tbuckley/cabot-search huggingface dataset:
STING-associated lung disease in mice relies on T cells but not type I interferon
Authors: Hella Luksch, W. Alexander Stinson, Derek J. Platt, Wei Qian, Gowri Kalugotla, Cathrine A. Miner, Brock G. Bennion, Alexander Gerbaulet, Angela Rösen-Wolff, Jonathan J. Miner
Journal: Journal of Allergy and Clinical Immunology (2019)
Do Educational Interventions Improve Pre-Hospital Providers’ Knowledge and Confidence in Recognizing and Treating Anaphylaxis?
Authors: Margaret Redmond, Kasey R. Strothman, Eric Cortez, Lauren Malthaner, Tara McCarthy, Andrew Murphy, Todd Heslep, Daniel Scherzer, Rebecca Scherzer, Julie Leonard
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 15285: Prognostic Value of 6-year Change in High Sensitivity Cardiac Troponin-T for Risk of Heart Failure, Heart Failure Subtype, and Death
Authors: Bill Mcevoy, Chiadi E Ndumele, Yuan Chen, Scott D Solomon, Michael Steffes, Vijay Nambi, Christie Ballantyne, Roger Blumenthal, Josef Coresh, Elizabeth Selvin
Journal: Circulation (2015)

Background: Serial changes in high-sensitivity cardiac troponin-T (hs-cTNT) indicate progressive subclinical myocardial damage and have been associated with heart failure (HF) and death in asymptomatic older adults. Whether these associations exist in middle-age and whether serial hs-cTNT is more strongly associated with HF with reduced ejection fraction (HFREF) or HF with preserved ejection fraction (HFPEF) is poorly understood. Methods: We studied 8,838 participants of the Atherosclerosis Risk in Communities Study, initially free of coronary heart disease and HF, who had hs-cTNT measured at two time-points, 6 years apart. Using proportional hazards regression, we examined the association of absolute and relative change in hs-cTNT with incident HF hospitalization or death. Sensitivity analyses for HFPEF and HFREF were also conducted. Results: Mean age at baseline was 57 years, 57% were female and 21% were black. Over a maximum of 16 years follow-up there were 965 HF events and 1813 deaths. In adjusted models, incident detectable hs-cTNT (≥5ng/L) was associated with subsequent HF (Hazard Ratio [HR] 1.86, 95% Confidence Interval [CI] 1.53-2.25) and death (1.46 [1.28-1.68]). HRs were larger for incident hs-cTNT elevation (≥14ng/L) but similar for those with a relative increase &gt;50% from baseline hs-cTNT (Table). In contrast, risk was lower for relative reductions &gt;50% from baseline hs-cTNT. Temporal increases in hs-cTNT were associated with both HFREF and HFPEF in categorical analyses, however, when modeled continuously (per SD increase), absolute 6-year hs-cTNT change appeared to be more strongly associated with HFPEF hospitalization (HR 1.30 [1.06-1.60]) than with HFREF hospitalization (1.08 [0.88-1.33]). Conclusions: Absolute and relative change in hs-cTNT were independently associated with incident CHD, HF and death, even after adjustment for baseline hs-cTNT. Associations were generally consistent for both the HFREF and HFPEF phenotypes
High Cure Rate By Allogeneic Stem Cell Transplantation for Myelofibrosis Patients Aged 65 or Older
Authors: Giulia Daghia, Tatjana Zabelina, Gaby Zeck, Ute-Marie von Pein, Maximilian Christopeit, Christine Wolschke, Francis Ayuketang Ayuk, Nicolaus Kroeger
Journal: Blood (2018)
Abstract PR09: Alterations in cell junctions and neuroendocrine differentiation are key early steps in Crebbp/Ep300 mutation-driven SCLC development
Authors: Dong-Wook Kim, Keebeom Kim, Colin T. Dunn, Kwon-Sik Park
Journal: Clinical Cancer Research (2018)

Abstract The abundance and heterogeneity of somatic alterations in small cell lung cancer (SCLC) present immense challenges in identifying key mechanisms of tumor development. Functional characterization of recurrent mutations is an essential step towards understanding the early stages of SCLC development, but this remains extremely difficult due to the scarcity of relevant and tractable models for defining oncogenic drivers and molecular pathways. In a previous study, we derived precancerous cells (preSCs) from the Rb/p53/Rbl2-mutant mouse model of SCLC and developed an engineered preSC-based model of early tumor development. In this model, activation of oncogenic drivers transforms preSCs into tumorigenic cells that form spheroid clusters characteristic of SCLC in culture and subcutaneous tumors in athymic nude mice. Using this streamlined approach, we found that both retroviral amplification of the Myc family members and CRISPR/Cas9-mediated mutation of Crebbp/Ep300 were sufficient to cause transformation of preSCs into SCLC cells. Notably, both sets of mutant preSC underwent a similar phenotypic change from adherent monolayers to spheroid aggregates, suggesting that the two different types of alterations interact with or converge on common molecular pathways. Comparative profiling of control preSCs and mutant preSCs carrying either a Myc family amplification or Crebbp/Ep300 mutation revealed that alterations in cell junctions and neuroendocrine differentiation are the most significant molecular changes during cellular transformation. The transformed preSCs exhibited decreased expression of adhesion-related genes, including Cdh1 and Dsp, but increased expression of mesenchymal genes Vim and Twist1. The transformed cells also showed reduced expression of neuroendocrine (NE) differentiation genes, including Ascl1, Chga, and Syp. Furthermore, these changes coincided with increased expression of Notch receptors and decreased expression of their ligands Dlls and Jags. Taken together, these novel findings suggest that a phenotypic switch from Dll/Jag-expressing NE cells to Notch-expressing non-NE cells is a key event in early SCLC development. This study also demonstrated that the preSC-based model can facilitate functional validation of recurrent mutations in SCLC and molecular pathways that will be further explored for mechanistic elucidation and development of targeted therapies. This abstract is also being presented as Poster A09. Citation Format: Dong-Wook Kim, Keebeom Kim, Colin T. Dunn, Kwon-Sik Park. Alterations in cell junctions and neuroendocrine differentiation are key early steps in Crebbp/Ep300 mutation-driven SCLC development [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr PR09.
Expression profiling of atopic dermatitis patients with a history of recurrent eczema herpeticum reveals dysregulation of type 2-inflammation and barrier-related pathways in uninvolved skin
Authors: Nathan T. Dyjack, Elena Goleva, Cydney Rios, Michael T. Montgomery, Brittany N. Richers, Kathryn A. Norquest, Donald Y.M. Leung, Max A. Seibold
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 17607: Impact of Percutaneous Transluminal Pulmonary Angioplasty for Patients With Chronic Thromboembolic Disease Without Pulmonary Hypertension
Authors: Ryoji Yanagisawa
Journal: Circulation (2017)

Introduction: Percutaneous transluminal pulmonary angioplasty (PTPA) in expert center may be considered in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are technically no...
MPs demand answers on medicine supply in a no deal Brexit
Authors: Jacqui Wise
Journal: BMJ (2019)

A House of Lords committee has again called on the government to provide clarity on whether access to medicines and medical products can be guaranteed after Brexit if no deal is agreed.

In a letter to England’s health secretary, Matt Hancock,1 the House of Lords EU Home Affairs subcommittee warned of a lack of clear information with just nine weeks to go before the UK leaves the European Union.

The committee initially wrote to the minister after an evidence session on “no deal” preparations for medicine provision in November last year, asking …
Psychological Profiles of Seasonal Allergy Patients in Vinnytsya, Ukraine
Authors: Victoria Rodinkova, Alla Kondratyuk, Olga Bondarchuk, Iryna Korytska, Lidiya Kyrychenko, Tamara Kryvonos, Olga Palamarchuk, Olena Tozyuk, Lawrence M. Dubuske
Journal: Journal of Allergy and Clinical Immunology (2019)
Identity fusion and fitness interdependence
Authors: Lee Cronk, Athena Aktipis
Journal: Behavioral and Brain Sciences (2018)

Abstract Fitness interdependence is the degree to which two or more organisms influence each other's success in replicating their genes. Identity fusion may be a proximate mechanism that aligns behavior with fitness interdependence. Although identity fusion may usually lead to behaviors that are fitness enhancing, in evolutionarily novel environments, it may be hijacked in ways that are highly detrimental to fitness.
‘Everything we see is a perspective, not the truth’
Authors: Arghya Chattopadhyay, Varun Dhir, Sanjay Jain
Journal: Annals of the Rheumatic Diseases (2019)

Everything we see is a perspective, not the truth'We read with interest the article on 'Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort' by Julie Sahuguet et al. 1 The results are exciting regarding the significantly lower prevalence of vertebral fracture (VF) among patients with 'early SpA' and the crucial aspect of recognising vertebral defects as confounding factors.However, certain aspects of this study require further clarifications.First, the external validity of the data remains questionable.The current study population has a higher number of female patients compared with the previous studies 2 3 where male:female ratio was 4:1.The proportion of patients who were HLA B27 positive is also substantially lower in the current cohort compared with the previous one. 3So, the present cohort may not be the true representative of the spondyloarthropathy (SpA) population.Second, the diagnostic utility of the low back pain criteria is much lower than expected as shown in a study by Poddubnyy et al.Specificity of the Calin criteria for diagnosing axial SpA is as low as 25%, and specificity for the Berlin criteria is 32%-44.8%depending on whether the physician was blinded or not.The specificity further reduced to 20% and 18%, respectively, if the patients applied the criteria. 4It will be interesting to know how many of the patients in the DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR) cohort subsequently satisfied the classification criteria for SpA.Third, the authors have selected patients having low back pain for a duration of 3 months to 3 years.It will be interesting to know the total number of patients screened to achieve these number of patients to be included, as in general, the available data suggests that the median delay to diagnosis has remained stable at 5 years for the patients diagnosed between 1999-2003, 2004-2008 and 2009-2013. 5 Could these patients be different from the usual axial SpA? Like having a higher incidence of peripheral arthritis that may be confounding factor for early case pickup. 5ourth, the higher percentage of the female population in the DESIR cohort may be due to higher proportion having nonradiographic SpA, that may behave differently from radiographic SpA like accruing damage or osteopenia and VFs.These informations would be crucial to the external validityextrapolating the findings of the study.
Risk Factors for Early Relapse after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia
Authors: Sagar S. Patel, Betty K. Hamilton, Lisa Rybicki, Dawn Thomas, Arden Emrick, Aziz Nazha, Sudipto Mukherjee, Anjali S. Advani, Hetty E. Carraway, Brad Pohlman, Brian J. Bolwell, Robert M. Dean, Aaron T. Gerds, Rabi Hanna, Matt Kalaycio, Aiwen Zhang, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Navneet S. Majhail, Medhat Askar, Ronald Sobecks
Journal: Blood (2018)
Abstract 18118: Hypothermic to Ischemic Ratio as a Predictor of Good Functional Outcome From Out-of-Hospital Cardiac Arrest in the Resuscitation Outcomes Consortium Amiodarone Lidocaine or Placebo Study
Authors: Kelly N Sawyer, Andrew Humbert, Brian G Leroux, Graham Nichol, Peter J Kudenchuck, Mohamud R Daya, Brian Grunau, Henry E Wang, Joseph P Ornato, Jon C Rittenberger, Tom P Aufderheide, Lynn Wittwer, M Riccardo Colella, Michael Austin, Takahisa Kawano, Debra Egan, Neal Richmond, Veer D Vithalani, Damon Scales, Andrew J Baker, Laurie J Morrison, Michael C Kurz
Journal: Circulation (2017)

Objectives: The hypothermic to ischemic ratio (HI Ratio) has been previously identified as a potential predictor of survival from out-of-hospital cardiac arrest (OHCA). We investigated its association with functional outcome in the Resuscitation Outcomes Consortium (ROC) Amiodarone, Lidocaine, or Placebo Study (ALPS). Methods: We included adult, non-traumatic, witnessed, OHCA patients screened for ROC-ALPS who survived to hospital between May 2012 and October 2015. Structured data were collected, including all Utstein variables and relevant time intervals to determine initiation and duration of hypothermia and rewarming. HI Ratio is defined as total time TTM applied (initiation through re-warming) divided by time from arrest to ROSC. Good functional status (mRS 0-3) at hospital discharge was the primary outcome of interest. We fit a logistic regression model to estimate the association between HI ratio and the primary outcome, adjusting for Utstein variables and ROC enrolling site. Results: A total of 2,2...
Association of Maternal Probiotic Supplementation With Human Milk Oligosaccharide Composition
Authors: Antti E. Seppo, Anna K. Kukkonen, Mikael Kuitunen, Erkki Savilahti, Chloe Yonemitsu, Lars Bode, Kirsi. M. Järvinen
Journal: JAMA Pediatrics (2019)

This study assesses the differences in composition of human milk oligosaccharides of mothers who received either probiotic supplements or placebos in the late stages of pregnancy.
A Low Prevalence of Pediatric Food Allergy (FA) Among Older Order Mennonites (OOM) Is Related to Robust IgA Production in Early Life
Authors: Kirsi M. Jarvinen-Seppo, Jonathan T. Phillips, Sade Fridy, Camille Martina, Maria Allen, Antti E. Seppo, Richard Stahlhut, Alex Rosenberg, James Kobie, Richard J. Looney
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract IA18: Evolution of acquired resistance in EGFR mutant NSCLC
Authors: Aaron N. Hata
Journal: Clinical Cancer Research (2018)

Abstract Lung cancers harboring activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors; however, acquired drug resistance inevitably develops. Although genetic mechanisms of acquired resistance have been well characterized, less is known about how resistant clones evolve during treatment. Emerging data are beginning to illuminate the complex interplay of genetic clonal heterogeneity, adaptive signaling changes, epigenetic plasticity, and microenvironment factors that shapes the evolution of acquired resistance. Novel therapeutic strategies that specifically target these processes may prevent or delay the development of drug resistance. Citation Format: Aaron N. Hata. Evolution of acquired resistance in EGFR mutant NSCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA18.
Comparison of Minimal Residual Disease Detection in Autografts of Patients with Multiple Myeloma between 8-Color Multiparameter Flow Cytometry (EuroFlow) and Next-Generation Sequencing
Authors: Hiroyuki Takamatsu, Naoki Takezako, Rachel K Wee, Takeshi Yoroidaka, Takeshi Yamashita, Ryoichi Murata, Kosei Matsue, Shinji Nakao
Journal: Blood (2018)
Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention
Authors: Daniel Chandramohan, Alassane Dicko, Issaka Zongo, Issaka Sagara, Matthew Cairns, Irene Kuepfer, Modibo Diarra, Amadou Barry, Amadou Tapily, Frederic Nikiema, Serge Yerbanga, Samba Coumare, Ismaila Thera, Abdourhamane Traore, Paul Milligan, Halidou Tinto, Ogobara Doumbo, Jean-Bosco Ouedraogo, Brian Greenwood
Journal: New England Journal of Medicine (2019)

Mass administration of azithromycin for trachoma control led to a sustained reduction in all-cause mortality among Ethiopian children. Whether the addition of azithromycin to the monthly sulfadoxine–pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention could reduce mortality and morbidity among African children was unclear.
Up-regulation of soluble RANKL at tumor-bone interface is critical for mammary tumor-induced osteolysis
Authors: Kalyan Nannuru, Mitsuru Futakuchi, Thomas Wilson, Rakesh Singh, Michelle Varney, Thomas Vincent, Eric Marcusson
Journal: Cancer Research (2007)

2795  Bone metastases are most common in patients with advanced breast cancer. The incidence is very high with 65 -75% patients suffer from bone metastasis. Bone metastatic lesions in breast cancer patients are predominantly osteolytic. We hypothesize that tumor-bone interaction is critical for tumor-induced osteolysis and establishment as bone metastasis. We have developed a murine model to examine tumor-stromal interaction in osteolytic bone metastasis. Using this model, we analyzed whether tumor-bone microenvironment regulates expression of genes critical for tumor-induced osteolysis. We used microarray analysis for gene expression profiling at the tumor bone interface versus the tumor alone area from syngenic mice injected with three different mammary tumor cell lines that differ in their metastatic potential (4T1 being the aggressive, Cl66 is moderately metastatic and Cl66M2 is poorly metastatic). Microarray analysis revealed the up-regulation of receptor activator of nuclear factor κB ligand (RANKL) in all three cell lines at the tumor bone interface as compared to tumor alone area. We did not observe significant difference in RANK expression. This observation was further validated by quantitative real time RT-PCR and immunohistochemistry. In addition, the levels of soluble RANKL was significantly elevated at TB-interface as compared to tumor alone area. Inhibition of RANKL using antisense oligonucleotides (AS-RANKL) in syngenic mice injected with Cl66 cells, abrogated mammary-tumor-induced osteolysis. mRNA analysis showed significantly decreased expression of RANKL at TB-interface in AS-RANKL-treated groups compared to control-oligonucleotide treated group. The levels of sRANKL and osteoprotegrin (OPG), a decoy receptor for RANKL, ratios significantly decreased following inhibition of RANKL expression. Together, these results demonstrate that soluble RANKL is an important mediator of mammary tumor-induced osteolysis and the inhibition of RANKL expression using antisense oligonucleotide might be a novel therapeutic strategy for breast cancer bone metastasis.
T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence
Authors: Matthieu Allez, Claire Auzolle, Marjolaine Ngollo, Hugo Bottois, Victor Chardiny, Ana Maria Corraliza, Azucena Salas, Kevin Perez, Carmen Stefanescu, Stéphane Nancey, Anthony Buisson, Benjamin Pariente, Mathurin Fumery, Harry Sokol, Xavier Tréton, Nicolas Barnich, Philippe Seksik, Lionel Le Bourhis
Journal: Gut (2019)

T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection. Methods T cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score &gt;i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively. Results TCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment. Conclusion Clonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven. Trial registration number NCT03458195.
Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation.
Authors: Carlos Roberto Becerra, Pamela Hoof, Andrew Scott Paulson, Gulam Abbas Manji, Olivia Gardner, Aditya Malankar, Joanne Shaw, Devin Blass, Brandon Ballard, Xiaohui Yi, Madhavi Anumula, Aaron E. Foster, Joseph Senesac, Paul Woodard
Journal: Journal of Clinical Oncology (2019)

283 Background: PSCA, a cell surface protein, is upregulated in many solid tumors and correlates with disease stage. BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3ζ CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain. BPX601 is optimized for antigen-directed and independent T cell activation, proliferation and persistence, potentially enhancing efficacy in solid tumors versus traditional CARs. This first-in-human study assesses the safety, biological and clinical activity of BPX601 plus Rim in select PSCA-positive cancers. Methods: NCT02744287 is a two-part, open-label trial. Part 1 is an ongoing 3+3 cell dose escalation to identify the recommended BPX601 cell dose (Day 0) given in combination with a fixed, single Rim dose (0.4 mg/kg; Day 7). Eligibility criteria include previously treated metastatic pancreatic cancer (mPDAC) with measurable disease &amp; positive PSCA expression. Results: Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within three days before BPX601 infusion. Nine adults have been treated across three cell dose levels (cells/kg): 1.25x10 6 (cells only), 1.25x10 6 +Rim, 2.5x10 6 +Rim. All had mPDAC with ≥ two prior therapies. Common AEs were fatigue and nausea. No DLTs, related SAEs, neurotoxicity or CRS events were reported. Rapid cell engraftment by Day 4 was observed in all patients. No evidence of LD with CTX was seen. Of six patients that received Rim: two had cell expansion 10- to 20-fold within seven days; two had cell persistence &gt; three weeks; all had elevated serum cytokines (IP-10, TNFα) correlated with cell expansion. Best response after ≥ one scan was 4 SD ≥ eight weeks with two minor responses (not confirmed; one patient had matched CA19-9 decrease) and 2 PD. Disease control without new therapy was 16 and &gt; 11 weeks (ongoing) in one and two patients, respectively. Conclusions: BPX601 with single-dose Rim was well-tolerated and resulted in enhanced T cell expansion and prolonged persistence in some patients despite lack of LD. Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon and will include CTX/fludarabine LD to maximize engraftment as well as gastric and prostate cancers. Clinical trial information: NCT02744287.
Direct Current Cardioversion of Atrial Arrhythmias in Adults With Cardiac Amyloidosis
Authors: Edward A. El-Am, Angela Dispenzieri, Rowlens M. Melduni, Naser M. Ammash, Roger D. White, David O. Hodge, Peter A. Noseworthy, Grace Lin, Sorin V. Pislaru, Alexander C. Egbe, Martha Grogan, Vuyisile T. Nkomo
Journal: Journal of the American College of Cardiology (2019)