tbuckley/cabot-search huggingface dataset:
Association of Postnatal Cytomegalovirus Infection With Head Growth
Authors: Sarah Thomas, Helen Puusepp-Benazzouz, Ralph Nanan
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
ZNF143-Mediated H3K9 Trimethylation Upregulates CDC6 by Activating MDIG in Hepatocellular Carcinoma
Authors: Lili Zhang, Qi Huo, Chao Ge, Fangyu Zhao, Qingqing Zhou, Xiaoxia Chen, Hua Tian, Taoyang Chen, Haiyang Xie, Ying Cui, Ming Yao, Hong Li, Jinjun Li
Journal: Cancer Research (2020)

Abstract Zinc finger protein 143 (ZNF143) belongs to the zinc finger protein family and possesses transcription factor activity by binding sequence-specific DNA. The exact biological role of ZNF143 in hepatocellular carcinoma (HCC) has not been investigated. Here we report that ZNF143 is overexpressed in HCC tissues and its overexpression correlates with poor prognosis. Gain- and loss-of-function experiments showed that ZNF143 promoted HCC cell proliferation, colony formation, and tumor growth in vitro and in vivo. ZNF143 accelerated HCC cell-cycle progression by activating cell division cycle 6 (CDC6). Mechanistically, ZNF143 promoted expression of CDC6 by directly activating transcription of histone demethylase mineral dust–induced gene (MDIG), which in turn reduced H3K9me3 enrichment in the CDC6 promoter region. Consistently, ZNF143 expression correlated significantly with MDIG and CDC6 expression in HCC. Collectively, we propose a model for a ZNF143–MDIG–CDC6 oncoprotein axis that provides novel insight into ZNF143, which may serve as a therapeutic target in HCC. Significance: These findings describe the mechanism by which ZNF143 promotes HCC proliferation and provide important clues for exploring new targets and strategies for clinical treatment of human liver cancer.
Genome-Wide CRISPR Screen Identifies Semaphorin 6A and 6B as Receptors for Paeniclostridium sordellii Toxin TcsL
Authors: Songhai Tian, Yang Liu, Hao Wu, Hao Liu, Ji Zeng, Mei Yuk Choi, Hong Chen, Ralf Gerhard, Min Dong
Journal: Cell Host & Microbe (2020)
The Use of Not-Negative Conclusions to Describe Results of Formally Negative Trials Presented at Oncology Meetings
Authors: Massimo Di Maio, Marco Audisio, Claudia Cardone, Emmanuele De Luca, Piera Gargiulo, Clizia Zichi, Francesco Perrone
Journal: JAMA Oncology (2020)

This quality improvement analysis of oral presentations of phase 3 randomized clinical trials evaluates the frequency and risks of emphasizing results of borderline significance.
APRIL-dependent lifelong plasmacyte maintenance and immunoglobulin production in humans
Authors: Tzu-Wen Yeh, Tsubasa Okano, Takuya Naruto, Motoi Yamashita, Miko Okamura, Kay Tanita, Likun Du, Qiang Pan-Hammarström, Noriko Mitsuiki, Satoshi Okada, Hirokazu Kanegane, Kohsuke Imai, Tomohiro Morio
Journal: Journal of Allergy and Clinical Immunology (2020)
Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD
Authors: Evy Ulijn, Nathan den Broeder, Maike Wientjes, Noortje van Herwaarden, Inger Meek, Lieke Tweehuysen, Aatke van der Maas, Bart JF van den Bemt, Alfons A den Broeder
Journal: Annals of the Rheumatic Diseases (2020)

After adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment.To validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders.A diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity.137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab.In contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.
Deletion in Chromosome 17p12 and Gains in Chromosome 9q33.3 by Array Comparative Hybridization Are Associated with R-CHOP Treatment Failure in Patients with Diffuse Large B Cell Lymphoma
Authors: Nathalie Johnson, Ronald J De Leeuw, Julia Chae, Sohrab P Shah, Wan L Lam, Thomas Relander, Joseph M. Connors, Douglas E. Horsman, Randy D. Gascoyne
Journal: Blood (2008)
Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma
Authors: Won Jin Ho, Ludmila Danilova, Su Jin Lim, Rohan Verma, Stephanie Xavier, James M Leatherman, Marcelo B Sztein, Elana J Fertig, Hao Wang, Elizabeth Jaffee, Mark Yarchoan
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background and aims Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear. Methods We conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)). Results Meta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=−1.4%, 95% CI: −13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC. Conclusion There is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy.
Abstract 20848: Late Gadolinium Enhancement Magnetic Resonance Imaging in Non-Atrial Fibrillation Individuals
Authors: Johannes Siebermair, Promporn Suksaranjit, Christopher McGann, Kathryn A Peterson, Mobin Kheirkhahan, Alex Baher, Reza Wakili, Kavitha Damal, Nassir F Marrouche, Brent D Wilson
Journal: Circulation (2017)

Introduction: Besides the traditional concept of AF perpetuating atrial remodeling (“AF begets AF”), there is increasing evidence that structural alterations precede AF as an atrial myopathy. There...
Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts
Authors: Wen Shi Lee, Masaru Kato, Eri Sugawara, Michihiro Kono, Yuki Kudo, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Olga Amengual, Kenji Oku, Shinsuke Yasuda, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
Journal: Arthritis & Rheumatology (2020)

Objective Optineurin ( OPTN ) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation. RANKL expressed by rheumatoid arthritis synovial fibroblasts ( RASF s) is primarily responsible for the development of bone erosions in patients with RA . The aim of the present study was to explore the role of OPTN in the pathogenesis of joint destruction in RA . Methods RASF s were left untreated or incubated with tumor necrosis factor ( TNF ) or interferon‐γ ( IFN γ), and expression of OPTN by RASF s was analyzed by reverse transcription–quantitative polymerase chain reaction ( RT ‐ qPCR ) and Western blotting. Expression of RANKL and osteoprotegerin ( OPG ) was evaluated in cultures of OPTN ‐reduced RASF s with or without TNF or IFN γ treatment. OPTN ‐reduced RASF s were cocultured with monocytes and stained for tartrate‐resistant acid phosphatase ( TRAP ). IκBα, NF ‐κB1, and RelA protein levels were measured to evaluate NF ‐κB signaling. Expression of messenger RNA ( mRNA ) for matrix metalloproteinase 3 ( MMP 3 ), interleukin‐6 ( IL 6 ), GATA binding protein 3 ( GATA 3 ), carbohydrate sulfotransferase 15 ( CHST 15 ), hyaluronan synthase 1 ( HAS 1 ), and GATA 1 was analyzed by RT ‐ qPCR . Results In RASF s incubated with TNF or IFN γ, OPTN expression was up‐regulated and RANKL expression was increased, and these effects were further pronounced in OPTN ‐reduced RASF s (all P &lt; 0.05 versus controls). OPG mRNA levels remained unchanged. Monocytes cocultured with OPTN ‐reduced RASF s differentiated to a greater extent into TRAP + multinucleated cells compared to monocytes cocultured with control RASF s ( P &lt; 0.05). IκBα degradation and nuclear NF ‐κB1 expression following TNF treatment were both prolonged in OPTN ‐reduced RASF s (each P &lt; 0.05 versus controls). MMP 3 mRNA levels were up‐regulated, while GATA 3 , CHST 15 , and HAS 1 mRNA levels were down‐regulated in OPTN ‐reduced RASF s (each P &lt; 0.05 versus controls). Conclusion OPTN plays a protective role in RA when it is up‐regulated in RASF s in the presence of proinflammatory cytokines. Absence of OPTN might worsen RA by generating a joint‐destructive state, as indicated by evidence of increased RANKL expression on RASF s and subsequent osteoclast differentiation.
Rapid Detection of Asymptomatic Coronavirus Disease 2019 by Computed Tomography Image Guidance for Stereotactic Ablative Radiotherapy
Authors: Gwendolyn J. McGinnis, Matthew S. Ning, Paige L. Nitsch, Michael S. O’Reilly, Mary Frances McAleer, Albert C. Koong, Joe Y. Chang
Journal: Journal of Thoracic Oncology (2020)
Bortezomib Induces Thrombocytopenia by Inhibiting Proplatelet Formation but Not Proliferation and Endomitosis in Human Primary Megakaryocytes
Authors: Wataru Nogami, Akiko Yamane, Takanori Nakamura, Eri Matsuki, Yasuo Ikeda, Yoshitaka Miyakawa
Journal: Blood (2008)
Bye, bye, bile: how altered bile acid composition changes small intestinal lipid sensing
Authors: Frank A Duca, Tony K T Lam
Journal: Gut (2020)

The gastrointestinal (GI) tract is increasingly recognised as a major contributor to energy homoeostasis that impact obesity progression. The gut represents the first site of interaction between incoming nutrients and the host, generating crucial negative feedback signalling to regulate food intake possibly by altering GI function like gastric emptying. In the case of proximal intestinal lipid sensing, several mechanisms have been identified to drive both satiety and satiation. For example, dietary fat is hydrolysed and absorbed into enterocytes. In the upper GI, this stimulates the synthesis of oleoylethanolamide (OEA), which can then act as a signalling molecule to induce satiety via activation of peroxisome proliferator-activated receptor-α and a gut-brain axis.1 Alternatively, activation of enteroendocrine cells (EECs) by free fatty acids binding to G protein-coupled receptor-40 leads to secretion of gut peptides, like cholecystokinin and glucagon-like peptide-1 (GLP-1), which slow gastric emptying and reduce food intake. Interestingly, activation of EECs via free fatty acids is hypothesised to occur on the basolateral side, requiring chylomicron formation, and thus dietary fat hydrolysis, similar to OEA production.2 Given that bile acids, especially cholic acid in mice, emulsify dietary lipids and thus promote efficient hydrolysis and absorption of lipids in the small intestine, their function would implicate a necessity in activating the aforementioned pathways to lower food intake.

In GUT , Higuchi et al observed that Cyp8b1-/- mice exhibited reduced body weight and adiposity due to an inhibition of food intake. As expected, lowering cholic acid and other 12α-hydroxylated bile acids via …
Association of Dermatomyositis Sine Dermatitis With Anti–Nuclear Matrix Protein 2 Autoantibodies
Authors: Michio Inoue, Jantima Tanboon, Shinya Hirakawa, Hirofumi Komaki, Takeshi Fukushima, Hiroyuki Awano, Takashi Tajima, Kenji Yamazaki, Ryutaro Hayashi, Tatsuo Mori, Kazumoto Shibuya, Takahiko Yamanoi, Hajime Yoshimura, Tomohiro Ogawa, Atsushi Katayama, Fuminobu Sugai, Yoichi Nakayama, Satoko Yamaguchi, Shinichiro Hayashi, Satoru Noguchi, Hisateru Tachimori, Naoko Okiyama, Manabu Fujimoto, Ichizo Nishino
Journal: JAMA Neurology (2020)

Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted.To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features.This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology.Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy.Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001).Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.
RAPID procedure for colorectal cancer liver metastasis
Authors: Silvio Nadalin, Utz Settmacher, Falk Rauchfuß, Deniz Balci, Alfred Königsrainer, Pål-Dag Line
Journal: International Journal of Surgery (2020)

Liver transplantation for colorectal cancer has regained renewed interest with reported good overall survival in selected patients. The scarcity of grafts is a major obstacle to wider implementation and exploration of this field of transplant oncology. The use of small segmental auxiliary grafts from deceased or living donors might be one way to expand the donor pool with minimal negative impact on the waiting list for deceased donor transplantation and minimal risk for the donor in case of living donor liver transplantation. This review provides an insight into the physiological background for this technique and summarizes technical and surgical considerations and the experiences with this novel concept. Although the international experience still is very limited, the short term outcome could suggest that this is technically feasible. There is not sufficient data to assess long term oncological outcome. The RAPID concept (i.e. resection and partial liver segment 2–3 transplantation with delayed total hepatectomy) is still an experimental surgical procedure and should be reserved for prospective clinical trials. Herein, we describe the main technical issues of RAPID procedure from deceased and from living donor as well and report preliminary results of the first cases performed worldwide.
Covid-19: Brazil’s president rallies supporters against social distancing
Authors: Owen Dyer
Journal: BMJ (2020)

Brazil’s president, Jair Bolsonaro, has fired his popular health minister, Luiz Henrique Mandetta, after weeks of conflicting messages from the two men about the risks associated with the covid-19 pandemic and what should be done about them.

Mandetta has supported state governors, most of whom have closed non-essential businesses and urged citizens to stay indoors, while Bolsonaro has argued that “the real problem is hysteria” and urged Brazilians to continue life as normal while making a point of greeting crowds of supporters and shaking hands.

Bolsonaro, who had earlier told an interviewer that Mandetta “lacked humility” and said that he would fire officials who were “full of themselves,” replaced Mandetta with the oncologist and entrepreneur Nelson Teich.

A recent poll showed 76% support for Mandetta’s handling of the crisis, while only 39% backed Bolsonaro’s approach.

In Brazil’s cities, …
Complete Transposition of the Great Vessels
Authors: LARRY P. ELLIOTT, RAY C. ANDERSON, NAIP TUNA, PAUL ADAMS, HENRY N. NEUFELD
Journal: Circulation (1963)

A correlative study of necropsy findings and electrocardiography in 54 cases of complete transposition of the great vessels was made to determine whether or not specific electrical patterns could predict the status of the ventricular septum. It became apparent that published criteria for distinguishing between patients with a ventricular septal defect and those with an intact ventricular septum were not uniformly reliable. Rather than the location of a communication, the important factor in differentiation depended upon the size of the opening, be it between the ventricles or through a patent ductus arteriosus. Cases were divided into two groups: In group I were those with a small communication, and in group II were those with a large communication between the greater and lesser circulations. The group with small communication showed a narrow or obliterated ductus arteriosus and an intact ventricular septum, or a small ventricular septal defect. In group II there was either a wide patent ductus arteriosus with an intact ventricular septum or a large ventricular septal defect. In group I the electrocardiogram predominantly showed isolated right ventricular hypertrophy, whereas, in group II, biventricular hypertrophy was the usual finding. Among the five patients in whom the mean manifest electrical axis was deviated to the left, two showed obstructive malformations of the aortic arch, and two left ventricular-right atrial communication. The fifth case was simply one of a large communication without complicating anomalies.
Emerging Lessons From COVID-19 Response in New York City
Authors: Dave A. Chokshi, Mitchell H. Katz
Journal: JAMA (2020)

Joseph Moscola, PA, MBA; Grace Sembajwe, DSc, MSc, CIH; Mark Jarrett, MD, MBA, MS; Bruce Farber, MD; Tylis Chang, MD; Thomas McGinn, MD, MPH; Karina W. Davidson, PhD, MASc; Northwell Health COVID-19 Research Consortium
Biodistribution of DiI-Labeled Bone Marrow-Derived Mononuclear Cells Following Intracoronary Injection in a Porcine Model of Chronic Myocardial Ischemia.
Authors: Shyam Bhakta, Matthew Joseph, Nicholas Greco, Paul Scheid, Daniel Winter, Jason Banks, Robert Hoffman, Vincent Pompili, Mary J. Laughlin
Journal: Blood (2005)