tbuckley/cabot-search huggingface dataset:
Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis
Authors: Philip J Mease, Atul A Deodhar, Désirée van der Heijde, Frank Behrens, Alan J Kivitz, Jeffrey Neal, Jonghyeon Kim, Shalabh Singhal, Miroslawa Nowak, Subhashis Banerjee
Journal: Annals of the Rheumatic Diseases (2022)

Objective To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). Methods In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16. Results ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p = 0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (≥5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment. Conclusions Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA. Trial registration number NCT03881059 .
Steatosis in chronic hepatitis B and its impact on the therapeutic response to entecavir
Authors: Hana Chaabouni, Ichrak Bougharriou, Nabil Lachiheb, Khouloud Mnif, Tarak Ben Jemaa, Khaoula Rekik, Fatma Smaoui, Makram Koubaa, Chakib Marrakchi, Boussayma Hammami, Mounir Ben Jemaa
Journal: Metabolism (2022)
Deaths
Journal: JAMA (1927)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The long and short non-coding RNAs modulating EZH2 signaling in cancer
Authors: Sepideh Mirzaei, Mohammad Hossein Gholami, Kiavash Hushmandi, Farid Hashemi, Amirhossein Zabolian, Israel Canadas, Ali Zarrabi, Noushin Nabavi, Amir Reza Aref, Francesco Crea, Yuzhuo Wang, Milad Ashrafizadeh, Alan Prem Kumar
Journal: Journal of Hematology & Oncology (2022)

Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.
Analeptics
Authors: J. H. Burn
Journal: BMJ (1939)

<h3>Bigger Picture</h3> Gene knockout (KO) experiments, using genetically altered animals, are a proven powerful approach to elucidate the role of a gene in a biological process. However, systematic KO experiments targeting many genes are usually prohibitive due to limited experimental and animal resources. Here, we present scTenifoldKnk, an efficient virtual KO tool that allows the systematic deletion of many genes individually. scTenifoldKnk uses single-cell RNA sequencing (scRNAseq) data from wild-type (WT) samples to predict gene function in a cell type-specific manner. We show that predictions made by scTenifoldKnk recapitulate findings from real-animal KO experiments. scTenifoldKnk has proven to be a powerful and effective approach for elucidating gene function, prioritizing KO targets, predicting experimental outcomes before real-animal KO experiments are conducted. <h3>Highlights</h3> scTenifoldKnk performs virtual KO experiments using scRNAseq data. scTenifoldKnk only requires data from WT samples; no data is needed from KO samples. Predictions made by scTenifoldKnk recapitulate findings from real-animal KO experiments. <h3>Data Science Maturity Level</h3> <h3>eTOC blurb</h3> scTenifoldKnk is a machine learning workflow performing virtual KO experiments to predict gene function. It constructs gene regulatory networks using single-cell RNA sequencing data from wild-type samples and then computationally deletes target genes. Real-data applications demonstrate that scTenifoldKnk recapitulates findings of real-animal KO experiments and accurately predicts gene function in analyzed cells. <h3>Summary</h3> Gene knockout (KO) experiments are a proven, powerful approach for studying gene function. However, systematic KO experiments targeting a large number of genes are usually prohibitive due to the limit of experimental and animal resources. Here, we present scTenifoldKnk, an efficient virtual KO tool that enables systematic KO investigation of gene function using data from single-cell RNA sequencing (scRNAseq). In scTenifoldKnk analysis, a gene regulatory network (GRN) is first constructed from scRNAseq data of wild-type samples, and a target gene is then virtually deleted from the constructed GRN. Manifold alignment is used to align the resulting reduced GRN to the original GRN to identify differentially regulated genes, which are used to infer target gene functions in analyzed cells. We demonstrate that the scTenifoldKnk-based virtual KO analysis recapitulates the main findings of real-animal KO experiments and recovers the expected functions of genes in relevant cell types.
Cabozantinib for Treatment of Brain Metastases in Patients With Renal Cell Carcinoma
Authors: Alessandro Rizzo, Veronica Mollica, Francesco Massari
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts
Authors: Amanda E Paluch, Shivangi Bajpai, David R Bassett, Mercedes R Carnethon, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, William E Kraus, I-Min Lee, Charles E Matthews, John D Omura, Alpa V Patel, Carl F Pieper, Erika Rees-Punia, Dhayana Dallmeier, Jochen Klenk, Peter H Whincup, Erin E Dooley, Kelley Pettee Gabriel, Priya Palta, Lisa A Pompeii, Ariel Chernofsky, Martin G Larson, Ramachandran S Vasan, Nicole Spartano, Marcel Ballin, Peter Nordström, Anna Nordström, Sigmund A Anderssen, Bjørge H Hansen, Jennifer A Cochrane, Terence Dwyer, Jing Wang, Luigi Ferrucci, Fangyu Liu, Jennifer Schrack, Jacek Urbanek, Pedro F Saint-Maurice, Naofumi Yamamoto, Yutaka Yoshitake, Robert L Newton, Shengping Yang, Eric J Shiroma, Janet E Fulton
Journal: The Lancet Public Health (2022)

Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality.
The Effect of Diabetes Mellitus and Revascularization Status on Cardiorespiratory Fitness in Multi-vessel Acute Coronary Syndrome Patients
Authors: Hye-Su Yun, Hee-Jung Lee, Cheol Hyun Lee, Yun-Kyeong Cho, Hyuck-Jun Yoon, Jin-Wook Chung, Hyungseop Kim, Chang-Wook Nam, Seung-Ho Hur, Jong-Chan Youn, In-Cheol Kim
Journal: Metabolism (2022)
Extracorporeal life support allows lung transplant in anti-MDA5+ rapidly progressive interstitial lung disease
Authors: Pierre Bay, Marc Pineton de Chambrun, Antoine Roux, Vincent Bunel, Alain Combes, Dominique Israël-Biet, Benjamin Zuber, Hilario Nunes, Yves Allenbach, Yurdagül Uzunhan
Journal: European Respiratory Journal (2022)

<b>Anti-MDA5 RP-ILD has a poor prognosis and a high mortality rate. This study found that emergency lung transplantation in anti-MDA5 RP-ILD patients requiring ECLS has a favourable disease outcome, irrespective of prior treatment regimen.</b>https://bit.ly/3gHKPt6
Assessment of BIV1-CovIran inactivated vaccine–elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern
Authors: Mohammadreza Salehi, Hamed Hosseini, Hamid Reza Jamshidi, Hasan Jalili, Payam Tabarsi, Minoo Mohraz, Hesam Karimi, Majid Lotfinia, Reza Aalizadeh, Mehrdad Mohammadi, Shahin Ramazi, Asghar Abdoli
Journal: Clinical Microbiology and Infection (2022)
Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota
Authors: Zheng-Wei Zhang, Chun-Sheng Gao, Heng Zhang, Jian Yang, Ya-Ping Wang, Li-Bin Pan, Hang Yu, Chi-Yu He, Hai-Bin Luo, Zhen-Xiong Zhao, Xin-Bo Zhou, Yu-Li Wang, Jie Fu, Pei Han, Yu-Hui Dong, Gang Wang, Song Li, Yan Wang, Jian-Dong Jiang, Wu Zhong
Journal: Acta Pharmaceutica Sinica B (2022)

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood–brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.
BIO89-100 Demonstrated Robust Reductions in Liver Fat, Improved Metabolic Parameters, Favorable Tolerability and Potential for Weekly (QW) or Every 2 Weeks (Q2W) Dosing in a Phase 1b/2a Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study in NASH
Authors: Juan Pablo Frias, Grisell Ortiz-Lasanta, Cynthia L. Hartsfield, Leo Tseng, R. William Charlton, Hank Mansbach, Maya Margalit, Rohit Loomba
Journal: Metabolism (2022)
T cells in the skin: Lymphoma and inflammatory skin disease
Authors: Ben Roediger, Christoph Schlapbach
Journal: Journal of Allergy and Clinical Immunology (2022)

T cells are established contributors to the pathogenesis of atopic dermatitis and psoriasis; yet, whether they are the key drivers or simply unwitting participants remains incompletely understood. Conversely, malignant T cells are the undisputed culprits of cutaneous T-cell lymphoma (CTCL), a group of diseases that share key clinical, histopathologic, and molecular features with inflammatory skin disease (ISD). Here, we compare the pathogenesis of ISD and CTCL and discuss the resulting insights. Recurrent, skin-limited disease implicates skin-resident memory T cells in both ISD and CTCL. In CTCL, malignant T cells recruit benign T cells into inflammatory skin lesions, a disease-amplifying function that has also been proposed for pathogenic T cells in ISD. Mechanistically, cytokines produced by malignant T cells in CTCL and by pathogenic T cells in ISD, respectively, are likely both necessary and sufficient to drive skin inflammation and pruritus, which in turn promotes skin barrier dysfunction and dysbiosis. Therapies for ISD target T-cell effector functions but do not address the chronicity of disease, whereas treatments for CTCL target malignant T cells but not primarily the symptoms of the disease. Integrating our understanding of ISD and CTCL can result in important insights into pathogenesis and therapy that may improve the lives of patients in both of these disease groups.
Unusual Metastases of Esophageal Squamous Cell Carcinoma
Authors: Yi-Hsun Chen, Chia-Yang Lin, Yi-Ting Chen, I-Chen Wu, Yao-Kuang Wang
Journal: Clinical Nuclear Medicine (2021)

Abstract Colonic or peritoneal metastasis from esophageal squamous cell carcinoma is extremely rare. We present the case of a 68-year-old man with esophageal squamous cell carcinoma who received concurrent chemoradiation therapy. The follow-up whole-body 18 F-FDG PET/CT was performed 6 months after initial chemotherapy and showed new lesions of increased FDG activity in the colon as well as peritoneum. The final pathological diagnosis proved these metastases were from esophageal squamous cell carcinoma.
De novo generation of the NPM-ALK fusion recapitulates the pleiotropic phenotypes of ALK+ ALCL pathogenesis and reveals the ROR2 receptor as target for tumor cells
Authors: Loélia Babin, Alice Darchen, Elie Robert, Zakia Aid, Rosalie Borry, Claire Soudais, Marion Piganeau, Anne De Cian, Carine Giovannangeli, Olivia Bawa, Charlotte Rigaud, Jean-Yves Scoazec, Lucile Couronné, Layla Veleanu, Agata Cieslak, Vahid Asnafi, David Sibon, Laurence Lamant, Fabienne Meggetto, Thomas Mercher, Erika Brunet
Journal: Molecular Cancer (2022)

Abstract Background Anaplastic large cell lymphoma positive for ALK (ALK+ ALCL) is a rare type of non-Hodgkin lymphoma. This lymphoma is caused by chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK). In this study, we aimed to identify mechanisms of transformation and therapeutic targets by generating a model of ALK+ ALCL lymphomagenesis ab initio with the specific NPM-ALK fusion. Methods We performed CRISPR/Cas9-mediated genome editing of the NPM-ALK chromosomal translocation in primary human activated T lymphocytes. Results Both CD4+ and CD8+ NPM-ALK-edited T lymphocytes showed rapid and reproducible competitive advantage in culture and led to in vivo disease development with nodal and extra-nodal features. Murine tumors displayed the phenotypic diversity observed in ALK+ ALCL patients, including CD4+ and CD8+ lymphomas. Assessment of transcriptome data from models and patients revealed global activation of the WNT signaling pathway, including both canonical and non-canonical pathways, during ALK+ ALCL lymphomagenesis. Specifically, we found that the WNT signaling cell surface receptor ROR2 represented a robust and genuine marker of all ALK+ ALCL patient tumor samples. Conclusions In this study, ab initio modeling of the ALK+ ALCL chromosomal translocation in mature T lymphocytes enabled the identification of new therapeutic targets. As ROR2 targeting approaches for other cancers are under development (including lung and ovarian tumors), our findings suggest that ALK+ ALCL cases with resistance to current therapies may also benefit from ROR2 targeting strategies.
Unlocking the secrets of long non-coding RNAs in asthma
Authors: Fien Gysens, Pieter Mestdagh, Eric de Bony de Lavergne, Tania Maes
Journal: Thorax (2022)

Asthma is a very heterozygous disease, divided in subtypes, such as eosinophilic and neutrophilic asthma. Phenotyping and endotyping of patients, especially patients with severe asthma who are refractory to standard treatment, are crucial in asthma management and are based on a combination of clinical and biological features. Nevertheless, the quest remains to find better biomarkers that distinguish asthma subtypes in a more clear and objective manner and to find new therapeutic targets to treat people with therapy-resistant asthma. In the past, research to identify asthma subtypes mainly focused on expression profiles of protein-coding genes. However, advances in RNA-sequencing technologies and the discovery of non-coding RNAs as important post-transcriptional regulators have provided an entire new field of research opportunities in asthma. This review focusses on long non-coding RNAs (lncRNAs) in asthma; these are non-coding RNAs with a length of more than 200 nucleotides. Many lncRNAs are differentially expressed in asthma, and several have been associated with asthma severity or inflammatory phenotype. Moreover, in vivo and in vitro functional studies have identified the mechanisms of action of specific lncRNAs. Although lncRNAs remain not widely studied in asthma, the current studies show the potential of lncRNAs as biomarkers and therapeutic targets as well as the need for further research.
Covid-19: Anti-inflammatory treatment baricitinib reduces deaths in patients admitted to hospital, finds trial
Authors: Elisabeth Mahase
Journal: BMJ (2022)

Covid-19: Anti-inflammatory treatment baricitinib reduces deaths in patients admitted to hospital, finds trial Elisabeth MahaseAnti-inflammatory treatment baricitinib, which is normally used to treat rheumatoid arthritis, reduces the risk of death in patients admitted to hospital with severe covid-19 by around one fifth, the Randomised Evaluation of Covid-19 Therapy (Recovery) trial has reported. 1
Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy
Authors: Jianjun Hu, Jiangyi He, Yunlong Wang, Yang Zhao, Kejing Fang, Yan Dong, Yanrong Chen, Yue Zhang, Chi Zhang, Hongwei Wang, Jun Tan, Junyi Wang, Ruiyang Zi, Chengxiang Liu, Houjie Liang, Yanli Guo, Juanjuan Ou
Journal: Journal for ImmunoTherapy of Cancer (2022)

The poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity.The antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy.USNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment.The administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.
CHEMOTHERAPEUTIC EQUILIBRIA
Authors: Allen E. Stearn, Esther Wagner Stearn
Journal: The Journal of Experimental Medicine (1930)

1. The general adequacy of the bacteriostatic mechanism for the action of dyes which postulates a mass law equilibrium between bacteriostat and organism, which latter is pictured chemically as an ampholyte, is discussed. 2. It is shown that, even in blood, where, with safe concentrations of dye, there seems to be a significant excess of protein over dye, the stoichiometric excess of dye required by the above mechanism is available. 3. Experiments are presented indicating that the time required for such a bacteriostat to act is very short, being probably conditioned largely by speed of mixing or of penetration. 4. Apparent disappearance of dye from blood stream need not mean that the blood has lost bacteriostatic value. 5. Data are presented indicating that the behavior of dyes in causing flocculation of organisms is affected by the same factors and in the same way as in inhibiting growth. 6. Direct evidence of ionic combination between dye ion and protein ion is presented by noting conductivity decrease when the two ions are mixed, and also noting the displacement of H-ion from unionized protein by dye cation, or of OH-ion by dye anion.