tbuckley/cabot-search huggingface dataset:
Increased CD55 expression on PC3 cells is regulated, in part, by activation of the PAR1 receptor
Authors: Viggo Van Tendeloo, Ann Van Driessche, Peter Ponsaerts, Liquan Gao, Marc Lenjou, Griet Nijs, Filip Lardon, Dirk Van Bockstaele, Hans J. Stauss, Zwi Berneman
Journal: Cancer Research (2004)

5447  cDNA microarray and tissue microarray experiments have previously identified the overexpression of protease activated receptor -1 (PAR1, thrombin receptor) in prostate cancer cells that metastasize to bone as compared to prostate cancer cells derived soft tissue metastases. The contribution of PAR1 upregulation to the metastatic potential and survival of prostate cancer cells remains unclear. Thrombin has been shown to induce the expression of membrane-bound complement regulatory proteins (mCRPs) on endothelial cells via activation of PAR1. We have hypothesized that activation of PAR1 induces overexpression of mCRPs on prostate cancer cells and that the overexpression of mCRPS protects these cells against complement-mediated opsonization and lysis. Real time PCR was used to assess the relative mRNA expression of CD55 and CD59 in several prostate cancer cell lines (i.e. PC3, Du145 and LNCaP). The results demonstrated an increase in both CD55 and CD59 expression in PC3 cells compared to RPWE-1 cells (an immortalized normal prostate cell line) (CD55 1.31 ± 0.27 and CD59 2.83 ± 0.23 fold increase to RPWE-1). Interestingly, Du145 and LNCaP demonstrated a decrease in CD55 and CD59 mRNA expression compared to RPWE-1 (Du145: CD55 0.38 ± 0.68 and CD59 0.248 ± 0.15, LNCaP: CD55 0.0008 ± 0.43 and CD59 0.04 ± 0.23 fold increase). Further, initial immunoblot analysis revealed an increase in CD55 and CD59 expression on PC3 cells compared to RPWE-1 cells. Interestingly, no change in CD46 expression was evident between PC3 and RPWE-1 cells. Additionally, stimulation of PC3 cells with TRAP 6 (10μM, a PAR1 specific agonist) resulted in an increase in CD55 expression. These data suggest the potential involvement of the membrane bound complement regulatory proteins in promoting prostate cancer cell survival and metastasis. However, further investigation is required to fully understand the mechanisms involved in the upregulation of complement protective proteins during tumorigenesis.
Clonal dynamics and clinical implications of postremission clonal hematopoiesis in acute myeloid leukemia
Authors: Tomoyuki Tanaka, Kiyomi Morita, Sanam Loghavi, Feng Wang, Ken Furudate, Yuya Sasaki, Latasha Little, Curtis Gumbs, Jairo Matthews, Naval Daver, Naveen Pemmaraju, Courtney D. DiNardo, Koji Sasaki, Musa Yilmaz, Tapan M. Kadia, Farhad Ravandi, Marina Y. Konopleva, Hagop M. Kantarjian, Richard E. Champlin, Gheath Al-Atrash, Guillermo Garcia-Manero, Sa A. Wang, P. Andrew Futreal, Koichi Takahashi
Journal: Blood (2021)
The 2019 Nobel Prize honors fundamental discoveries in hypoxia response
Authors: Javid Moslehi, W. Kimryn Rathmell
Journal: Journal of Clinical Investigation (2019)

Farber Cancer Institute) for their discoveries of a fundamental aspect of cellular physiology, the cellular sensing of oxygen levels and regulation of physiologic hypoxia.Each of these physician-scientists was intrigued by a different clinically relevant observation and utilized very basic biochemical tools to address their questions.These separate lines of investigation converged, delineating a central cellular pathway with far-ranging implications for human physiology, disease states, and medicine.The story of how they uncovered hypoxia response begins with a deep interest in basic human biology.
Extended Follow-Up and Analysis with Central Radiological Review of Patients Receiving FavId® (Id/KLH) Vaccine Following Rituximab.
Authors: Omer Koc, Charles Redfern, Peter Wiernik, Fred Rosenfelt, Jane Winter, Troy Guthrie, Lawrence Kaplan, Peter Holman, John Densmore, John Hainsworth, Thomas Lin, Rene Castillo, Nalini Janakiraman, Dan Gold, John Gutheil, John Bender
Journal: Blood (2005)
Proposed Ohio bill asks doctors to re-implant ectopic pregnancies or face “abortion murder” charges
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

Legislators in Ohio, USA, have introduced a bill that would outlaw abortion and could charge doctors and patients with “abortion murder.” In ectopic pregnancies, doctors would be required to try to re-implant the pregnancy in the woman’s uterus.1

The bill says, “No person shall purposely, and with prior calculation and design, perform or have an abortion. Whoever violates this section is guilty of aggravated abortion murder . . . A court shall regard the unborn child victim of an aggravated abortion murder or abortion murder as a person who is less than thirteen years of age.” Punishment would be 15 years to life in prison.

There are certain exceptions, however, and a doctor would not face punishment if an abortion was performed because a woman’s life was …
Maintenance of clinical response and consistent safety profile with up to 3 years of continuous treatment with guselkumab: Results from the VOYAGE 1 and VOYAGE 2 trials
Authors: Kristian Reich, Christopher E.M. Griffiths, Kenneth B. Gordon, Kim A. Papp, Michael Song, Bruce Randazzo, Shu Li, Yaung-Kaung Shen, Chenglong Han, Alexa B. Kimball, April W. Armstrong, Peter Foley, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2019)

Long-term maintenance treatment is required for patients with psoriasis.To evaluate the efficacy and safety of guselkumab in patients with moderate to severe psoriasis through 3 years of treatment.In 2 ongoing, phase 3 trials of guselkumab (VOYAGE 1 and VOYAGE 2), the proportions of patients achieving at least 90% and 100% improvement in the Psoriasis Area and Severity Index (PASI 90 and PASI 100, respectively) and Investigator's Global Assessment (IGA) scores of 0/1 and 0 were summarized for the guselkumab group (including placebo-to-guselkumab crossover). Patients who met treatment failure rules were considered nonresponders. Safety outcomes (rates/100 patient-years [PY]) were evaluated based on data pooled across studies through week 156.Three-year response rates for the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 82.8% and 77.2% for PASI 90, 50.8% and 48.8% for PASI 100, 82.1% and 83.0% for IGA score of 0/1, and 53.1% and 52.9% for IGA score of 0. Safety event rates across studies occurred through week 156 as follows: serious adverse events, 5.68/100 PY; serious infections, 1.15/100 PY; nonmelanoma skin cancers, 0.28/100 PY; malignancies other than nonmelanoma skin cancer, 0.47/100 PY; and major adverse cardiovascular events, 0.28/100 PY. Week 156 and week 100 rates were consistent.There was no comparator arm beyond 1 year.Guselkumab shows durable efficacy and a consistent safety profile in patients with moderate to severe psoriasis treated for up to 3 years.
Clinical Outcome of B-Cell Chronic Lymphocytic Leukemia Following Alemtuzumab Therapy: Retrospective Study within Various Cytogenetic Risk Categories
Authors: Michael Fiegl, Martin Erdel, Inge Tinhofer, Georg Hopfinger, Karin Eigenberger, Florian Falkner, Andreas Falkner, Yvona Brychtova, Anna Panovska, Michael Doubek, August Zabernigg, Sigrun Sodia, Helmut Mühlberger, Christa Fonatsch, Günther Gastl, Jiri Mayer, Richard Greil
Journal: Blood (2008)
Disease Phenotype and Clonal Amplification in Calreticulin del52 and ins5 Knock-in Mice Are Dependent on the Type of Mutations and Gene Dosage
Authors: Camélia Benlabiod, Maira da Costa Cacemiro, Thomas Balligand, Barbara Panneau-Schmaltz, Delphine Muller, Laure Touchard, Patrick Gonin, Jean-Luc Villeval, Stefan N Constantinescu, Hana Raslova, William Vainchenker, Isabelle Plo, Caroline Marty
Journal: Blood (2019)
脑卒中的神经影像学诊断 “即病即扫”策略能够改善预后并降低费用
Authors: JMWardlaw, AJFarrall, 辛晓瑜, 陈生弟
Journal: BMJ (2004)

脑卒中是一种急性起病、由血管性原因致使局灶性或全脑神经功能缺损的临床综合征，临床症状通常持续超过24小时或死亡，其中80％是缺血性卒中，15％为脑内出血，5％为蛛网膜下腔出血。正确诊断脑卒中是非常重要的，因为缺血性卒中的治疗方案。对于脑出血来说是禁忌证’。卒中的诊断需要脑部影像学检查。，但选择何种影像检查，是CT还是磁共振成像(MRI)?在发病后
CARD8/BCL-2 cascade in early adaptive drug resistant tumor escape against targeted inhibitors in NSCLC.
Authors: Rakesh K. Bagai, Wei Zhang, Patrick Leahy, Lihong Yin, Patrick C. Ma
Journal: Journal of Clinical Oncology (2013)

e22032 Background: Lung cancer targeted therapy is largely limited by inevitable recurrent resistant disease after initial response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), typically accompanied with divergent late acquired resistance mechanisms. We now focused on studying the emergence of early adaptive resistance to uncover attractive therapeutic targets to overcome drug resistance. Methods: HCC827 cells were treated with EGFR-TKI (0-9 days) with apoptosis pathway-specific QPCR array and TLVM analysis performed. MTS and crystal violet assays were performed. Western blot analysis was performed to examine prosurvival signaling developed against erlotinib, alone or in combination with MET inhibitor SU11274. IHC was performed on lung cancer tumor microarray (TMA) using BCL-2 and caspase-recruitment domain-containing protein 8 (CARD8) antibodies and graded (4 tier scoring system). NSCLC cell lines and murine xenograft models (HCC827, H1975) were developed for resistance biomarkers expression analysis in pre-/post-TKI treatment using anti-human CARD8, p-STAT3 and BCL-2 antibodies. Results: We characterized the emergence of early resistant lung cancer cells in escape against targeted TKIs with 100-fold higher IC 50 in adaptive drug resistance. The resistant cells that evaded EGFR-TKI based targeted inhibition exhibited MET-independent induction of CARD8 and STAT3/BCL-2 mitochondrial prosurvival signaling in cellular quiescence, and inhibited cytoskeletal functions. Expression analysis studies demonstrated common tumor-associated expression of CARD8 but relatively low BCL-2 level in NSCLC. In vitro cell line studies suggest that CARD8 induction was preceded by a resurgence of STAT3 activation. In vivo xenograft model (HCC827/erlotinib; H1975/erlotinib+ SU11274) also verified upregulated CARD8/BCL-2 activation within early resistant cells. Conclusions: Resistant tumor cells that evaded EGFR inhibitors, alone or in combination with MET inhibitors, exhibited increased expression of CARD8-STAT3/BCL-2 prosurvival signaling cascade. Further studies to define the mechanism of CARD8 in promoting adaptive tumor drug resistance would be warranted.
Multidisciplinary Authorship in Clinical Practice Guidelines: An Opportunity for Inclusion
Authors: Elias B. Chahine
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

findings are consistent with our previously reported finding that tobacco and menthol flavors were more contaminated with microbial toxins.The main limitation of the current study is that we did not evaluate contamination of aerosols inhaled by users.Further research is needed to assess microbial contamination in aerosol samples and to evaluate the health effects of microbial toxins in users of nicotine vaping products.This study highlights the microbial contamination in nicotine vaping pod products sold in the United States.The contamination in tobacco-flavored vaping products is of particular concern because, as of this writing, tobacco flavors are excluded from the plan by the U.S. Food and Drug Administration to ban flavored e-cigarettes and pods from the market (6).
Significance of <i>BRCA2</i> and <i>RB1</i> Co-loss in Aggressive Prostate Cancer Progression
Authors: Goutam Chakraborty, Joshua Armenia, Ying Z. Mazzu, Subhiksha Nandakumar, Konrad H. Stopsack, Mohammad O. Atiq, Kazumasa Komura, Lina Jehane, Rahim Hirani, Kalyani Chadalavada, Yuki Yoshikawa, Nabeela A. Khan, Yu Chen, Wassim Abida, Lorelei A. Mucci, Gwo-Shu Mary Lee, Gouri J. Nanjangud, Philip W. Kantoff
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Previous sequencing studies revealed that alterations of genes associated with DNA damage response (DDR) are enriched in men with metastatic castration-resistant prostate cancer (mCRPC). BRCA2, a DDR and cancer susceptibility gene, is frequently deleted (homozygous and heterozygous) in men with aggressive prostate cancer. Here we show that patients with prostate cancer who have lost a copy of BRCA2 frequently lose a copy of tumor suppressor gene RB1; importantly, for the first time, we demonstrate that co-loss of both genes in early prostate cancer is sufficient to induce a distinct biology that is likely associated with worse prognosis. Experimental Design: We prospectively investigated underlying molecular mechanisms and genomic consequences of co-loss of BRCA2 and RB1 in prostate cancer. We used CRISPR-Cas9 and RNAi-based methods to eliminate these two genes in prostate cancer cell lines and subjected them to in vitro studies and transcriptomic analyses. We developed a 3-color FISH assay to detect genomic deletions of BRCA2 and RB1 in prostate cancer cells and patient-derived mCRPC organoids. Results: In human prostate cancer cell lines (LNCaP and LAPC4), loss of BRCA2 leads to the castration-resistant phenotype. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype. Importantly, PARP inhibitors attenuate cell growth in human mCRPC-derived organoids and human CRPC cells harboring single-copy loss of both genes. Conclusions: Our findings suggest that early identification of this aggressive form of prostate cancer offers potential for improved outcomes with early introduction of PARP inhibitor–based therapy. See related commentary by Mandigo and Knudsen, p. 1784
CRISPR-Cas13d mediates robust RNA virus interference in plants
Authors: Ahmed Mahas, Rashid Aman, Magdy Mahfouz
Journal: Genome biology (2019)

CRISPR-Cas systems endow bacterial and archaeal species with adaptive immunity mechanisms to fend off invading phages and foreign genetic elements. CRISPR-Cas9 has been harnessed to confer virus interference against DNA viruses in eukaryotes, including plants. In addition, CRISPR-Cas13 systems have been used to target RNA viruses and the transcriptome in mammalian and plant cells. Recently, CRISPR-Cas13a has been shown to confer modest interference against RNA viruses. Here, we characterized a set of different Cas13 variants to identify those with the most efficient, robust, and specific interference activities against RNA viruses in planta using Nicotiana benthamiana.Our data show that LwaCas13a, PspCas13b, and CasRx variants mediate high interference activities against RNA viruses in transient assays. Moreover, CasRx mediated robust interference in both transient and stable overexpression assays when compared to the other variants tested. CasRx targets either one virus alone or two RNA viruses simultaneously, with robust interference efficiencies. In addition, CasRx exhibits strong specificity against the target virus and does not exhibit collateral activity in planta.Our data establish CasRx as the most robust Cas13 variant for RNA virus interference applications in planta and demonstrate its suitability for studying key questions relating to virus biology.
Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).
Authors: Barbara F. Eichhorst, Raymonde Busch, Clemens M. Wendtner, Michael Hallek
Journal: Blood (2005)
Housing Mobility and Addressing Social Determinants of Health Within the Health Care System
Authors: Alexandra Yurkovic, Michael Silverstein, Alastair Bell
Journal: JAMA (2019)

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X-Linked Clonality Analysis of Human Embryonic Stem Cells ( hESC ) Before and after induction of Hematopoietic Differentiation
Authors: Maria Teresa Mitjavila-Garcia, Frank Yates, Marie-Laure Bonnet, Claire Rougeulle, Melanie Makhlouf, Olivier Feraud, Aurelie Magniez, Annelise Bennaceur-Griscelli, Ali G Turhan
Journal: Blood (2008)
Tuberculosis in biologic users for rheumatic diseases: results from the South African Biologics Registry (SABIO)
Authors: Clive Pettipher, Romela Benitha
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome. Methods TB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical companies. Demographics, LTBI screening and treatment, biological and disease modifying antirheumatic drug (DMARD) therapies, TB diagnosis and outcomes were recorded. Results 96 TB cases were collected from 1999 to June 2017: rheumatoid arthritis 55, ankylosing spondylitis 27, psoriatic arthritis 4, and juvenile inflammatory arthritis 10. The TB rate was 1240/100 000 person years for biologic users (n=96) versus the biologic naive cohort of 0/100 000 years with an incidence rate difference of 0.0124 (p&lt;0.0001). 60/96 had pulmonary and 36/96 had extra-pulmonary TB. Reactivation TB occurred in 45/96 cases. TB occurred in all biologics licenced in South Africa, the majority in monoclonal inhibitors (1683/100 000 person years) compared with etanercept (861/100 000 person years) and non-tumour necrosis factor (TNF) inhibitors (681/100 000 person years). The incidence rate ratio for monoclonal inhibitors compared with etanercept was 1.96 (p=0.005) and 2.47 (p=0.002) compared with non-TNF inhibitors with no significant difference between non-TNF inhibitors and etanercept (p=0.336). From those (12.9%) who screened LTBI positive, 14 developed TB, while the majority (77) screened LTBI negative. Black race, male sex, younger age and residence in the Western Cape were statistical risk factors. Two drug resistant TB cases and six deaths occurred. Conclusion Reactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.
Investigating Lipoprotein(A) as a Risk Factor for Ischemic Arterial Stroke in U.S. Children. New Understanding from a Case-Control Study with Gold-Standard Laboratory Assessment.
Authors: Neil A. Goldenberg, R. Knapp-Clevenger, Linda Jacobson, Taru Hays, Santica M. Marcovina, Marilyn J. Manco-Johnson
Journal: Blood (2005)
Early Stage Adaptation of a Mesophilic Green Alga to Antarctica: Systematic Increases in Abundance of Enzymes and LEA Proteins
Authors: Yali Wang, Xiaoxiang Liu, Hong Gao, Hong-Mei Zhang, An-Yuan Guo, Jian Xu, Xudong Xu
Journal: Molecular Biology and Evolution (2019)

It is known that adaptive evolution in permanently cold environments drives cold adaptation in enzymes. However, how the relatively high enzyme activities were achieved in cold environments prior to cold adaptation of enzymes is unclear. Here we report that an Antarctic strain of Chlorella vulgaris, called NJ-7, acquired the capability to grow at near 0 °C temperatures and greatly enhanced freezing tolerance after systematic increases in abundance of enzymes/proteins and positive selection of certain genes. Having diverged from the temperate strain UTEX259 of the same species 2.5 (1.1-4.1) to 2.6 (1.0-4.5) Ma, NJ-7 retained the basic mesophilic characteristics and genome structures. Nitrate reductases in the two strains are highly similar in amino acid sequence and optimal temperature, but the NJ-7 one showed significantly higher abundance and activity. Quantitative proteomic analyses indicated that several cryoprotective proteins (LEA), many enzymes involved in carbon metabolism and a large number of other enzymes/proteins, were more abundant in NJ-7 than in UTEX259. Like nitrate reductase, most of these enzymes were not upregulated in response to cold stress. Thus, compensation of low specific activities by increased enzyme abundance appears to be an important strategy for early stage cold adaptation to Antarctica, but such enzymes are mostly not involved in cold acclimation upon transfer from favorable temperatures to near 0 °C temperatures.
新患者要求开苯二氮[艹卓]处方
Authors: Simon, Lusignan, Andy, Kent, 车璐
Journal: BMJ (2009)

某星期五，你的最后一个患者是一位26岁的男性。他是一位新患者，要求你为他开连续2个月地西泮（安定类药物）的处方，每次5mg，每天高达4次。他说他需要这些药物来缓解神经紧张，已经这样服用过一段时间，现在没有药了。你并没有这位患者的病历。
Matched Pair Analysis of Intravenous vs Oral Busulphan as Part of Fludarabine-Busulphan-Campath (Alemtuzumab) Reduced Intensity Conditioning (RIC) Haematopoietic Stem Cell Transplantation (HSCT).
Authors: ZiYi Lim, Dragana Milojkovic, Laurence Pearce, Michelle Kenyon, Aloysius Ho, Stephen Devereux, Antonio Pagliuca, Ghulam Mufti
Journal: Blood (2005)
Abstract 9574: The Correlation Between Renin Angiotensin Aldosterone System Blockers and Future Osteoporotic Fractures in a Hypertensive Population - A Population-based Cohort Study in Taiwan
Authors: Yung-Ta Kao, Chun-Yao Huang, Yu-Ann Fang, Ju-Chi Liu
Journal: Circulation (2019)

Objective: The activation of the tissue renin-angiotensin-aldosterone system (RAAS) in sites of osteoporosis has been evaluated in animal studies. There were some cohort studies showing the possibi...
Functional Neuroimaging in the New Era of Big Data
Authors: Xiang Li, Ning Guo, Quanzheng Li
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract The field of functional neuroimaging has substantially advanced as a big data science in the past decade, thanks to international collaborative projects and community efforts. Here we conducted a literature review on functional neuroimaging, with focus on three general challenges in big data tasks: data collection and sharing, data infrastructure construction, and data analysis methods. The review covers a wide range of literature types including perspectives, database descriptions, methodology developments, and technical details. We show how each of the challenges was proposed and addressed, and how these solutions formed the three core foundations for the functional neuroimaging as a big data science and helped to build the current data-rich and data-driven community. Furthermore, based on our review of recent literature on the upcoming challenges and opportunities toward future scientific discoveries, we envisioned that the functional neuroimaging community needs to advance from the current foundations to better data integration infrastructure, methodology development toward improved learning capability, and multi-discipline translational research framework for this new era of big data.
MRD Monitoring Reveals a Specific Biology of BCR/ABL-Positive ALL
Authors: Marketa Zaliova, Leona Reznickova, Eva Fronkova, Katerina Krejcikova, Katerina Muzikova, Claus Meyer, Rolf Marschalek, Jan Stary, Jan Trka, Jan Zuna
Journal: Blood (2008)