tbuckley/cabot-search huggingface dataset:
肺静脈洞および心門の大きさ | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Kiuchi Kunihiko, Matsuda Yuichi, Yoshikawa Ryohei, Kamemura Kohei, Arai Kenichi, Okada Taito, Oosue Tsuyoshi, Hamada Akiko, Sano Hiroshi, Kizaki Tomohiko
Journal: Circulation (2008)
In healthy adults, high-dose vitamin D did not improve radial or tibial BMD or strength
Authors: Rebecca D. Jackson
Journal: Annals of Internal Medicine (2020)

Source Citation Burt LA, Billington EO, Rose MS, et al. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a randomized clinical trial. JAMA. 2019;322:736-45. 31454046
Favorable Impact on Mainly Intermediate Cytogenetic Risk AML Can be Predicted by Gene Expression Profiling- Results of a Phase I/II Trial of Belinostat in Combination with Idarubicin in AML
Authors: L. Bullinger, S. Knudsen, H. Dombret, M. Dennis, A. Neubauer, M. Pfreundschuh, J. Rossi, P. Knoblauch, J. Tjørnelund, R.F. Schlenk
Journal: Annals of Oncology (2012)
Abstract 17064: Enrichment of Cardiotoxic Gene Expression Profile in Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes in Response to Tyrosine Kinase Inhibitor Nilotinib
Authors: Praful Aggarwal, Matthew White, Andrea Matter, Amy Turner, Benjamin Olson, Ulrich Broeckel
Journal: Circulation (2018)

Small molecule tyrosine kinase inhibitors (TKIs) are a valuable class of therapeutics with widespread clinical utility against multiple cancers. However, there is strong evidence that TKIs are associated with cardiotoxicity and adverse cardiovascular events. Our understanding of the underlying mechanisms related to TKI induced cardiotoxicity is limited. Human iPSC derived cardiomyocytes (hiPSC-CMs) provide a flexible platform and unique model to study the underlying molecular mechanisms associated with TKI associated cardiotoxicity. In this study we describe the gene expression profile between hiPSC-CM cell lines which exhibit susceptibility vs. resistance. RNA-seq analysis was performed in hiPSC-CM cell lines from six participants in the NHLBI HyperGEN study (A to F). Experiments were performed in triplicate using sunitinib (SUN), vandetanib (VAN), gefitinib (GEF) and nilotinib (NIL). We analyzed beat rate, cell index and ATP viability as physiological measurements of CM toxicity and defined a 20% change from the normalized control as TKI susceptibility. Differential gene expression analysis was performed using DESeq2. We observed significant physiological differences between the different hiPSC-CMs after TKI treatment (beat rate, cell index and ATP viability). The most variable cell index and beat rate response was observed for NIL. Based on cell index, lines B, D, E were resistant while A, C, F were significantly more susceptible to NIL. Principal component analysis showed that the variance in gene expression was the highest after NIL treatment when compared to controls (16% for NIL; 11% for VAN; 6% for SUN and 5% for GEF). A total of 567 genes exhibited significant differential expression changes (adj. p-value ≤ 0.1) after NIL treatment in susceptible versus resistant lines. Pathway analysis showed significant enrichment for cardiotoxicity including pathways implicated in cardiac infarction, fibrosis, hypertrophy, and congestive cardiac failure. Taken together, our results identify unique gene expression changes associated with TKI cardiotoxicity. Furthermore, the variability in TKI susceptibility between different hiPSC-CM lines highlights the need to comprehensively assess cardiotoxicity in a diverse set of lines on a physiological and molecular level.
多発性骨髄腫におけるシルツキシマブ(抗IL-6)併用下または非併用下でのボルテゾミブ-メルファラン-プレドニゾンに関する第2相無作為化試験
Authors: San-Miguel Jesus, Blade Joan, Shpilberg Ofer, Grosicki Sebastian, Maloisel Frederic, Min Chang-Ki, Zarzuela Marta Polo, Robak Tadeusz, Prasad Sripada V. S. S, Goh Yeow Tee, Laubach Jacob, Spencer Andrew, Mateos Maria-Victoria, Palumbo Antonio, Puchalski Tom, Reddy Manjula, Uhlar Clarissa, Qin Xiang, Van De Velde Helgi, Xie Hong, Z Orlowski Robert
Journal: Blood (2014)
Anaplastic Large Cell Lymphoma Involving 7 Different Organs in a Pediatric Patient Demonstrated by FDG PET/CT
Authors: Mingyu Zhang, Xu Yang, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2019)

An 11-year-old girl presented with vomiting, abdominal pain, nausea, and scleral icterus for 7 days. FDG PET/CT demonstrated multiple FDG-avid lesions in muscle, bone, kidney, pancreas, ovary, lymph nodes, and central nervous system. Biopsy from the lesion in the muscle of the right upper arm demonstrated ALK-positive anaplastic large cell lymphoma. The present case highlights the advantage of FDG PET/CT in better staging pediatric patients with anaplastic large cell lymphoma.
The utility and safety of linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the paediatric population
Authors: Haider Al-Najjar, Ronan Breen, George Santis, Omendra Narayan
Journal: European Respiratory Journal (2020)

<b>This first European case series demonstrates that EBUS-TBNA, well established in the diagnosis of mediastinal and hilar adenopathy in adults, is a safe and useful diagnostic alternative to invasive surgical biopsy in the paediatric population</b>http://bit.ly/389Uvq4
A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors
Authors: Sandip P. Patel, Megan Othus, Young Kwang Chae, Francis J. Giles, Donna E. Hansel, Preet Paul Singh, Annette Fontaine, Manisha H. Shah, Anup Kasi, Tareq Al Baghdadi, Marc Matrana, Zoran Gatalica, W. Michael Korn, Jourdain Hayward, Christine McLeod, Helen X. Chen, Elad Sharon, Edward Mayerson, Christopher W. Ryan, Melissa Plets, Charles D. Blanke, Razelle Kurzrock
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART). Patients and Methods: We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease &amp;gt;6 months, and toxicity. Results: Thirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13–64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%–52%); median OS was 11 months (95% CI, 6–∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events. Conclusions: Ipilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.
Trends in HIV-2 Diagnoses and Use of the HIV-1/HIV-2 Differentiation Test — United States, 2010–2017
Authors: Anne H. Peruski, Laura G. Wesolowski, Kevin P. Delaney, Pollyanna R. Chavez, S. Michele Owen, Timothy C. Granade, Vickie Sullivan, William M. Switzer, Xueyuan Dong, John T. Brooks, M. Patricia Joyce
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Since 2014, the recommended laboratory testing algorithm for diagnosing human immunodeficiency virus (HIV) infection has included a supplemental HIV-1/HIV-2 differentiation test to confirm infection type on the basis of the presence of type-specific antibodies (1). Correctly identifying HIV-1 and HIV-2 infections is vital because their epidemiology and clinical management differ. To describe the percentage of diagnoses for which an HIV-1/HIV-2 differentiation test result was reported and to categorize HIV type based on laboratory test results, 2010-2017 data from CDC's National HIV Surveillance System (NHSS) were analyzed. During 2010-2017, a substantial increase in the number of HIV-1/HIV-2 differentiation test results were reported to NHSS, consistent with implementation of the HIV laboratory-based testing algorithm recommended in 2014. However, >99.9% of all HIV infections identified in the United States were categorized as HIV-1, and the number of HIV-2 diagnoses (mono-infection or dual-infection) remained extremely low (<0.03% of all HIV infections). In addition, the overall number of false positive HIV-2 test results produced by the HIV-1/HIV-2 differentiation increased. The diagnostic value of a confirmatory antibody differentiation test in a setting with sensitive and specific screening tests and few HIV-2 infections might be limited. Evaluation and consideration of other HIV tests approved by the Food and Drug Administration (FDA) that might increase efficiencies in the CDC and Association of Public Health Laboratories-recommended HIV testing algorithm are warranted.
Osimertinib Overcomes Alectinib Resistance Caused by Amphiregulin in a Leptomeningeal Carcinomatosis Model of ALK-Rearranged Lung Cancer
Authors: Sachiko Arai, Shinji Takeuchi, Koji Fukuda, Hirokazu Taniguchi, Akihiro Nishiyama, Azusa Tanimoto, Miyako Satouchi, Kaname Yamashita, Koshiro Ohtsubo, Shigeki Nanjo, Toru Kumagai, Ryohei Katayama, Makoto Nishio, Mei-mei Zheng, Yi-Long Wu, Hiroshi Nishihara, Takushi Yamamoto, Mitsutoshi Nakada, Seiji Yano
Journal: Journal of Thoracic Oncology (2020)

IntroductionLeptomeningeal carcinomatosis (LMC) occurs frequently in anaplastic lymphoma kinase (ALK)–rearranged NSCLC and develops acquired resistance to ALK tyrosine kinase inhibitors (ALK TKIs). This study aimed to clarify the resistance mechanism to alectinib, a second-generation ALK TKI, in LMC and test a novel therapeutic strategy.MethodsWe induced alectinib resistance in an LMC mouse model with ALK-rearranged NSCLC cell line, A925LPE3, by continuous oral alectinib treatment, established A925L/AR cells. Resistance mechanisms were analyzed using several assays, including Western blot and receptor tyrosine kinase array. We also measured amphiregulin (AREG) concentrations in cerebrospinal fluid from patients with ALK-rearranged NSCLC with alectinib-refractory LMC by enzyme-linked immunosorbent assay.ResultsA925L/AR cells were moderately resistant to various ALK TKIs, such as alectinib, crizotinib, ceritinib, and lorlatinib, compared with parental cells in vitro. A925L/AR cells acquired the resistance by EGFR activation resulting from AREG overexpression caused by decreased expression of microRNA-449a. EGFR TKIs and anti-EGFR antibody resensitized A925L/AR cells to alectinib in vitro. In the LMC model with A925L/AR cells, combined treatment with alectinib and EGFR TKIs, such as erlotinib and osimertinib, successfully controlled progression of LMC. Mass spectrometry imaging showed accumulation of the EGFR TKIs in the tumor lesions. Moreover, notably higher AREG levels were detected in cerebrospinal fluid of patients with alectinib-resistant ALK-rearranged NSCLC with LMC (n = 4), compared with patients with EGFR-mutated NSCLC with EGFR TKI–resistant LMC (n = 30), or patients without LMC (n = 24).ConclusionsThese findings indicate the potential of novel therapies targeting both ALK and EGFR for the treatment of ALK TKI–resistant LMC in ALK-rearranged NSCLC.
Abstract 101: Effect of Extracorporeal Membrane Oxygenation for Accidental Hypothermia With Absent Vital Signs: A Nationwide Observational Study
Authors: Hiroyuki Ohbe, Hideo Yasunaga
Journal: Circulation (2019)

Introduction: Patients with accidental hypothermia and absent vital signs are increasingly receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, there is limited knowledge on the efficacy of this advanced rewarming method. Despite the limited evidence, the resuscitation guidelines from the European Resuscitation Council and the American Heart Association both recommended the use of extracorporeal life support in patients with accidental hypothermia and absent vital signs. Hypothesis: We hypothesized that VA-ECMO is associated with lower in-hospital mortality compared with cardiopulmonary resuscitation (CPR) only in patients with accidental hypothermia and absent vital signs. Methods: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2017, we identified patients diagnosed with accidental hypothermia (International Classification of Diseases Tenth Revision code T68) who received closed-chest cardiac massage in hospital on admission day. Patients who received VA-ECMO on admission day were allocated to the VA-ECMO group, and those who received CPR only were allocated to the conventional CPR group. The primary outcome was in-hospital mortality. The secondary outcome was alert consciousness for Japan Coma Scale status at discharge. Propensity score analyses were performed to compare the outcomes between the two groups. Results: We identified 1,624 eligible patients during the 81-month study period. Of these, 19% (314 of 1,624) received VA-ECMO on admission day. Crude in-hospital mortality was 65.3% (205 of 314) and 84.1% (1,102 of 1,310) in the VA-ECMO and conventional CPR groups, respectively. Propensity score-matching analyses demonstrated significantly lower in-hospital mortality (risk difference, –14.1%; 95% confidence interval, –21.9% to –6.3%) and higher proportion of alert consciousness at discharge (risk difference, 8.5%; 95% confidence interval, 2.1% to 15.0%) in the VA-ECMO group compared with the conventional CPR group. Conclusions: VA-ECMO was significantly associated with decreased in-hospital mortality and favorable neurologic outcome compared with conventional CPR in patients with accidental hypothermia and absent vital signs.
Framework for “N-of-1” Experimental Therapies
Authors: Joe Brierley, Sarah Aylett, Dave Archard
Journal: New England Journal of Medicine (2020)

To the Editor: The editorial by Woodcock and Marks (Oct. 24 issue)1 on the use of a personalized antisense oligonucleotide to treat a child with Batten’s disease is important, not least because of ...
Treatment patterns and outcomes in Chinese gastric cancer by HER2 status: A non-interventional registry study (EVIDENCE).
Authors: Shukui Qin, Jiafu Ji, Rui-hua Xu, Wei Wang, Yong Tang, Feng Bi, Jin Li, Kang Wang, Jianming Xu, Qingxia Fan, Wuyun Su, Lin Shen
Journal: Journal of Clinical Oncology (2019)

4025 Background: Gastric cancer (GC) is the second leading cause of cancer-related deaths in China. Trastuzumab (TRA) has been used to treat HER2+ metastatic gastric cancer (mGC) in China since 2012. However, real-world data on effectiveness and safety in Chinese patients are limited. Methods: This prospective, multicenter (85 hospitals), real-world noninterventional registry study evaluated the effectiveness and safety of TRA in five cohorts of Chinese GC patients with different HER2 statuses from April 2013 to June 2018. Effectiveness analysis was conducted in three cohorts: Cohort I (HER2+ mGC with TRA), Cohort II (HER2+ mGC untreated with TRA) and Cohort IV (HER2− mGC untreated with TRA). Safety outcomes of TRA-related adverse events (AEs) were analyzed in Cohort I. Results: Cohorts I, II and IV included 709 patients (174, 113 and 422, respectively; mean age 57.8 years; 72% male); 64.9% of patients were ECOG 0–1, 93.7% had a primary GC tumor and 42.3% were at stage T4. Progressive disease was the cause of death in 32.8%, 27.4% and 29.9% in Cohorts I, II and IV, respectively. Respective mean duration of follow-up was 422.5, 287.5 and 277.5 days. Median overall survival (OS) was 22.3, 17.2 and 17.4 months, respectively. After excluding patients who had surgery, the respective median OS was 19.9, 15.3, and 12.6 months. For the first-line treatment, the median OS in Cohort I was 22.1 months, and the median progression free survival (PFS) was 8.2, 6.9 and 6.2 months in Cohorts I, II and IV, respectively. Response rates (RR) for first-line treatment in Cohorts I, II and IV were 51.7%, 18.4% and 32.8%, respectively. After propensity score matching, OS, PFS and RR were all significantly better in Cohort I versus II (all P&lt;0.05). The most common regimen, TRA+XELOX (capecitabine+oxaliplatin), was estimated to have the longest median OS at 34.6 months. Grade ≥3 AEs were reported in 33.9% (59/174) of patients in Cohort I; anemia was the most common AE (12.1%). Conclusions: TRA improved OS and PFS in Chinese HER2+ mGC patients compared with chemotherapy alone and was well tolerated and effective when combined with a range of other therapies in a real-world setting. Clinical trial information: NCT01839500.
Risk of herpes zoster after exposure to varicella to explore the exogenous boosting hypothesis: self controlled case series study using UK electronic healthcare data
Authors: Harriet Forbes, Ian Douglas, Adam Finn, Judith Breuer, Krishnan Bhaskaran, Liam Smeeth, Simon Packer, Sinéad M Langan, Kathryn E Mansfield, Robin Marlow, Heather Whitaker, Charlotte Warren-Gash
Journal: BMJ (2020)

To assess the magnitude and duration of any hypothesised protective effect of household exposure to a child with varicella on the relative incidence of herpes zoster in adults.Self controlled case series.UK general practices contributing to Clinical Practice Research Datalink.9604 adults (≥18 years) with a diagnosis of herpes zoster (in primary care or hospital records) between 1997 and 2018, who during their observation period lived with a child (<18 years) with a diagnosis of varicella.Relative incidence of herpes zoster in the 20 years after exposure to a child with varicella in the household compared with baseline time (all other time, excluding the 60 days before exposure).6584 of the 9604 adults with herpes zoster (68.6%) were women. Median age of exposure to a child with varicella was 38.3 years (interquartile range 32.3-48.8 years) and median observation period was 14.7 (11.1-17.7) years. 4116 adults developed zoster in the baseline period, 433 in the 60 days before exposure and 5055 in the risk period. After adjustment for age, calendar time, and season, strong evidence suggested that in the two years after household exposure to a child with varicella, adults were 33% less likely to develop zoster (incidence ratio 0.67, 95% confidence interval 0.62 to 0.73) compared with baseline time. In the 10-20 years after exposure, adults were 27% less likely to develop herpes zoster (0.73, 0.62 to 0.87) compared with baseline time. A stronger boosting effect was observed among men than among women after exposure to varicella.The relative incidence of zoster was lower in the periods after exposure to a household contact with varicella, with modest but long lasting protective effects observed. This study suggests that exogenous boosting provides some protection from the risk of herpes zoster, but not complete immunity, as assumed by previous cost effectiveness estimates of varicella immunisation.
Abstract 409: Predictive Value of ’OHCA’ and ’C-GRApH’ Score to Predict Neurological Outcome in Cardiac Arrest Patients Treated With Targeted Temperature Management
Authors: Hyun Soo Kim, Kyu Nam Park, Soo Hyun Kim, Sang Hoon Oh, Chun Song Youn
Journal: Circulation (2019)

Introduction: Despite recent advances in critical care, out-of-hospital cardiac arrest (OHCA) patients still have a low probability of survival. For the purpose of an objective assessment of a patient’s risk of death or neurological deficits, several clinical tools have recently been developed. Hypothesis: The first hypothesis is that OHCA and C-GRApH score could predict neurologic outcome after OHCA patients treated with targeted temperature management (TTM). The second hypothesis is that adding neurologic examination to those scores could further improve outcome prediction after OHCA. Methods: This retrospective study included OHCA patients treated with TTM from 2009 to 2017 in a tertiary teaching hospital in Seoul, Korea. We calculated two cardiac arrest specific risk scores (OHCA and C-GRApH) at the time of admission. Initial neurologic examination (Full Outline of UnResponsiveness Brainstem reflexes (FOUR_B) score and Glasgow Coma Scale motor score (GCS_M)) was also evaluated. The primary outcome was neurological outcome at 6 months after CA. Results: Of 311 subjects, 100 (32.2%) had a good neurologic outcome at 6 months after CA. OHCA score had AUC of 0.843 (95% CI 0.797 - 0.888) and C-GRApH score had AUC of 0.774 (95% CI 0.717 - 0.830). Addition of FOUR_B or GCS_M to OHCA score improved prediction of poor neurologic outcome (AUC 0.891, p = 0.001 for FOUR_B and AUC 0.878, p=0.004 for GCS_M). Results were similar for C-GRApH score to predict poor neurologic outcome. Conclusions: This study confirms the good prognostic performance of cardiac arrest specific scores to predict neurological outcomes in OHCA patients treated with TTM. Addition of neurologic examination variables further improved prognostication for neurologic outcome.
Abstract 127: Machine Learning Techniques to Predict Cardiac Re-Arrest in Out-Of-Hospital Setting
Authors: Andoni Elola, Elisabete Aramendi, Unai Irusta, Naroa Amezaga, Jon Urteaga, Pamela Owens, Ahamed H Idris
Journal: Circulation (2019)

Background: Re-arrest occurs when a cardiac arrest patient being treated by the emergency medical services experiences another cardiac arrest after return of spontaneous circulation (ROSC).The incidence of re-arrest is high, close to 40% in out-of-hospital cardiac arrest (OHCA), and it is associated with lower survival. Prediction of re-arrest could improve prehospital care. The aim of this study was to develop a re-arrest prediction model based on heart rate variability (HRV) features. Materials and methods: OHCA cases treated by Dallas-FortWorth Center of Resuscitation Research were analyzed. Patients with at least two minutes of ROSC were included. Re-arrest was ascertained by the presence of life-threatening ECG and/or presence of chest compressions within 12 minutes after ROSC. Eighteen HRV characteristics for 1 min and 2 min intervals after ROSC were computed. Features were fed into a Random Forest (RF) classifier with 100 trees to predict re-arrest cases. Ten-fold cross-validation with 30 repetitions was applied to train the model and assess the performance in terms of area under the curve (AUC). Results: Inclusion criteria were met by 98 patients, 41 of which suffered re-arrest. The median time (interquartile range) to re-arrest from ROSC onset was 5 (3-7) min. The re-arrest prediction model showed a median AUC of 0.71 and 0.75 for 1 and 2 min post ROSC intervals, respectively. The most important HRV features in the RF predictor were the SD1/SD2 ratio (where SD1 and SD2 are the dispersions of points both perpendicular and parallel to the line-of-identity in the Poincaré plot), SD2, the interquartile range of the RR intervals, peak frequency in the high frequency band (0.15-0.4 Hz) and coefficient of variation of RR intervals (the ratio between the mean and standard deviation of RR intervals). Conclusions: HRV metrics predict re-arrest in OHCA. Further studies with larger datasets are needed to better understand re-arrest dynamics and confirm conclusions.
B13 Selectively Targeting Lung Cancer with a Novel Small Molecule that Induces Lethality Through Dual Inhibition of Disulfide Reductases
Authors: F.D. Johnson, S. Jansen, A. Liu, C. Brandstädter, D. Lu, A. Nagelberg, D. Farnsworth, T. Sihota, J. An, G.C. Forcina, A. Prudova, J. Luu, P.H.B. Sorensen, H. Varmus, R. Somwar, S.J. Dixon, S.J.M. Jones, K. Becker, G.B. Morin, W.W. Lockwood
Journal: Journal of Thoracic Oncology (2020)