tbuckley/cabot-search huggingface dataset:
AB0090 Is there any role of anti-annexin v autoantibodies in the thrombotic events of behÇet’s syndrome
Authors: H Aslan, S Pay, F Gök, A Sengül, M Saglam, M Güleç
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Is there a role for anti-phospholipid-binding protein antibodies in the pathogenesis of thrombosis in Behcets disease? <h3>Objectives</h3> We have proposed that thrombosis in the Behçet's syndrome may be due to the disruption of the annexin-V shield by antiphospholipid antibodies. Measurement of anti-annexin V antibodies may be of value in confirming the diagnosis and in evaluating risk of venous and arterial thrombosis in patients with Behçet's syndrome. <h3>Methods</h3> In group one 26 patients with Behçet's with well documented thrombosis, in group two 27 patients with Behçet's without trombosis and in group three 27 healthy controls are included in the study. Sera were examined for both IgG and IgM anti-annexin V antibodies by ELISA. (American Diagnostica, IMUCLONE<sup>®</sup> Anti-Annexin V, IgG and 1 gM (#652G and #652M)). <h3>Results</h3> Quantitative ELISA test results were used for statistical purpose. Statistical analysis was done with using Oneway Anova tests under the SPSS 9.0 for Windows software package. There were no statistical difference between groups for both IgM and IgG anti-annexin V antibody ELISA test results. Results were as follows: <h3>Conclusion</h3> These results indicated that these antibodies may not be associated with the pathogenesis of thrombotic events of the patients with Behçet's syndrome. IgG anti-annexin V antibodies were detected in 5 of 27 healthy subjects (18%). Compare to previous study results this may indicate the possibility of high prevalence of IgG anti-annexin V antibodies in the healthy Turkish population. <h3>Reference</h3> Priori R, Conti F, Pittoni V, Garofalo T, Sorice M, Valesini G. Is there a role for anti-phospholipid-binding protein antibodies in the pathogenesis of thrombosis in Behcet's disease? Thromb Haemost. 2000;83(1):173–4
Oncogene-Induced Senescence Limits the Progression of Pancreatic Neoplasia through Production of Activin A
Authors: Yajie Zhao, Zhichong Wu, Marie Chanal, Fabienne Guillaumond, Delphine Goehrig, Sophie Bachy, Moitza Principe, Audrey Ziverec, Jean-Michel Flaman, Guillaume Collin, Richard Tomasini, Arja Pasternack, Olli Ritvos, Sophie Vasseur, David Bernard, Ana Hennino, Philippe Bertolino
Journal: Cancer Research (2020)

Pancreatic ductal adenocarcinoma (PDAC) is a deadly and aggressive cancer. Understanding mechanisms that drive preneoplastic pancreatic lesions is necessary to improve early diagnostic and therapeutic strategies. Mutations and inactivation of activin-like kinase (ALK4) have been demonstrated to favor PDAC onset. Surprisingly, little is known regarding the ligands that drive ALK4 signaling in pancreatic cancer or how this signaling pathway limits the initiation of neoplastic lesions. In this study, data mining and histologic analyses performed on human and mouse tumor tissues revealed that activin A is the major ALK4 ligand that drives PDAC initiation. Activin A, which is absent in normal acinar cells, was strongly induced during acinar-to-ductal metaplasia (ADM), which was promoted by pancreatitis or the activation of KrasG12D in mice. Activin A expression during ADM was associated with the cellular senescence program that is induced in precursor lesions. Blocking activin A signaling through the use of a soluble form of activin receptor IIB (sActRIIB-Fc) and ALK4 knockout in mice expressing KrasG12D resulted in reduced senescence associated with decreased expression of p21, reduced phosphorylation of H2A histone family member X (H2AX), and increased proliferation. Thus, this study indicates that activin A acts as a protective senescence-associated secretory phenotype factor produced by Kras-induced senescent cells during ADM, which limits the expansion and proliferation of pancreatic neoplastic lesions. SIGNIFICANCE: This study identifies activin A to be a beneficial, senescence-secreted factor induced in pancreatic preneoplastic lesions, which limits their proliferation and ultimately slows progression into pancreatic cancers.
Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B
Authors: George V. Papatheodoridis, George N. Dalekos, Ramazan Idilman, Vana Sypsa, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Margarita Papatheodoridi, Nikolaos Gatselis, Rhea Veelken, Marta Lopez-Gomez, Bettina E. Hansen, Savvoula Savvidou, Anastasia Kourikou, John Vlachogiannakos, Kostas Galanis, Cihan Yurdaydin, Rafael Esteban, Harry L.A. Janssen, Thomas Berg, Pietro Lampertico
Journal: Journal of Hepatology (2020)
3D-printable supramolecular hydrogels with shear-thinning property: fabricating strength tunable bioink via dual crosslinking
Authors: Tian Hu, Xiaoliang Cui, Meng Zhu, Man Wu, Ye Tian, Bin Yao, Wei Song, Zhongwei Niu, Sha Huang, Xiaobing Fu
Journal: Bioactive Materials (2020)

3-dimensional (3D) bioprinting technology provides promising strategy in the fabrication of artificial tissues and organs. As the fundamental element in bioprinting process, preparation of bioink with ideal mechanical properties without sacrifice of biocompatibility is a great challenge. In this study, a supramolecular hydrogel-based bioink is prepared by polyethylene glycol (PEG) grafted chitosan, α-cyclodextrin (α-CD) and gelatin. It has a primary crosslinking structure through the aggregation of the pseudo-polyrotaxane-like side chains, which are formed from the host-guest interactions between α-CD and PEG side chain. Apparent viscosity measurement shows the shear-shinning property of this bioink, which might be due to the reversibility of the physical crosslinking. Moreover, with β-glycerophosphate at different concentrations as the secondary crosslinking agent, the printed constructs demonstrate different Young's modulus (p < 0.001). They could also maintain the Young's modulus in cell culture condition for at least 21 days (p < 0.05). By co-culturing each component with fibroblasts, CCK-8 assay demonstrate cellular viability is higher than 80%. After bioprinting and culturing, immunofluorescence staining with quantification indicate the expression of Ki-67, Paxillin, and N-cadherin is higher in day 14 than those in day 3 (p < 0.05). Oil red O and Nissl body specific staining reflect strength tunable bioink may have impact on the cell fate of mesenchymal stem cells (p < 0.05). This work might provide new idea for advanced bioink in the application of re-establishing complicated tissues and organs.
Administration of end-of-life drugs by family caregivers during covid-19: opportunity for future home prescribing plans
Authors: Miguel Julião
Journal: BMJ (2020)

Bowers and colleagues’ editorial on the administration of end-of-life drugs by family caregivers during the covid-19 pandemic highlights two things.1 The first is the lack of an evidence base and the second the effect of different cultures and healthcare systems on prescribing essential drugs for home use.

The standard practice of our home based palliative care teams is to prescribe anticipatory drugs …
Abstract B10: Feasibility of bronchial washing fluid-based approach to early-stage lung cancer diagnosis
Authors: Jeong Seon Ryu, Myoung Kyu Lee, Seung Jae Lee
Journal: Clinical Cancer Research (2020)

Abstract Circulating tumor DNA has few applications for detecting early-stage lung cancers. Bronchial washing (BW) is minimally invasive, and BW fluids can contain tumor DNA. Thus, analysis of BW fluids could be used for precision medicine. Forty-eight paired specimens (primary tumor tissue, normal tissue, BW supernatant, and BW precipitate) from twelve patients with early-stage non-small cell lung cancer were analyzed using ultradeep next-generation sequencing with a custom panel containing 113 genes. In primary tumors, 130 missense mutations/indels (5–16 per patient) and 20 driver mutations (0–3) were found; 105 (80.8%) and 97 (74.6%) of these missense mutations/indels were identified in BW supernatants and precipitates, respectively, and 19 (95.0%) of the driver mutations in both BW supernatants and precipitates. Concordance between EGFR mutations in primary tumors, BW supernatants, and BW precipitates was 100%. The median allele frequencies (AFs) for missense mutations/indels in primary tumors, BW supernatants, and BW precipitates were 13.0%, 0.3%, and 0.1%, respectively. The AFs of missense mutations/indels in BW supernatants correlated with those in primary tumors and in BW precipitates (P&amp;lt;0.001). In conclusion, this study provides evidence that the BW fluids, especially supernatants, can be an alternative to overcome the limitation that clinical utility of ctDNA is often not reliable in early-stage NSCLC. Citation Format: Jeong Seon Ryu, Myoung Kyu Lee, Seung Jae Lee. Feasibility of bronchial washing fluid-based approach to early-stage lung cancer diagnosis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B10.
Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade
Authors: Pierpaolo Correale, Rita Emilena Saladino, Diana Giannarelli, Rocco Giannicola, Rita Agostino, Nicoletta Staropoli, Alessandra Strangio, Teresa Del Giudice, Valerio Nardone, Maria Altomonte, Pierpaolo Pastina, Paolo Tini, Antonia Consuelo Falzea, Natale Imbesi, Valentina Arcati, Giuseppa Romeo, Daniele Caracciolo, Amalia Luce, Michele Caraglia, Antonio Giordano, Luigi Pirtoli, Alois Necas, Evzen Amler, Vito Barbieri, Pierfrancesco Tassone, Pierosandro Tagliaferri
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients. Methods We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients’ outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing. Results A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1. Conclusions This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.
Association of Recreational Cannabis Laws in Colorado and Washington State With Changes in Traffic Fatalities, 2005-2017
Authors: Julian Santaella-Tenorio, Katherine Wheeler-Martin, Charles J. DiMaggio, Alvaro Castillo-Carniglia, Katherine M. Keyes, Deborah Hasin, Magdalena Cerdá
Journal: JAMA Internal Medicine (2020)

An important consequence of cannabis legalization is the potential increase in the number of cannabis-impaired drivers on roads, which may result in higher rates of traffic-related injuries and fatalities. To date, limited information about the effects of recreational cannabis laws (RCLs) on traffic fatalities is available.To estimate the extent to which the implementation of RCLs is associated with traffic fatalities in Colorado and Washington State.This ecological study used a synthetic control approach to examine the association between RCLs and changes in traffic fatalities in Colorado and Washington State in the post-RCL period (2014-2017). Traffic fatalities data were obtained from the Fatality Analysis Reporting System from January 1, 2005, to December 31, 2017. Data from Colorado and Washington State were compared with synthetic controls. Data were analyzed from January 1, 2005, to December 31, 2017.The primary outcome was the rate of traffic fatalities. Sensitivity analyses were performed (1) excluding neighboring states, (2) excluding states without medical cannabis laws (MCLs), and (3) using the enactment date of RCLs to define pre-RCL and post-RCL periods instead of the effective date.Implementation of RCLs was associated with increases in traffic fatalities in Colorado but not in Washington State. The difference between Colorado and its synthetic control in the post-RCL period was 1.46 deaths per 1 billion vehicle miles traveled (VMT) per year (an estimated equivalent of 75 excess fatalities per year; probability = 0.047). The difference between Washington State and its synthetic control was 0.08 deaths per 1 billion VMT per year (probability = 0.674). Results were robust in most sensitivity analyses. The difference between Colorado and synthetic Colorado was 1.84 fatalities per 1 billion VMT per year (94 excess deaths per year; probability = 0.055) after excluding neighboring states and 2.16 fatalities per 1 billion VMT per year (111 excess deaths per year; probability = 0.063) after excluding states without MCLs. The effect was smaller when using the enactment date (24 excess deaths per year; probability = 0.116).This study found evidence of an increase in traffic fatalities after the implementation of RCLs in Colorado but not in Washington State. Differences in how RCLs were implemented (eg, density of recreational cannabis stores), out-of-state cannabis tourism, and local factors may explain the different results. These findings highlight the importance of RCLs as a factor that may increase traffic fatalities and call for the identification of policies and enforcement strategies that can help prevent unintended consequences of cannabis legalization.
Covid-19: Public health agencies review whether vitamin D supplements could reduce risk
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Covid-19: Public health agencies review whether vitamin D supplements could reduce risk As agencies announce they are examining whether vitamin D supplements could reduce the risk of covid-19, Ingrid Torjesen finds out what the existing evidence shows Ingrid Torjesen Public health agencies in England and Scotland are conducting urgent reviews into the potential for vitamin D to reduce the risk of covid-19.
Coronavirus disease 2019 (COVID-19) hospitalized patients with acute kidney injury treated with acute peritoneal dialysis do not have infectious peritoneal dialysis effluent
Authors: Osama El Shamy, Joseph A. Vassalotti, Shuchita Sharma, Teresa Aydillo-Gomez, Nada Marjanovic, Irene Ramos, Adolfo García-Sastre, Jaime Uribarri
Journal: Kidney International (2020)
Epidemiology of Atrial Fibrillation in the 21st Century
Authors: Jelena Kornej, Christin S. Börschel, Emelia J. Benjamin, Renate B. Schnabel
Journal: Circulation Research (2020)

Accompanying the aging of populations worldwide, and increased survival with chronic diseases, the incidence and prevalence of atrial fibrillation (AF) are rising, justifying the term global epidemic. This multifactorial arrhythmia is intertwined with common concomitant cardiovascular diseases, which share classical cardiovascular risk factors. Targeted prevention programs are largely missing. Prevention needs to start at an early age with primordial interventions at the population level. The public health dimension of AF motivates research in modifiable AF risk factors and improved precision in AF prediction and management. In this review, we summarize current knowledge in an attempt to untangle these multifaceted associations from an epidemiological perspective. We discuss disease trends, preventive opportunities offered by underlying risk factors and concomitant disorders, current developments in diagnosis and risk prediction, and prognostic implications of AF and its complications. Finally, we review current technological (eg, eHealth) and methodological (artificial intelligence) advances and their relevance for future prevention and disease management.
Abstract B39: Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients
Authors: Dorothea Schott, Monika Pizon, Katharina Pachmann, Ulrich Pachmann, Matthias Maeurer
Journal: Clinical Cancer Research (2020)

Abstract Background: Preclinical studies have suggested that radiotherapy (RT) followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. RT induces immunogenic changes in cancer cells that can lead to adaptive upregulation of PD-L1 expression. Moreover, RT not only reduces local recurrence but also improves overall survival by preventing distant metastases, which indicates its influence on the remaining occult tumor, such as circulating tumor cells. For this reason, the aim of this study was to determine the PD-L1 status on CETCs before and during RT. Methods: CETCs were determined in 54 primary breast cancer patients in early and locally advanced stages. The number of CETCs and their expression of PDL-L1 were investigated using the maintrac method. The fraction of PD-L1 positive CETCs was assessed prior to (baseline), 3 and 6 weeks after the start of RT. Results: We found a correlation between the PD-L1 status of CETCs and aggressiveness of cancer disease prior to radiotherapy. Patients with positive lymph node status presented more PD-L1 positive CETCs compared to patients with negative lymph nodes (mean 73% vs. 50%, p&amp;lt;0.01). Moreover, the HER2 expression of the primary tumor was also positively correlated with PD-L1 expression. Lower numbers of CETCs were detected in patients who had not received chemotherapy or adjuvant chemotherapy before RT than in those who received neoadjuvant chemotherapy (median 20 vs. 25 vs. 120 CETC/100μL blood, p&amp;lt;0.001). Surprisingly, the fraction of PD-L1 positive CETCs decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy. Conclusion: Although the number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy, radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients. Citation Format: Dorothea Schott, Monika Pizon, Katharina Pachmann, Ulrich Pachmann, Matthias Maeurer. Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B39.
Language as a mental travel guide
Authors: Charles P. Davis, Gerry T. M. Altmann, Eiling Yee
Journal: Behavioral and Brain Sciences (2020)

Abstract Gilead et al.'s approach to human cognition places abstraction and prediction at the heart of “mental travel” under a “representational diversity” perspective that embraces foundational concepts in cognitive science. But, it gives insufficient credit to the possibility that the process of abstraction produces a gradient, and underestimates the importance of a highly influential domain in predictive cognition: language, and related, the emergence of experientially based structure through time.
Spending and quality after three years of Medicare’s bundled payments for medical conditions: quasi-experimental difference-in-differences study
Authors: Joshua A Rolnick, Joshua M Liao, Ezekiel J Emanuel, Qian Huang, Xinshuo Ma, Eric Z Shan, Claire Dinh, Jingsan Zhu, Erkuan Wang, Deborah Cousins, Amol S Navathe
Journal: BMJ (2020)

Abstract Objective To evaluate whether longer term participation in the bundled payments for care initiative (BPCI) for medical conditions in the United States, which held hospitals financially accountable for all spending during an episode of care from hospital admission to 90 days after discharge, was associated with changes in spending, mortality, or health service use. Design Quasi-experimental difference-in-differences analysis. Setting US hospitals participating in bundled payments for acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease (COPD), or pneumonia, and propensity score matched to non-participating hospitals. Participants 238 hospitals participating in the Bundled Payments for Care Improvement initiative (BPCI) and 1415 non-BPCI hospitals. 226 BPCI hospitals were matched to 700 non-BPCI hospitals. Main outcome measures Primary outcomes were total spending on episodes and death 90 days after discharge. Secondary outcomes included spending and use by type of post-acute care. BPCI and non-BPCI hospitals were compared by patient, hospital, and hospital market characteristics. Market characteristics included population size, competitiveness, and post-acute bed supply. Results In the 226 BPCI hospitals, episodes of care totaled 261 163 in the baseline period and 93 562 in the treatment period compared with 211 208 and 78 643 in the 700 matched non-BPCI hospitals, respectively, with small differences in hospital and market characteristics after matching. Differing trends were seen for some patient characteristics (eg, mean age change −0.3 years at BPCI hospitals v non- BPCI hospitals, P&lt;0.001). In the adjusted analysis, participation in BPCI was associated with a decrease in total episode spending (−1.2%, 95% confidence interval −2.3% to −0.2%). Spending on care at skilled nursing facilities decreased (−6.3%, −10.0% to −2.5%) owing to a reduced number of facility days (−6.2%, −9.8% to −2.6%), and home health spending increased (4.4%, 1.4% to 7.5%). Mortality at 90 days did not change (−0.1 percentage points, 95% confidence interval −0.5 to 0.2 percentage points). Conclusions In this longer term evaluation of a large national programme on medical bundled payments in the US, participation in bundles for four common medical conditions was associated with savings at three years. The savings were generated by practice changes that decreased use of high intensity care after hospital discharge without affecting quality, which also suggests that bundles for medical conditions could require multiple years before changes in savings and practice emerge.
Association of mediastinal lymphadenopathy with COVID-19 prognosis
Authors: Francesco Sardanelli, Andrea Cozzi, Lorenzo Monfardini, Claudio Bnà, Riccardo Alessandro Foà, Angelo Spinazzola, Silvia Tresoldi, Maurizio Cariati, Francesco Secchi, Simone Schiaffino
Journal: The Lancet Infectious Diseases (2020)