tbuckley/cabot-search huggingface dataset:
Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer
Authors: Sonia Dagnino, Barbara Bodinier, Florence Guida, Karl Smith-Byrne, Dusan Petrovic, Matthew D. Whitaker, Therese Haugdahl Nøst, Claudia Agnoli, Domenico Palli, Carlotta Sacerdote, Salvatore Panico, Rosario Tumino, Matthias B. Schulze, Mikael Johansson, Pekka Keski-Rahkonen, Augustin Scalbert, Paolo Vineis, Mattias Johansson, Torkjel M. Sandanger, Roel C.H. Vermeulen, Marc Chadeau-Hyam
Journal: Cancer Research (2021)

Abstract Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer–related dysregulation of CDCP1 expression years before diagnosis. Significance: Prospective proteomics analyses reveal an association between increased levels of circulating CDCP1 and lung carcinogenesis irrespective of smoking and years before diagnosis, and integrating gene expression indicates potential underlying mechanisms. See related commentary by Itzstein et al., p. 3441.
Sequence meets function—microbiota and cardiovascular disease
Authors: Myungsuk Kim, Md Nazmul Huda, Brian J Bennett
Journal: Cardiovascular Research (2021)

The discovery that gut-microbiota plays a profound role in human health has opened a new avenue of basic and clinical research. Application of ecological approaches where the bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of cardiovascular disease (CVD) including atherosclerosis, coronary artery disease, and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequence-based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short-chain fatty acids and trimethylamine N-Oxide. Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways, and fecal microbiota transplant.
American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease
Authors: Oren K. Fix, Emily A. Blumberg, Kyong‐Mi Chang, Jaime Chu, Raymond T. Chung, Elizabeth K. Goacher, Bilal Hameed, Daniel R. Kaul, Laura M. Kulik, Ryan M. Kwok, Brendan M. McGuire, David C. Mulligan, Jennifer C. Price, Nancy S. Reau, K. Rajender Reddy, Andrew Reynolds, Hugo R. Rosen, Mark W. Russo, Michael L. Schilsky, Elizabeth C. Verna, John W. Ward, Robert J. Fontana
Journal: Hepatology (2021)

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.
Hexa Histidine–Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species
Authors: Ninh Quoc Dat, Le Thi Thanh Thuy, Vu Ngoc Hieu, Hoang Hai, Dinh Viet Hoang, Nguyen Thi Thanh Hai, Tuong Thi Van Thuy, Tohru Komiya, Krista Rombouts, Minh Phuong Dong, Ngo Vinh Hanh, Truong Huu Hoang, Misako Sato‐Matsubara, Atsuko Daikoku, Chiho Kadono, Daisuke Oikawa, Katsutoshi Yoshizato, Fuminori Tokunaga, Massimo Pinzani, Norifumi Kawada
Journal: Hepatology (2021)

Background and Aims Antifibrotic therapy remains an unmet medical need in human chronic liver disease. We report the antifibrotic properties of cytoglobin (CYGB), a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis. Approach and Results Cygb ‐deficient mice that had bile duct ligation–induced liver cholestasis or choline‐deficient amino acid–defined diet–induced steatohepatitis significantly exacerbated liver damage, fibrosis, and reactive oxygen species (ROS) formation. All of these manifestations were attenuated in Cygb ‐overexpressing mice. We produced hexa histidine–tagged recombinant human CYGB (His‐CYGB), traced its biodistribution, and assessed its function in HSCs or in mice with advanced liver cirrhosis using thioacetamide (TAA) or 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC). In cultured HSCs, extracellular His‐CYGB was endocytosed and accumulated in endosomes through a clathrin‐mediated pathway. His‐CYGB significantly impeded ROS formation spontaneously or in the presence of ROS inducers in HSCs, thus leading to the attenuation of collagen type 1 alpha 1 production and α‐smooth muscle actin expression. Replacement the iron center of the heme group with cobalt nullified the effect of His‐CYGB. In addition, His‐CYGB induced interferon‐β secretion by HSCs that partly contributed to its antifibrotic function. Momelotinib incompletely reversed the effect of His‐CYGB. Intravenously injected His‐CYGB markedly suppressed liver inflammation, fibrosis, and oxidative cell damage in mice administered TAA or DDC mice without adverse effects. RNA‐sequencing analysis revealed the down‐regulation of inflammation‐ and fibrosis‐related genes and the up‐regulation of antioxidant genes in both cell culture and liver tissues. The injected His‐CYGB predominantly localized to HSCs but not to macrophages, suggesting specific targeting effects. His‐CYGB exhibited no toxicity in chimeric mice with humanized livers. Conclusions His‐CYGB could have antifibrotic clinical applications for human chronic liver diseases.
Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from Cantabria (Northern Spain)
Authors: Diego Ferrer, Lucia Lavin, Pablo Sanchez, Fernando Ausin, Ramón Agüero, Francisco Leyva, J. Gonzalo Ocejo
Journal: European Respiratory Journal (2013)

Background: Mannose-binding lectin (MBL) is a central molecule of the innate immune system. Mannose-binding lectin 2 (MBL2) promoter polymorphisms and structural variants have been associated with susceptibility to pulmonary tuberculosis (PTB). However, contradictory results among different populations have been reported, resulting in no convincing evidence of association between MBL2 and susceptibility to tuberculosis.  Objectives: To investigate the association of MBL2 promoter polymorphisms and structural variants with PTB in a well genetically conserved Spanish population (Cantabria, Northern Spain).  Methods:. We analysed the six promoter and structural MBL2 gene variants in 107 patients with PTB and 441 healthy controls by using a line immuno-probe assay (LIPA).  Results: Only D variant and HYPD haplotype were significantly more frequents in healthy controls which would indicate that this allele could confer protection against PTB, but this difference disappeared after statistical correction. Neither the rest of alleles nor the haplotypes were significantly associated with the disease.  Conclusions: These results would indicate that MBL2 promoter polymorphisms and gene variants would not be associated with an increased risk to PTB. Despite the slight trend of the D allele and HYPD haplotype in conferring protection against PTB, susceptibility to this disease would probably be due to other genetic factors, at least in our population.
Functional analysis of IGFBP-3 gene expression in ovarian endometrioid carcinoma.
Authors: Pao-Ling Torng, Jia-Hung Ye, Chi-Ying F. Huang, Pinchas Cohen, Su-Cheng Huang, Chin-Tarng Lin
Journal: Cancer Research (2005)

240  To identify the signaling pathway responsible for the establishment of a metastatic phenotype in carcinoma cells is of crucial importance for the understanding of the pathogenesis of cancer metastasis. The process of metastasis usually involves several steps, including increase of the cell motility to invade, the degradation of extracellular matrix and basement membranes and the cell proliferation. In our study, we used an ovarian cancer invasion model to define five OVTW59 sublines P0 to P4, with progressive increase of invasion capabilities for investigation of genes involved in invasion and metastasis. By cDNA microarray and quantitative real-time RT-PCR analysis, we performed global gene screening and found 39 genes related with invasion and metastasis. Thirteen genes of them were down-regulated and twenty-six genes were up-regulated with the increase of ovarian cancer invasion. One of the down-regulated invasion-related genes, insulin-like growth factor-binding protein 3 (IGFBP-3), showed surprisingly differential expression in the ovarian cancer invasion model. For investigation of the functional role of differential expression of IGFBP-3 in the tumor progression, especially in the invasion and metastasis of ovarian cancer, we transfected a plasmid containing IGFBP-3 cDNA into the P0 and P4 cells. It was found that IGFBP-3 could inhibit cell migration in the scratch analysis and cell invasion in the invasion chamber assay; in addition, it could also inhibit tumor growth and metastasis and cause apoptosis in the animal model. Transfection of shRNA into the IGFBP-3 transfected stable line could reverse these functions. We further studied the inhibitory mechanism of IGFBP-3 in cancer migration, invasion and metastasis, especially focusing in the signaling pathways and the interacting genes related to IGFBP-3. Our result revealed that IGFBP-3 could inhibit the activation of extracellular signal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK)-mitogen-activated protein kinase (MAPK) signaling pathways but not the p38-MAPK pathway. It is concluded that the IGFBP-3 gene, selected from the progressive increase in invasion capability subline of ovarian cancer cell line, plays a role as a tumor suppressor in ovarian cancer pathogenesis to inhibit tumor cell proliferation, migration, invasion and metastasis through a mechanism of inhibition of ERK 1/2 and JNK-MAPK signaling pathways.
Krüppel-like factor 14 deletion in myeloid cells accelerates atherosclerotic lesion development
Authors: Huilun Wang, Yanhong Guo, Haocheng Lu, Yonghong Luo, Wenting Hu, Wenying Liang, Minerva T Garcia-Barrio, Lin Chang, Anna Schwendeman, Jifeng Zhang, Y Eugene Chen
Journal: Cardiovascular Research (2021)

Atherosclerosis is the dominant pathologic basis of many cardiovascular diseases. Large genome-wide association studies have identified that single-nucleotide polymorphisms proximal to Krüppel-like factor 14 (KLF14), a member of the zinc finger family of transcription factors, are associated with higher cardiovascular risks. Macrophage dysfunction contributes to atherosclerosis development and has been recognized as a potential therapeutic target for treating many cardiovascular diseases. Herein, we address the biologic function of KLF14 in macrophages and its role during the development of atherosclerosis.
Mets-Ir as a Useful Tool for the Diagnosis of Insulin Resistance in Non-Diabetic Euthyroid Adults from Lima, Peru
Authors: Diego Urrunaga-Pastor, Carlos Toro-Huamanchumo, Vicente A. Benites-Zapata, Mirella Guarnizo-Poma, Herbert Lazaro-Alcantara, Betzi Pantoja-Torres, Socorro Paico-Palacios, Vitalia Del Carmen Ranilla-Seguin
Journal: Metabolism (2021)
Randomized Controlled Trials
Authors: Janet M. Torpy, Cassio Lynm, Richard M. Glass
Journal: JAMA (2006)

Randomized Controlled TrialsM edical research answers many questions about health, illness, and treatment options.Evaluating new medicines and other treatments may involve research using randomized controlled trials.In such trials the participants who receive the treatment under study are assigned at random (by chance, like the flip of a coin).This is necessary to ensure that the outcomes are determined only by the treatment under study and not by other factors that could otherwise influence treatment assignment.Other participants who, by the randomization process, serve as controls receive a standard treatment or placebo treatment (a pill or procedure that does not include active ingredients).The June 21, 2006, issue of JAMA includes an article about clinical trials.This Patient Page is based on one previously published in the November 2, 2005, issue of JAMA.
New twists in humoral immune regulation by SLAM family receptors
Authors: Hai Qi
Journal: The Journal of Experimental Medicine (2021)

SLAM family receptors are involved in humoral immune regulation. In this issue of JEM, Zhong et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20200756) provide evidence that these receptors collectively suppress germinal center reaction but promote production of antigen-specific antibodies.
Author Correction: Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia
Authors: Joseph A. Fraietta, Simon F. Lacey, Elena J. Orlando, Iulian Pruteanu-Malinici, Mercy Gohil, Stefan Lundh, Alina C. Boesteanu, Yan Wang, Roddy S. O’Connor, Wei-Ting Hwang, Edward Pequignot, David E. Ambrose, Changfeng Zhang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Lifeng Tian, Harit Parakandi, Minnal Gupta, Regina M. Young, F. Brad Johnson, Irina Kulikovskaya, Li Liu, Jun Xu, Sadik H. Kassim, Megan M. Davis, Bruce L. Levine, Noelle V. Frey, Donald L. Siegel, Alexander C. Huang, E. John Wherry, Hans Bitter, Jennifer L. Brogdon, David L. Porter, Carl H. June, J. Joseph Melenhorst
Journal: Nature Medicine (2021)
Immunodeficiency during COVID-19 pandemic: analysis of a 243 patients' cohort followed at a Brazilian tertiary hospital
Authors: Laís Cunha, Priscila Franco, Bruna Gehlen, Mariana Fernandes, Alex Prado, Grazielly Pereira, Pereira Gf, Ana Karolina Marinho, Otavio Grecco, Myrthes Barros, Jorge Kalil, Cristina Kokron
Journal: Journal of Allergy and Clinical Immunology (2021)

COVID-19 pandemic raised doubts about susceptibility and disease prognosis of immunodeficient patients compared to general population. Our objective was to evaluate these patients' profile and their evolution during pandemic. Retrospective analysis of 243 immunodeficientpatients' medical records from March-July 2020. We evaluated socioeconomic conditions, adherence to social distancing, symptoms and type of immunodeficiency and comorbidities. Diagnosis was established through symptoms and positive SARS-CoV-2 PCR. Most were women (58%), mean age 42.3y. The majority presented CVID (48.2%), followed by IgA deficiency (14.8%), agammaglobulinemia (4.1%). Some presented secondary immunodeficiency (14.4%). Comorbidities: bronchiectasis (22.6%), asthma (20.2%), COPD (9.5%), SAH (17.7%), obesity (14%), diabetes (7.8%) and cardiovascular diseases (5%). COVID-19 was confirmed in 10(4.1%) patients, of which 55.6% had positive IgG. About housing, 94.2% lived in the city, 72% in houses, with an average of 6.3 rooms and 3.1 residents/household. During pandemic, patients left home on average 7 times/month and 93.4% usedmask, 63.4% used their own car, 23.9% used public transport. Those infected with SARS-CoV-2 had a higher mean of visitors compared to total cohort(2.4x1.4), lived more in apartments (50%x27.6%),left home more often (8.8x7,0 times/month) and were more obese (60% x14%) Lower percentage of immunodeficient patients infected with COVID-19 (4.1%) was observed compared to that in general population of the city of São Paulo (11%), possibly due to greater isolation and fear of being contaminated. Those infected were less adherent to preventive measures and had higher incidence of comorbidities (obesity) related to worse prognosis of COVID-19.
Reply
Authors: Alan C. Cameron, Karla B. Neves, Jeff White, Rhian M. Touyz, Ninian N. Lang
Journal: JACC CardioOncology (2021)

We are grateful to Dr. Nguyen and colleagues for their interest in our recent study (1), published in JACC: CardioOncology, that assessed the vascular effects of cisplatin-based chemotherapy in patients with testicular cancer.We read with interest their work that highlights 37 cases of aortic thrombosis associated with cisplatin in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and in medical publications.Their data are
Excavating bioactivities of nanozyme to remodel microenvironment for protecting chondrocytes and delaying osteoarthritis
Authors: Weiduo Hou, Chenyi Ye, Mo Chen, Wei Gao, Xue Xie, Jianrong Wu, Kai Zhang, Wei Zhang, Yuanyi Zheng, Xiaojun Cai
Journal: Bioactive Materials (2021)

Osteoarthritis (OA) is the main cause of disability in the elderly. Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease, and reduce the probability of joint replacement. However, there is to date no effective intervention for early and middle-stage OA. OA microenvironment mainly destroys the balance of oxidative stress, extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors. Herein, hollow Prussian blue nanozymes (HPBzymes) were designed via a modified hydrothermal template-free method. The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA. The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo, remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species (ROS) and Rac1/nuclear factor kappa-B (NF-κB) signaling in a rat model. HPBzyme significantly diminished interleukin (IL)-1β-stimulated inflammation, extracellular matrix degradation, and apoptosis of human chondrocytes. HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB. Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases. This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.
Fluoroquinolones vs. amoxicillin–clavulanate or ampicillin–sulbactam were not linked to aortic aneurysm or dissection
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2021)

Dong YH, Chang CH, Wang JL, et al. Association of infections and use of fluoroquinolones with the risk of aortic aneurysm or aortic dissection. JAMA Intern Med. 2020;180:1587-95. 32897358.
Abstract 11225: Chronic Beta3-Adrenergic Receptor Blockade Causes Regression of Cardiac Dysfunction in Chronically-Instrumented Conscious Dogs With Pacing-Induced Heart Failure
Authors: Zhi Zhang, Heng-Jie Cheng, Xiaowei Zhang, Tiankai Li, Tomohiko Ukai, Nobuyuki Ohte, David Herrington, Che-Ping Cheng
Journal: Circulation (2018)

Background: In heart failure (HF), cardiac β3-adrenergic receptor (AR)-mediated inhibitory pathway is up-regulated, which suggests a direct contributing role of β3-AR activation on HF progression a...