tbuckley/cabot-search huggingface dataset:
Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients
Authors: Masataka Sawaki, Naruto Taira, Yukari Uemura, Tsuyoshi Saito, Shinichi Baba, Kokoro Kobayashi, Hiroaki Kawashima, Michiko Tsuneizumi, Noriko Sagawa, Hiroko Bando, Masato Takahashi, Miki Yamaguchi, Tsutomu Takashima, Takahiro Nakayama, Masahiro Kashiwaba, Toshiro Mizuno, Yutaka Yamamoto, Hiroji Iwata, Takuya Kawahara, Yasuo Ohashi, Hirofumi Mukai
Journal: Journal of Clinical Oncology (2020)

Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer.This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2-positive invasive breast cancer received trastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST).The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93; P = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P = .53). Common AEs were anorexia (7.4% v 44.3%; P < .0001) and alopecia (2.2% v 71.7%; P < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .009).The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.
Reduced maximal aerobic capacity after COVID-19 in young adult recruits, Switzerland, May 2020
Authors: Giovanni Andrea Gerardo Crameri, Michel Bielecki, Roland Züst, Thomas Werner Buehrer, Zeno Stanga, Jeremy Werner Deuel
Journal: Eurosurveillance (2020)

In March 2020, we observed an outbreak of COVID-19 among a relatively homogenous group of 199 young (median age 21 years; 87% men) Swiss recruits. By comparing physical endurance before and in median 45 days after the outbreak, we found a significant decrease in predicted maximal aerobic capacity in COVID-19 convalescent but not in asymptomatically infected and SARS-CoV-2 naive recruits. This finding might be indicative of lung injury after apparently mild COVID-19 in young adults.
Abstract 19632: Inherited Cardiac Arrhythmias as a Cause of Sudden Cardiac Arrest in Korea: A Cohort From National Health Insurance Service Database
Authors: Seung-Young Roh, Jong-Il Choi, Eun Young Cho, Yun Gi Kim, Suk-kyu Oh, Hee-Soon Park, Kwang No Lee, Jaemin Shim, Young-Hoon Kim
Journal: Circulation (2017)

Introduction: The incidence of inherited arrhythmias leading sudden cardiac arrest (SCA) in Asian remains unknown. Hypothesis: Prevalence of SCA related with inherited arrhythmia can be estimated. ...
Trial Design Principles for Patients at High Bleeding Risk Undergoing PCI
Authors: Davide Capodanno, Marie-Claude Morice, Dominick J. Angiolillo, Deepak L. Bhatt, Robert A. Byrne, Roisin Colleran, Thomas Cuisset, Donald Cutlip, Pedro Eerdmans, John Eikelboom, Andrew Farb, C. Michael Gibson, John Gregson, Michael Haude, Stefan K. James, Hyo-Soo Kim, Takeshi Kimura, Akihide Konishi, Martin B. Leon, P.F. Adrian Magee, Yoshiaki Mitsutake, Darren Mylotte, Stuart J. Pocock, Sunil V. Rao, Ernest Spitzer, Norman Stockbridge, Marco Valgimigli, Olivier Varenne, Ute Windhovel, Mitchel W. Krucoff, Philip Urban, Roxana Mehran
Journal: Journal of the American College of Cardiology (2020)
Guillain–Barré Syndrome Associated with JEV Infection
Authors: Guowei Wang, Haining Li, Xiaojun Yang, Tao Guo, Libin Wang, Zhijun Zhao, Haifeng Sun, Xiaolin Hou, Xiangchun Ding, Chunyang Dou, Qiaoli Ma, Xiao Yang, Yanbo Wang, Zhao Wang, Luxuan Wang, Jixiang Liu, Zhenhai Wang, Huanyu Wang, Peng Xie
Journal: New England Journal of Medicine (2020)

To the Editor: We report data from a large series of patients in whom the Guillain-Barré syndrome developed after they had been infected with Japanese encephalitis virus (JEV).JEV is a single-stranded RNA virus that is transmitted by mosquitoes.The first case of Japanese encephalitis was reported in China in 1940. 1
Biliary pneumatosis: a new finding in a patient with cholangitis
Authors: Carolina Mangas-Sanjuan, Belén Martínez-Moreno, Juan Martínez, Luis Compañy, Francisco Ruíz, Juan Antonio Casellas, José Ramón Aparicio
Journal: Endoscopy (2020)

A 72-year-old man with a previous history of renal transplantation for autosomal dominant polycystic kidney disease and secondary sclerosing cholangitis caused by recurrent bile duct injury with hepatolithiasis was admitted with a new episode of cholangitis, with a gallstone, but no signs of septic shock. Additionally, he had undergone cholecystectomy and Roux-en-Y hepaticojejunostomy 2 years previously.
Reply to Rappaport <i>et al.</i>: Anti-FXa Activity with Intermediate-Dose Thromboprophylaxis in COVID-19
Authors: Tina Dutt, David Simcox, Colin Downey, Daniella McLenaghan, Charlotte King, Manish Gautam, Steven Lane, Hassan Burhan
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Dutt T, Simcox D, Downey C, McLenaghan, D, King, C, Gautam, M, Lane, S, Burhan, H, Thromboprophylaxis in COVID-19: Anti-FXa - The Missing Factor? [published online ahead of print, 2020 Jun 8]. Am J Respir Crit Care Med. 2020;10.1164/rccm.202005-1654LE. doi:10.1164/rccm.202005-1654LE.
High Dose Cyclophosphamide and Pre-Treatment Disease Burden Dictate Response and Survival in a Multicenter Clinical Trial Using CD19-Specific CAR T Cells for Relapsed/Refractory B-ALL
Authors: Kevin J. Curran, Steven P. Margossian, Nancy A. Kernan, Lewis B. Silverman, Jae H. Park, Craig S. Sauter, Eric L Smith, Farid Boulad, Maria I. Cancio, Christopher Forlenza, Carolyn Jackson, Neerav Shukla, Barbara Spitzer, Susan Prockop, Peter G. Steinherz, Andrew L. Kung, Richard J. O'Reilly, Isabelle Riviere, Michel Sadelain, Renier J. Brentjens
Journal: Blood (2017)
Periostin: contributor to abnormal airway epithelial function in asthma?
Authors: Janette K. Burgess, Marnix R. Jonker, Marijn Berg, Nick T.H. ten Hacken, Kerstin B. Meyer, Maarten van den Berge, Martijn C. Nawijn, Irene H. Heijink
Journal: European Respiratory Journal (2020)

Periostin (POSTN) may serve as a biomarker for Type-2 mediated eosinophilic airway inflammation in asthma. We hypothesised that a Type-2 cytokine, interleukin (IL)-13, induces airway epithelial expression of POSTN , which in turn contributes to epithelial changes observed in asthma. We studied the effect of IL-13 on POSTN expression in BEAS-2B and air–liquid interface differentiated primary bronchial epithelial cells (PBECs). Additionally, the effects of recombinant human POSTN on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. POSTN single cell gene expression and protein levels were analysed in bronchial biopsies and induced sputum from asthma patients and healthy controls. IL-13 increased POSTN expression in both cell types and this was accompanied by EMT-related features in BEAS-2B. In air–liquid interface differentiated PBECs, IL-13 increased POSTN basolateral and apical release. Apical administration of POSTN increased the expression of MMP-9 , MUC5B and MUC5AC . In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus those from controls. A higher level of POSTN protein expression in epithelial and subepithelial layers was confirmed in bronchial biopsies from asthma patients when compared to healthy controls. Although sputum POSTN levels were not higher in asthma, levels correlated with eosinophil numbers and with the coughing-up of mucus. POSTN expression is increased by IL-13 in bronchial epithelial cells and is higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of POSTN increases epithelial expression of mucin genes, supporting the relationship of POSTN with Type-2 mediated asthma and mucus secretion.
Phylogenomic Resolution of Sea Spider Diversification through Integration of Multiple Data Classes
Authors: Jesús A Ballesteros, Emily V W Setton, Carlos E Santibáñez-López, Claudia P Arango, Georg Brenneis, Saskia Brix, Kevin F Corbett, Esperanza Cano-Sánchez, Merai Dandouch, Geoffrey F Dilly, Marc P Eleaume, Guilherme Gainett, Cyril Gallut, Sean McAtee, Lauren McIntyre, Amy L Moran, Randy Moran, Pablo J López-González, Gerhard Scholtz, Clay Williamson, H Arthur Woods, Jakob T Zehms, Ward C Wheeler, Prashant P Sharma
Journal: Molecular Biology and Evolution (2020)

Abstract Despite significant advances in invertebrate phylogenomics over the past decade, the higher-level phylogeny of Pycnogonida (sea spiders) remains elusive. Due to the inaccessibility of some small-bodied lineages, few phylogenetic studies have sampled all sea spider families. Previous efforts based on a handful of genes have yielded unstable tree topologies. Here, we inferred the relationships of 89 sea spider species using targeted capture of the mitochondrial genome, 56 conserved exons, 101 ultraconserved elements, and 3 nuclear ribosomal genes. We inferred molecular divergence times by integrating morphological data for fossil species to calibrate 15 nodes in the arthropod tree of life. This integration of data classes resolved the basal topology of sea spiders with high support. The enigmatic family Austrodecidae was resolved as the sister group to the remaining Pycnogonida and the small-bodied family Rhynchothoracidae as the sister group of the robust-bodied family Pycnogonidae. Molecular divergence time estimation recovered a basal divergence of crown group sea spiders in the Ordovician. Comparison of diversification dynamics with other marine invertebrate taxa that originated in the Paleozoic suggests that sea spiders and some crustacean groups exhibit resilience to mass extinction episodes, relative to mollusk and echinoderm lineages.
A multicenter study evaluating the effectiveness and safety of single‐dose low molecular weight iron dextran vs single‐dose ferumoxytol for the treatment of iron deficiency
Authors: Jonathan Cohen, Arpine Khudanyan, Jessica Lu, Jason Wing, Sven Olson, Thomas Deloughery, Joseph J. Shatzel
Journal: American Journal of Hematology (2020)

Abstract There are multiple intravenous (IV) iron formulations available, of which several may be administered as single‐dose infusions such as low‐molecular weight iron dextran (LMWID), ferumoxytol, ferric carboxymaltose, and ferric derisomaltose. However, administration of ferumoxytol as a single‐dose infusion is off‐label as it is approved as a two‐dose series. Previous studies of ferumoxytol alone support the effectiveness and safety of the single‐dose regimen, but there is a paucity of data directly comparing single‐dose ferumoxytol to other single‐dose IV iron formulations. This multicenter cohort study sought to affirm the safety and effectiveness of single‐dose ferumoxytol compared to single‐dose LMWID. Overall, 906 patients who received single‐dose LMWID (n = 439) or ferumoxytol (n = 467) were identified, of whom 351 met criteria for the primary effectiveness endpoint defined as median change in hemoglobin (Hb), hematocrit (Hct), and ferritin 8 to 12 weeks from baseline. All 906 patients were included for the secondary analysis evaluating the incidence of adverse events (AE) and requirement of additional IV iron infusions. Median change in Hb (LMWID 0.5 g/dL; ferumoxytol 0.8 g/dL; P = .24), Hct (LMWID 1.1%; ferumoxytol 1.25%; P = .89), and ferritin (LMWID 87 ng/dL; ferumoxytol 71 ng/dL; P = .47) was not significantly different between groups. Both groups experienced similar rates of AEs (LMWID 2.3%; ferumoxytol 2.8%; P = .63). The LMWID patients more frequently required additional IV iron infusions (LMWID 28.5%; ferumoxtyol 16.1%; P &lt; .001). These findings support that single‐dose ferumoxytol is effective and safe, and that patients may require fewer additional infusions compared to patients who received LMWID.
Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study
Authors: Chao Zeng, Kim Bennell, Zidan Yang, Uyen-Sa D T Nguyen, Na Lu, Jie Wei, Guanghua Lei, Yuqing Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Osteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator.We conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model.VTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-adjusted HR=0.88, 95% CI 0.67 to 1.16).Our large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement.
Long-term Results of Differentiated Anatomic Reconstruction of Bicuspid Aortic Valves
Authors: Ulrich Schneider, Christopher Hofmann, Jakob Schöpe, Ann-Kristin Niewald, Christian Giebels, Irem Karliova, Hans-Joachim Schäfers
Journal: JAMA Cardiology (2020)

Bicuspid aortic valve (BAV) repair has been used in limited cohorts, but its long-term results in a large population are unknown.To analyze the long-term stability of BAV repair for survival and the factors associated with repair failure and to evaluate whether a differentiated anatomic repair approach may improve repair stability.In this case series, 1024 patients underwent BAV repair for aortic regurgitation or aneurysm between October 1995 and June 2018, with a mean (SD) follow-up time of 56 (49) months and maximum follow-up of 271 months. Systematic modifications in technique based on anatomic principles were introduced in 2009 and applied for the last 727 patients. Data were acquired prospectively and analyzed retrospectively.Repair of BAV with or without concomitant aortic replacement, as well as postoperative clinical and echocardiographic follow-up.Survival and incidence of reoperation or recurrent aortic regurgitation, as well as factors associated with valve repair failure.Among the 1024 patients in the study (920 male [89.8%]; mean [SD] age, 47 [13] years [range, 15-86 years]), the survival rate at 15 years was 82.1%. The cumulative incidence of reoperation was 30.7% (95% CI, 22.7%-38.7%) at 15 years. Cusp calcification (subdistribution hazard ratio, 1.78; 95% CI, 1.14-2.77; P = .01), asymmetric commissural orientation (subdistribution hazard ratio, 1.95; 95% CI, 1.02-3.72; P = .04), and use of a pericardial patch for cusp repair (subdistribution hazard ratio, 5.25; 95% CI, 3.52-7.82; P < .001) were associated with time to reoperation. At 10 years, the incidence of reoperation was significantly reduced among patients who received the anatomic repair concept compared with those who had undergone surgery in the earlier period (8.8% vs 24.6%; P < .001).This study suggests that survival after BAV repair is excellent and that a large proportion of BAV repairs will remain stable. Repair stability can be markedly improved by an anatomic repair concept. Cusp calcification and the need for cusp repair using a patch remain the factors most strongly associated with valve failure. In those instances, valve replacement should be preferred.
Familial Clustering of Erosive Hand Osteoarthritis in a Large Statewide Cohort
Authors: Nikolas H. Kazmers, Huong D. Meeks, Kendra A. Novak, Zhe Yu, Gail L. Fulde, Joy L. Thomas, Tyler Barker, Michael J. Jurynec
Journal: Arthritis & Rheumatology (2020)

Erosive hand osteoarthritis (OA) is a severe and rapidly progressing subset of hand OA. Its etiology remains largely unknown, which has hindered development of successful treatments. This study was undertaken to test the hypothesis that erosive hand OA demonstrates familial clustering in a large statewide population linked to genealogical records, and to determine the association of potential risk factors with erosive hand OA.Patients diagnosed as having erosive hand OA were identified by searching 4,741,840 unique medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of erosive hand OA as defined by a familial standardized incidence ratio (FSIR) of ≥2.0. The magnitude of familial risk of erosive hand OA in related individuals was calculated using Cox regression models. Association of potential erosive hand OA risk factors was analyzed using multivariate conditional logistic regression and logistic regression models.We identified 703 affected individuals linked to 240 unrelated high-risk pedigrees with excess clustering of erosive hand OA (FSIR ≥2.0, P < 0.05). The relative risk of developing erosive hand OA was significantly elevated in first-degree relatives (P < 0.001). There were significant associations between a diagnosis of erosive hand OA and age, sex, diabetes, and obesity (all P < 0.05).Familial clustering of erosive hand OA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Age, sex, diabetes, and obesity are risk factors for erosive hand OA. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to erosive hand OA onset and progression.
Self‐Assembled GO Honeycomb Microarray for Selective Cancer Cell Capture and Single Cell Analysis of Proteolytic Expression
Authors: Shuangshuang Chen, Qinghua Lu
Journal: Advanced Healthcare Materials (2020)

Abstract Proteolytic enzymes expressed by circulating tumor cells are proved to facilitate their invasion into multiple organs via cleaving natural ECM networks, leading to consequent metastasis colonization and malignant lethality. Recent evidence suggests the rare metastasis initiating cells with higher proteolytic levels among circulating tumor cells (CTCs) may strongly increase the risk of metastasis. Beyond selective CTC capture, the heterogeneity in proteases expression provides a promising indicator for metastasis happening. To this end, the graphene oxide (GO) honeycomb microarray with single CTC matched sizes is fabricated via the self‐assembly breath figure approach, which serves as an integrated protocol for selective CTC capture and single‐cell analysis of protease activity. Contributing to synergistic effects of structure and chemistry, CTCs can be efficiently isolated and individually trapped in each honeycomb hole. Meanwhile, the crosstalk among CTCs can be erased by blocking direct cell‐to‐cell contact, which offers promising potentials in the single‐cell analysis of protease expression. Integrating specific capture and in situ analysis of single CTCs on GO micropatterned surface is of significant importance in various biological and clinical applications such as cancer diagnostics and cancer therapeutic evaluation.
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
Authors: Kalil Alves de Lima, Justin Rustenhoven, Sandro Da Mesquita, Morgan Wall, Andrea Francesca Salvador, Igor Smirnov, Guilherme Martelossi Cebinelli, Tornike Mamuladze, Wendy Baker, Zach Papadopoulos, Maria Beatriz Lopes, William Sam Cao, Xinmin Simon Xie, Jasmin Herz, Jonathan Kipnis
Journal: Nature Immunology (2020)
Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities
Authors: Young Sun Choi, Hyeonha Jang, Biki Gupta, Ji-Hak Jeong, Yun Ge, Chul Soon Yong, Jong Oh Kim, Jong-Sup Bae, Im-Sook Song, In-San Kim, You Mie Lee
Journal: Journal of Hematology & Oncology (2020)

Conventional therapeutic approaches for tumor angiogenesis, which are primarily focused on the inhibition of active angiogenesis to starve cancerous cells, target the vascular endothelial growth factor signaling pathway. This aggravates hypoxia within the tumor core and ultimately leads to increased tumor proliferation and metastasis. To overcome this limitation, we developed nanoparticles with antiseptic activity that target tumor vascular abnormalities.Ferritin-based protein C nanoparticles (PCNs), known as TFG and TFMG, were generated and tested in Lewis lung carcinoma (LLC) allograft and MMTV-PyMT spontaneous breast cancer models. Immunohistochemical analysis was performed on tumor samples to evaluate the tumor vasculature. Western blot and permeability assays were used to explore the role and mechanism of the antitumor effects of PCNs in vivo. For knocking down proteins of interest, endothelial cells were transfected with siRNAs. Statistical analysis was performed using one-way ANOVA followed by post hoc Dunnett's multiple comparison test.PCNs significantly inhibited hypoxia and increased pericyte coverage, leading to the inhibition of tumor growth and metastasis, while increasing survival in LLC allograft and MMTV-PyMT spontaneous breast cancer models. The coadministration of cisplatin with PCNs induced a synergistic suppression of tumor growth by improving drug delivery as evidenced by increased blood prefusion and decreased vascular permeability. Moreover, PCNs altered the immune cell profiles within the tumor by increasing cytotoxic T cells and M1-like macrophages with antitumor activity. PCNs induced PAR-1/PAR-3 heterodimerization through EPCR occupation and PAR-1 activation, which resulted in Gα13-RhoA-mediated-Tie2 activation and stabilized vascular tight junctions via the Akt-FoxO3a signaling pathway.Cancer treatment targeting the tumor vasculature by inducing antitumor immune responses and enhancing the delivery of a chemotherapeutic agent with PCNs resulted in tumor regression and may provide an effective therapeutic strategy.