tbuckley/cabot-search huggingface dataset:
<i>LACC1</i> gene mutation in three sisters with polyarthritis without systemic features
Authors: Ankita Singh, Deepti Suri, Pandiarajan Vignesh, Gummadi Anjani, Prince Jacob, Katta M Girisha
Journal: Annals of the Rheumatic Diseases (2019)

Juvenile idiopathic arthritis (JIA) refers to a group of disorders characterised by wide phenotypic diversity and genetic heterogeneity. Disordered immune response to an environmental trigger in a genetically predisposed individual is the proposed mechanism for most JIA subtypes.1 2 There are emerging reports on new gene locus being identified especially in families with many affected members.3 4 We report three sisters with polyarthritis who were identified to have causative variant in Laccase domain containing one ( LACC1 ) gene by whole exome sequencing.

A non-consanguineous family from north-western part of India reported with three daughters (P1, P2 and P3) having polyarticular joint disease. The onset of symptoms in the third child (11 months) prompted the parents to seek medical help. The eldest sister was 5 years and 9 months old, while the second daughter was 3 years old at the time of presentation. The chronology of symptoms was similar in all three children. Joint symptoms started in infancy at around 9–10 months of age with involvement of knee and ankle and rapidly progressed to involve small joints and cervical spine too (figure 1A–C). Over the next 2 years, multiple joint involvement, pain, deformities and contractures …
Induction of Adipocyte Differentiation and Reduction of Hematopoesis-Supporting Activity of Mouse Stromal Cells by Suppression of Transcription Factor GATA-2.
Authors: Yoko Okitsu, Hideo Harigae, Masanori Seki, Toru Fujiwara, Shinichiro Takahashi, Hisayuki Yokoyama, Junichi Kameoka, Naoko Minegishi, Takeshi Sasaki
Journal: Blood (2005)
Minimal Residual Disease (MRD) and T/NK Cell Dynamics during Fludarabine, Cyclophosphamide Plus Rituximab (FCR) Followed by Fludarabine Plus Rituximab (FR) and Remission Maintenance Therapy with Rituximab in Previously Untreated B-Chronic Lymphocytic Leukemia (B-CLL): Riskfactor Stratification in the Chairos Study
Authors: Alexander Egle, Lukas Weiss, Franz Gassner, Gudrun Russ, Lisa Pleyer, Eberhard Gunsilius, Inge Tinhofer, Josef Thaler, Andreas L. Petzer, Richard Greil
Journal: Blood (2008)
Pleural effusion in hemodialysis patients with chronic kidney disease
Authors: F Rashid Farokhi, G Pourdowlat, M R Nikonia, N Behzadnia, S Kakoi, A A Nasiri
Journal: European Respiratory Journal (2012)

Background: Uremic patients are susceptible to many causes of pleural effusions. Moreover, uremia directly creates a kind of exudative pleural effusion. Uremic pleuritis has been introduced as a clinicipathologic entity for the past four decades. However, knowledge of pathogenesis, clinical course and management of this complication is still limited.  Materials and methods: In this study, 76 chronic hemodialysis patients with pleural effusion admitted in hospital between June 2005 and May 2011, and evaluated for the etiology of pleural effusion and associated clinicopathological findings. Statistical tests of Chi square, ANOVA and Kruskal Wallis were used to compare patient9s data with the most common etiologies of pleural effusion.  Results: Parapneumonic effusion (23.7%), uremic pleuritis(23.7%) CHF (19.7%) volume overload (6.6%) tuberculosis (6.6%) and malignancy (5.4%) were the most common causes of pleural effusion. There was not any significant difference in the frequency of presenting symptoms such as; Dyspnea, cough, weight loss, anorexia, chest pain and fever, in patients with CHF and uremic pleuritis. Moreover, pleural Adenosine Deaminase levels were not different in patients with tuberculosis, uremic pleuritis, parapneumonic effusion and CHF.  Conclusion: Infectious disease including parapneumonic effusion and tuberculosis can be the most common causes of pleural effusion in hemodialysis patients. This study showed that some inflammatory pleural reactions such as increase in pleural leukocyte count and ADA may be attenuated in hemodialysis patients.
Ott1(Rbm15) Is Essential for Pre-B Differentiation and Has an Inhibitory Role in Myeloid and Megakaryocytic Lineages.
Authors: Glen D. Raffel, Thomas Mercher, Hirokazu Shigematsu, Ifor R. Williams, Dana E. Cullen, Koichi Akashi, Olivier A. Bernard, D. Gary Gilliland
Journal: Blood (2006)
A winter’s tale of promises
Authors: Rebecca Coombes
Journal: BMJ (2019)

The NHS is heading into winter with its performance against key targets the worst on record. These telling signs of pressure have had the consequence of putting the NHS, and not Brexit, centre stage of this unseasonably timed general election.

This week The BMJ tackles one significant pain point: the chronic workforce gap in nursing, where the vacancy rate is around 11% in England. The problem, says John Appleby (doi:10.1136/bmj.l6664), is not only the many unfilled nursing vacancies but a growing gap between the supply of labour and the demands on …
Identification of Genes Sustaining Bcr-Abl Oncogenic Signalling and CML Progression through a Genetic Tool Based on Human Bcr-Abl Transgenic Drosophila Melanogaster.
Authors: Daniela Cilloni, Francesca Messa, Roberto Bernardoni, Francesca Arruga, Monica Pradotto, Enrico Bracco, Cristina Panuzzo, Chiara Maffè, Emanuela Messa, Ilaria Iacobucci, Thea Kalebic, Giovanni Martinelli, Michele Baccarani, Giuseppe Saglio
Journal: Blood (2008)
Predictive Markers for Acute Graft-Versus-Host Disease in the Peripheral Blood - Surface Receptor Profile Defines Alloreactive T Cells In Vivo.
Authors: Andreas Beilhack, Robert Zeiser, Stephan Schulz, Janelle A. Olson, Ryosei Nishimura, Dennis Leveson-Gower, Robert S. Negrin
Journal: Blood (2006)
Changes in Management of Left-Sided Obstructive Colon Cancer: National Practice and Guideline Implementation
Authors: Joyce Valerie Veld, Femke Julie Amelung, Wernard Aat Antoine Borstlap, Emo Eise van Halsema, Esther Catharina Josephina Consten, Peter Derk Siersema, Frank ter Borg, Edwin Silvester van der Zaag, Paul Fockens, Willem Adrianus Bemelman, Jeanin Elise van Hooft, Pieter Job Tanis, _ _
Journal: Journal of the National Comprehensive Cancer Network (2019)

Previous analysis of Dutch practice in treatment of left-sided obstructive colon cancer (LSOCC) until 2012 showed that emergency resection (ER) was preferred, with high mortality in patients aged ≥70 years. Consequently, Dutch and European guidelines in 2014 recommended a bridge to surgery (BTS) with either self-expandable metal stent (SEMS) or decompressing stoma (DS) in high-risk patients. The implementation and effects of these guidelines have not yet been evaluated. Therefore, our aim was to perform an in-depth update of national practice concerning curative treatment of LSOCC, including an evaluation of guideline implementation.This multicenter cohort study was conducted in 75 of 77 hospitals in the Netherlands. We included data on patients who underwent curative resection of LSOCC in 2009 through 2016 obtained from the Dutch ColoRectal Audit. Additional data were retrospectively collected.A total of 2,587 patients were included (2,013 ER, 345 DS, and 229 SEMS). A trend was observed in reversal of ER (decrease from 86.2% to 69.6%) and SEMS (increase from 1.3% to 7.8%) after 2014, with an ongoing increase in DS (from 5.2% in 2009 to 22.7% in 2016). DS after 2014 was associated with more laparoscopic resections (66.0% vs 35.5%; P<.001) and more 2-stage procedures (41.5% vs 28.6%; P=.01) with fewer permanent stomas (14.7% vs 29.5%; P=.005). Overall, more laparoscopic resections (25.4% vs 13.2%; P<.001) and shorter total hospital stays (14 vs 15 days; P<.001) were observed after 2014. However, similar rates of primary anastomosis (48.7% vs 48.6%; P=.961), 90-day complications (40.4% vs 37.9%; P=.254), and 90-day mortality (6.5% vs 7.0%; P=.635) were observed.Guideline revision resulted in a notable change from ER to BTS for LSOCC. This was accompanied by an increased rate of laparoscopic resections, more 2-stage procedures with a decreased permanent stoma rate in patients receiving DS as BTS, and a shorter total hospital stay. However, overall 90-day complication and mortality rates remained relatively high.
Integration of DNA Copy Number and Gene Expression Alterations Reveal Novel Insights into the Molecular Pathogenesis and Prognosis of Multiple Myeloma
Authors: Yiming Zhou, Bart Barlogie, Damir Herman, Owen Stephens, Erming Tian, David Williams, Marie-astrid Cartron, Frits van Rhee, Mauricio Pineda-Roman, Yazan Alsayed, Elias Anaissie, Jeffrey Sawyer, John D. Shaughnessy
Journal: Blood (2008)
Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares
Authors: Arnaud M Didierlaurent, Christophe Desssart, Anthony L Cunningham
Journal: Annals of the Rheumatic Diseases (2019)

We have read with great interest the article addressing the risk of gout flares after vaccination in a case crossover study by Yokose et al .1 The authors suggest that vaccines may be associated with an increased odds of gout flares potentially via activation of the NLRP3 inflammasome. The study was conducted between 2003 and 2010 prior to the availability of the recombinant zoster vaccine (RZV); however, the authors make reference to two phase III clinical trials for RZV which, they state, demonstrated a higher risk of gout flares in the vaccine group. Even though RZV was not assessed in the study by Yokose et al , we would like to clarify this statement about RZV and gout flares.

The two large pivotal phase III clinical trials, ZOSTER-006/ZOE-50 (NCT01165177) and −022/ZOE-70 (NCT01165229), that involved a total of 29 305 subjects ≥50 years of age who received at least one dose of RZV (n=14 645) or placebo (n=14 660) were designed to assess the efficacy and safety of the RZV vaccine, but not to statistically assess a potential risk of gout among RZV recipients.2–4

We confirm that the analysis of the unsolicited adverse events (AE) reported during 30 days after each vaccination showed a numerical imbalance in the reporting rate of gout. Indeed, there were 27 (0.18% (95% CI 0.12 to 0.27)) versus 8 (0.05% (95% CI 0.02 to 0.11)) (unadjusted risk rario=3.38 (95% CI 1.49 to 8.60)) subjects in the RZV and placebo groups, respectively, who experienced an AE of gout or gouty arthritis.5 However, these are …
A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors
Authors: Ezra E. W. Cohen, Michael J. Pishvaian, Dale R. Shepard, Ding Wang, Jared Weiss, Melissa L. Johnson, Christine H. Chung, Ying Chen, Bo Huang, Craig B. Davis, Francesca Toffalorio, Aron Thall, Steven F. Powell
Journal: Journal for ImmunoTherapy of Cancer (2019)

Expressed on activated T and natural killer cells, 4-1BB/CD137 is a costimulatory receptor that signals a series of events resulting in cytokine secretion and enhanced effector function. Targeting 4-1BB/CD137 with agonist antibodies has been associated with tumor reduction and antitumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed in various solid tumor indications and associated with poor prognosis. This phase Ib, open-label study in patients with advanced solid tumors assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of utomilumab (PF-05082566), a human monoclonal antibody (mAb) agonist of the T-cell costimulatory receptor 4-1BB/CD137, in combination with mogamulizumab, a humanized mAb targeting CCR4 reported to deplete subsets of regulatory T cells (Tregs).Utomilumab 1.2-5 mg/kg or 100 mg flat dose every 4 weeks plus mogamulizumab 1 mg/kg (weekly in Cycle 1 followed by biweekly in Cycles ≥2) was administered intravenously to 24 adults with solid tumors. Blood was collected pre- and post-dose for assessment of drug pharmacokinetics, immunogenicity, and pharmacodynamic markers. Baseline tumor biopsies from a subset of patients were also analyzed for the presence of programmed cell death-ligand 1 (PD-L1), CD8, FoxP3, and 4-1BB/CD137. Radiologic tumor assessments were conducted at baseline and on treatment every 8 weeks.No dose-limiting toxicities occurred and the maximum tolerated dose was determined to be at least 2.4 mg/kg per the time-to-event continual reassessment method. No serious adverse events related to either treatment were observed; anemia was the only grade 3 non-serious adverse event related to both treatments. Utomilumab systemic exposure appeared to increase with dose. One patient with PD-L1-refractory squamous lung cancer achieved a best overall response of partial response and 9 patients had a best overall response of stable disease. No patients achieved complete response. Objective response rate was 4.2% (95% confidence interval: 0.1-21.1%) per RECIST 1.1. Depletion of Tregs in peripheral blood was accompanied by evidence of T-cell expansion as assessed by T-cell receptor sequence analysis.The combination of utomilumab/mogamulizumab was safe and tolerable, and may be suitable for evaluation in settings where CCR4-expressing Tregs are suppressing anticancer immunity.ClinicalTrials.gov identifier: NCT02444793.
Familial dilated cardiomyopathy
Authors: Luisa Mestroni, Chiara Rocco, Dario Gregori, Gianfranco Sinagra, Andrea Di Lenarda, Snjezana Miocic, Matteo Vatta, Bruno Pinamonti, Francesco Muntoni, Alida L.P. Caforio, William J. McKenna, Arturo Falaschi, Mauro Giacca, Fulvio Camerini
Journal: Journal of the American College of Cardiology (1999)
A 3-Year Prospective Surveillance Study of Microbiological Isolates among Hematologic Inpatients Shows a High Frequency of Both Community-Acquired and Nosocomial Methicillin-Resistant (MR) and Fluoroquinolone-Resistant (FqR) Strains and the Recent Increase of Enterococci, Viridans Streptococci and Pseudomonaceae with Frequent Antibiotic Multiresistance.
Authors: Chiara Cattaneo, Salvatore Casari, Erika Borlenghi, Maria Adele Capucci, Moira Micheletti, Alessandro Re, Giampiero Carosi, Giuseppe Rossi
Journal: Blood (2007)
Murine Oviductal High-Grade Serous Carcinomas Mirror the Genomic Alterations, Gene Expression Profiles, and Immune Microenvironment of Their Human Counterparts
Authors: Kevin W. McCool, Zachary T. Freeman, Yali Zhai, Rong Wu, Kevin Hu, Chia-Jen Liu, Scott A. Tomlins, Eric R. Fearon, Brian Magnuson, Rork Kuick, Kathleen R. Cho
Journal: Cancer Research (2019)

Abstract Robust preclinical models of ovarian high-grade serous carcinoma (HGSC) are needed to advance our understanding of HGSC pathogenesis and to test novel strategies aimed at improving clinical outcomes for women with the disease. Genetically engineered mouse models of HGSC recapitulating the likely cell of origin (fallopian tube), underlying genetic defects, histology, and biologic behavior of human HGSCs have been developed. However, the degree to which the mouse tumors acquire the somatic genomic changes, gene expression profiles, and immune microenvironment that characterize human HGSCs remains unclear. We used integrated molecular characterization of oviductal HGSCs arising in the context of Brca1, Trp53, Rb1, and Nf1 (BPRN) inactivation to determine whether the mouse tumors recapitulate human HGSCs across multiple domains of molecular features. Targeted DNA sequencing showed the mouse BPRN tumors, but not endometrioid carcinoma-like tumors based on different genetic defects (e.g., Apc and Pten), acquire somatic mutations and widespread copy number alterations similar to those observed in human HGSCs. RNA sequencing showed the mouse HGSCs most closely resemble the so-called immunoreactive and mesenchymal subsets of human HGSCs. A combined immuno-genomic analysis demonstrated the immune microenvironment of BPRN tumors models key aspects of tumor-immune dynamics in the immunoreactive and mesenchymal subtypes of human HGSC, with enrichment of immunosuppressive cell subsets such as myeloid-derived suppressor cells and regulatory T cells. The findings further validate the BPRN model as a robust preclinical experimental platform to address current barriers to improved prevention, diagnosis, and treatment of this often lethal cancer. Significance: The acquired gene mutations, broad genomic alterations, and gene expression and immune cell–tumor axis changes in a mouse model of oviductal serous carcinoma closely mirror those of human tubo-ovarian high-grade serous carcinoma.
Anti–PD-L1 antibody direct activation of macrophages contributes to a radiation-induced abscopal response in glioblastoma
Authors: Chibawanye I Ene, Shannon A Kreuser, Miyeon Jung, Huajia Zhang, Sonali Arora, Kara White Moyes, Frank Szulzewsky, Jason Barber, Patrick J Cimino, Hans-Georg Wirsching, Anoop Patel, Paul Kong, Timothy R Woodiwiss, Sharon J Durfy, A McGarry Houghton, Robert H Pierce, Ian F Parney, Courtney A Crane, Eric C Holland
Journal: Neuro-Oncology (2019)

Abstract Background Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an “abscopal effect,” whereby unirradiated neoplastic cells outside treatment sites are recognized and attacked by the immune system. Radiation combined with anti–programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma clinical trials, but the mechanism and relevance of the abscopal effect during this response remain unknown. Methods We modified an immune-competent, genetically driven mouse glioma model (forced platelet derived growth factor [PDGF] expression + phosphatase and tensin homolog loss) where a portion of the tumor burden is irradiated (PDGF) and another unirradiated luciferase-expressing tumor (PDGF + luciferase) is used as a readout of the abscopal effect following systemic anti–PD-L1 immunotherapy. We assessed relevance of tumor neoepitope during the abscopal response by inducing expression of epidermal growth factor receptor variant III (EGFRvIII) (PDGF + EGFRvIII). Statistical tests were two-sided. Results Following radiation of one lesion, anti–PD-L1 immunotherapy enhanced the abscopal response to the unirradiated lesion. In PDGF-driven gliomas without tumor neoepitope (PDGF + luciferase, n = 8), the abscopal response occurred via anti–PD-L1 driven, extracellular signal-regulated kinase–mediated, bone marrow–derived macrophage phagocytosis of adjacent unirradiated tumor cells, with modest survival implications (median survival 41 days vs radiation alone 37.5 days, P = 0.03). In PDGF-driven gliomas with tumor neoepitope (PDGF + EGFRvIII, n = 8), anti–PD-L1 enhanced abscopal response was associated with macrophage and T-cell infiltration and increased survival benefit (median survival 36 days vs radiation alone 28 days, P = 0.001). Conclusion Our results indicate that anti–PD-L1 immunotherapy enhances a radiation- induced abscopal response via canonical T-cell activation and direct macrophage activation in glioblastoma.
Impact of different definitions of atopic dermatitis
Authors: T. Nakamura, S. Haider, S. Colicino, C.S. Murray, J. Holloway, A. Simpson, P. Cullinan, A. Custovic
Journal: British Journal of Dermatology (2019)

Atopic dermatitis (AD) is one of the most common skin diseases, but there is no single term used to define this illness. Although AD is currently the most commonly used name for this condition, other names (such as eczema) are also common. This may make it difficult to compare the results between studies and to understand the true burden of the disease. We found that researchers in different countries and different medical specialties used different names (AD or eczema), but that these two names do not always relate to the same illness. We then investigated whether researchers would find different results and draw different conclusions if they used the same name (AD), but defined it in a slightly different way in their studies. To do this, we first reviewed medical literature to find the most common ways researchers defined AD. We found a staggering 59 different definitions of AD in 45 studies which we reviewed. We then selected four definitions which were most commonly used and applied them to >1000 children in two birth cohorts (they were born in the same set time period) from the UK. Using these different definitions resulted in a major difference in the number of children labelled as having AD (so called prevalence of the disease), as well as differences in the evaluation of the importance of genes and other risk factors for the disease. The authors conclude that a common and universally accepted definition of this disease is urgently needed, in order to fully appreciate its impact on patients, their families and society, and to identify how important various genes and environmental exposures are.
Mice Engineered To Express a Form of Thrombin Favoring Protein C Are Resistant to S. aureus-Induced Sepsis.
Authors: Matthew J. Flick, Anil K. Chauhan, Sara Welch, Maureen A. Shaw, Kathryn E. Talmage, Eric S. Mullins, Joseph S. Palumbo, Sherry Thornton, Denisa D. Wagner, Jay L. Degen
Journal: Blood (2007)
Coactivation of Endogenous Wnt10b and Foxc2 by CRISPR Activation Enhances BMSC Osteogenesis and Promotes Calvarial Bone Regeneration
Authors: Mu-Nung Hsu, Kai-Lun Huang, Fu-Jen Yu, Po-Liang Lai, Anh Vu Truong, Mei-Wei Lin, Nuong Thi Kieu Nguyen, Chih-Che Shen, Shiaw-Min Hwang, Yu-Han Chang, Yu-Chen Hu
Journal: Molecular Therapy (2019)

CRISPR activation (CRISPRa) is a burgeoning technology for programmable gene activation, but its potential for tissue regeneration has yet to be fully explored. Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into osteogenic or adipogenic pathways, which are governed by the Wnt (Wingless-related integration site) signaling cascade. To promote BMSC differentiation toward osteogenesis and improve calvarial bone healing by BMSCs, we harnessed a highly efficient hybrid baculovirus vector for gene delivery and exploited a synergistic activation mediator (SAM)-based CRISPRa system to activate Wnt10b (that triggers the canonical Wnt pathway) and forkhead c2 (Foxc2) (that elicits the noncanonical Wnt pathway) in BMSCs. We constructed a Bac-CRISPRa vector to deliver the SAM-based CRISPRa system into rat BMSCs. We showed that Bac-CRISPRa enabled CRISPRa delivery and potently activated endogenous Wnt10b and Foxc2 expression in BMSCs for >14 days. Activation of Wnt10b or Foxc2 alone was sufficient to promote osteogenesis and repress adipogenesis in vitro. Furthermore, the robust and prolonged coactivation of both Wnt10b and Foxc2 additively enhanced osteogenic differentiation while inhibiting adipogenic differentiation of BMSCs. The CRISPRa-engineered BMSCs with activated Wnt10b and Foxc2 remarkably improved the calvarial bone healing after implantation into the critical-sized calvarial defects in rats. These data implicate the potentials of CRISPRa technology for bone tissue regeneration.
Risk Factors for Infections Involving Cardiac Implanted Electronic Devices
Authors: David H Birnie, Jia Wang, Marco Alings, François Philippon, Ratika Parkash, Jaimie Manlucu, Paul Angaran, Claus Rinne, Benoit Coutu, R Aaron Low, Vidal Essebag, Carlos Morillo, Damian Redfearn, Satish Toal, Giuliano Becker, Michel Degrâce, Bernard Thibault, Eugene Crystal, Stanley Tung, John LeMaitre, Omar Sultan, Matthew Bennett, Jamil Bashir, Felix Ayala-Paredes, Philippe Gervais, Leon Rioux, Martin E W Hemels, Leon H R Bouwels, Derek V Exner, Paul Dorian, Stuart J Connolly, Yves Longtin, Andrew D Krahn
Journal: Journal of the American College of Cardiology (2019)
Not all lesions are created equal: removal of a cavernous hemangioma
Authors: Qais Dawod, Danny Issa, Reem Z. Sharaiha
Journal: Endoscopy (2019)

A 63-year-old woman was referred for evaluation of a subepithelial esophageal mass and dysphagia. Endoscopy at an outside hospital reported an increase in the size of the mass. Endoscopic ultrasound showed a hypoechoic well-defined subepithelial mass originating within the submucosa and measuring 23 mm in maximum diameter. Fine-needle aspiration of the mass was nondiagnostic. Owing to the dysphagia and the increase in size, we proceeded with endoscopic resection ([Video 1]).