tbuckley/cabot-search huggingface dataset:
<scp>Plasmablast‐like</scp> Phenotype Among Antigen‐Experienced <scp>CXCR5</scp>–<scp>CD19<sup>low</sup></scp> B Cells in Systemic Lupus Erythematosus
Authors: Franziska Szelinski, Ana Luisa Stefanski, Eva Schrezenmeier, Hector Rincon‐Arevalo, Annika Wiedemann, Karin Reiter, Jacob Ritter, Marie Lettau, Van Duc Dang, Sebastian Fuchs, Andreas P. Frei, Tobias Alexander, Andreia C. Lino, Thomas Dörner
Journal: Arthritis & Rheumatology (2022)

Objective Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD–CD27– double‐negative B cell populations. Previous studies showed that double‐negative B cells represent a heterogeneous subset, and further characterization is needed. Methods We analyzed 2 independent cohorts of healthy donors and SLE patients, using a combined approach of flow cytometry (for 16 healthy donors and 28 SLE patients) and mass cytometry (for 18 healthy donors and 24 SLE patients) and targeted RNA‐Seq analysis. To compare B cell subset formation during the acute immune response versus that during autoimmune disease, we investigated healthy donors at various time points after receipt of the BNT162b2 messenger RNA COVID‐19 vaccine and patients with acute SARS–CoV‐2 infection, using flow cytometry. Results We found that IgD–CD27+ switched and atypical IgD–CD27– memory B cells, the levels of which were increased in SLE patients, represented heterogeneous populations composed of 3 different subsets each. CXCR5+CD19 intermediate , CXCR5–CD19 high , and CXCR5–CD19 low populations were found in the switched memory and double‐negative compartments, suggesting the relatedness of IgD–CD27+ and IgD–CD27– B cells. We characterized a hitherto unknown and antigen‐experienced CXCR5–CD19 low subset that was enhanced in SLE patients, had a plasmablast phenotype with diminished B cell receptor responsiveness, and expressed CD38, CD95, CD71, PRDM1 , XBP1 , and IRF4 . Levels of CXCR5–CD19 low subsets were increased and correlated with plasmablast frequencies in SLE patients and in healthy donors who received BNT162b2, suggesting their interrelationship and contribution to plasmacytosis. The detection of CXCR5–CD19 low B cells among both CD27+ and CD27– populations calls into question the role of CD27 as a reliable marker of B cell differentiation. Conclusion Our data suggest that CXCR5–CD19 low B cells are precursors of plasmablasts. Thus, cotargeting this subset may have therapeutic value in SLE.
Secretion of IL1 by Dedifferentiated Melanoma Cells Inhibits JAK1-STAT3–Driven Actomyosin Contractility of Lymph Node Fibroblastic Reticular Cells
Authors: Christopher Rovera, Ilona Berestjuk, Margaux Lecacheur, Cassandre Tavernier, Serena Diazzi, Sabrina Pisano, Marie Irondelle, Aude Mallavialle, Jean Albrengues, Cédric Gaggioli, Christophe A. Girard, Thierry Passeron, Marcel Deckert, Sophie Tartare-Deckert, Virginie Prod'homme
Journal: Cancer Research (2022)

Fibroblastic reticular cells (FRC) are immunologically specialized myofibroblasts that control the elasticity of the lymph node, in part through their contractile properties. Swelling of tumor-draining lymph nodes is a hallmark of lymphophilic cancers such as cutaneous melanoma. Melanoma displays high intratumoral heterogeneity with the coexistence of melanoma cells with variable differentiation phenotypes from melanocytic to dedifferentiated states. Factors secreted by melanoma cells promote premetastatic lymph node reprograming and tumor spreading. Elucidating the impact of the melanoma secretome on FRC could help identify approaches to prevent metastasis. Here we show that melanocytic and dedifferentiated melanoma cells differentially impact the FRC contractile phenotype. Factors secreted by dedifferentiated cells, but not by melanocytic cells, strongly inhibited actomyosin-dependent contractile forces of FRC by decreasing the activity of the RHOA-RHO-kinase (ROCK) pathway and the mechano-responsive transcriptional coactivator Yes1 associated transcriptional regulator (YAP). Transcriptional profiling and biochemical analyses indicated that actomyosin cytoskeleton relaxation in FRC is driven by inhibition of the JAK1-STAT3 pathway. This FRC relaxation was associated with increased FRC proliferation and activation and with elevated tumor invasion in vitro. The secretome of dedifferentiated melanoma cells also modulated the biomechanical properties of distant lymph node in premetastatic mouse models. Finally, IL1 produced by dedifferentiated cells was involved in the inhibition of FRC contractility. These data highlight the role of the JAK1-STAT3 and YAP pathways in spontaneous contractility of resting FRC. They also suggest that dedifferentiated melanoma cells specifically target FRC biomechanical properties to favor tumor spreading in the premetastatic lymph node niche. Targeting this remote communication could be an effective strategy to prevent metastatic spread of the disease.Communication between dedifferentiated melanoma cells and lymph node fibroblasts reprograms the biomechanical properties of the premetastatic lymph node niche to promote tumor invasion. See related commentary by Lund, p. 1692.
An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice
Authors: John B. Lees-Shepard, Sean J. Stoessel, Julian T. Chandler, Keith Bouchard, Patricia Bento, Lorraine N. Apuzzo, Parvathi M. Devarakonda, Jeffrey W. Hunter, David J. Goldhamer
Journal: Journal of Clinical Investigation (2022)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO) of skeletal muscle and associated soft tissues. FOP is caused by dominantly acting mutations in the gene encoding the bone morphogenetic protein (BMP) type I receptor, ACVR1 (ALK2), the most prevalent of which results in an arginine to histidine substitution at position 206 (ACVR1[R206H]). The fundamental pathological consequence of FOP-causing ACVR1 receptor mutations is to enable activin A to initiate canonical BMP signaling in fibro-adipogenic progenitors (FAPs), which drives HO. We developed a monoclonal blocking antibody (JAB0505) against the extracellular domain of ACVR1 and tested its effect on HO in 2 independent FOP mouse models. Although JAB0505 inhibited BMP-dependent gene expression in wild-type and ACVR1(R206H)-overexpressing cell lines, JAB0505 treatment profoundly exacerbated injury-induced HO. JAB0505-treated mice exhibited multiple, distinct foci of heterotopic lesions, suggesting an atypically broad anatomical domain of FAP recruitment to endochondral ossification. This was accompanied by dysregulated FAP population growth and an abnormally sustained immunological reaction following muscle injury. JAB0505 drove injury-induced HO in the absence of activin A, indicating that JAB0505 has receptor agonist activity. These data raise serious safety and efficacy concerns for the use of bivalent anti-ACVR1 antibodies to treat patients with FOP.
EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling
Authors: Xingkang Jiang, Shanqi Guo, Shuo Wang, Yangyi Zhang, Haojie Chen, Yong Wang, Ranlu Liu, Yuanjie Niu, Yong Xu
Journal: Cancer Research (2021)

Docetaxel-based chemotherapy is a standard-of-care treatment for metastatic prostate cancer, and chemoresistance remains a major challenge in clinical practice. Recent studies have demonstrated that circular RNAs (circRNA) play critical roles in the development and progression of prostate cancer. However, the biological roles and potential functions of circRNAs in mediating docetaxel-resistant prostate cancer have yet to be well elucidated. In this study, we analyzed the expression profiles of circRNAs in docetaxel-resistant and -sensitive prostate cancer cells through RNA sequencing and found that expression of circARHGAP29 was significantly upregulated in docetaxel-resistant cell lines and clinical samples. Ectopic expression of circARHGAP29 triggered docetaxel resistance and aerobic glycolysis in prostate cancer cells, which was reduced by silencing circARHGAP29. Moreover, eukaryotic initiation factor 4A3, which bound the back-spliced junction site and the downstream flanking sequence of circARHGAP29, induced cyclization and cytoplasmic export of circARHGAP29. circARHGAP29 increased the stability of lactate dehydrogenase A (LDHA) mRNA by strengthening its interaction with insulin-like growth factor 2 mRNA-binding protein 2, leading to enhanced glycolytic metabolism. In addition, circARHGAP29 interacted with and stabilized c-Myc mRNA and protein, which further increased LDHA expression by facilitating its transcription. These findings reveal the crucial function of circARHGAP29 in prostate cancer glycolysis by increasing and stabilizing LDHA mRNA, providing a promising therapeutic target in docetaxel-resistant prostate cancer.Upregulation of a novel circRNA, circARHGAP29, promotes docetaxel resistance and glycolytic metabolism, suggesting it could be a prognostic biomarker and therapeutic target in chemoresistant prostate cancer.
Leveraging the Health Services Research Toolbox for Surgical Education Research
Authors: Rachel R. Kelz, Benjamin Brooke, Lesly Dossett
Journal: JAMA Surgery (2022)

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 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 Surgery journal
Diagnosis of Persistent Chemotherapy-Induced Alopecia in Breast Cancer Survivors
Authors: Azael Freites-Martinez, Jerry Shapiro
Journal: JAMA Dermatology (2022)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Dermatology journal
Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study
Authors: Habib El-Khoury, David J Lee, Jean-Baptiste Alberge, Robert Redd, Christian J Cea-Curry, Jacqueline Perry, Hadley Barr, Ciara Murphy, Dhananjay Sakrikar, David Barnidge, Mark Bustoros, Houry Leblebjian, Anna Cowan, Maya I Davis, Julia Amstutz, Cody J Boehner, Elizabeth D Lightbody, Romanos Sklavenitis-Pistofidis, Mark C Perkins, Stephen Harding, Clifton C Mo, Prashant Kapoor, Joseph Mikhael, Ivan M Borrello, Rafael Fonseca, Scott T Weiss, Elizabeth Karlson, Lorenzo Trippa, Timothy R Rebbeck, Gad Getz, Catherine R Marinac, Irene M Ghobrial
Journal: The Lancet Haematology (2022)
Subcutaneous Fat Necrosis of the Newborn
Authors: Lisbeth Andreasen, Regitze Henrik-Nielsen, Beatrice Dyring-Andersen
Journal: JAMA Dermatology (2022)

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 Dermatology 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 Dermatology journal
Discovery of small molecule Gαq/11 protein inhibitors against uveal melanoma
Authors: Yang Ge, Jun-Jie Deng, Jianzheng Zhu, Lu Liu, Shumin Ouyang, Zhendong Song, Xiaolei Zhang, Xiao-Feng Xiong
Journal: Acta Pharmaceutica Sinica B (2022)

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.
荷兰一项化脓性汗腺炎调查的结果
Journal: British Journal of Dermatology (2022)

British Journal of DermatologyVolume 186, Issue 5 p. e210-e210 Plain Language Summary 荷兰一项化脓性汗腺炎调查的结果 First published: 02 May 2022 https://doi.org/10.1111/bjd.21263AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Prens et al. Br J Dermatol 2022; 186:814–822. 化脓性汗腺炎(HS)是一种令人痛苦的复发性长期疾病，在腋窝、乳房和腹股沟等部位发生炎症(发红、触痛和肿胀)。在HS中，毛囊会被堵塞。这会导致烫伤样的肿块、病变部位出脓并形成瘢痕，对患者的生活质量造成影响。 作者旨在探究HS在荷兰北部的普遍程度，更多了解HS患者还会出现哪些其他健康问题。调查向超过 167,000 人发出了问卷，约有 56,000 人做出了回复。作者原本预期大约 1%的人口患有HS，但获得的数值更高，达到了 2%。很多人尚未确诊HS，也没有接受治疗。 我们已经知道肥胖、2 型糖尿病、慢性阻塞性肺疾病、抑郁和克罗恩氏病更常见于HS患者。这项研究还发现一些其他疾病更常见于HS患者，比如纤维肌痛、肠易激综合症、慢性疲劳综合征和偏头痛。与其他研究一样，这项研究还发现HS患者更有可能吸烟。 这项研究显示，很多人目前没有被诊断为HS，或没有针对HS接受治疗。 Volume186, Issue5May 2022Pages e210-e210 RelatedInformation
Polygenic risk scores for melanoma: a stepwise process towards clinical implementation
Authors: Marlies Wakkee
Journal: British Journal of Dermatology (2022)

In this issue of the BJD, Alavi et al. report two multicentre phase II trials designed to evaluate the safety and tolerability of the Janus kinase (JAK)1 inhibitor INCB054707 in patients with moderate-to-severe hidradenitis suppurativa (HS). 1 Treatment of patients with HS can be challenging, with variable and
Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension
Authors: Christopher J. Rhodes, John Wharton, Emilia M. Swietlik, Lars Harbaum, Barbara Girerd, J. Gerry Coghlan, James Lordan, Colin Church, Joanna Pepke-Zaba, Mark Toshner, Stephen J. Wort, David G. Kiely, Robin Condliffe, Allan Lawrie, Stefan Gräf, David Montani, Athénaïs Boucly, Olivier Sitbon, Marc Humbert, Luke S. Howard, Nicholas W. Morrell, Martin R. Wilkins
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: NT-proBNP (N-terminal pro–brain natriuretic peptide), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH. Objectives: Identify prognostic proteins in PAH that complement NT-proBNP and clinical risk scores. Methods: An aptamer-based assay (SomaScan version 4) targeting 4,152 proteins was used to measure plasma proteins in patients with idiopathic, heritable, or drug-induced PAH from the UK National Cohort of PAH (n = 357) and the French EFORT (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n = 79). Prognostic proteins were identified in discovery–replication analyses of UK samples. Proteins independent of 6-minute-walk distance and NT-proBNP entered least absolute shrinkage and selection operator modeling, and the best combination in a single score was evaluated against clinical targets in EFORT. Measurements and Main Results: Thirty-one proteins robustly informed prognosis independent of NT-proBNP and 6-minute-walk distance in the UK cohort. A weighted combination score of six proteins was validated at baseline (5-yr mortality; area under the curve [AUC], 0.73; 95% confidence interval [CI], 0.63–0.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75–0.94; P = 9.96 × 10−6). The protein score risk stratified patients independent of established clinical targets and risk equations. The addition of the six-protein model score to NT-proBNP improved prediction of 5-year outcomes from AUC 0.762 (0.702–0.821) to 0.818 (0.767–0.869) by receiver operating characteristic analysis (P = 0.00426 for difference in AUC) in the UK replication and French samples combined. Conclusions: The plasma proteome informs prognosis beyond established factors in PAH and may provide a more sensitive measure of therapeutic response.
Association of Health Policy With Payment and Regional Shifts in Gender-Affirming Surgery
Authors: Sacha C. Hauc, Aaron S. Long, Mohammad Ali Mozaffari, Kirby L. Mateja, Alicia P. Stephan, Adam H. Junn, Michael Alperovich
Journal: JAMA Surgery (2022)

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 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 Surgery journal
Associating Violence With Schizophrenia—Risks and Biases
Authors: Chih-Wei Hsu, Ping-Tao Tseng, Yu-Kang Tu
Journal: JAMA Psychiatry (2022)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Psychiatry journal
Mediastinal Lymph Node Silicotic Nodules and Occupational Exposure to Respirable Crystalline Silica: A Controlled Study in Patients with Lung Cancer
Authors: Patrick Brochard, Hugues Begueret, Matthieu Thumerel, Rachida Bakhiyi, Isabelle Leclerc, Carine Audoin, François Laurent, Lucile Sésé, Jean-François Bernaudin
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Mediastinal Lymph Node Silicotic Nodules and Occupational Exposure to Respirable Crystalline Silica: A Controlled Study in Patients with Lung Cancer ." American Journal of Respiratory and Critical Care Medicine, 206(3), pp. 356–358