tbuckley/cabot-search huggingface dataset:
Cytokinesis, Beta-Blockers, and Congenital Heart Disease
Authors: Katherine E. Yutzey
Journal: New England Journal of Medicine (2020)

Cardiomyocytes in persons with tetralogy of Fallot and pulmonary stenosis have activated beta-adrenergic–receptor signaling. A recent study in human cells and in mice suggests that administration of beta-blockers represents an experimental strategy for the treatment of infants and children with tetralogy of Fallot.
Continuous Infusion Bleomycin in the Bep Regimen: A Therapeutic Alternative in the Management of Patients with Germ-Cell Tumors?
Authors: C. Helissey, L. Védrine, B. Ceccaldi, A. Houlgatte, H. Mullot, O. Bauduceau, C. Chargari, C. Massard, K. Fizazi, S. Le Moulec
Journal: Annals of Oncology (2012)
Polygenic Patterns of Adaptive Introgression in Modern Humans Are Mainly Shaped by Response to Pathogens
Authors: Alexandre Gouy, Laurent Excoffier
Journal: Molecular Biology and Evolution (2019)

Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (subnetworks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.
Impact of Number of Previous Treatment Lines and Pre-Treatment with Bortezomib or Lenalidomide on Efficacy of Bortezomib-Bendamustine-Dexamethasone (BBD) in Patients with Relapsed/Refractory Multiple Myeloma (MM)
Authors: H. Ludwig, H. Kasparu, C. Leitgeb, R. Greil, E. Rauch, W. Linkesch, N. Zojer, L. Pour, M. Fillitz, Z. Adam
Journal: Annals of Oncology (2012)
Association of Low-Dose Whole-Body Computed Tomography With Missed Injury Diagnoses and Radiation Exposure in Patients With Blunt Multiple Trauma
Authors: Dirk Stengel, Sven Mutze, Claas Güthoff, Moritz Weigeldt, Konrad von Kottwitz, Domenique Runge, Filip Razny, Anna Lücke, Dirk Müller, Axel Ekkernkamp, Thomas Kahl
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Initial whole-body computed tomography (WBCT) for screening patients with suspected blunt multiple trauma remains controversial and a source of excess radiation exposure. <h3>Objective</h3> To determine whether low-dose WBCT scanning using an iterative reconstruction algorithm does not increase the rate of missed injury diagnoses at the point of care compared with standard-dose WBCT with the benefit of less radiation exposure. <h3>Design, Setting, and Participants</h3> This quasi-experimental, prospective time-series cohort study recruited 1074 consecutive patients admitted for suspected blunt multiple trauma to an academic metropolitan trauma center in Germany from September 3, 2014, through July 26, 2015, for the standard-dose protocol, and from August 7, 2015, through August 20, 2016, for the low-dose protocol. Five hundred sixty-five patients with suspected blunt multiple trauma prospectively received standard-dose WBCT, followed by 509 patients who underwent low-dose WBCT. Confounding was controlled by segmented regression analysis and a secondary multivariate logistic regression model. Data were analyzed from January 16, 2017, through October 14, 2019. <h3>Interventions</h3> Standard- or low-dose WBCT. <h3>Main Outcomes and Measures</h3> The primary outcome was the incidence of missed injury diagnoses at the point of care, using a synopsis of clinical, surgical, and radiological findings as an independent reference test. The secondary outcome was radiation exposure with either imaging strategy. <h3>Results</h3> Of 1074 eligible patients, 971 (mean [SD] age, 52.7 [19.5] years; 649 men [66.8%]) completed the study. A total of 114 patients (11.7%) had multiple trauma, as defined by an Injury Severity Score of 16 or greater. The proportion of patients with any missed injury diagnosis at the point of care was 109 of 468 (23.3%) in the standard-dose and 107 of 503 (21.3%) in the low-dose WBCT groups (risk difference, −2.0% [95% CI, −7.3% to 3.2%]; unadjusted odds ratio, 0.89 [95% CI, 0.66-1.20];<i>P</i> = .45). Adjustments for autocorrelation and multiple confounding variables did not alter the results. Radiation exposure, measured by the volume computed tomography dose index, was lowered from a median of 11.7 (interquartile range, 11.7-17.6) mGy in the standard-dose WBCT group to 5.9 (interquartile range, 5.9-8.8) mGy in the low-dose WBCT group (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Low-dose WBCT using iterative image reconstruction does not appear to increase the risk of missed injury diagnoses at the point of care compared with standard-dose protocols while almost halving the exposure to diagnostic radiation.
A Phase I Trial of Irinotecan (IRI) and BKM120 in Previously Treated Patients (PTS) With Metastic Colorectal Cancer (MCRC)
Authors: J.C. Baranda, G. Reed, S. Williamson, E. Dickman, M. Stoltz, R. Madan, L. Wright, K. Bhalla, A. Godwin
Journal: Annals of Oncology (2012)
In suspected AMI, an extended algorithm increased sensitivity and decreased specificity for predicting 30-day MACE
Authors: Michael Hudson
Journal: Annals of Internal Medicine (2020)

ACP Journal Club21 January 2020In suspected AMI, an extended algorithm increased sensitivity and decreased specificity for predicting 30-day MACEMichael Hudson, MD, MHS, FACCMichael Hudson, MD, MHS, FACCHenry Ford Hospital, Detroit Michigan, USA (M.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202001210-011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNestelberger T, Boeddinghaus J, Wussler D, et al. Predicting major adverse events in patients with acute myocardial infarction. J Am Coll Cardiol. 2019;74:842-54. https://pubmed.ncbi.nlm.nih.gov/31416527Clinical Impact RatingsEmergency Med: Hospitalists: Cardiology: Reference1 Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267-315. [PMID: 26320110] Google Scholar Author, Article, and Disclosure InformationAffiliations: Henry Ford Hospital, Detroit Michigan, USA (M.H.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-2922.This article was published at Annals.org on 7 January 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 January 2020Volume 172, Issue 2Page: JC11KeywordsAcute coronary syndromeAcute myocardial infarctionAlgorithmsCohort studiesDiagnostic techniquesEmergency departmentHeartHigh sensitivity cardiac troponinIschemiaSpecificity ePublished: 21 January 2020 Issue Published: 21 January 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Docetaxel, Carboplatin and Fluoro-Uracil (TCF) Induction Therapy in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) Patients with Contraindication for Cisplatin Based Combination (TPF)
Authors: E. Saada, F.R. Ferrand, M. Fekih, D. Hamdan, F. Janot, S. Temam, M. Julieron, A.M. Leridant, A. Schilf, J. Guigay
Journal: Annals of Oncology (2012)
Difference in Incidence and Pattern of Salvage Treatment After Failure to 1ST-Line EGFR-TKI Therapy and Standard Cytotoxic Chemotherapy in Patients with EGFR-Mutant Advanced NSCLC: Okayama Lung Cancer Study Group Experience
Authors: Y. Kato, E. Ichihara, K. Hotta, A. Hisamoto, N. Takigawa, N. Nogami, T. Kozuki, K. Kudo, M. Tabata, T. Shinkai, M. Tanimoto, K. Kiura
Journal: Annals of Oncology (2012)
Vitamin B6 Addiction in Acute Myeloid Leukemia
Authors: Chi-Chao Chen, Bo Li, Scott E. Millman, Cynthia Chen, Xiang Li, John P. Morris, Allison Mayle, Yu-Jui Ho, Evangelia Loizou, Hui Liu, Weige Qin, Hardik Shah, Sara Violante, Justin R. Cross, Scott W. Lowe, Lingbo Zhang
Journal: Cancer Cell (2020)
O-0008 Phase II Study of Gemcitabine + TH-302 vs Gemcitabine Alone in Patients with Locally Advanced and Metastatic Pancreatic Cancer
Authors: D. Ryan, S. Reddy, N. Bahary, H. Uronis, D.S. Sigal, Allen Cohn, W.R. Schelman, E.G. Chiorean, P.J. Rosen, B. Ulrich, T. Dragovich, S. Del Prete, M. Rarick, C. Eng, S. Kroll
Journal: Annals of Oncology (2012)
Pharmacogenetics of Tamoxifen Adjuvant Therapy and its Efficiacy: MDR1 Polymorphisms in CYP2D6 Extensive Metabolizers with Breast Cancer
Authors: S. Argal csov, O. Slanař, H. Bakhouche, M. Dražďáková, O. Matoušková, T. Zima, L. Pertuželka
Journal: Annals of Oncology (2012)
Quality of Life (QOL) and Survival Survey for Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC): JNUQ-LC Study: TORG0912
Authors: T. Harada, S. Atagi, F. Imamura, A. Yokoyama, K. Minato, Y. Ohashi, K. Eguchi, K. Watanabe
Journal: Annals of Oncology (2012)
Early Relapse is Associated with the High Serum Soluble Interleukin-2 Receptor Level after the Sixth Cycle of R-CHOP Chemotherapy in Patients with Advanced Diffuse Large B-Cell Lymphoma
Authors: T. Yamauchi, Y. Matsuda, K. Ito, K. Fujita, S. Lee, M. Takai, N. Hosono, S. Ikegaya, K. Takagi, S. Kishi, A. Yoshida, Y. Urasaki, H. Iwasaki, T. Ueda
Journal: Annals of Oncology (2012)
Equality in Lynch Syndrome Screening: Why Should We Hold Patients With Endometrial Cancer to a Different Standard? Reply
Authors: Daniel D Buchanan, Yen Y Tan, Michael D Walsh, Mark Clendenning, Alexander M Metcalf, Kaltin Ferguson, Sven T Arnold, Bryony A Thompson, Felicity A Lose, Michael T Parsons, Rhiannon J Walters, Sally-Ann Pearson, Margaret Cummings, Martin K Oehler, Penelope B Blomfield, Michael A Quinn, Judy A Kirk, Colin J Stewart, Andreas Obermair, Joanne P Young, Penelope M Webb, Amanda B Spurdle
Journal: Journal of Clinical Oncology (2014)
Association of Plasma Concentration of Vitamin B<sub>12</sub>With All-Cause Mortality in the General Population in the Netherlands
Authors: Jose L. Flores-Guerrero, Isidor Minovic, Dion Groothof, Eke G. Gruppen, Ineke J. Riphagen, Jenny Kootstra-Ros, Anneke Muller Kobold, Eelko Hak, Gerjan Navis, Ron T. Gansevoort, Martin H. de Borst, Robin P. F. Dullaart, Stephan J. L. Bakker
Journal: JAMA Network Open (2020)

Higher plasma concentrations of vitamin B12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B12 with mortality in the general population remains unclear.To investigate the association of plasma concentrations of vitamin B12 with all-cause mortality.This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B12 plasma concentrations or used vitamin B12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019.Plasma vitamin B12 concentration level.Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands.A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B12 concentration levels, mortality rates were 33.8 deaths per 10 000 person-years for the quartile with the lowest plasma concentration of vitamin B12 and 65.7 deaths per 10 000 person-years for the quartile with the highest plasma concentration of vitamin B12. After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P = .006).These findings suggest that higher levels of plasma concentrations of vitamin B12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established.
Preclinical and Preliminary Clinical Activity of NVP-BKM120, an Oral Pan-Class I PI3K Inhibitor, in the Brain
Authors: M. Maira, C. Schnell, P. Lollini, C. Chouaid, P. Schmid, P. Nanni, D. Lam, E. Di Tomaso, C. Massacesi, J. Rodon
Journal: Annals of Oncology (2012)
Colon Cancer Adjuvant Mfolfox-6 – Survival Impact of Oxaliplatin Reduced Dose-Intensity
Authors: A.F. Carneiro, J. Godinho Bexiga, D.S. Marques, C. Faustino, N. Sousa, M. Machado, P. Ferreira, A. Raimundo, R. Fragoso
Journal: Annals of Oncology (2012)
High-throughput targeted resequencing of lung adenocarcinoma.
Authors: Byung Chul Kim, Eun-Hye Kim, Byoung-Chul Ghim, So-Jung Choi, Jinseon Lee, Jhingook Kim
Journal: Journal of Clinical Oncology (2012)

7053 Background: The mutational profiles are crucial for cancer diagnosis and classification, which lead to tailoring the best therapeutic strategy to each patient. Here, we present target sequencing of 30 hot spot genes in lung adenocarcinoma to identify new hot spot mutations in never-smoker, female lung adenocarcinoma patients. Methods: We targeted 30 genes that are known to be mutated frequently in lung adenocarcinoma. The exome capture was done using selector technology and sequencing was done using Illumina GA IIx Genome Analyzer. Exomic short reads from Illumina Pipeline 1.4 were aligned to human genome (NCBI build 36) with BWA 0.5.0. Variations and small indels were called by Samtools 0.1.7 and filtered by custom R scripts. Potential effects of these identified alterations were assessed with sequence analysis. Results: On average, 1.5 billion bases were uniquely mapped, and mean depth and coverage of exon regions were 38X and 96%, respectively. Filtering of data against public SNP database (dbSNP130), resulted in ~2,000 novel genetic alterations per sample, including single nucleotide variations, and small insertion and deletions in protein-coding regions. Among them, there were novel variants in LTK and EPHA5 genes. Conclusions: Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples. We identified novel variants in hot target genes, which may provide an insight into the tumorigenesis signaling of lung adenocarcinoma.
TOC GENERATION TEST: Suicide and Ambient Temperature: A Multi-Country Multi-City Study
Authors: Yoonhee Kim, Ho Kim, Antonio Gasparrini, Ben Armstrong, Yasushi Honda, Yeonseung Chung, Chris Fook Sheng Ng, Aurelio Tobias, Carmen Íñiguez, Eric Lavigne, Francesco Sera, Ana M. Vicedo-Cabrera, Martina S. Ragettli, Noah Scovronick, Fiorella Acquaotta, Bing-Yu Chen, Yue-Liang Leon Guo, Xerxes Seposo, Tran Ngoc Dang, Micheline de Sousa Zanotti Stagliorio Coelho, Paulo Hilario Nascimento Saldiva, Anna Kosheleva, Antonella Zanobetti, Joel Schwartz, Michelle L. Bell, Masahiro Hashizume
Journal: Environmental Health Perspectives (2019)

Background: Previous literature suggests that higher ambient temperature may play a role in increasing the risk of suicide. However, no multi-country study has explored the shape of the association and the role of moderate and extreme heat across different locations. Objectives: We examined the short-term temperature–suicide relationship using daily time-series data collected for 341 locations in 12 countries for periods ranging from 4 to 40 y. Methods: We conducted a two-stage meta-analysis. First, we performed location-specific time-stratified case-crossover analyses to examine the temperature–suicide association for each location. Then, we used a multivariate meta-regression to combine the location-specific lag-cumulative nonlinear associations across all locations and by country. Results: A total of 1,320,148 suicides were included in this study. Higher ambient temperature was associated with an increased risk of suicide in general, and we observed a nonlinear association (inverted J-shaped curve) with the highest risk at 27°C. The relative risk (RR) for the highest risk was 1.33 (95% CI: 1.30, 1.36) compared with the risk at the first percentile. Country-specific results showed that the nonlinear associations were more obvious in northeast Asia (Japan, South Korea, and Taiwan). The temperature with the highest risk of suicide ranged from the 87th to 88th percentiles in the northeast Asian countries, whereas this value was the 99th percentile in Western countries (Canada, Spain, Switzerland, the UK, and the United States) and South Africa, where nearly linear associations were estimated. The country-specific RRs ranged from 1.31 (95% CI: 1.19, 1.44) in the United States to 1.65 (95% CI: 1.40, 1.93) in Taiwan, excluding countries where the results were substantially uncertain. Discussion: Our findings showed that the risk of suicide increased with increasing ambient temperature in many countries, but to varying extents and not necessarily linearly. This temperature–suicide association should be interpreted cautiously, and further evidence of the relationship and modifying factors is needed. https://doi.org/10.1289/EHP4898
Genetic Interaction Profile May Predict Bevacizumab (BV) Efficacy in Metastatic Breast Cancer (MBC) Patients (PTS): An Exploratory Retrospective Analysis
Authors: G. Allegrini, G. Bocci, A. Fontana, A. Camerini, A. Ferro, M.E. Cazzaniga, V. Casadei, E. Bona, M. Scalese, A. Falcone
Journal: Annals of Oncology (2012)
A Phase IB Clinical Study with 18F-Fdg-Pet Response Evaluation of the Combination of Temsirolimus (T) And Pegylated Liposomal Doxorubicin (PLD) in Breast, Endometrial and Ovarian Cancer
Authors: M.J. Sonderen, I.M.E. Desar, L. De Geus-Oei, W.T.A. van der Graaf, W.J.G. Oyen, P.B. Ottevanger, C.M.L. van Herpen
Journal: Annals of Oncology (2012)
Assessing the Risk for Gout With Sodium–Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes
Authors: Michael Fralick, Sarah K. Chen, Elisabetta Patorno, Seoyoung C. Kim
Journal: Annals of Internal Medicine (2020)

Background: Hyperuricemia is common in patients with type 2 diabetes mellitus and is known to cause gout. Sodium–glucose cotransporter-2 (SGLT2) inhibitors prevent glucose reabsorption and lower serum uric acid levels. Objective: To compare the rate of gout between adults prescribed an SGLT2 inhibitor and those prescribed a glucagon-like peptide-1 (GLP1) receptor agonist. Design: Population-based new-user cohort study. Setting: A U.S. nationwide commercial insurance database from March 2013 to December 2017. Patients: Persons with type 2 diabetes newly prescribed an SGLT2 inhibitor were 1:1 propensity score matched to patients newly prescribed a GLP1 agonist. Persons were excluded if they had a history of gout or had received gout-specific treatment previously. Measurements: The primary outcome was a new diagnosis of gout. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of the primary outcome and 95% CIs. Results: The study identified 295 907 adults with type 2 diabetes mellitus who were newly prescribed an SGLT2 inhibitor or a GLP1 agonist. The gout incidence rate was lower among patients prescribed an SGLT2 inhibitor (4.9 events per 1000 person-years) than those prescribed a GLP1 agonist (7.8 events per 1000 person-years), with an HR of 0.64 (95% CI, 0.57 to 0.72) and a rate difference of −2.9 (CI, −3.6 to −2.1) per 1000 person-years. Limitation: Unmeasured confounding, missing data (namely incomplete laboratory data), and low baseline risk for gout. Conclusion: Adults with type 2 diabetes prescribed an SGLT2 inhibitor had a lower rate of gout than those prescribed a GLP1 agonist. Sodium–glucose cotransporter-2 inhibitors may reduce the risk for gout among adults with type 2 diabetes mellitus, although future studies are necessary to confirm this observation. Primary Funding Source: Brigham and Women's Hospital.
Targeting the undruggable in pancreatic cancer using nano-based gene silencing drugs
Authors: John Kokkinos, Rosa Mistica C. Ignacio, George Sharbeen, Cyrille Boyer, Estrella Gonzales-Aloy, David Goldstein, None Australian Pancreatic Cancer Genome Initiative (APGI), Joshua A. McCarroll, Phoebe A. Phillips
Journal: Biomaterials (2020)

Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2025. The best chemotherapy only extends survival by an average of 18 weeks. The extensive fibrotic stroma surrounding the tumor curbs therapeutic options as chemotherapy drugs cannot freely penetrate the tumor. RNA interference (RNAi) has emerged as a promising approach to revolutionize cancer treatment. Small interfering RNA (siRNA) can be designed to inhibit the expression of any gene which is important given the high degree of genetic heterogeneity present in pancreatic tumors. Despite the potential of siRNA therapies, there are hurdles limiting their clinical application such as poor transport across biological barriers, limited cellular uptake, degradation, and rapid clearance. Nanotechnology can address these challenges. In fact, the past few decades have seen the conceptualization, design, pre-clinical testing and recent clinical approval of a RNAi nanodrug to treat disease. In this review, we comment on the current state of play of clinical trials evaluating siRNA nanodrugs and review pre-clinical studies investigating the efficacy of siRNA therapeutics in pancreatic cancer. We assess the physiological barriers unique to pancreatic cancer that need to be considered when designing and testing new nanomedicines for this disease.
Cabazitaxel (CBZ) + Prednisone (P; CBZP) in Patients (PTS) with Metastatic Castration-Resistant Prostate Cancer (MCRPC) Previously Treated with Docetaxel (D): Interim Results from Compassionate-Use Programme (CUP) and Early-Access Programme (EAP)
Authors: Z.I. Malik, G. Di Lorenzo, M. Basaran, P. Parente, W. de Schultz, W.R. Gerritsen, L.M. Anton Aparicio, S. Hitier, A. Heidenreich, A. Bahl
Journal: Annals of Oncology (2012)