tbuckley/cabot-search huggingface dataset:
Quantitative proteomics of α-and β-tubulin isotype expression in human cancer cells
Authors: Pascal Verdier-Pinard, Berta Burd, Susan B. Horwitz, George A. Orr
Journal: Cancer Research (2004)

593  Tubulin, the constitutive protein of microtubules, is an α/β heterodimer. In humans, there are six α-tubulin isotypes and seven β-tubulin isotypes, each the product of a unique gene. Heterogenous distribution of the isotypes has been observed among different tissues. The functional significance and the factors regulating this differential expression of tubulin isotypes are poorly understood. In cancer cells, alterations in tubulin isotype composition and tubulin mutations have been associated with resistance to drugs that interact with microtubules. Mass spectrometry-based methods have been developed in our laboratory to analyze tubulin isotype expression, mutations and posttranslational modifications in human cell lines and tissues. Since mass spectrometry is an inherently non-quantitative technique, we have used stable isotope-containing amino acids in cell culture (SILAC) to differentially label proteins in Taxol-sensitive- and resistant cell lines . In the SILAC method, two cell lines are cultured for several generations in media containing either deuterated leucine (d3-Leu) or normal leucine (d0-Leu). After incorporation, equal amounts of total cytosolic proteins from each cell line were mixed and tubulin was isolated by Taxol-induced polymerization. For relative quantitation of total α- and β-tubulin levels, the region containing tubulin was excised from a SDS-PAGE gel and subjected to trypsin digestion followed by MALDI-TOF mass spectrometry. Depending on the number of leucine residues contained in a tryptic peptide, this peptide was represented by two m/z peaks separated by a multiple of 3 Da in the mass spectra. The signal intensity of each peak in these doublets was used to calculate the relative abundance of a given isotype within the two cell lines. We compared the tubulin content of MDA-MB-231 cell line and MDA-MB-231.K20T, a Taxol-resistant cell line bearing a Glu198Gly mutation in βI-tubulin. Our data indicated that both α- and β-tubulin expression increased about 1.5-fold in MDA-MB-231.K20T. For relative quantitation of individual tubulin isotype levels, tubulin isotypes were separated by IEF and each gel band containing a particular isotype was analyzed by tryptic mass mapping. In MDA-MB-231.K20T, βIII-tubulin was increased by 2-fold, βIVb decreased by 0.7-fold, Kα1 increased by 2-fold and α6 increased by 1.3-fold. In the case of βI, a small amount of wild type protein was detected in MDA-MB-231.K20T (2.5-fold less than in MDA-MB-231), whereas most of this isotype was represented by the more basic mutated protein. We are utilizing the SILAC approach to analyze tubulin isotype expression in other cell lines, and also the differential expression of proteins associated with the microtubule cytoskeleton. This quantitative proteomic study will highlight those changes in cellular microtubule composition that may be related to Taxol resistance.
Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Lymphoblastic Leukemia and Karnofsky Performance Status Score Equal or Lower Than 80%. a Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Francesco Saraceni, Myriam Labopin, Riitta Niittyvuopio, Gerard Socie, Nicolaus Kröger, Edouard Forcade, Paul V Browne, Péter Reményi, Jan J Cornelissen, Stephen Robinson, Ibrahim Yakoub-Agha, Thierry Lamy, Eolia Brissot, Bipin N. Savani, Arnon Nagler, Mohamad Mohty
Journal: Blood (2019)
335MO Intervention combining nurse navigators (NNs) and a mobile application vs standard of care (SOC) in neuro-oncology patients (pts) treated with oral anticancer agents (OAA): A subgroup analysis of CAPRI, a single-center, randomized phase III trial
Authors: A. Duflot-Boukobza, D. Mathivon, J. Legendre, M. Khettab, S. Oinino, M. Ferrua, A. Fourcade, N. Lezghed, F. Dhermain, F. Lemare, M. Guillet, V. Puglisi, M. Abbas, M. Pons, M. Di Palma, E. Minvielle, O. Mir, S.N. Dumont
Journal: Annals of Oncology (2020)
Amiodarone or Dronedarone for Atrial Fibrillation: Too Early to Know the Winner?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Paul S. Chan, Brahmajee K. Nallamothu, Hakan Oral
Journal: Journal of the American College of Cardiology (2009)
Metatranscriptomic analyses of the oral microbiome
Authors: Ana E. Duran‐Pinedo
Journal: Periodontology 2000 (2020)

Abstract Although the composition of the oral human microbiome is now well studied, regulation of genes within oral microbial communities remains mostly uncharacterized. Current concepts of periodontal disease and caries highlight the importance of oral biofilms and their role as etiological agents of those diseases. Currently, there is increased interest in exploring and characterizing changes in the composition and gene‐expression profiles of oral microbial communities. These efforts aim to identify changes in functional activities that could explain the transition from health to disease and the reason for the chronicity of those infections. It is now clear that the functions of distinct species within the subgingival microbiota are intimately intertwined with the rest of the microbial community. This point highlights the relevance of examining the expression profile of specific species within the subgingival microbiota in the case of periodontal disease or caries lesions, in the context of the other members of the biofilm in vivo. Metatranscriptomic analysis of the oral community is the starting point for identifying environmental signals that modulate the shift in metabolism of the community from commensal to dysbiotic. These studies give a snapshot of the expression patterns of microbial communities and also allow us to determine triggers to diseases. For example, in the case of caries, studies have unveiled a potential new pathway of sugar metabolism, namely the use of sorbitol as an additional source of carbon by Streptococcus mutans ; and in the case of periodontal disease, high levels of extracellular potassium could be a signal of disease. Longitudinal studies are needed to identify the real markers of the initial stages of caries and periodontal disease. More information on the gene‐expression profiles of the host, along with the patterns from the microbiome, will lead to a clearer understanding of the modulation of health and disease. This review presents a summary of these initial studies, which have opened the door to a new understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.
Surveillance for Violent Deaths — National Violent Death Reporting System, 34 States, Four California Counties, the District of Columbia, and Puerto Rico, 2017
Authors: Emiko Petrosky, Allison Ertl, Kameron J. Sheats, Rebecca Wilson, Carter J. Betz, Janet M. Blair
Journal: MMWR Surveillance Summaries (2020)

Problem/Condition: In 2017, approximately 67,000 persons died of violence-related injuries in the United States.This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 34 states, four California counties, the District of Columbia, and Puerto Rico in 2017.Results are reported by sex, age group, race/ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics.
One Responsive Stone, Three Birds: Mn(III)‐Hemoporfin Frameworks with Glutathione‐Enhanced Degradation, MRI, and Sonodynamic Therapy
Authors: Peng Geng, Nuo Yu, Jiulong Zhang, Zilin Jin, Mei Wen, Qin Jiang, Li Kang, Chen Peng, Maoquan Li, Haijun Zhang, Meifang Zhu, Zhigang Chen
Journal: Advanced Healthcare Materials (2020)

Abstract Ultrasound‐driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep‐seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)‐hemoporfin frameworks (Mn(III)‐HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl‐ether (HMME) to coordinate with Mn(III) ions. Mn(III)‐HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)‐HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d‐electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost 1 O 2 generation ability under US irradiation. As a result, when Mn(III)‐HFs/PEG dispersion is intravenously administered into mice, it exhibits high‐contrast T 1 / T 2 dual‐modal MRI and significant suppression for the growth rate of the deep‐seated tumor. Furthermore, Mn(III)‐HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)‐HFs/PEG exhibit GSH‐enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.
MR Imaging-Verified Plaque Delipidation With Lipid-Lowering Therapy: Important Questions Remain⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Christopher M. Kramer, Venkatesh Mani, Zahi A. Fayad
Journal: JACC. Cardiovascular imaging (2011)
64P Pre-treatment absolute white blood cell profile count as metastatic predictive factors in invasive ductal carcinoma breast cancer
Authors: W.W.W.I. Gede, N.P.S.I. Remitha, I.G.A.S. Sadvika, D.M. Wihandani, I.G.P. Supadmanaba, P.A.T. Adiputra
Journal: Annals of Oncology (2020)
The Type II Anti‐CD20 Antibody Obinutuzumab (GA101) Is More Effective Than Rituximab at Depleting B Cells and Treating Disease in a Murine Lupus Model
Authors: Anthony D. Marinov, Haowei Wang, Sheldon I. Bastacky, Erwin van Puijenbroek, Thomas Schindler, Dario Speziale, Mario Perro, Christian Klein, Kevin M. Nickerson, Mark J. Shlomchik
Journal: Arthritis & Rheumatology (2020)

Depleting pathogenic B cells could treat systemic lupus erythematosus (SLE). However, depleting B cells in an inflammatory setting such as lupus is difficult. This study was undertaken to investigate whether a type II anti-CD20 monoclonal antibody (mAb) with a different mechanism of action, obinutuzumab (GA101), is more effective than a type I anti-CD20 mAb, rituximab (RTX), in B cell depletion in lupus, and whether efficient B cell depletion results in amelioration of disease.We treated lupus-prone MRL/lpr mice expressing human CD20 on B cells (hCD20 MRL/lpr mice) with either RTX or GA101 and measured B cell depletion under various conditions, as well as multiple clinical end points.A single dose of GA101 was markedly more effective than RTX in depleting B cells in diseased MRL/lpr mice (P < 0.05). RTX overcame resistance to B cell depletion in diseased MRL/lpr mice with continuous treatments. GA101 was more effective in treating hCD20 MRL/lpr mice with early disease, as GA101-treated mice had reduced glomerulonephritis (P < 0.05), lower anti-RNA autoantibody titers (P < 0.05), and fewer activated CD4+ T cells (P < 0.0001) compared to RTX-treated mice. GA101 also treated advanced disease, and continual treatment prolonged survival. Using variants of GA101, we also elucidated B cell depletion mechanisms in vivo in mice with lupus.Albeit both anti-CD20 antibodies ameliorated early disease, GA101 was more effective than RTX in important parameters, such as glomerulonephritis score. GA101 proved beneficial in an advanced disease model, where it prolonged survival. These data support clinical testing of GA101 in SLE and lupus nephritis.
Association of Job Expectations Among High School Students With Early Death During Adulthood
Authors: Chandra Muller, Alicia Duncombe, Jamie M. Carroll, Anna S. Mueller, John Robert Warren, Eric Grodsky
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Deaths from self-injury are increasing. Understanding the sources of risk is important for prevention and treatment. <h3>Objective</h3> To estimate the risks of suicide and drug poisoning deaths among adult men whose adolescent occupational expectations were not met in adulthood. <h3>Design, Setting, and Participants</h3> This cohort study included a sample of men interviewed as part of the High School and Beyond study, a nationally representative study of US high school sophomores and seniors in 1980, who were interviewed every 2 years through 1986; those who were sophomores in 1980 were reinterviewed in 1992. Men who survived to 1992 and reported occupational expectations were included in the present study. Death records prior to 2018 were linked to mortality databases and released in 2019. Data analysis was conducted from May to October 2020. <h3>Exposure</h3> Occupational expectations. <h3>Main Outcomes and Measures</h3> Survival or death by suicide, drug poisoning, chronic liver disease, heart disease, cancer, or some other cause, categorized from<i>International Classification of Diseases, Ninth Revision </i>and<i>Tenth Revision</i>codes. Competing risk Fine-Gray survival models regressed cause of death on adolescent occupational expectations and covariates. <h3>Results</h3> The 11 680 men in the High School and Beyond cohort study had a median (interquartile range) age of 29 (28-30) years in 1992, when the analysis of their future mortality began. Most men survived until 2015 (11 060 [weighted percentage, 95.0%]). Reported causes of death were suicide (60 [weighted percentage, 0.5%]), drug poisoning (40 [weighted percentage, 0.4%]), chronic liver disease (20 [weighted percentage, 0.2%]), heart disease (130 [weighted percentage, 1.0%]), cancer (100 [weighted percentage, 1.0%]), and other (280 [weighted percentage, 2.0%]). Subhazard ratios for death by suicide and drug poisoning were 2.91 (95% CI, 1.07-7.88;<i>P</i> = .04) and 2.62 (95% CI, 1.15-5.94;<i>P</i> = .02) times higher, respectively, among those who in 1980 expected to hold a subbaccalaureate occupation that later declined in labor market share compared with those with professional occupational expectations. The actual job held by men did not attenuate the hazards of deaths from suicide and drug poisoning. <h3>Conclusions and Relevance</h3> In this cohort study, men whose occupational expectations were not met because of labor market declines were at a higher risk of death from suicide or drug poisoning than men with different occupational expectations. Interventions to mitigate labor market changes should account for individuals' expectational ideals.
Third left pulmonary lobe
Authors: Liang Zeng, Qinqin Xu, Nong Yang, Analyn Lizaso, Yongchang Zhang
Journal: Thorax (2020)

A 67-year-old man with a 20 pack-year smoking history presented to our hospital with a month-long persistent cough. Blood tests showed elevated serum tumour biomarkers including neuron-specific enolase and carcinoembryonic antigen up to 10-fold the normal range. CT examination of the chest and whole abdomen revealed a 5 cm mass located on the left upper lobe with diffuse metastasis in both lobes of the lung. In addition to the mass in the left upper lung lobe, we also observed extra lung tissue with notable interstitial markings and the presence …
219MO Real-world utilization pattern of bone-targeted agents for metastatic prostate cancer: Web-based questionnaire study by Hong Kong Society of Uro-Oncology (HKSUO)
Authors: D.M.C. Poon, K. Chan, T. Chan, F.Y. Cheung, M. Lam, D. Lam, K. Law, A. Leung, C. Lee, K.C. Lee, H. Sze, K. Wong, C.C. Tong, P. Kwong
Journal: Annals of Oncology (2020)
Children are “highly unlikely” to be able to consent to taking puberty blockers, rules High Court
Authors: Clare Dyer
Journal: BMJ (2020)

Children under 16 cannot consent to the use of puberty blockers for gender dysphoria unless they can understand the immediate and long term consequences of the treatment, which is unlikely, the High Court in London has ruled.1

Even for over 16s, clinicians might well want to seek court authorisation before administering puberty blockers, said three senior judges.

The legal challenge was brought against the Tavistock and Portman NHS Trust, which runs the UK’s only gender reassignment service for young people. Keira Bell, 23, who was treated as a teenager, and “Mrs A,” the mother …
14402 Serum levels of thymus and activation-regulated chemokine in patients with psoriasis: Higher in patients with generalized pustular psoriasis
Authors: Yurika Kawasaki, Masahiro Kamata, Mayumi Nagata, Saki Fukaya, Kotaro Hayashi, Atsuko Fukuyasu, Takamitsu Tanaka, Takeko Ishikawa, Takamitsu Ohnishi, Yayoi Tada
Journal: Journal of the American Academy of Dermatology (2020)
Design of a prospective patient‐level pooled analysis of two parallel trials of empagliflozin in patients with established heart failure
Authors: Milton Packer, Javed Butler, Gerasimos Filippatos, Faiez Zannad, Joao Pedro Ferreira, Cordula Zeller, Martina Brueckmann, Waheed Jamal, Stuart J Pocock, Stefan D Anker
Journal: European Journal of Heart Failure (2020)

The EMPEROR-Reduced trial demonstrated that empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with a reduced ejection fraction, and the EMPEROR-Preserved trial is currently evaluating the effect of the drug on the same endpoint in patients with an ejection fraction >40%. However, neither the trial was designed to have adequate statistical power to evaluate the effects of empagliflozin and dapagliflozin on major adverse renal outcomes or on mortality. Herein we describe the design of a prospective individual patient-level pooled analysis of two large-scale trials with empagliflozin (EMPEROR-Reduced and EMPEROR-Preserved) in patients with heart failure across the spectrum of ejection fraction.The trials were carried out in parallel using the same administrative structure and committees, randomization procedure, schedule of study visits and adjudication criteria and similar groups of investigators and case report forms. The two component trials specified the same primary and key secondary endpoints and used an identical hierarchical testing procedure, which included a pooled analysis of the two trials as a key component of the hierarchy. Consequently, the pooled analysis has been prospectively assigned a false positive error rate, which is conditional on one or both trials first achieving success on their primary and one or both key secondary endpoints. The pooled analysis has its own statistical plan with its own endpoints, and this plan was finalized before either trial had begun recruitment of patients into either study. The primary endpoint of the pooled analysis is a composite of serious adverse renal outcomes, defined by chronic dialysis, renal transplantation and a profound or sustained decrease in glomerular filtration rate. All-cause and cardiovascular mortality are specified as secondary endpoints.The planned pooled analysis has an unusually high degree of statistical rigour that will allow it to address important questions that cannot be fully addressed by the individual trials.
Abstract PO-40: FOXO1 mutations mimic positive selection signals to promote germinal center B-cell expansion and lymphomagenesis
Authors: Mark P. Roberto, Gabriele Varano, Rosa Viñas-Castells, Antony B. Holmes, Rahul Kumar, Pedro Farinha, David W. Scott, David Dominguez-Sola
Journal: Blood Cancer Discovery (2020)

Abstract The transcription factor FOXO1 directs germinal center (GC) polarity and supports affinity maturation by modulating immune activation programs in GC B cells. Recurrent somatic mutations targeting FOXO1 in GC-derived B-cell non-Hodgkin lymphomas (B-NHL) are thought to disrupt its negative regulation by PI3K and function as gain-of-function, constitutively active alleles. Herein, we demonstrate that B-NHL FOXO1 mutants are instead hypomorphic alleles encoding proteins with altered transcriptional activities. Analysis of Foxo1 mutant mouse models, engineered cell lines, and primary samples shows that B-NHL FOXO1 mutations induce simultaneous hyperactivation of Stress Activated Protein Kinase -SAPK/JNK and Phosphoinositide 3-kinase -PI3K/AKT signaling pathways and gene expression programs characteristic of GC B cells undergoing positive selection. These alterations confer mutant B cells with a competitive advantage in response to key immune signals, leading to abnormal amplification of GC responses. Moreover, we find that FOXO1 mutant-driven transcriptional programs are prevalent in human B-NHL and predict poor clinical outcomes. These results imply the frequent co-option of GC positive selection programs in the pathogenesis of GC-derived lymphomas. Citation Format: Mark P. Roberto, Gabriele Varano, Rosa Viñas-Castells, Antony B. Holmes, Rahul Kumar, Pedro Farinha, David W. Scott, David Dominguez-Sola. FOXO1 mutations mimic positive selection signals to promote germinal center B-cell expansion and lymphomagenesis [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-40.
Mild parenchymal lung disease is still lung disease
Authors: Laurent Godinas, Sergio Harari, Joan A. Barberà, David Montani
Journal: European Respiratory Journal (2020)

We read with interest the article by Lewis et al . [1], which reports an increased mortality in patients with idiopathic pulmonary arterial hypertension (IPAH) and mild impairment in computed tomography (CT). They also show that low diffusing capacity of the lung for carbon monoxide ( D LCO) was associated with worse outcomes. It is an important paper pointing out interesting issues on which we would like to comment. PAH patients with mild parenchymal disease/low D LCO should be considered as group 3 patients with pulmonary vascular phenotype <https://bit.ly/33awS0J> This article was written on behalf of the PHAROS Clinical Research Collaboration members.
15418 Tolerance of a new dermocosmetic shampoo dedicated to scalp psoriasis treated by topical treatments
Authors: Marie-Dominique Thouvenin, Sandrine Dalmon, Pierre Fabre Dermo-Cosmétique, Valérie Mengeaud, Héla Coubetergues, Bénédicte Calvet
Journal: Journal of the American Academy of Dermatology (2020)
Pharmacokinetics and safety of early nevirapine-based antiretroviral therapy for neonates at high risk for perinatal HIV infection: a phase 1/2 proof of concept study
Authors: Theodore D Ruel, Edmund V Capparelli, Camlin Tierney, Bryan S Nelson, Anne Coletti, Yvonne Bryson, Mark F Cotton, Stephen A Spector, Mark Mirochnick, Rebecca LeBlanc, Christina Reding, Bonnie Zimmer, Deborah Persaud, Mutsa Bwakura-Dangarembizi, Kimesh L Naidoo, Rohan Hazra, Patrick Jean-Philippe, Ellen G Chadwick
Journal: The Lancet HIV (2020)
Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model
Authors: Anika Habener, Christine Happle, Ruth Grychtol, Jelena Skuljec, Mandy Busse, Kathleen Dalüge, Helena Obernolte, Katherina Sewald, Armin Braun, Almut Meyer-Bahlburg, Gesine Hansen
Journal: Journal of Allergy and Clinical Immunology (2020)
A Glimpse Into Multigene Rare Variant Genetics: Triple Mutations in Hypertrophic Cardiomyopathy**Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Ray E. Hershberger
Journal: Journal of the American College of Cardiology (2010)