tbuckley/cabot-search huggingface dataset:
Global Lung Initiative equations for pulmonary hypertension screening in systemic sclerosis
Authors: Thibaud Soumagne, Alicia Guillien, Arnaud Chambellan, Thông Hua-Huy, Anh Tuan Dinh-Xuan, Bruno Degano
Journal: European Respiratory Journal (2018)

Systemic sclerosis (SSc) is a connective tissue disease characterised by widespread vasculopathy and excessive fibrosis in multiple organs, including the lungs [1]. The most frequent pulmonary involvement in SSc is interstitial lung disease (ILD), but the most harmful is pulmonary hypertension (PH), a complication found in about 10% of SSc patients [2]. In patients with SSc, early diagnosis of and prompt therapy for PH (either isolated or associated with ILD) are beneficial from a prognostic standpoint and recommendations for active screening of PH in SSc have therefore been established [3]. GLI equations provide new cut-offs for T LCO for detection of PH in patients with SSc, either with or without ILD <http://ow.ly/aCpD30l2zch>
Therapeutic effect of vitamin D3-containing nanostructured lipid carriers on inflammatory bowel disease
Authors: Khadijah Zai, Masato Hirota, Takahiro Yamada, Narumi Ishihara, Takeshi Mori, Akihiro Kishimura, Koichiro Suzuki, Koji Hase, Yoshiki Katayama
Journal: Journal of Controlled Release (2018)
Evaluation of Medicare’s Bundled Payments Initiative for Medical Conditions
Authors: Karen E. Joynt Maddox, E. John Orav, Jie Zheng, Arnold M. Epstein
Journal: New England Journal of Medicine (2018)

The Center for Medicare and Medicaid Innovation (CMMI) launched the Bundled Payments for Care Improvement (BPCI) initiative in 2013. A subsequent study showed that the initiative was associated with reductions in Medicare payments for total joint replacement, but little is known about the effect of BPCI on medical conditions.
AB0912 Two-year efficacy and safety of guselkumab for treatment of moderate-to-severe psoriasis: phase 3 voyage 1 trial
Authors: C.E. Griffiths, K.A. Papp, A.B. Kimball, B. Randazzo, Y. Wasfi, S. Li, Y.-K. Shen, A. Blauvelt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Guselkumab (GUS) is an interleukin-23 inhibitor recently approved in the US for treatment of moderate-to-severe psoriasis. <h3>Objectives</h3> Efficacy and safety data for up to 100 wks of GUS treatment are reported. <h3>Methods</h3> In the VOYAGE 1 Phase 3, randomised, double-blind, placebo/active comparator-controlled trial, 837 patients were randomised at baseline to placebo (PBO) at wks0/4/12 then GUS 100 mg at wks16/20 and q8w (n=174); GUS at wks0/4/12, and q8w (n=329); or adalimumab (ADA) 80 mg at wk 0, 40 mg at wk1, and q2w through wk47 then GUS at wk52 and q8w (n=334). Efficacy was assessed using nonresponder imputation through wk48 and treatment failure rules from wks52–100. <h3>Results</h3> Among patients randomised to GUS, or PBO→GUS at wk16, efficacy (PASI, Psoriasis Area and Severity Index; IGA, Investigator's Global Assessment) was maintained from wks52–100 with continuous GUS treatment. Among those randomised to ADA (→GUS at wk52), efficacy improved from wks52–100. Similar findings were observed for patient-reported outcomes (PSSD, Psoriasis Symptoms and Signs Diary; DLQI, Dermatology Life Quality Index; table 1). Through wk100, there were no disproportionate increases in rates of Adverse Events (AEs) compared with rates through wk48. Serious AE rates were low and remained stable; no TB, opportunistic infections, or serious hypersensitivity reactions were reported. <h3>Conclusions</h3> Efficacy among GUS patients was maintained through 2 years of continuous treatment. Efficacy among ADA→GUS patients improved from wks52–100. GUS was well-tolerated, with a similar safety profile as previously reported. <h3>Disclosure of Interest</h3> C. Griffiths Grant/research support from: Janssen Research and Development, LLC, K. Papp Grant/research support from: Janssen Research and Development, LLC, A. Kimball Grant/research support from: Janssen Research and Development, LLC, B. Randazzo Employee of: Janssen Research and Development, LLC, Y. Wasfi Employee of: Janssen Research and Development, LLC, S. Li Employee of: Janssen Research and Development, LLC, Y.-K. Shen Employee of: Janssen Research and Development, LLC, A. Blauvelt Grant/research support from: Janssen Research and Development, LLC
Spectrum and functional validation of PSMB5 mutations in multiple myeloma
Authors: Santiago Barrio, Thorsten Stühmer, Matteo Da-Viá, Clara Barrio-Garcia, Nicola Lehners, Andrej Besse, Isabel Cuenca, Andoni Garitano-Trojaola, Severin Fink, Ellen Leich, Manik Chatterjee, Christoph Driessen, Joaquin Martinez-Lopez, Andreas Rosenwald, Roland Beckmann, Ralf C. Bargou, Esteban Braggio, A. Keith Stewart, Marc S. Raab, Hermann Einsele, K. Martin Kortüm
Journal: Leukemia (2018)
Suppression of PDHX by microRNA-27b deregulates cell metabolism and promotes growth in breast cancer
Authors: Steven C. Eastlack, Shengli Dong, Cristina Ivan, Suresh K. Alahari
Journal: Molecular Cancer (2018)

The disruption of normal gene regulation due to microRNA dysfunction is a common event in cancer pathogenesis. MicroRNA-27b is an example of an oncogenic miRNA, and it is frequently upregulated in breast cancer. MicroRNAs have been found to deregulate tumor metabolism, which typically manifests as heightened cellular glucose uptake in consort with increased flux through glycolysis, followed by the preferential conversion of glycolytic pyruvate into lactate (a phenomenon known as the Warburg Effect). Pyruvate Dehydrogenase, an enzyme complex linking glycolysis with downstream oxidative metabolism, represents a key location where regulation of metabolism occurs; PDHX is a key structural component of this complex and is essential for its function. We sought to characterize the role of miR-27b in breast cancer by identifying novel transcripts under its control. We began by utilizing luciferase, RNA, and protein assays to establish PDHX as a novel target of miR-27b. We then tested whether miR-27b could alter metabolism using several metabolite assay kits and performed a seahorse analysis. We also examined how the altered metabolism might affect cell proliferation. Lastly, we confirmed the relevance of our findings in human breast tumor samples. Our data indicate that Pyruvate Dehydrogenase Protein X is a credible target of miR-27b in breast cancer. Mechanistically, by suppressing PDHX, miR-27b altered levels of pyruvate, lactate and citrate, as well as reducing mitochondrial oxidation and promoting extracellular acidification. These changes corresponded with an increased capacity for cell proliferation. In human breast tumor samples, PDHX expression was deficient, and low levels of PDHX were associated with reduced patient survival. MicroRNA-27b targets PDHX, resulting in an altered metabolic configuration that is better suited to fuel biosynthetic processes and cell proliferation, thereby promoting breast cancer progression.
Prevention of allergy by virus‐like nanoparticles (<scp>VNP</scp>) delivering shielded versions of major allergens in a humanized murine allergy model
Authors: Bernhard Kratzer, Cordula Köhler, Sandra Hofer, Ursula Smole, Doris Trapin, Jagoba Iturri, Dietmar Pum, Philip Kienzl, Adelheid Elbe‐Bürger, Pia Gattinger, Irene Mittermann, Birgit Linhart, Gabriele Gadermaier, Beatrice Jahn‐Schmid, Alina Neunkirchner, Rudolf Valenta, Winfried F. Pickl
Journal: Allergy (2018)

In high-risk populations, allergen-specific prophylaxis could protect from sensitization and subsequent development of allergic disease. However, such treatment might itself induce sensitization and allergies, thus requiring hypoallergenic vaccine formulations. We here characterized the preventive potential of virus-like nanoparticles (VNP) expressing surface-exposed or shielded allergens.Full-length major mugwort pollen allergen Art v 1 was selectively targeted either to the surface or to the inner side of the lipid bilayer envelope of VNP. Upon biochemical and immunological analysis, their preventive potential was determined in a humanized mouse model of mugwort pollen allergy.Virus-like nanoparticles expressing shielded version of Art v 1, in contrast to those expressing surface-exposed Art v 1, were hypoallergenic as they hardly induced degranulation of rat basophil leukemia cells sensitized with Art v 1-specific mouse or human IgE. Both VNP versions induced proliferation and cytokine production of allergen-specific T cells in vitro. Upon intranasal application in mice, VNP expressing surface-exposed but not shielded allergen induced allergen-specific antibodies, including IgE. Notably, preventive treatment with VNP expressing shielded allergen-protected mice from subsequent sensitization with mugwort pollen extract. Protection was associated with a Th1/Treg-dominated cytokine response, increased Foxp3+ Treg numbers in lungs, and reduced lung resistance when compared to mice treated with empty particles.Virus-like nanoparticles represent a novel and versatile platform for the in vivo delivery of allergens to selectively target T cells and prevent allergies without inducing allergic reactions or allergic sensitization.
Cutaneous B‐cell lymphomas: 2019 update on diagnosis, risk stratification, and management
Authors: Ryan A. Wilcox
Journal: American Journal of Hematology (2018)

Approximately one-fourth of cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT).Diagnosis and disease classification are based on histologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement.Disease histology remains the most important prognostic determinant. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.PCFCL and PCMZL patients with solitary or relatively few skin lesions may be affectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
Abstract P094: Accuracy of Self-reported Heart Failure Following a Hospitalized Heart Failure Event: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ricky Camplain, Anna Kucharska-Newton, Lisa M Wruck, Aaron R Folsom, Jacqueline Wright, Amil Shah, Alain Bertoni, Gerardo Heiss
Journal: Circulation (2016)

Background: Self-reports of heart failure (HF) are relied upon to quantify the burden of HF in the community. While self-report of HF is often considered subject to recall bias, accuracy of self-reported HF following a HF hospitalization has not been estimated. Methods: Hospital admission of ARIC cohort members is monitored on an ongoing basis. Starting in 2005, hospital records with HF were abstracted and events validated with a standardized protocol based on review of history and physical examination, echocardiography, nuclear imaging, chest X-ray, catheterization reports, cardiac markers, and discharge summary. HF was classified as acute decompensated HF (ADHF) or chronic stable HF (CSHF). Also starting in 2005, ARIC participants were asked annually to report whether a physician had told them they have HF or a weak heart. Those self-reporting HF were asked to authorize release of medical information and their providers of medical care were sent a survey to confirm their patient’s HF status, HF characteristics, and treatment status. After excluding participants with a HF hospitalization prior to 2005 (defined by an ICD-9 discharge code of 428 in any position), self-reported HF following an incident HF hospitalization was quantified as the proportion of hospitalized participants who self-reported HF (sensitivity) and the proportion of non-hospitalized participants who did not self-report HF (specificity). The proportion of self-reported HF confirmed by physicians was calculated among those with a returned survey. Results: Of the 10,509 ARIC participants alive from 2005-2013, 512 were hospitalized with ADHF and 154 were hospitalized with CSHF prior to self-reporting their HF status and 328 self-reported having HF. Comparing self-reported to hospitalized HF, sensitivity was poor (0.28) and specificity excellent (0.99), although some participants who self-reported HF but were not hospitalized may have been diagnosed in the outpatient setting. A physician survey was available for 92 participants who self-reported HF. In 64 (70%; 95% confidence interval (CI): 61, 80) instances, self-reported HF was confirmed by their physician. Of the latter, 23 (36%; 95% CI: 24, 48) were reported as diastolic dysfunction while 19 (30%; 95% CI: 18, 41) and 8 (13%; 95% CI: 4, 21) were characterized as systolic dysfunction or mixed, respectively. HF type was not specified by the physician in 14 cases. Seventy-eight percent (95% CI: 68, 89) of patients with confirmed HF, the physician also reported HF treatment. Conclusion: Self-report of HF was highly specific and quite insensitive calling into question the validity of self-reports of HF. Our results underscore the need for methods more effective than self-report to identify persons with clinically manifest HF.
Introduction to the Special Section: Convergence of Automation Technology, Biomedical Engineering, and Health Informatics Toward the Healthcare 4.0
Authors: Zhibo Pang, Geng Yang, Ridha Khedri, Yuan-Ting Zhang
Journal: IEEE Reviews in Biomedical Engineering (2018)

Industry 4.0 is spilling out from manufacturing to healthcare. In this article, we provide a brief history and key enabling technologies of Industry 4.0, and its revolution in healthcare-Healthcare 4.0-and its reshaping of the landscape of the entire healthcare value chain. We discuss the shift in the system design paradigm from open, small, and single loop to closed, large, and multiple loops. We provide the example of a Caregiving Home, and discuss emerging research topics and challenges, including healthcare big data, automated medical production, healthcare robotics, and human-robot symbiosis. Relevant papers published in this special section are also presented.
A Novel, Fully Human Anti–fucosyl-GM1 Antibody Demonstrates Potent <i>In Vitro</i> and <i>In Vivo</i> Antitumor Activity in Preclinical Models of Small Cell Lung Cancer
Authors: Paul Ponath, Daniel Menezes, Chin Pan, Bing Chen, Miho Oyasu, Debbie Strachan, Heidi LeBlanc, Huadong Sun, Xi-Tao Wang, Vangipuram S. Rangan, Shrikant Deshpande, Sandra Cristea, Kwon-Sik Park, Julien Sage, Pina M. Cardarelli
Journal: Clinical Cancer Research (2018)

Purpose: The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in a large percentage of human small cell lung cancer (SCLC) tumors, but absent in most normal adult tissues, making it a promising target in immuno-oncology. This study was undertaken to evaluate the preclinical efficacy of BMS-986012, a novel, nonfucosylated, fully human IgG1 antibody that binds specifically to FucGM1.Experimental Design: The antitumor activity of BMS-986012 was evaluated in in vitro assays using SCLC cells and in mouse xenograft and syngeneic tumor models, with and without chemotherapeutic agents and checkpoint inhibitors.Results: BMS-986012 showed a high binding affinity for FcγRIIIa (CD16), which resulted in enhanced antibody-dependent cellular cytotoxicity (ADCC) against FucGM1-expressing tumor cell lines. BMS-986012-mediated tumor cell killing was also observed in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) assays. In several mouse SCLC models, BMS-986012 demonstrated efficacy and was well tolerated. In the DMS79 xenograft model, tumor regression was achieved with BMS-986012 doses of 0.3 mg/kg and greater; antitumor activity was enhanced when BMS-986012 was combined with standard-of-care cisplatin or etoposide. In a syngeneic model, tumors derived from a genetically engineered model of SCLC were treated with BMS-986012 or anti-FucGM1 with a mouse IgG2a Fc and their responses evaluated; when BMS-986012 was combined with anti-PD-1 or anti-CD137 antibody, therapeutic responses significantly improved.Conclusions: Single-agent BMS-986012 demonstrated robust antitumor activity, with the addition of chemotherapeutic or immunomodulatory agents further inhibiting SCLC growth in the same models. These preclinical data supported evaluation of BMS-986012 in a phase I clinical trial of patients with relapsed, refractory SCLC. Clin Cancer Res; 24(20); 5178-89. ©2018 AACR.
MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML
Authors: Mathijs A. Sanders, Edward Chew, Christoffer Flensburg, Annelieke Zeilemaker, Sarah E. Miller, Adil S. al Hinai, Ashish Bajel, Bram Luiken, Melissa Rijken, Tamara Mclennan, Remco M. Hoogenboezem, François G. Kavelaars, Stefan Fröhling, Marnie E. Blewitt, Eric M. Bindels, Warren S. Alexander, Bob Löwenberg, Andrew W. Roberts, Peter J. M. Valk, Ian J. Majewski
Journal: Blood (2018)
Abstract 17490: Coenzyme Q10 Levels Are Associated With Occurrence of Cardiogenic Shock and In-hospital Death in Patients Admitted to Coronary Care Unit
Authors: Tetsuro Miyazaki, Megumi Shimizu, Atsutoshi Takagi, Takao Kato, Shoko Suda, Masaru Hiki, Hidemori Hayashi, Takatoshi Kasai, Kazunori Shimada, Katsumi Miyauchi, Hiroyuki Daida
Journal: Circulation (2013)

Background:  Coenzyme Q10 (CoQ10) is a mitochondrial coenzyme which is essential for the production of Adenosine triphosphate (ATP). CoQ10 has a potential role for prevention and treatment of heart failure by improving cellular bioenergetics. In addition it has an antioxidant, a free radical scavenging and a vasodilator effect which may be helpful in these conditions. However, clinical significance of measuring serum CoQ10 levels in patients admitted coronary care unit (CCU) remains unclear.   Methods:  We enrolled consecutive 276 patients who admitted to the CCU and 54 age- and gender-matched healthy controls. Serum CoQ10 levels were measured after an overnight fast within 24 hours from admission. We examined the associations of serum CoQ10 levels with patient characteristics and occurrence of in-hospital death.   Results:  In 276 patients, 146 patients showed acute decompensated heart failure. There were 8 In-hospital deaths. CoQ10 levels were significantly lower in patients admitted to CCU than in healthy controls (0.54±0.34 vs. 0.90±0.31 mg/L, p   Conclusion:  Low CoQ10 levels are significantly associated with various risks of cardiovascular disease, including renal dysfunction, inflammation, lipid disorder and hypotension. Low CoQ10 levels correlates with the risk of cardiogenic shock and in-hospital death in patients admitted to CCU, suggesting that measuring CoQ10 levels is useful to detect the high risk patients in CCU.
Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1
Authors: Xiangge Tian, Chao Wang, Peipei Dong, Yue An, Xinyu Zhao, Weiru Jiang, Gang Wang, Jie Hou, Lei Feng, Yan Wang, Guangbo Ge, Xiaokui Huo, Jing Ning, Xiaochi Ma
Journal: Acta Pharmaceutica Sinica B (2018)

Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.
Abstract 16210: Stratified Coronary Restenosis Risk by Aldehyde Dehydrogenase Polymorphism and Endotherial Function
Authors: Takayoshi Yamashita, Seiji Hokimoto, Daisuke Sueta, Noriaki Tabata, Tomonori Akasaka, Yuichirou Arima
Journal: Circulation (2016)

Background:  Endothelial dysfunction is considered as an independent factor that influences clinical outcome in coronary artery disease patients (CAD). Endothelial dysfunction is associated with increased oxidative stress, and recently mitochondrial aldehyde dehydrogenase 2 (ALDH2*2) polymorphism has been reported to cause decreased ALDH2 activity, increased reactive aldehydes, and increased reactive oxygen species. Thus in the present study, we examined the role and the interaction of endothelial function and ALDH2 variant in cardiovascular outcomes.   Methods:  Consecutive 158 patients requiring percutaneous coronary intervention were enrolled. ALDH2 variant is defined having the ALDH2 *2 allele (*1/*2 or *2/*2). We assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) using the EndoPAT2000 system, and divided patients into low- and high- RHI groups using the median value of the natural logarithm of RH-PAT index (Ln-RHI). Clinical outcome in the present study was the target lesion revascularization (TLR).   Results:  There were 88 (55.7%), 54 (34.2%) and 16 (10.1%) patients with regard to *1/*1, *1/*2 and *2/*2 ALDH2 genotypes. There was no significant difference in Ln-RHI among them (0.52 ± 0.21, 0.56 ± 0.22, and 0.62 ± 0.25; P = 0.26, respectively). A total of 30 patients suffered a cardiovascular event. Kaplan-Meyer analysis showed a significant higher probability of clinical outcome in low RHI patients than high RHI patients in the ALDH2 variant group (log-rank test: P=0.023), but there was no significant difference in the ALDH2 non-variant group (log-rank test: P=0.704). In the ALDH2 variant group, multivariate Cox hazard analysis among various clinical factors found low RHI as a significant and independent predictor of clinical outcome (hazard ratio, 5.34; 95% confidence interval, 1.41-20.2; P=0.014). The interaction between ALDH2 variant and low RHI was significant (P=0.051).   Conclusion:  The present study demonstrated a possible contribution of ALDH2 polymorphism to the risk stratification of TLR in patients with endothelial dysfunction.