tbuckley/cabot-search huggingface dataset:
Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer
Authors: Divya Thomas, Satish Sagar, Xiang Liu, Hye-Rim Lee, James A. Grunkemeyer, Paul M. Grandgenett, Thomas Caffrey, Kelly A. O’Connell, Benjamin Swanson, Lara Marcos-Silva, Catharina Steentoft, Hans H. Wandall, Hans Carlo Maurer, Xianlu Laura Peng, Jen Jen Yeh, Fang Qiu, Fang Yu, Ragupathy Madiyalakan, Kenneth P. Olive, Ulla Mandel, Henrik Clausen, Michael A. Hollingsworth, Prakash Radhakrishnan
Journal: Molecular Therapy (2020)

Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3β oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.
Priority COVID-19 Vaccination for Patients with Cancer while Vaccine Supply Is Limited
Authors: Antoni Ribas, Rajarshi Sengupta, Trevan Locke, Sayyed Kaleem Zaidi, Katie M. Campbell, John M. Carethers, Elizabeth M. Jaffee, E. John Wherry, Jean-Charles Soria, Gypsyamber D'Souza
Journal: Cancer Discovery (2020)

Abstract Summary: Published series on COVID-19 support the notion that patients with cancer are a particularly vulnerable population. There is a confluence of risk factors between cancer and COVID-19, and cancer care and treatments increase exposure to the virus and may dampen natural immune responses. The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the very high-risk groups for priority COVID-19 vaccination.
Th2-like T Follicular Helper Cells Promote Functional Antibody Production during Plasmodium falciparum Infection
Authors: Jo-Anne Chan, Jessica R. Loughland, Fabian de Labastida Rivera, Arya SheelaNair, Dean W. Andrew, Nicholas L. Dooley, Bruce D. Wines, Fiona H. Amante, Lachlan Webb, P. Mark Hogarth, James S. McCarthy, James G. Beeson, Christian R. Engwerda, Michelle J. Boyle
Journal: Cell Reports Medicine (2020)

CD4+ T follicular helper cells (Tfh) are key drivers of antibody development. During Plasmodium falciparum malaria in children, the activation of Tfh is restricted to the Th1 subset and not associated with antibody levels. To identify Tfh subsets that are associated with antibody development in malaria, we assess Tfh and antibodies longitudinally in human volunteers with experimental P. falciparum infection. Tfh cells activate during infection, with distinct dynamics in different Tfh subsets. Th2-Tfh cells activate early, during peak infection, while Th1-Tfh cells activate 1 week after peak infection and treatment. Th2-Tfh cell activation is associated with the functional breadth and magnitude of parasite antibodies. In contrast, Th1-Tfh activation is not associated with antibody development but instead with plasma cells, which have previously been shown to play a detrimental role in the development of long-lived immunity. Thus, our study identifies the contrasting roles of Th2 and Th1-Tfh cells during experimental P. falciparum malaria.
Characteristics and Outcome of COAPT-Eligible Patients in the MITRA-FR Trial
Authors: Bernard Iung, David Messika-Zeitoun, Florent Boutitie, Jean-Noël Trochu, Xavier Armoiry, Delphine Maucort-Boulch, Jean-Francois Obadia, Alec Vahanian
Journal: Circulation (2020)
SP0095 EULAR/ERA-EDTA Recommendations for The Management of ANCA-Associated Vasculitis
Authors: C. Mukhtyar
Journal: Annals of the Rheumatic Diseases (2016)

We published the EULAR recommendations for the management of systemic vasculitis in 2009. We proposed and received a mandate from EULAR to revise the recommendations for the management of ANCA associated vasculitis. This project was done in partnership with the ERA-EDTA. A team of 22 experts representing rheumatology, renal medicine, chest medicine, clinical immunology, internal medicine, ENT medicine, ophthalmology, vasculitis nursing and patient support group was formed. There was representation from 11 European countries and the USA. EULAR standardised operating procedures were followed throughout. 10 items for update and 5 new items for consideration were identified via a Delphic process. Search strings were created to identify 1347 papers. Quality scoring of manuscripts was performed using the Critical Appraisals Skills Programme. 44 papers were identified to inform the recommendations. Level of evidence was ascertained as per EULAR SOP. Statements were formed and graded for strength by the task force and by the membership of the European vasculitis society for ascertaining further validity. The level of evidence for EGPA was poor and is reflected by the low grade of recommendations. Patients with AAV should have expert involvement in their care. A biopsy remains the gold standard for diagnosis and should be performed whenever clinically feasible. Cyclophosphamide or rituximab are the mainstay of remission induction but methotrexate and mycophenolate mofetil may be appropriate for a small number of cases. Major relapses should be treated as new – but rituximab maybe favoured over cyclophosphamide in this category. Consideration should be given to strengthening immunosuppression even for patients with minor relapses. Patients with severe renal disease or diffuse alveolar haemorrhage should be considered for plasma exchange. Remission can be maintained with either azathioprine or rituximab. In a small number of patients, methotrexate of mycophenolate mofetil may be appropriate. Remission maintenance should be continued for a minimum of 24 months after which tapering should be considered. Refractory disease should be managed at an expert centre. The role of follow-up monitoring, urological assessment, immunoglobulin monitoring, cardiovascular risk, educational needs &amp; comorbidity assessment has also been discussed. <h3>Disclosure of Interest</h3> None declared
Acoel Single-Cell Transcriptomics: Cell Type Analysis of a Deep Branching Bilaterian
Authors: Jules Duruz, Cyrielle Kaltenrieder, Peter Ladurner, Rémy Bruggmann, Pedro Martìnez, Simon G Sprecher
Journal: Molecular Biology and Evolution (2020)

Bilaterian animals display a wide variety of cell types, organized into defined anatomical structures and organ systems, which are mostly absent in prebilaterian animals. Xenacoelomorpha are an early-branching bilaterian phylum displaying an apparently relatively simple anatomical organization that have greatly diverged from other bilaterian clades. In this study, we use whole-body single-cell transcriptomics on the acoel Isodiametra pulchra to identify and characterize different cell types. Our analysis identifies the existence of ten major cell type categories in acoels all contributing to main biological functions of the organism: metabolism, locomotion and movements, behavior, defense, and development. Interestingly, although most cell clusters express core fate markers shared with other animal clades, we also describe a surprisingly large number of clade-specific marker genes, suggesting the emergence of clade-specific common molecular machineries functioning in distinct cell types. Together, these results provide novel insight into the evolution of bilaterian cell types and open the door to a better understanding of the origins of the bilaterian body plan and their constitutive cell types.
Fludarabine modulates expression of type VII collagen during haematopoietic stem cell transplantation for recessive dystrophic epidermolysis bullosa*
Authors: M. Vanden Oever, D. Muldoon, W. Mathews, J. Tolar
Journal: British Journal of Dermatology (2020)

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe, complicated inherited blistering skin disease with few treatment options currently available. Recently, haematopoietic stem cell transplantation (HCT) has been used as an alternative therapy that can improve skin integrity, but it is not known if the preparative HCT regimen also contributes to the therapeutic response.To determine whether chemotherapy drugs used in the HCT preparative regimen influence type VII collagen (C7) expression, which is inherently reduced or absent in RDEB skin, and to explore the pathomechanisms of such responses, if present.Drugs from the HCT preparative regimen (busulfan, cyclophosphamide, ciclosporin A, fludarabine and mycophenolate) with inhibitors (PD98059, U0126, LY294002, SR11302, SIS3 and N-acetyl-l-cysteine) were added to normal human dermal and human RDEB fibroblasts. C7 expression was measured using reversetranscription polymerase chain reaction and immunoblotting.We uncovered a previously unknown consequence of fludarabine whereby dermal fibroblasts exposed to fludarabine upregulate C7. This effect is mediated, in part, through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/protein kinase B and transforming growth factor-β pathways. Activation of these pathways leads to activation of downstream transcription factors, including activator protein 1 (AP-1) and SMAD. Subsequently, both AP-1 and SMAD bind the COL7A1 promoter and increase COL7A1 expression.Fludarabine influences the production of type VII collagen in RDEB fibroblasts.
Frequency, Timing, Risk Factors, and Outcomes of Desaturation in Infants With Acute Bronchiolitis and Initially Normal Oxygen Saturation
Authors: Fabiola Stollar, Alban Glangetas, Fanny Luterbacher, Alain Gervaix, Constance Barazzone-Argiroffo, Annick Galetto-Lacour
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Little is known about the natural course of oxygen desaturation in acute bronchiolitis. Information on risk factors associated with desaturation as well as the time to desaturation in infants with bronchiolitis could help physicians better treat these infants before deciding whether to hospitalize them. <h3>Objective</h3> To prospectively determine the frequency of desaturation in infants with bronchiolitis, along with the time to desaturation and risk factors associated with desaturation, and to compare infants who were hospitalized with those discharged home and evaluate risk factors for rehospitalization. <h3>Design, Setting, and Participants</h3> This cohort study was conducted during the 2017 to 2018 and 2018 to 2019 respiratory syncytial virus seasons in a tertiary care pediatric emergency department in Switzerland. Included individuals were 239 otherwise-healthy infants aged younger than 1 year, diagnosed with acute bronchiolitis and oxygen saturation of 90% or more on arrival. Data were analyzed from July 2019 to October 2020. <h3>Exposures</h3> After receiving triage care, study participants admitted to the emergency department were equipped with a pulse oximeter to continuously record oxygen saturation (Spo<sub>2</sub>levels), regardless of subsequent hospitalization or discharge home. <h3>Main Outcomes and Measures</h3> The primary outcome was desaturation (ie, Spo<sub>2</sub> &lt; 90%) during the first 36 hours. <h3>Results</h3> Of 239 infants enrolled, with a median (interquartile range [IQR]) age of 3.9 (1.5-6.5) months, 116 (48.5%) were boys and desaturation occurred in 165 infants (69.0%). Median (IQR) time to desaturation was 3.6 (1.8-9.4) hours. The rate of desaturation was similar between infants hospitalized and those discharged home (137 of 200 infants [68.5%] vs 28 of 39 infants [71.8%]; difference, −3.3%; 95% CI, −18.8% to 12.2%;<i>P</i> = .85). A more severe initial clinical presentation with moderate or severe retractions was the only independent risk factor associated with desaturation (odds ratio, 2.73; 95% CI, 1.49 to 5.02;<i>P</i> = .001). Of 39 infants discharged home, 22 infants (56.4%) experienced major desaturations. However, infants with desaturations, including those with major desaturations, had rates of rehospitalization similar to those of infants without desaturations (8 of 28 infants [28.5%] vs 3 of 11 infants [27.3%]; difference, 1.2%; 95% CI, −29.9% to 32.5;<i>P</i> &gt; .99). <h3>Conclusions and Relevance</h3> These findings suggest that rates of desaturation in infants with acute bronchiolitis were high and similar between infants who were hospitalized and those discharged home. A more severe initial clinical presentation was the only risk factor associated with desaturation. However, for infants discharged home, desaturation was not a risk factor associated with rehospitalization.
Phenolic-amine chemistry mediated synergistic modification with polyphenols and thrombin inhibitor for combating the thrombosis and inflammation of cardiovascular stents
Authors: Hua Qiu, Qiufen Tu, Peng Gao, Xiangyang Li, Manfred F. Maitz, Kaiqin Xiong, Nan Huang, Zhilu Yang
Journal: Biomaterials (2020)
Lifestyle Factors Can Lead to Multiple Cancers Over a Lifetime—Here We Go Again
Authors: Domingo G. Perez, Charles Loprinzi, Kathryn J. Ruddy
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Health inequalities must be tackled head on, warns Whitty in annual review of nation’s health
Authors: Adrian O’Dowd
Journal: BMJ (2020)

The gap in life expectancy between people living in the most affluent and the most deprived areas is rising again, despite years of efforts to reverse the pattern, according to the latest annual report from England’s chief medical officer (CMO).1

While Chris Whitty’s overview of the nation’s health contains a short chapter on covid-19, the focus is broader, as he plans to publish a separate report on lessons learnt from the pandemic.

Data in the report shows that life expectancy in 2019 was lowest for people who live in north Cumbria, County Durham, and areas of Lancashire and Yorkshire, where the average age of death was between 74 and 79 …
Isoniazid preventive therapy plus antiretroviral therapy for the prevention of tuberculosis: a systematic review and meta-analysis of individual participant data
Authors: Jennifer M Ross, Anani Badje, Molebogeng X Rangaka, A Sarah Walker, Adrienne E Shapiro, Katherine K Thomas, Xavier Anglaret, Serge Eholie, Delphine Gabillard, Andrew Boulle, Gary Maartens, Robert J Wilkinson, Nathan Ford, Jonathan E Golub, Brian G Williams, Ruanne V Barnabas
Journal: The Lancet HIV (2020)
Pre-Clinical Efficacy of the Anti-CD38 Monoclonal Antibody (mAb) Isatuximab in Acute Myeloid Leukemia (AML)
Authors: Tomas Jelinek, Aintzane Zabaleta, Cristina Perez, Daniel Ajona, Diego Alignani, Idoia Rodriguez, Sonia Garate, Sarai Sarvide, Marta Lasa, Patricia Maiso, Felipe Prosper, Roman Hajek, Jesus F. San Miguel, Bruno Paiva
Journal: Blood (2017)
Chromosomal aberrations in breast cancer tumors using cDNA microarray CGH.
Authors: Lucine Bosnoyan-Collins, Sarah Colby, Nalan Gokgoz, Sean Minaker, Shelley B. Bull, Irene L. Andrulis
Journal: Cancer Research (2005)

105  In this study we have taken advantage of a large cohort of axillary node negative (ANN) breast cancer patients to look for the chromosomal aberrations using array based comparative genomic hybridization (a-CGH). To date we have completed a-CGH on more than 50 ANN tumors from a cohort of cases from the Toronto area. In order to confirm that our experimental microarray platform could be used to assess CGH we used tumor cell lines including BT474, UACC812, T47D, SKBR3 and found several different amplification and deletions to be consistent with published results from several laboratories using different microarray platforms. The same optimum conditions used in those experiments were applied to tumor genomic DNA where 1ug of Alu1 and Rsa1 digested genomic DNA was labeled with Cy3 and control placenta DNA was labeled with Cy5 using random Bioprime labeling kit. After overnight labeling the labeled products were purified, pooled together and hybridized on 19K cDNA microarray chips. The fluorescence intensity of the fluors was quantitated using an Axon scanner and the quantity was converted into an actual signal to noise ratio using GenePix Pro. In the first stage of the analysis, we delineated regions of chromosomal loss and gain for each patient using the Olshen Bioconductor package DNAcopy. Each region was assigned an alteration type (i.e., normal, loss /deletion, gain/amplification) based on the log2 copy number ratios of the contained clones. In the second stage of the analysis, the alterations were tabulated across patients yielding a ranking according to alteration frequency of the top regions for further examination. Overall, 58 regions of gain and 31 regions of loss were identified. Many of the regions of alterations detected are known genes or candidate oncogenes such as ERBB2 at 17q12, CND1 at 11q13, FGFR1 at8p11.2-11.1 and MYC at 8q24.12-q24.13. Hence from these observations we conclude that array based CGH may be useful for the identification of new genetic targets in breast cancer tumorigenesis.
Structural and Functional Characterization of a Na <sub>v</sub> 1.5-Mitochondrial Couplon
Authors: Marta Pérez-Hernández, Alejandra Leo-Macias, Sarah Keegan, Mariam Jouni, Joon-Chul Kim, Esperanza Agullo-Pascual, Sarah Vermij, Mingliang Zhang, Feng-Xia Liang, Paul Burridge, David Fenyo, Eli Rothenberg, Mario Delmar
Journal: Circulation Research (2020)

The cardiac sodium channel Na
Cancer-Induced Muscle Wasting Requires p38β MAPK Activation of p300
Authors: Thomas K. Sin, Guohua Zhang, Zicheng Zhang, James Z. Zhu, Yan Zuo, Jeffrey A. Frost, Min Li, Yi-Ping Li
Journal: Cancer Research (2020)

Abstract Cancer-associated cachexia, characterized by muscle wasting, is a lethal metabolic syndrome without defined etiology or established treatment. We previously found that p300 mediates cancer-induced muscle wasting by activating C/EBPβ, which then upregulates key catabolic genes. However, the signaling mechanism that activates p300 in response to cancer is unknown. Here, we show that upon cancer-induced activation of Toll-like receptor 4 in skeletal muscle, p38β MAPK phosphorylates Ser-12 on p300 to stimulate C/EBPβ acetylation, which is necessary and sufficient to cause muscle wasting. Thus, p38β MAPK is a central mediator and therapeutic target of cancer-induced muscle wasting. In addition, nilotinib, an FDA-approved kinase inhibitor that preferentially binds p38β MAPK, inhibited p300 activation 20-fold more potently than the p38α/β MAPK inhibitor, SB202190, and abrogated cancer cell–induced muscle protein loss in C2C12 myotubes without suppressing p38α MAPK–dependent myogenesis. Systemic administration of nilotinib at a low dose (0.5 mg/kg/day, i.p.) in tumor-bearing mice not only alleviated muscle wasting, but also prolonged survival. Therefore, nilotinib appears to be a promising treatment for human cancer cachexia due to its selective inhibition of p38β MAPK. Significance: These findings demonstrate that prevention of p38β MAPK–mediated activation of p300 by the FDA-approved kinase inhibitor, nilotinib, ameliorates cancer cachexia, representing a potential therapeutic strategy against this syndrome.
Co-mutation pattern, clonal hierarchy, and clone size concur to determine disease phenotype of SRSF2P95-mutated neoplasms
Authors: Gabriele Todisco, Maria Creignou, Anna Gallì, Paola Guglielmelli, Elisa Rumi, Marco Roncador, Ettore Rizzo, Yasuhito Nannya, Daniela Pietra, Chiara Elena, Elisa Bono, Elisabetta Molteni, Vittorio Rosti, Silvia Catricalá, Martina Sarchi, Marios Dimitriou, Johanna Ungerstedt, Alessandro Maria Vannucchi, Eva Hellström-Lindberg, Seishi Ogawa, Mario Cazzola, Luca Malcovati
Journal: Leukemia (2020)
Population Dynamics and Structural Effects at Short and Long Range Support the Hypothesis of the Selective Advantage of the G614 SARS-CoV-2 Spike Variant
Authors: Emiliano Trucchi, Paolo Gratton, Fabrizio Mafessoni, Stefano Motta, Francesco Cicconardi, Filippo Mancia, Giorgio Bertorelle, Ilda D’Annessa, Daniele Di Marino
Journal: Molecular Biology and Evolution (2020)

Abstract SARS-CoV-2 epidemics quickly propagated worldwide, sorting virus genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries or an actual selective advantage could explain the global high frequency reached by some genomic variants. Using statistical analyses, demographic reconstructions, and molecular dynamics simulations, we show that the globally invasive G614 spike variant 1) underwent a significant demographic expansion in most countries explained neither by stochastic effects nor by overrepresentation in clinical samples, 2) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and 3) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our results support the hypothesis of a selective advantage at the basis of the spread of the G614 variant, which we suggest may be due to structural modification of the spike protein at the S1/S2 proteolytic site, and provide structural information to guide the design of variant-specific drugs.