tbuckley/cabot-search huggingface dataset:
Abstract 12299: Rejuvenation of the Bone Marrow-Derived Cardiac Resident Sca-1+ Stem Cell Subset Improved Healing of the Aged Heart
Authors: Shu-Hong Li, Lu Sun, Lei Yang, Zhengbo Shao, Pan Yu, Guo-Qing Du, Jun Wu, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2015)

Introduction: We previously reported that bone marrow (BM) reconstitution with young BM cells into aged recipients restored progenitors in both the BM and the myocardium and improved functional recovery post-injury. Here, our goal was to identify the specific cell type responsible for the improved cardiac regeneration and to restore that capacity in aged individuals after myocardial infarction (MI). Methods and Results: We reconstituted old mice with BM cells from young or old GFP+ mice to generate young chimeras and old chimeras. The number of BM-derived Sca-1+ progenitors homing to the heart was significantly greater in young chimeras compared to old ones (7.14±0.32/field for young vs 2.48±0.78/field for old, P&lt;0.01, 5 high-powered fields/section, 3 sections/heart, 3 animals/group). We then separated Sca-1+ from Sca-1- young donor BM cells using magnetic cell sorting and transplanted them into lethally-irradiated old recipients to generate Sca-1+ and Sca-1- chimeras. Quantification by flow cytometry of heart tissue revealed: 1) the Sca-1+ chimeras had more BM-derived cells that co-expressed PDGFRβ (1.65±0.13% for Sca-1+ vs 0.52±0.09% for Sca-1-, P&lt;0.05, n=4/group) and 2) the number of GFP+ PDGFRβ+ cells was greater in the Sca-1+ chimeric hearts than the Sca-1- chimeric hearts after MI (3.77±0.55% for Sca-1+ vs 0.85±0.106% for Sca-1-, P&lt;0.05, n=3/group). The BM-derived cells that homed to the heart in the Sca-1+ chimeras actively proliferated, stimulated proliferation of the host’s aged progenitors and improved ventricular function after MI. BM chimerism with Sca-1+ cells in aged mice restored the regenerative capability of cardiac resident progenitors and improved functional healing of the aged heart. Conclusions: BM Sca-1+ cells that homed to the heart in aged recipients proliferated and stimulated the propagation of host aged progenitor cells post-MI. This improved regeneration involved activation of the PDGFRβ/Akt/p27Kip1 signaling pathway. The number of BM-derived Sca-1+ progenitor cells in the aged myocardium was the major determinant for successful cardiac functional recovery. Restoration of the Sca-1 subset of stem cells by BM reconstitution improved cardiac repair and prevented heart failure.
Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in <i>BRCA1</i> Mutation Carriers
Authors: Rodrigo Santa Cruz Guindalini, Yonglan Zheng, Hiroyuki Abe, Kristen Whitaker, Toshio F. Yoshimatsu, Tom Walsh, David Schacht, Kirti Kulkarni, Deepa Sheth, Marion S. Verp, Angela R. Bradbury, Jane Churpek, Elias Obeid, Jeffrey Mueller, Galina Khramtsova, Fang Liu, Akila Raoul, Hongyuan Cao, Iris L. Romero, Susan Hong, Robert Livingston, Nora Jaskowiak, Xiaoming Wang, Marcio Debiasi, Colin C. Pritchard, Mary-Claire King, Gregory Karczmar, Gillian M. Newstead, Dezheng Huo, Olufunmilayo I. Olopade
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. Results: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. Conclusions: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening. See related commentary by Kuhl and Schrading, p. 1693
Heart Failure With Preserved Ejection Fraction in the Young
Authors: Jasper Tromp, Michael R. MacDonald, Wan Ting Tay, Tiew-Hwa K. Teng, Chung-Lieh Hung, Calambur Narasimhan, Wataru Shimizu, Lieng Hsi Ling, Tze Pin Ng, Jonathan Yap, John J.V. McMurray, Michael R. Zile, A. Mark Richards, Inder S. Anand, Carolyn S.P. Lam
Journal: Circulation (2018)

Background: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young. Methods: We prospectively enrolled 1203 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions. We grouped HFpEF patients into very young (&lt;55 years of age; n=157), young (55–64 years of age; n=284), older (65–74 years of age; n=355), and elderly (≥75 years of age; n=407) and compared clinical and echocardiographic characteristics, quality of life, and outcomes across age groups and between very young individuals with HFpEF and age- and sex-matched control subjects without heart failure. Results: Thirty-seven percent of our HFpEF population was &lt;65 years of age. Younger age was associated with male preponderance and a higher prevalence of obesity (body mass index ≥30 kg/m 2 ; 36% in very young HFpEF versus 16% in elderly) together with less renal impairment, atrial fibrillation, and hypertension (all P &lt;0.001). Left ventricular filling pressures and prevalence of left ventricular hypertrophy were similar in very young and elderly HFpEF. Quality of life was better and death and heart failure hospitalization at 1 year occurred less frequently ( P &lt;0.001) in the very young (7%) compared with elderly (21%) HFpEF. Compared with control subjects, very young HFpEF had a 3-fold higher death rate and twice the prevalence of hypertrophy. Conclusions: Young and very young patients with HFpEF display similar adverse cardiac remodeling compared with their older counterparts and very poor outcomes compared with control subjects without heart failure. Obesity may be a major driver of HFpEF in a high proportion of HFpEF in the young and very young.
In vivo genome editing of mucopolysaccharidosis I mice using the CRISPR/Cas9 system
Authors: Roselena Silvestri Schuh, Édina Poletto, Gabriela Pasqualim, Angela Maria Vicente Tavares, Fabíola Shons Meyer, Esteban Alberto Gonzalez, Roberto Giugliani, Ursula Matte, Helder Ferreira Teixeira, Guilherme Baldo
Journal: Journal of Controlled Release (2018)
Abstract 19332: Cardiac Kir2.1 and NaV1.5 Channels Associate in a Macromolecular Complex Early in Their Forward Trafficking Pathway
Authors: Daniela Ponce-Balbuena, Carmen R Valdivia, Cicero B Willis, Francisco J Alvarado, Guadalupe Guerrero-Serna, Manuel Zarzoso, Eva Delpón, Ricardo Caballero, Juan Tamargo, Rafael R Ramirez, Kuljeet Kaur, Héctor H Valdivia, José Jalife
Journal: Circulation (2016)

Introduction: The factors that control the expression of Kir2.1 and NaV1.5 channels and the mechanisms that target such channels to subcellular and membrane macrodomains are incompletely understood...
Response to Dual Crizotinib and Osimertinib Treatment in a Lung Cancer Patient with MET Amplification Detected by Liquid Biopsy Who Acquired Secondary Resistance to EGFR Tyrosine Kinase Inhibition
Authors: Lei Deng, Lesli A. Kiedrowski, Elizabeth Ravera, Haiying Cheng, Balazs Halmos
Journal: Journal of Thoracic Oncology (2018)
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome
Authors: Michael Y. Mi, Michael A. Matthay, Alan H. Morris
Journal: New England Journal of Medicine (2018)

This interactive feature about the care of patients with severe acute respiratory distress syndrome offers a case vignette accompanied by essays that support either treatment with extracorporeal membrane oxygenation (ECMO) or the use of other adjunctive therapies.
Treatment of mycophenolate-resistant immune-related organizing pneumonia with infliximab
Authors: Guacimara Ortega Sanchez, Kathleen Jahn, Spasenija Savic, Alfred Zippelius, Heinz Läubli
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> The development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. While many published articles and guidelines are focusing on the presentation and upfront treatment of pulmonary irAEs, the strategy in patients with late-onset pneumonia that are resistant to commonly used immunosuppressive drugs remains unclear. <h3>Case presentation</h3> Here, we report the successful treatment of a mycophenolate-resistant organizing pneumonia (OP) with infliximab in a patient with metastatic melanoma after PD-1 blockade. The patient received two years of PD-1 targeted immunotherapy when he developed multiple nodular lung lesions mimicking a metastatic progression. However, wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, new foci of OP developed which were resistant to high-dose steroids and mycophenolate treatment. The TNFα antagonist infliximab led to a rapid and durable regression of the inflammatory lesions. <h3>Conclusion</h3> This case describes a not well-studied situation, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated with a TNFα neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/−dependent late onset pulmonary irAEs.
Pulmonary Transplantation of Human Induced Pluripotent Stem Cell–derived Macrophages Ameliorates Pulmonary Alveolar Proteinosis
Authors: Christine Happle, Nico Lachmann, Mania Ackermann, Anja Mirenska, Gudrun Göhring, Kathrin Thomay, Adele Mucci, Miriam Hetzel, Torsten Glomb, Takuji Suzuki, Claudia Chalk, Silke Glage, Oliver Dittrich-Breiholz, Bruce Trapnell, Thomas Moritz, Gesine Hansen
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Although the transplantation of induced pluripotent stem cell (iPSC)–derived cells harbors enormous potential for the treatment of pulmonary diseases, in vivo data demonstrating clear therapeutic benefits of human iPSC–derived cells in lung disease models are missing.Objectives: We have tested the therapeutic potential of iPSC-derived macrophages in a humanized disease model of hereditary pulmonary alveolar proteinosis (PAP). Hereditary PAP is caused by a genetic defect of the GM-CSF (granulocyte–macrophage colony–stimulating factor) receptor, which leads to disturbed macrophage differentiation and protein/surfactant degradation in the lungs, subsequently resulting in severe respiratory insufficiency.Methods: Macrophages derived from human iPSCs underwent intrapulmonary transplantation into humanized PAP mice, and engraftment, in vivo differentiation, and therapeutic efficacy of the transplanted cells were analyzed.Measurements and Main Results: On intratracheal application, iPSC-derived macrophages engrafted in the lungs of humanized PAP mice. After 2 months, transplanted cells displayed the typical morphology, surface markers, functionality, and transcription profile of primary human alveolar macrophages. Alveolar proteinosis was significantly reduced as demonstrated by diminished protein content and surfactant protein D levels, decreased turbidity of the BAL fluid, and reduced surfactant deposition in the lungs of transplanted mice.Conclusions: We here demonstrate for the first time that pulmonary transplantation of human iPSC–derived macrophages leads to pulmonary engraftment, their in situ differentiation to an alveolar macrophage phenotype, and a reduction of alveolar proteinosis in a humanized PAP model. To our knowledge, this finding presents the first proof-of-concept for the therapeutic potential of human iPSC-derived cells in a pulmonary disease and may have profound implications beyond the rare disease of PAP.
Abbott HCV core Ag and HCV RNA comparison study in country of Georgia
Authors: N. Chitadze, R. Sukhiashvili, J. Drobeniuc, G. Chanturia, M. Alkhazashvili, F. Averhoff, J.W. Ward, S. Kamili, B. Skaggs, J. Morgan, G. Cloherty, A. Gamkrelidze
Journal: Journal of Hepatology (2017)
Adding baseline protein biomarkers to clinical predictors does not enhance prediction of treatment response to a methotrexate strategy in early rheumatoid arthritis
Authors: Xavier M Teitsma, Johannes W G Jacobs, Pascal H P de Jong, Johanna M W Hazes, Angelique E A M Weel, Paco M J Welsing, Attila Pethö-Schramm, Michelle E A Borm, Jacob M van Laar, Johannes W J Bijlsma, Floris P J G Lafeber
Journal: Annals of the Rheumatic Diseases (2018)

Recently, we identified baseline higher disease activity score assessing 28 joints, current smoking and no alcohol consumption as predictors of inadequate response (IR) to methotrexate (MTX), used with or without other conventional synthetic disease modifying anti-rheumatic drugs, here designated as ‘MTX+’, in new-onset rheumatoid arthritis (RA).1 For those with a predicted IR to ‘MTX+’, a more intensive treatment strategy could be initiated, if prediction would be reliable. Therefore, we investigated, within the same patient population, protein biomarkers for additive predictive value to these clinical predictors.

A model was developed using data from patients with RA in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) treated with a step-up MTX strategy (n=106) and was validated in patients who received MTX therapy (n=80) in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH, ISRCTN26791028).2,3 IR to ‘MTX+’ therapy was defined as the need to initiate a biological within the first treatment year. In baseline serum, 85 proteins were analysed in 2014 using multiplex Luminex profiling; seven candidate proteins, identified by partial least square discriminant analyses, were remeasured in 2018.

Clinical baseline characteristics of the patients in both studies are shown in table 1. Of the proteins identified in the development cohort, in the …
Doctors call for tighter UK rules on tissue importation after controversial Real Bodies exhibition
Authors: Declan Murphy
Journal: BMJ (2018)

Regulations governing tissue importation into the UK should be tightened in the wake of ethical concerns about an exhibition of dead bodies from China, a group of doctors and others have argued.

Doctors, human rights activists, and MPs wrote an open letter to the prime minister and other political leaders on 6 August 2018,1 outlining concerns that human cadaveric specimens displayed in the Real Bodies exhibition in Birmingham could be executed prisoners of conscience from Dalian, in northeast China.2 The exhibition has stated that the bodies are “unclaimed” and that no documentation of consent has been provided.3

Exhibitions displaying plastinated human specimens are legal in the UK under the Human Tissue Act 2004. While the legal storage and use of …
Identifying research priorities for digital technology in mental health care: results of the James Lind Alliance Priority Setting Partnership
Authors: Chris Hollis, Stephanie Sampson, Lucy Simons, E Bethan Davies, Rachel Churchill, Victoria Betton, Debbie Butler, Kathy Chapman, Katherine Easton, Toto Anne Gronlund, Thomas Kabir, Mat Rawsthorne, Elizabeth Rye, André Tomlin
Journal: The Lancet Psychiatry (2018)
Abstract 18295: Comparison of Long Term Health and Economic Outcomes of ED Triage Strategies for Patients With Acute Chest Pain
Authors: Alexander Goehler, Thomas Mayrhofer, Amit Pursnani, Heidi Lumish, Cordula Barth, John T Nagurney, Quynh A Truong, Pamela McMahon, Scott G Gazelle, Udo Hoffmann
Journal: Circulation (2013)

Background: Cardiac CT, functional testing and expedited ED triage with subsequent outpatient testing have been proposed as viable strategies to triage patients presenting with acute chest pain. However, long term health and economic outcomes data are not available. Methods: We developed a Markov microsimulation model to examine 4 ED triage strategies: early CCTA (CCTA) and standard ED evaluation (SOC) based on ROMICAT II, a consensus guideline based strategy, and a previously published expedited ED triage protocol using two troponin measurements. As model input parameters, we used demographics, risk factors and resource utilization as observed in the ROMICAT II study. The model predicted the number of diagnostic tests and costs for the initial ED presentation, 5-year mortality and lifetime outcomes and determined the incremental cost-effectiveness ratios (ICER). Result: The model accurately predicted multiple ROMICAT II endpoints: Length of stay (CCTA: 23.2 hr (model) vs. 23.2 hr (ROMICAT II trial); SOC: 30.3 hr vs. 30.8 hr), frequency of PCI (CCTA: 5% vs. 5%; SOC: 3% vs. 3%), cumulative radiation exposure (CCTA: 14.0 mSv vs. 14.3 mSv; SOC: 6.1 mSv vs. 5.3 mSv), and total costs during initial ED presentation (CCTA: $4,356 vs. $4,289; SOC: $4,179 vs. $4,060). The expedited ED protocol resulted in substantial savings of resources during the initial ED presentation (Table). After 5 years, however, mortality was highest in the expedited ED strategy and lowest after early CCTA. Moreover, lifetime ICER was $39,700/QALY for CCTA compared to the expedited ED protocol, while SOC and consensus optimal SOC strategies were dominated (i.e., less effective and more expensive). Conclusion: A Markov microsimulation analysis based on ROMICAT II outcomes predicts that for long term health and economic outcomes CCTA is a cost-effective ED triage strategy for patients presenting with acute chest pain compared to alternative strategies.
Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis
Authors: Ishita Banerjee, Bharat Behl, Morena Mendonca, Gaurav Shrivastava, Ashley J. Russo, Antoine Menoret, Arundhati Ghosh, Anthony T. Vella, Sivapriya Kailasan Vanaja, Saumendra N. Sarkar, Katherine A. Fitzgerald, Vijay A.K. Rathinam
Journal: Immunity (2018)
Three-year cost-effectiveness analysis of the DRESS study: protocolised tapering is key
Authors: Nathan den Broeder, Chantal A M Bouman, Wietske Kievit, Noortje van Herwaarden, Frank H J van den Hoogen, Ronald F van Vollenhoven, Hans W J Bijlsma, Aatke van der Maas, Alfons A den Broeder
Journal: Annals of the Rheumatic Diseases (2018)

The DRESS (Dose REduction Strategy of Subcutaneous TNF inhibitors) study previously showed clinical non-inferiority and superior cost-effectiveness of disease activity-guided tapering of tumour necrosis factor inhibitors (TNFi) (dose reduction, DR group) over full dose continuation (usual care, UC group) in patients with rheumatoid arthritis (RA) with low disease activity.1 2 The safety and efficacy of this strategy were maintained up to 3 years, with a large reduction in TNFi use.3 During the extension phase, the majority of the UC group attempted dose reduction. This prevented a valid comparison of disease activity-guided tapering with full dose continuation over the entire study period but presented an opportunity to make the following comparisons:

1.  Tapering long-term results (in the DR group 18–36 months) versus short-term results (in the DR group 0–18 months).

2.  Tapering at the rheumatologist’s discretion (in the UC group 18–36 months) compared with full dose continuation (in the UC group 0–18 months). …
Biodegradable and elastomeric vascular grafts enable vascular remodeling
Authors: Meifeng Zhu, Yifan Wu, Wen Li, Xianhao Dong, Hong Chang, Kai Wang, Pingli Wu, Jun Zhang, Guanwei Fan, Lianyong Wang, Jianfeng Liu, Hongjun Wang, Deling Kong
Journal: Biomaterials (2018)
Structural Basis of Cross‐Reactivity of Anti–Citrullinated Protein Antibodies
Authors: Changrong Ge, Bingze Xu, Bibo Liang, Erik Lönnblom, Susanna L. Lundström, Roman A. Zubarev, Burcu Ayoglu, Peter Nilsson, Thomas Skogh, Alf Kastbom, Vivianne Malmström, Lars Klareskog, René E. M. Toes, Theo Rispens, Doreen Dobritzsch, Rikard Holmdahl
Journal: Arthritis & Rheumatology (2018)

Objective Anti–citrullinated protein antibodies ( ACPA s) develop many years before the clinical onset of rheumatoid arthritis ( RA ). This study was undertaken to address the molecular basis of the specificity and cross‐reactivity of ACPA s from patients with RA . Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross‐reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen‐binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x‐ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity‐determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPA s derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone‐mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA ‐specific ACPA s.
Effects of Anorexia Nervosa on Bone Metabolism
Authors: Pouneh K Fazeli, Anne Klibanski
Journal: Endocrine Reviews (2018)

Anorexia nervosa is a psychiatric disease characterized by a low-weight state due to self-induced starvation. This disorder, which predominantly affects women, is associated with hormonal adaptations that minimize energy expenditure in the setting of low nutrient intake. These adaptations include GH resistance, functional hypothalamic amenorrhea, and nonthyroidal illness syndrome. Although these adaptations may be beneficial to short-term survival, they contribute to the significant and often persistent morbidity associated with this disorder, including bone loss, which affects >85% of women. We review the hormonal adaptions to undernutrition, review hormonal treatments that have been studied for both the underlying disorder as well as for the associated decreased bone mass, and discuss the important challenges that remain, including the lack of long-term treatments for bone loss in this chronic disorder and the fact that despite recovery, many individuals who experience bone loss as adolescents have chronic deficits and an increased risk of fracture in adulthood.
Why do people think that others should earn this or that?
Authors: Daniel Sznycer, Elsa Ermer, John Tooby
Journal: Behavioral and Brain Sciences (2018)

Abstract Some questions, such as when a statistical distribution of incomes becomes too unequal, seem highly attention-grabbing, inferentially productive, and morally vexing. Yet many other questions that are crucial to the functioning of a modern economy seem uninteresting non-issues. An evolutionary–psychological framework to study folk-economic beliefs has the potential to illuminate this puzzle.