortes
Journal: Annals of Oncology (2012)
Immediate Allogeneic Hematopoietic Cell Transplantation (HCT) in Acute Myeloid Leukemia (AML) Arising from Myleodysplastic Syndrome (MDS)
Authors: Y. Choi, S.-D. Kim, Y.-H. Park, J.S. Lee, D.-Y. Kim, J.-H. Lee, K.-H. Lee, M. Seol, Y.-S. Lee, Y.-A. Kang, M. Jeon, A.R. Jung, J.-H. Lee
Journal: Annals of Oncology (2012)
Evolution of a New Function by Fusion between Phage DNA and a Bacterial Gene
Authors: Omar Warsi, Michael Knopp, Serhiy Surkov, Jon Jerlström Hultqvist, Dan I Andersson
Journal: Molecular Biology and Evolution (2020)

Mobile genetic elements, such as plasmids, phages, and transposons, are important sources for evolution of novel functions. In this study, we performed a large-scale screening of metagenomic phage libraries for their ability to suppress temperature-sensitivity in Salmonella enterica serovar Typhimurium strain LT2 mutants to examine how phage DNA could confer evolutionary novelty to bacteria. We identified an insert encoding 23 amino acids from a phage that when fused with a bacterial DNA-binding repressor protein (LacI) resulted in the formation of a chimeric protein that localized to the outer membrane. This relocalization of the chimeric protein resulted in increased membrane vesicle formation and an associated suppression of the temperature sensitivity of the bacterium. Both the host LacI protein and the extracellular 23-amino acid stretch are necessary for the generation of the novel phenotype. Furthermore, mutational analysis of the chimeric protein showed that although the native repressor function of the LacI protein is maintained in this chimeric structure, it is not necessary for the new function. Thus, our study demonstrates how a gene fusion between foreign DNA and bacterial DNA can generate novelty without compromising the native function of a given gene.
Retrospective Analysis of Clinical Features of 5-Year-Survival Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)
Authors: T. Hirashima, N. Okamoto, H. Suzuki, N. Morishita, M. Tamiya, T. Shiroyama, Y. Kondoh, N. Ryota, I. Kawase
Journal: Annals of Oncology (2012)
Corrections to “Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab”
Authors: D. Lenihan, T. Suter, M. Brammer, C. Neate, G. Ross, J. Baselga
Journal: Annals of Oncology (2019)

Ann Oncol 2012; 23: 791–800 (doi: 10.1093/annonc/mdr294) In the original article, the disclosure was incomplete. This has now been updated to add the statement for J. Baselga: JB is the consultant and on the advisory board for Roche and Novartis. Pooled analysis of cardiac safety in patients with cancer treated with pertuzumabAnnals of OncologyVol. 23Issue 3PreviewPertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Full-Text PDF Open Archive
Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort
Authors: Daniel A Mulrooney, Geehong Hyun, Kirsten K Ness, Matthew J Ehrhardt, Yutaka Yasui, Daniel Duprez, Rebecca M Howell, Wendy M Leisenring, Louis S Constine, Emily Tonorezos, Todd M Gibson, Leslie L Robison, Kevin C Oeffinger, Melissa M Hudson, Gregory T Armstrong
Journal: BMJ (2020)

Abstract Objective To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer. Design Retrospective cohort study. Setting 27 institutions participating in the Childhood Cancer Survivor Study. Participants 23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included. Main outcome measures Cumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments. Results The 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P&lt;0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10). Conclusions Historical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes. Trial registration ClinicalTrials.gov NCT01120353 .
When leukocytes bite off more than they can chew
Authors: Doriane Dechaux‐Blanc, Farid Zerimech, Anne‐Sophie Guemann, Nicolas Duployez, Elise Fournier
Journal: American Journal of Hematology (2020)

We report the case of a newborn male diagnosed with a severe polymalformative syndrome. He was the first child from consanguineous parents born at term. Fetal ultrasound during pregnancy demonstrated peri-cephalic edema, severe cerebral abnormalities (microcephaly, cerebellum and corpus callosum abnormalities) and hydramnios. Physical examination at birth showed a facial dysmorphism with hypertelorism, exophthalmos, micrognathism, low implanted and badly hemmed ears and bilateral coloboma. He also exhibited arthrogryposis and bilateral cryptorchidism. The full blood count showed: leukocytes count 7.74 × 109/L, hemoglobin concentration 164 g/L and platelet count 101 × 109/L. Peripheral blood smear examination revealed some abnormal lymphocytes displaying large or medium-sized vacuoles, sometimes harboring a pink or grayish color (Images 1A-B). Morphological abnormalities were more striking in granulocytes since all of them showed abundant large and abnormal granules (Images 1C-F). Considering clinical and biological findings, the diagnosis of congenital metabolic disorder was suspected. Further biochemical explorations demonstrated an elevated urinary excretion of glycosaminoglycans (47.4 mg/mmol of creatinin; normal range: 6.1-36.8 mg/mmol). The cellulose acetate electrophoretic profile of urine finally identified a large amount of chondroitin sulfate together with an abnormal excretion of heparan sulfate. All clinical and biological findings suggested a diagnosis of lysosomal storage disease, especially mucopolysaccharidosis type III (Sanfilipo disease) or type VII (Sly disease). Unfortunately, the patient died after 3 days of life due to severe neurological defects. Lysosomal storage diseases include a range of metabolic diseases resulting in abnormal accumulation of metabolic byproducts. In some cases, lymphocytes and more rarely granulocytes may exhibit abnormal cytoplasmic vacuoles or granules, reflecting the underlying mechanism of the disorder. This case illustrates the usefulness of careful examination of all blood smear elements for first-line screening also for the diagnosis of congenital metabolic disorders. The authors have no relevant conflict of interest to disclose. E.F. and N.D. performed morphological analyses. F.D. performed metabolic assays. A.-S.G. provided clinical data. D.D., N.D. and E.F. wrote the manuscript which was approved by all authors.
P-0008 Follow-up Results of Expendable Metal Stents for Malignant Esophageal Obstruction and Fistulae in 177 Patients
Authors: Hye Jin Kim, Heon Young Lee, Byung Seok Lee, Eaum Seok Lee, Hee Seok Moon, Seok Hyun Kim
Journal: Annals of Oncology (2012)
A Phase III, Multicenter, Randomized Trial of Maintenance Versus Observation after Achieving Clinical Response in Patients with Metastatic Breast Cancer who Received Six Cycles of Gemcitabine Plus Paclitaxel as First-Line Chemotherapy (KCSG-BR 0702, NCT00561119)
Authors: Y.-H. Im, Y.H. Park, K.H. Jung, S.-A. Im, J.H. Sohn, J. Ro, S.-B. Kim, S.-W. Han, S. Lee, I.H. Park, J.H. Kim, S.Y. Kang, M.H. Lee, H.S. Park, J.S. Ahn
Journal: Annals of Oncology (2012)
O-0011 Evaluation of Met-Pathway Biomarkers in a Phase 2 Study of Rilotumumab Plus Epirubicin, Cisplatin, and Capecitabine in Gastric/Esophagogastric Junction Cancer
Authors: Kelly Oliner, Rui Tang, Abraham Anderson, Yun Lan, Timothy Iveson, Ross Donehower, Yizhou Jiang, Sarita Dubey, Elwyn Loh
Journal: Annals of Oncology (2012)
Investigating PSMA-Targeted Radioligand Therapy Efficacy as a Function of Cellular PSMA Levels and Intratumoral PSMA Heterogeneity
Authors: Kyle Current, Catherine Meyer, Clara E. Magyar, Christine E. Mona, Joel Almajano, Roger Slavik, Andreea D. Stuparu, Chloe Cheng, David W. Dawson, Caius G. Radu, Johannes Czernin, Katharina Lueckerath
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Prostate-specific membrane antigen (PSMA) targeting radioligands deliver radiation to PSMA-expressing cells. However, the relationship between PSMA levels and intralesion heterogeneity of PSMA expression, and cytotoxic radiation by radioligand therapy (RLT) is unknown. Here we investigate RLT efficacy as function of PSMA levels/cell, and the fraction of PSMA+ cells in a tumor. Experimental Design: RM1 cells expressing different levels of PSMA (PSMA−, PSMA+, PSMA++, PSMA+++; study 1) or a mix of PSMA+ and PSMA− RM1 (study 2, 4) or PC-3/PC-3-PIP (study 3) cells at various ratios were injected into mice. Mice received 177Lu- (studies 1–3) or 225Ac- (study 4) PSMA617. Tumor growth was monitored. Two days post-RLT, tumors were resected in a subset of mice. Radioligand uptake and DNA damage were quantified. Results: 177Lu-PSMA617 efficacy increased with increasing PSMA levels (study 1) and fractions of PSMA positive cells (studies 2, 3) in both, the RM1 and PC-3-PIP models. In tumors resected 2 days post-RLT, PSMA expression correlated with 177Lu-PSMA617 uptake and the degree of DNA damage. Compared with 177Lu-PSMA617, 225Ac-PSMA617 improved overall antitumor effectiveness and tended to enhance the differences in therapeutic efficacy between experimental groups. Conclusions: In the current models, both the degree of PSMA expression and the fraction of PSMA+ cells correlate with 177Lu-/225Ac-PSMA617 tumor uptake and DNA damage, and thus, RLT efficacy. Low or heterogeneous PSMA expression represents a resistance mechanism to RLT. See related commentary by Ravi Kumar and Hofman, p. 2774
The Prognostic Significance of Multiple Pelvic Node Metastases in Cervical Cancer Patients Treated with Radical Hysterectomy Plus Adjuvant Chemoradiotherapy
Authors: M. Okazawa, S. Mabuchi, E. Daimon, T. Iwamiya, T. Miyatake, Y. Ohta, K. Yoshino, M. Fujita, T. Enomoto, S. Kamiura, T. Kimura
Journal: Annals of Oncology (2012)
Predicting Factors of Secondary Resection after Neoadjuvant Chemotherapy in Locally Advanced Epithelial Ovarian Cancers. a Retrospective Study of 82 Cases
Authors: L. Ben Fatma, S. Said, M. Boudagga, M. Hochlef, F. Zairi, H. Khairi, O. Gharbi, H. Boussen, S. Ben Ahmed
Journal: Annals of Oncology (2012)
A Randomized Phase II Study of Docetaxel with or without Bevacizumab After Platinum-Based Chemotherapy Plus Bevacizumab in Patients with Advanced Nonsquamous Non-Small Cell Lung Cs (WJOG 5910L)
Authors: M. Takeda, I. Okamoto, T. Yamanaka, S. Nakamura, K. Nakagawa, Y. Nakanishi
Journal: Annals of Oncology (2012)
ALK and EGFR Mutation Analysis in a Phase II Trial of Cisplatin/Pemetrexed in Japanese Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer
Authors: N. Yanagitani, K. Kaburaki, F. Ohyanagi, K. Kudo, A. Horiike, N. Motoi, K. Takeuchi, Y. Ishikawa, T. Horai, M. Nishio
Journal: Annals of Oncology (2012)
Clinical trial reporting: compliance with US rules is poor and not improving, study finds
Authors: Jacqui Wise
Journal: BMJ (2020)

Only 41% of clinical trials reported their results to the US clinical trials registry within a year of completion as required by law, a study has found. Researchers from Oxford University, UK, who identified 2497 clinical trials that had breached the rules, called for better enforcement from the US Food and Drug Administration.1

The FDA Amendments Act 2007 requires trial sponsors to report results directly to ClinicalTrials.gov within one year of completion, regardless of whether the results are positive or negative. The first trials covered by the final rule of this act came due to report results in January 2018.

The first comprehensive study of compliance since the new regulations came into effect found that, of the …