tbuckley/cabot-search huggingface dataset:
B Cell Reconstitution Is Strongly Associated With <scp>COVID</scp>‐19 Vaccine Responsiveness in Rheumatic Disease Patients Who Received Treatment With Rituximab
Authors: Sarah Jinich, Kaitlin Schultz, Deanna Jannat‐Khah, Robert Spiera
Journal: Arthritis & Rheumatology (2021)

To assess the association of a detectable antibody response to COVID-19 vaccination with factors including B cell depletion in patients who received treatment with rituximab (RTX).We conducted a retrospective review of the charts of adult patients who received treatment with RTX and completed messenger RNA vaccination for SARS-CoV-2. The primary outcome measure was the presence or absence and strength of the serologic antibody response to vaccination. Comparisons between those with and those without a detectable serologic response were calculated using t-tests, Fisher's exact test, and Wilcoxon's rank sum test. The relationship between the serologic response to COVID-19 vaccination and B cell reconstitution status was assessed using negative predictive values and positive predictive values with data reported as percentages with 95% confidence intervals (95% CIs).In 56 patients being treated with RTX, a significant difference in terms of the level of B cell reconstitution was observed in those with a positive serologic response compared to those with a negative serologic response to vaccination (proportion of B cells reconstituted among total lymphocytes, median 2% [interquartile range (IQR) 0.13-10%] versus median 0% [IQR 0-0%]; P < 0.001).There was also a significant difference in the time since the last RTX infusion between patients with a positive serologic response compared to those with a negative serologic response to vaccination (median time since last infusion 594 days [IQR 262-1,163] versus median 138 days [IQR 68-197]; P < 0.001). There was no serologic response to COVID-19 vaccination after the last exposure to RTX in 13% of patients (3 of 24) at >12 months after last exposure, 55% of patients (6 of 11) at 6-12 months after last exposure, and 86% of patients (18 of 21) at <6 months after last exposure.B cell reconstitution and a longer time since a patient's last exposure to RTX are associated with a positive serologic response to the COVID-19 vaccine. Strategies for maximizing vaccine responsiveness in patients who receive treatment with RTX should incorporate assessment of B cell reconstitution.
Error in Affiliation
Journal: JAMA Network Open (2021)

Li Zhang, MD; JingNan Chen, PhD; JianWei Zhang, MM; Wei Wu, MD; Ke Huang, MD; RuiMin Chen, MM; Mireguli Maimaiti, MD; ShaoKe Chen, MM; BingYan Cao, MD; Min Zhu, MM; ChunLin Wang, MD; Zhe Su, MD; Yan Liang, MD; Hui Yao, MD; HaiYan Wei, MM; RongXiu Zheng, MD; HongWei Du, MD; FeiHong Luo, MD; Pin Li, MD; MinJia Mo, BS; YunXian Yu, PhD; Ergang Wang, BS; Robert M. Dorazio, PhD; Junfen Fu, MD, PhD
Overcoming multidrug resistance by knockout of ABCB1 gene using CRISPR/Cas9 system in SW620/Ad300 colorectal cancer cells
Authors: Zi‐Ning Lei, Qiu‐Xu Teng, Zhuo‐Xun Wu, Feng‐Feng Ping, Peng Song, John N.D. Wurpel, Zhe‐Sheng Chen
Journal: MedComm (2021)

Abstract Multidrug resistance (MDR) has been extensively reported in colorectal cancer patients, which remains a major cause of chemotherapy failure. One of the critical mechanisms of MDR in colorectal cancer is the reduced intracellular drug level led by the upregulated expression of the ATP‐binding cassette (ABC) transporters, particularly, ABCB1/P‐gp. In this study, the CRISPR/Cas9 system was utilized to target ABCB1 in MDR colorectal cancer SW620/Ad300 cell line with ABCB1 overexpression. The results showed that stable knockout of ABCB1 gene by the CRISPR/Cas9 system was achieved in the MDR cancer cells. Reversal of MDR against ABCB1 chemotherapeutic drugs increased intracellular accumulation of [ 3 H]‐paclitaxel accumulation, and decreased drug efflux activity was observed in MDR SW620/Ad300 cells after ABCB1 gene knockout. Further tests using the 3D multicellular tumor spheroid model suggested that deficiency in ABCB1 restrained tumor spheroid growth and restore sensitivity to paclitaxel in MDR tumor spheroids. Overall, the CRISPR/Cas9 system targeting the ABCB1 gene can be an effective approach to overcome ABCB1‐mediated MDR in colorectal cancer SW620/Ad300 cells.
Re: Pietro Piazza, Luca Sarchi, Stefano Puliatti, Carlo Andrea Bravi, Sophie Knipper, Alexandre Mottrie. The Unsolved Issue of Reporting of Late Complications in Urology. Eur Urol 2021;80:527–528
Authors: Niranjan J Sathianathen, Nathan Lawrentschuk, Marc A Furrer
Journal: European Urology (2021)
Benefit of a Live Donor for Patients With Hepatocellular Carcinoma on the Waiting List
Authors: Bo-Han Zhang, Yun-Shi Cai, Jia-Yin Yang
Journal: JAMA Surgery (2021)

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 Surgery 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 2022 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 Surgery journal
Human papillomavirus vaccination in the European Union/European Economic Area and globally: a moral dilemma
Authors: Edoardo Colzani, Kari Johansen, Helen Johnson, Lucia Pastore Celentano
Journal: Eurosurveillance (2021)

While many European Union/European Economic Area (EU/EEA) countries recently expanded human papillomavirus (HPV) vaccination to boys, HPV vaccine supply is currently limited for girls in low- and middle-income countries (LMIC) that are severely affected by HPV.Globally, about 50% of countries have introduced HPV vaccination. Some LMIC with high burden of cervical cancer have not yet introduced HPV vaccination, or are reaching suboptimal vaccination coverage. While WHO issued a call for cervical cancer elimination in 2018, a global shortage of HPV vaccines is currently predicted to last at least until 2024.We reviewed national policies of EU/EEA countries and recommendations of the World Health Organization (WHO) Strategic Advisory Group of Experts on immunisation to discuss current challenges and dose-sparing options. Several EU/EEA countries have extended HPV vaccination to boys and the European Cancer Organisation has issued a resolution for elimination of all HPV-associated cancers in both sexes. The European Centre for Disease Prevention and Control concluded in its 2020 guidance that cost-effectiveness of extending routine vaccination to boys depends on several context-specific factors. The extension of HPV vaccination to boys in EU/EEA countries may affect global availability of vaccines. Temporary dose-sparing options could be considered during the COVID-19 post-pandemic period.
Modulation of H4K16Ac levels reduces pro-fibrotic gene expression and mitigates lung fibrosis in aged mice
Authors: Xiangyu Zhang, Hui Liu, Jennifer Q Zhou, Stefanie Krick, Jarrod W Barnes, Victor J Thannickal, Yan Y Sanders
Journal: Theranostics (2021)

Histone H4 lysine16 acetylation (H4K16Ac) modulates chromatin structure by serving as a switch from a repressive to a transcriptionally active state.This euchromatin mark is associated with active transcription.In this study, we investigated the effects of H4K16Ac on the expression of pro-fibrotic genes in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and in an aging murine model of lung fibrosis.Methods: The lung tissues and fibroblasts from human IPF/non-IPF donors and from aged mice with/without bleomycin induced lung fibrosis were used in this study.The H4K16Ac levels were examined by immunohistochemistry or western blots.RNA silencing of H4K16Ac acetyltransferase Mof was used to reduce H4K16Ac levels in IPF fibroblasts.The effects of reduced H4K16Ac on pro-fibrotic gene expression were examined by western blots and real-time PCR.The association of H4K16Ac with these genes' promoter region were evaluated by ChIP assays.The gene expression profile in siRNA Mof transfected IPF cells were determined by RNA-Seq.The impact of H4K16Ac levels on lung fibrosis was evaluated in an aging murine model.Results: Aged mice with bleomycin induced lung fibrosis showed increased H4K16Ac levels.Human lung fibroblasts with siRNA Mof silencing demonstrated reduced H4K16Ac, and significantly down-regulated profibrotic genes, such as α-smooth muscle actin (α-SMA), collagen I, Nox4, and survivin.ChIP assays confirmed the associations of these pro-fibrotic genes' promoter region with H4K16Ac, while in siRNA Mof transfected cells the promoter/H4K16Ac associations were depleted.RNA-seq data demonstrated that Mof knockdown altered gene expression and cellular pathways, including cell damage and repair.In the aging mice model of persistent lung fibrosis, 18-month old mice given intra-nasal siRNA Mof from week 3 to 6 following bleomycin injury showed improved lung architecture, decreased total hydroxyproline content and lower levels of H4K16Ac.Conclusions: These results indicate a critical epigenetic regulatory role for histone H4K16Ac in the pathogenesis of pulmonary fibrosis, which will aid in the development of novel therapeutic strategies for age-related diseases such as IPF.
Quality assurance in colonoscopy: is case mix a problem?
Authors: Geir Hoff
Journal: Endoscopy (2021)

The importance of colonoscopy quality assurance measures was properly embraced when the European Union in 2003 recommended organized colorectal cancer (CRC) screening programs in member states provided quality assurance monitoring at all levels of the service [1]. Independently, or in the wake of this, the first two colonoscopy quality assurance programs were launched in the United Kingdom and Norway in the autumn of 2003 [2] [3]. Many countries followed suit and convincing results, mostly from CRC screening studies, emerged. After some years, reduced interval cancer rates were found to be correlated with adenoma detection rates (ADR) and polypectomy [4] [5].
Myeloproliferative Neoplasms (MPN) Clonal Evolution Landscape and Its Impact on Patients' Prognosis
Authors: Lin-Pierre Zhao, Marine Cazaux, Nabih Maslah, Rafael Daltro De Oliveira, Emmanuelle Verger, Juliette Soret-Dulphy, Clemence Marcault, Nathalie Parquet, Christine Dosquet, William Vainchenker, Emmanuel Raffoux, Stephane Giraudier, Jean-Jacques Kiladjian, Bruno Cassinat, Lina Benajiba
Journal: Blood (2021)
A novel role of BK potassium channel activity in preventing the development of kidney fibrosis
Authors: Yinhang Wang, Mengling Wang, Fengling Ning, Dadui Ren, Jie Tao, Weiyi Xie, Douglas C. Eaton, Gengru Jiang, Alton B. Farris, Hong Xin, Hui Cai, Xuemei Zhang
Journal: Kidney International (2021)
Abatacept in IgG4-related disease: a prospective, open-label, single-arm, single-centre, proof-of-concept study
Authors: Mark A Matza, Cory A Perugino, Liam Harvey, Ana D Fernandes, Zachary S Wallace, Hang Liu, Hugues Allard-Chamard, Shiv Pillai, John H Stone
Journal: The Lancet Rheumatology (2021)
Abstract 17083: Hunting For Clot: Strokes In Patients With Cardiac Amyloid
Authors: Douglas Kyrouac, Kartik Agusala
Journal: Circulation (2021)

Case Presentation: A 76-year-old female with history of amyloid light chain (AL) cardiac amyloidosis and prior stroke presented with acute bilateral leg weakness. MRI of the brain revealed subacute infarcts in the right basal ganglia and precentral gyrus as well as chronic left cerebellar infarctions. CT angiogram of the head and neck did not show any significant intracranial or carotid artery disease. All current and previous admission ECGs and telemetry showed sinus rhythm with no atrial arrhythmias. Transthoracic echocardiogram with bubble study noted LV ejection fraction of 62%, normal left atrial size and no evidence of an intracardiac shunt. Despite the lack of traditional indicators, a cardioembolic source was feared given the high risk of intracardiac thrombi in AL amyloid patients. A TEE was performed and confirmed a large left atrial appendage (LAA) thrombus with severely reduced velocities and spontaneous echo contrast (Figure 1). The patient was started on apixaban for secondary stroke prevention. Discussion: Amyloid proteins deposit throughout heart tissue, distorting mechanical function and electric conduction resulting in reduced blood flow and a high risk of intracardiac thrombi that is 10 times that of nonamyloid patients. Patients with cardiac amyloidosis have a high prevalence of atrial arrhythmias, particularly atrial fibrillation, but remain at significant risk of thrombi even in the absence of these arrhythmias, ranging from 3-20%. Risk factors for clot include AL type amyloid and features of worsened hemodynamics such as LV systolic and diastolic dysfunction, elevated heart rates and lower systolic blood pressure. This case demonstrates the importance of aggressively “hunting” for intracardiac thrombi in amyloid patients presenting with stroke even without perceived risk factors, especially given the protective effect of starting anticoagulation.
BIOM-35. CLINICALLY TRACTABLE OUTCOME PREDICTION OF GROUP 3/4 MEDULLOBLASTOMA BASED ON TPD52 IMMUNOHISTOCHEMISTRY: A MULTICOHORT STUDY
Authors: Alberto Delaidelli, Christopher Dunham, Mariarita Santi, Gian Luca Negri, Andreas von Deimling, Stefan Pfister, Marcel Kool, Vijay Ramaswamy, Andrey Korshunov, Michael Taylor, Poul Sorensen
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND International consensus and the 2021 WHO classification recognize eight molecular subgroups among Group 3/4 medulloblastoma (representing ~60% of tumors). However, very few clinical centers worldwide possess the technical capabilities to determine DNA-methylation patterns or other molecular parameters of high-risk for Group 3/4 tumors. As a result, biomarker-driven risk stratification and therapy assignment constitutes a major challenge in medulloblastoma research. Here, we identify an immunohistochemistry (IHC) marker as a clinically tractable method for improved medulloblastoma risk-stratification. PATIENTS AND METHODS We bioinformatically analyzed published medulloblastoma transcriptomes and proteomes identifying as a potential biomarker TPD52, whose IHC prognostic value was validated across three Group 3/4 medulloblastoma clinical cohorts (n = 387) treated with conventional therapies. Risk stratification and prediction capability were computed utilizing uni- and multivariate survival analysis. Newly developed risk classifiers including TPD52 IHC were compared to state-of-the-art risk stratification schemes in terms of prediction error, area under the time-dependent receiver operating characteristic (ROC) curves and C-statistic. Biomarker-driven prognostic stratification models identified were cross validated in different cohorts. RESULTS TPD52 IHC positivity represents a significant independent predictor of early relapse and death for Group 3/4 medulloblastoma (HRs between 3.67-26.7 [95% CIs between 1.00-706.23], p = 0.05, 0.017 and 0.0058). Cross-validated survival models incorporating TPD52 IHC with clinical features outperformed existing disease risk-stratification schemes, and reclassified ~50% of patients into more appropriate risk categories. Finally, TPD52 immunopositivity is a predictive indicator of poor response to chemotherapy (HR 12.66 [95% CI 3.53-45.40], p &amp;lt; 0.0001), suggesting important implication for therapeutic choices. CONCLUSION The current study redefines the approach to risk-stratification in Group 3/4 medulloblastoma. Integration of TPD52 IHC in classification algorithms significantly improves outcome prediction and can be rapidly adopted for risk stratification on a global scale, independently of advanced but technically challenging molecular profiling techniques.
Dissecting GATA1 Protein Interactions in Normal and Malignant Human Erythroblasts
Authors: Samantha Tauchmann, Frederik Otzen Bagger, Thomas Bock, Roos Krimpenfort, Francesca Aglialoro, Peter Valent, Alexandre Fagnan, Marieke von Lindern, Thomas Mercher, Juerg Schwaller
Journal: Blood (2021)
Targeting MDS Stem Cells with Omacetaxine and Azacitidine for Newly Diagnosed High Grade Patients: Phase 1 Trial Results and Preliminary Mechanistic Studies
Authors: Brett M. Stevens, Amanda C. Winters, Mohammad Minhajuddin, Maria L. Amaya, Christine M. McMahon, Jonathan A. Gutman, Clayton Smith, Deng Wang, Connor Adkins, Olivia Ondracek, Craig T. Jordan, Daniel A. Pollyea
Journal: Blood (2021)
Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance
Authors: Felicity Newell, Ines Pires da Silva, Peter A. Johansson, Alexander M. Menzies, James S. Wilmott, Venkateswar Addala, Matteo S. Carlino, Helen Rizos, Katia Nones, Jarem J. Edwards, Vanessa Lakis, Stephen H. Kazakoff, Pamela Mukhopadhyay, Peter M. Ferguson, Conrad Leonard, Lambros T. Koufariotis, Scott Wood, Christian U. Blank, John F. Thompson, Andrew J. Spillane, Robyn P.M. Saw, Kerwin F. Shannon, John V. Pearson, Graham J. Mann, Nicholas K. Hayward, Richard A. Scolyer, Nicola Waddell, Georgina V. Long
Journal: Cancer Cell (2021)
Determinants of Plaque Progression Despite Very Low Low-Density Lipoprotein–Cholesterol Levels With the PCSK9 Inhibitor, Evolocumab
Authors: Satoshi Honda, Rishi Puri, Todd Anderson, John J.P. Kastelein, Danielle M. Brennan, Helina Kassahun, Ransi Somaratne, Scott M. Wasserman, Steve E. Nissen, Stephen J. Nicholls
Journal: JACC. Cardiovascular imaging (2021)
Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG
Authors: Anna Schnell, Mehmet Davrandi, Moritz Saxenhofer, Clara Leboreiro, Stefanie Graeter, Fernando Moreira, Maria Hauswald, Carolin Witte, Irina Irincheeva, Annette Feussner, Cedric Vonarburg, Ilka Schulze, Alexander Schaub, Siobhan O. Burns, David M. Lowe
Journal: Journal of Allergy and Clinical Immunology (2021)
Reprogramming of RNA silencing triggered by cucumber mosaic virus infection in Arabidopsis
Authors: Maria Luz Annacondia, German Martinez
Journal: Genome biology (2021)

Abstract Background RNA silencing has an important role mediating sequence-specific virus resistance in plants. The complex interaction of viruses with RNA silencing involves the loading of viral small interfering RNAs (vsiRNAs) into its host ARGONAUTE (AGO) proteins. As a side effect of their antiviral activity, vsiRNAs loading into AGO proteins can also mediate the silencing of endogenous genes. Here, we analyze at the genome-wide level both aspects of the interference of cucumber mosaic virus (CMV) with the RNA silencing machinery of Arabidopsis thaliana. Results We observe CMV-derived vsiRNAs affect the levels of endogenous sRNA classes. Furthermore, we analyze the incorporation of vsiRNAs into AGO proteins with a described antiviral role and the viral suppressor of RNA silencing (VSR) 2b, by combining protein immunoprecipitation with sRNA high-throughput sequencing. Interestingly, vsiRNAs represent a substantial percentage of AGO-loaded sRNAs and displace other endogenous sRNAs. As a countermeasure, the VSR 2b loaded vsiRNAs and mRNA-derived siRNAs, which affect the expression of the genes they derive from. Additionally, we analyze how vsiRNAs incorporate into the endogenous RNA silencing pathways by exploring their target mRNAs using parallel analysis of RNA end (PARE) sequencing, which allow us to identify vsiRNA-targeted genes genome-wide. Conclusions This work exemplifies the complex relationship of RNA viruses with the endogenous RNA silencing machinery and the multiple aspects of virus resistance and virulence that this interaction induces.
Super Enhancer-Mediated Upregulation of<i>HJURP</i>Promotes Growth and Survival of t(4;14)-Positive Multiple Myeloma
Authors: Yunlu Jia, Jianbiao Zhou, Tze King Tan, Tae-Hoon Chung, Yongxia Chen, Jing-Yuan Chooi, Takaomi Sanda, Melissa J. Fullwood, Sinan Xiong, Sabrina H.M. Toh, Kalpnaa Balan, Regina W.J. Wong, Julia S.L. Lim, Enfan Zhang, Zhen Cai, Peng Shen, Wee Joo Chng
Journal: Cancer Research (2021)

Abstract Multiple myeloma is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in multiple myeloma. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE). We used chromatin immunoprecipitation sequencing of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs in t(4;14)-translocated multiple myeloma. The histone chaperone HJURP was aberrantly overexpressed in t(4;14)-positive multiple myeloma due to transcriptional activation by a distal SE induced by the histone lysine methyltransferase NSD2. Silencing of HJURP with short hairpin RNA or CRISPR interference of SE function impaired cell viability and led to apoptosis. Conversely, HJURP overexpression promoted cell proliferation and abrogated apoptosis. Mechanistically, the NSD2/BRD4 complex positively coregulated HJURP transcription by binding the promoter and active elements of its SE. In summary, this study introduces SE profiling as an efficient approach to identify new targets and understand molecular pathogenesis in specific subtypes of cancer. Moreover, HJURP could be a valuable therapeutic target in patients with t(4;14)-positive myeloma. Significance: A super-enhancer screen in t(4;14) multiple myeloma serves to identify genes that promote growth and survival of myeloma cells, which may be evaluated in future studies as therapeutic targets.