tbuckley/cabot-search huggingface dataset:
INTERBIO-21st Phenotypes—Additional Considerations—Reply
Authors: Jose Villar, María C. Restrepo-Méndez, Stephen Kennedy
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma
Authors: Nicolas Belforte, Jessica Agostinone, Luis Alarcon-Martinez, Deborah Villafranca-Baughman, Florence Dotigny, Jorge L. Cueva Vargas, Adriana Di Polo
Journal: Molecular Neurodegeneration (2021)

Abstract Background The maintenance of complex dendritic arbors and synaptic transmission are processes that require a substantial amount of energy. Bioenergetic decline is a prominent feature of chronic neurodegenerative diseases, yet the signaling mechanisms that link energy stress with neuronal dysfunction are poorly understood. Recent work has implicated energy deficits in glaucoma, and retinal ganglion cell (RGC) dendritic pathology and synapse disassembly are key features of ocular hypertension damage. Results We show that adenosine monophosphate-activated protein kinase (AMPK), a conserved energy biosensor, is strongly activated in RGC from mice with ocular hypertension and patients with primary open angle glaucoma. Our data demonstrate that AMPK triggers RGC dendrite retraction and synapse elimination. We show that the harmful effect of AMPK is exerted through inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Attenuation of AMPK activity restores mTORC1 function and rescues dendrites and synaptic contacts. Strikingly, AMPK depletion promotes recovery of light-evoked retinal responses, improves axonal transport, and extends RGC survival. Conclusions This study identifies AMPK as a critical nexus between bioenergetic decline and RGC dysfunction during pressure-induced stress, and highlights the importance of targeting energy homeostasis in glaucoma and other neurodegenerative diseases.
Improving prognostic assignment in older adults with multiple myeloma using acquired genetic features, clonal hemopoiesis and telomere length
Authors: Eileen M. Boyle, Louis Williams, Patrick Blaney, Cody Ashby, Michael Bauer, Brian A. Walker, Hussein Ghamlouch, Jinyoung Choi, Emeline Perrial, Yubao Wang, Jessica Caro, James H. Stoeckle, Arnaldo Arbini, David Kaminetzky, Marc Braunstein, Benedetto Bruno, Beatrice Razzo, Benjamin Diamond, Kylee Maclachlan, Francesco Maura, Ola Landgren, Rachel Litke, Christopher D. Fegan, Johnathan Keats, Daniel Auclair, Faith E. Davies, Gareth J. Morgan
Journal: Leukemia (2021)
Reply to: ‘Real-world prevalence across 159 872 patients with cancer supports the clinical utility of TMB-H to define metastatic solid tumors for treatment with pembrolizumab.’ by D. Fabrizio et al.
Authors: D.J. McGrail, P.G. Pilié, N.U. Rashid, L. Voorwerk, M. Slagter, M. Kok, E. Jonasch, M. Khasraw, A.B. Heimberger, N.T. Ueno, R. Ferrarotto, J.T. Chang, S.-Y. Lin
Journal: Annals of Oncology (2021)
Respiratory disease, and treatment / thematic poster session lung function in COVID-19 intensive care unit (icu) survivors assessed with respiratory oscillometry (osc) and conventional pulmonary function tests (pft)
Authors: A. Jiang, J. Wu, C. Nohra, N. Belousova, Z. Hantos, C. M. Ryan, M. S. Herridge, C. Chow
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Early follow-up of COVID-19 patients identified a primary restrictive defect with reduced diffusing capacity that resembled defects previously observed in patients with acute respiratory distress syndrome. The long-term pulmonary consequences of COVID-19, particularly in severe cases requiring ICU admission, are not known. The objective of the current study is to prospectively follow the pulmonary function of COVID-19 survivors who required ICU admission and compare outcomes amongst patients who needed high-flow oxygen (HFO), mechanical ventilation (MV) and extracorporeal life support (ECLS) for 1-year post-recovery. Osc is particularly sensitive to peripheral lung dysfunction and has been shown to identify lung disease earlier than conventional PFT. Thus, we will also compare Osc with conventional PFT in detecting respiratory dysfunction amongst the three groups. Methods: COVID-19 patients who survived ICU admission and were followed at the TGH post-recovery outpatient clinic are prospectively enrolled for quarterly Osc and conventional PFT. Demographic and clinical information are extracted from patients' electronic medical records. Results: From August 20-November 26, 2020, we enrolled 15 patients (12 M/3 F;mean age 53±15 years) who were 5.6±1.1 months post-infection. Conventional PFT showed restrictive defects only in the MV [%predicted total lung capacity (%TLC) =77±16, %predicted forced vital capacity (%FVC) =79±16, n=6] and ECLS (%TLC=71±14, %FVC=74±12, n=5) groups. Diffusing capacity and 6-minute walk distance were normal in all patient groups. In contrast, Osc was abnormal in all groups, particularly in the indices of peripheral airway obstruction and ventilatory inhomogeneity: R5-19 (difference in respiratory resistance between 5 and 19 Hz) and AX (area of reactance). The respective median (IQR) values for the HFO, MV and ECLS groups are as follows: R5-19 =1.47 (0.92-1.49), 1.02 (0.62-1.31), 1.29 (0.61-1.48) cmH2O.s/L (normal median range=0.11-0.66 cmH2O.s/L) and AX=12.65 (7.67-15.62), 10.83 (9.15-15.82), 14.32 (12.22-22.63) cmH2O/L (normal median range=2.11-5.79 cmH2O/L). Conclusion: Early findings in a cross-section of severe COVID-19 survivors revealed restrictive defects in the MV and ECLS groups when assessed by conventional PFT. However, abnormalities in respiratory mechanics were detectable by Osc in all patients suggesting that Osc may provide an early biomarker of subsequent lung function impairment. .
癌研究における次の10年間のロードマップ【JST・京大機械翻訳】
Authors: Bernards Rene, Jaffee Elizabeth, A Joyce Johanna, W Lowe Scott, R Mardis Elaine, J Morrison Sean, Polyak Kornelia, L Sears Cynthia, H Vousden Karen, Zhang Zemin
Journal: Nature Cancer (2020)
THE-1195 G > A CYCLOOXYGENASE-2 PROMOTER POLYMORPHISM IS ASSOCIATED WITH HEPATIC INFLAMMATION AND FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: Imawari M, Kumada H, Kobayashi M, Hiroishi K, Nozawa H, Uchikoshi M, Ito T, Miyashita M
Journal: Hepatology (2011)
Author Correction: APOE4 accelerates advanced-stage vascular and neurodegenerative disorder in old Alzheimer’s mice via cyclophilin A independently of amyloid-β
Authors: Axel Montagne, Angeliki M. Nikolakopoulou, Mikko T. Huuskonen, Abhay P. Sagare, Erica J. Lawson, Divna Lazic, Sanket V. Rege, Alexandra Grond, Edward Zuniga, Samuel R. Barnes, Jacob Prince, Meghana Sagare, Ching-Ju Hsu, Mary J. LaDu, Russell E. Jacobs, Berislav V. Zlokovic
Journal: Nature Aging (2021)
Response to: ‘Correspondence on ‘Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial’’ by Cai and Peng
Authors: Anna Molto, Désirée van der Heijde, Filip E Van den Bosch, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2021)

We would like to thank Cai and Peng1 for the interest they have expressed in our recently published article ‘Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial’2 and the ARD editorial team to give us the opportunity to address their comments.

First, Cai and Peng pinpoint another reason behind the lack of statistical significance of our primary outcome, that is, the shortage of our sample size. As suggested by Cai and Peng we have performed a post-hoc power calculation based on our estimated results (and sample), with p1=0.47 and p2=0.36 (p1 and p2 being the proportion of responders in the active arm and control arms, respectively) and an α risk of 5%, the post-hoc-calculated power is 29.9%. However, we have also performed a post-hoc power calculation based on the sample size that we aimed for (ie, 116 patients per arm) and the results observed in the trial: with an α risk of 5% and the p1 and p2 mentioned earlier, the power was still 41%, that is, very …
Review of Hip and Knee Osteoarthritis—Reply
Authors: Jeffrey N. Katz, Kaetlyn Arant, Richard F. Loeser
Journal: JAMA (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 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
Abstract 14906: Computational Fluid Dynamics (BypassCFD) Trumps Anatomic Predictors of Saphenous Vein Graft Failure in CABG Patients
Authors: M. Owais Khan, Justin S Tran, Han Zhu, Rene S Packard, Ronald P Karlsberg, Andrew Kahn, Alison L Marsden
Journal: Circulation (2018)

Introduction: Saphenous vein grafts (SVG) are commonly used in CABG surgeries but have much higher rates of failure than arterial grafts. Abnormal hemodynamics and wall biomechanics may play a key ...
RASAL2 Confers Collateral MEK/EGFR Dependency in Chemoresistant Triple-Negative Breast Cancer
Authors: Siang-Boon Koh, Kenneth Ross, Steven J. Isakoff, Nsan Melkonjan, Lei He, Karina J. Matissek, Andrew Schultz, Erica L. Mayer, Tiffany A. Traina, Lisa A. Carey, Hope S. Rugo, Minetta C. Liu, Vered Stearns, Adam Langenbucher, Srinivas Vinod Saladi, Sridhar Ramaswamy, Michael S. Lawrence, Leif W. Ellisen
Journal: Clinical Cancer Research (2021)

Abstract Purpose: While chemotherapy remains the standard treatment for triple-negative breast cancer (TNBC), identifying and managing chemoresistant tumors has proven elusive. We sought to discover hallmarks and therapeutically actionable features of refractory TNBC through molecular analysis of primary chemoresistant TNBC specimens. Experimental Design: We performed transcriptional profiling of tumors from a phase II clinical trial of platinum chemotherapy for advanced TNBC (TBCRC-009), revealing a gene expression signature that identified de novo chemorefractory tumors. We then employed pharmacogenomic data mining, proteomic and other molecular studies to define the therapeutic vulnerabilities of these tumors. Results: We reveal the RAS-GTPase-activating protein (RAS-GAP) RASAL2 as an upregulated factor that mediates chemotherapy resistance but also an exquisite collateral sensitivity to combination MAP kinase kinase (MEK1/2) and EGFR inhibitors in TNBC. Mechanistically, RASAL2 GAP activity is required to confer kinase inhibitor sensitivity, as RASAL2-high TNBCs sustain basal RAS activity through suppression of negative feedback regulators SPRY1/2, together with EGFR upregulation. Consequently, RASAL2 expression results in failed feedback compensation upon co-inhibition of MEK1/2 and EGFR that induces synergistic apoptosis in vitro and in vivo. In patients with TNBC, high RASAL2 levels predict clinical chemotherapy response and long-term outcomes, and are associated via direct transcriptional regulation with activated oncogenic Yes-Associated Protein (YAP). Accordingly, chemorefractory patient-derived TNBC models exhibit YAP activation, high RASAL2 expression, and tumor regression in response to MEK/EGFR inhibitor combinations despite well-tolerated intermittent dosing. Conclusions: These findings identify RASAL2 as a mediator of TNBC chemoresistance that rewires MAPK feedback and cross-talk to confer profound collateral sensitivity to combination MEK1/2 and EGFR inhibitors.
Expression of the MAGE-1 and NY-ESO-1 cancer testis antigens in childhood astrocytomas
Authors: Bela Bodey, Stuart Siegel
Journal: Cancer Research (2008)

5308  The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms and is silent in normal tissues, except for the testis. These antigens might therefore represent potential targets for specific antigen-directed immunotherapy. Expression of two members of this family, MAGE-1 and NY-ESO-1, has been described in various cancers, including melanomas, serous ovarian neoplasms, certain carcinomas and sarcomas, and lung cancer, to name a few. The objective of this study was to evaluate the extent and prognostic significance of CT antigen expression in childhood astrocytomas. During our immunohistochemical study, a four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results of the study demonstrate immunocytochemical presence and cellular localization of the MAGE-1 CT-antigen only in anaplastic, high-grade ASTRs (100%), including glioblastomas. NY-ESO-1 expression levels were more diversified across the grades of ASTRS, but demonstrated significantly higher expression in high grade anaplastic ASTRs and glioblastomas when compared to low grade pilocytic ASTRs. Our results demonstrate that CT antigen expression in astrocytomas correlates directly with the degree of the malignancy because both MAGE-1 and NY-ESO-1 overexpression increased as the grade of the astrocytic tumor increased. These data suggest that CT antigen expression could be used for prognostic purposes and that immunotherapy of primary brain tumors could possibly target CT antigens, especially those expressed at higher frequency such as MAGE-1 and NY-ESO-1. Future observations will guide the use of CT antigens in brain tumor immunotherapy.
Admission serum ferritin levels and effect of methylprednisolone in nonintubated patients with severe COVID-19 pneumonia
Authors: A. Papamanoli, A. Kalogeropoulos, J. Hotelling, J. Yoo, P. Grewal, W. Predun, R. Jacob, S. Rawal, L. Marcos, H. Skopicki
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Systemic corticosteroids control the inflammatory overresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID- 19). Ferritin, an acute phase reactant which can also protect the host cell from oxidative stress and has in previous studies increased the cell tolerability to infection and sepsis, could be a marker of response to corticosteroids. We sought to examine whether response to methylprednisolone differed according to admission ferritin levels in severe COVID-19. Methods: Retrospective cohort study of consecutive adults with severe COVID-19 pneumonia on high-flow oxygen (FiO2 ≥50%) admitted to an academic center from March 1 to April 15, 2020, i.e., before incorporation of corticosteroids in the guidelines for severe COVID-19. We used inverse probability of treatment weights to balance patient characteristics according to methylprednisolone use and Cox proportional hazards models to examine for significant interaction of admission serum ferritin levels with methylprednisolone for outcomes. The outcomes of interest were mortality and the composite of death or mechanical ventilation. Results: Ferritin was available in 380 of 447 (85.0%) patients (age, 60±17 years;34.2% female;13.4% Black;34.5% Hispanic;body mass index, 30.4±6.4 kg/m2;O2 saturation, 89±7%;respiratory rate, 24±8 breaths/min). Of these, 142/380 (37.4%) received methylprednisolone (median dose, 160mg/day). Ferritin did not differ between patients who received methylprednisolone vs. those who did not (median [25th-75th percentile], 992 μg/L [509, 1610] vs. 893 μg/L [474, 1467];P=0.32). Patients with elevated (>1000 μg/L) ferritin had higher procalcitonin, creatinine, and transaminase, but lower Creactive protein on admission. At 28 days, 80 patients (21.1%) had died and 102 (26.8%) were intubated. Ferritin was not associated with mortality or the composite endpoint. However, in weighted analyses, methylprednisolone use was associated with significantly lower mortality in patients with ferritin >1000 μg/L (HR 0.29;95%CI 0.12-0.67;P=0.004) and significantly higher mortality in patients with ferritin ≤1000 μg/L (HR 2.88;95%CI 1.59-5.20;P 1000 μg/L (HR 0.47;95%CI 0.30-0.74;P=0.001) but not in patients with ferritin ≤1000 μg/L (HR 1.09;95%CI 0.72-1.63;P=0.69);P=0.006 for interaction (Figure 1B). Conclusions: In nonintubated patients with severe COVID-19, methylprednisolone use was associated with reduced mortality and intubation only in patients with elevated admission ferritin levels. In contrast, there was a strong signal for higher mortality with methylprednisolone in patients with low baseline ferritin. These findings need prospective validation.
グルタミン代謝は毛包における幹細胞運命可逆性と長期維持を制御する【JST・京大機械翻訳】
Authors: S Kim Christine, Ding Xiaolei, Allmeroth Kira, C Biggs Leah, I Kolenc Olivia, L’Hoest Nina, Chacon-Martinez Carlos Andres, Edlich-Muth Christian, Giavalisco Patrick, P Quinn Kyle, S Denzel Martin, A Eming Sabine, A Wickstrom Sara
Journal: Cell Metabolism (2020)
Covid-19: Government must tackle stark regional health inequalities exposed by pandemic, says Marmot
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Greater Manchester had a 25% higher covid-19 death rate during the pandemic than England as a whole, a sign of how the pandemic has worsened existing inequalities, a report from Michael Marmot has found.1

As a result of the pandemic, life expectancy throughout England has fallen, but it has declined most steeply in the north west—falling by 1.6 years in men and 1.2 years in women in 2020, compared with 1.3 years (men) and 0.9 years (women) in the country overall.

The striking findings were revealed as part of a review carried out by Marmot, who is known for his decades of work on health inequalities, including the 2010 “Marmot review.”2

Build Back Fairer in Greater Manchester ,1 a new report commissioned by the Greater Manchester Health and Social Care Partnership and published on 30 June, links …
Abstract 240: Differential Impact of RBFox Family Proteins in Adult Murine Heart
Authors: Chen Gao, Shuxun Ren, Yibin Wang
Journal: Circulation Research (2016)

Background: The complexity of cardiac transcriptome and proteome is significantly contributed by alternative splicing of mRNA. Alternative splicing is regulated by the cis-regulatory elements located in pre-mRNA together with the trans-activating factors guiding the assembling and function of the spliceosome. In our earlier study, we have observed global changes of alternative splicing events during pressure-overload induced heart failure, and identified RBFox1 as a key regulator for cardiac RNA splicing regulation during postnatal development and pathological remodeling. Both RBFox1 and RBFox2 are highly enriched in cardiomyocytes, and their expression are both significantly repressed in response to pathological stress. Loss-of-function studies for RBFox1 and RBFox2 are achieved using cardiac specific but constitutively active Cre. Therefore, the isoform specific contribution of RBFox1 vs. RBFox2 in maintaining cardiac physiology and homeostasis in adult heart is unknown. Methods and Results: We generated mouse models of cardiac specific and inducible knockout of RBFox1 and RBFox2 individually in adult hearts by breeding the individual floxed alleles with the αMHC-Mer-Cre-Mer mice. At baseline, inactivating RBFox1 in adult heart caused a slight but significant decrease of cardiac function without activating hypertrophy gene expression. However, following myocardial infarction, the RBFox1 deficient hearts showed enhanced global fibrosis in non-infarcted areas comparing to the control animals. In contrast, inactivating RBFox2 in adult mouse heart caused overt heart failure associated with chamber dilation without external stress as early as 2 weeks post tamoxifen administration. Conclusion: We have identified differential impact of RBFox1 and RBFox2 deficiency in adult mouse heart. Our in vivo study illustrate the functional importance of the RBFox family RNA splicing regulators in normal physiology of adult heart, and support the pathogenic contribution of loss of RBFox expression to heart failure. Further analysis focusing on the underlying molecular mechanisms for their differential impact would yield new insights on transcriptome regulation and complexity in cardiac physiology and diseases.
Announcing the Lancet Psychiatry Commission on Psychoses in Global Context
Authors: Craig Morgan, Paola Dazzan, Oye Gureje, Charlotte Hanlon, Nev Jones, Georgina Miguel Esponda, Ashok Malla, Soumitra Pathare, Mao-Sheng Ran, Tessa Roberts, Rangaswamy Thara, Alberto Vasquez
Journal: The Lancet Psychiatry (2021)
Development of a Novel Mouse Model of Spontaneous High-Risk HPVE6/E7–Expressing Carcinoma in the Cervicovaginal Tract
Authors: Talia R. Henkle, Brandon Lam, Yu Jui Kung, John Lin, Ssu-Hsueh Tseng, Louise Ferrall, Deyin Xing, Chien-Fu Hung, T.-C. Wu
Journal: Cancer Research (2021)

Abstract Current preclinical models for cervical cancer lack important clinical and pathologic features. To improve upon these models, we aimed to develop a novel, spontaneous HPV16-expressing carcinoma model that captures major aspects of HPV-associated cancer in the female genital tract. This novel preclinical model features (i) expression of HPV oncogenes E6 and E7 in the tumors in female reproductive tract of mice, (ii) spontaneous progression through high-grade squamous intraepithelial lesion (HSIL) to carcinoma, and (iii) flexibility to model cancers from different high-risk HPV genotypes. This was accomplished by injecting plasmids expressing HPV16 E6/E7-luciferase, AKT, c-myc, and Sleeping Beauty transposase into the cervicovaginal tract of C57BL/6 mice followed by electroporation. Cell lines derived from these tumors expressed HPV16 E6/E7 oncogenes, formed tumors in immunocompetent mice, and displayed carcinoma morphology. In all, this novel HPV-associated cervicogenital carcinoma model and HPV16E6/E7–expressing tumor cell line improves upon current HPV16-E6/E7–expressing tumor models. These tumor models may serve as important preclinical models for the development of therapeutic HPV vaccines or novel therapeutic interventions against HPV E6/E7–expressing tumors. Significance: This study describes the development of a clinically relevant mouse model of cervicovaginal carcinoma that progresses from high-grade lesions and recapitulates key features of human HPV+ cervical cancer.