tbuckley/cabot-search huggingface dataset:
Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis
Authors: Adrià Aterido, Juan D Cañete, Jesús Tornero, Carlos Ferrándiz, José Antonio Pinto, Jordi Gratacós, Rubén Queiró, Carlos Montilla, Juan Carlos Torre-Alonso, José J Pérez-Venegas, Antonio Fernández Nebro, Santiago Muñoz-Fernández, Carlos M González, Daniel Roig, Pedro Zarco, Alba Erra, Jesús Rodríguez, Santos Castañeda, Esteban Rubio, Georgina Salvador, Cesar Díaz-Torné, Ricardo Blanco, Alfredo Willisch Domínguez, José Antonio Mosquera, Paloma Vela, Simon Angel Sánchez-Fernández, Héctor Corominas, Julio Ramírez, Pablo de la Cueva, Eduardo Fonseca, Emilia Fernández, Lluis Puig, Esteban Dauden, José Luís Sánchez-Carazo, José Luís López-Estebaranz, David Moreno, Francisco Vanaclocha, Enrique Herrera, Francisco Blanco, Benjamín Fernández‐Gutiérrez, Antonio González, Carolina Pérez-García, Mercedes Alperi‐López, Alejandro Olivé Marques, Víctor Martínez‐Taboada, Isidoro González-Álvaro, Raimon Sanmartí, Carlos Tomás Roura, Andrés C García-Montero, Sílvia Bonàs-Guarch, Josep Maria Mercader, David Torrents, Laia Codó, Josep Lluís Gelpí, Mireia López-Corbeto, Andrea Pluma, Maria López-Lasanta, Raül Tortosa, Nuria Palau, Devin Absher, Richard Myers, Sara Marsal, Antonio Julià
Journal: Annals of the Rheumatic Diseases (2018)

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs.These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.
Small Nucleolar RNAs Tell a Different Tale
Authors: Joanna Kufel, Pawel Grzechnik
Journal: Trends in Genetics (2018)

Transcribing RNA Polymerase II interacts with multiple factors that orchestrate maturation and stabilisation of messenger RNA. For the majority of noncoding RNAs, the polymerase complex employs entirely different strategies, which usually direct the nascent transcript to ribonucleolytic degradation. However, some noncoding RNA classes use endo- and exonucleases to achieve functionality. Here we review processing of small nucleolar RNAs that are transcribed by RNA Polymerase II as precursors, and whose 5' and 3' ends undergo processing to release mature, functional molecules. The maturation strategies of these noncoding RNAs in various organisms follow a similar pattern but employ different factors and are strictly correlated with genomic organisation of their genes.
Abstract 15806: Temporal Patterns of 7 Blood Biomarkers of Cardiac Remodeling in Relation to Prognosis of Patients With Chronic Heart Failure - The Bio-shift Study
Authors: Elke Bouwens, Milos Brankovic, Henk Mouthaan, Sara J Baart, Nick van Boven, Kadir C Caliskan, Olivier C Manintveld, Tjeerd Germans, Jan van Ramshorst, Victor A Umans, K. M Akkerhuis, Isabella Kardys
Journal: Circulation (2017)

Introduction: Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure(CHF) patients. However, detailed temporal patterns of these biomarkers during the cou...
P040 Highly Sensitivity and Fast Genetic Diagnosis by Mean of a Novel NGS-Based Resequencing Gene Panel Underlying SCLC Patients
Authors: J. Wang, L. Zhao, X. Sun, F. Zhou, Y. Zhang, S. Zhao, S. Liu, L. Chin, L. Wang, T. Guo, Z. Sun, F. Li, C. Gu
Journal: Journal of Thoracic Oncology (2018)
The predictive value of 18F-FDG PET/CT after ipilimumab for treatment response evaluation in metastatic melanoma patients
Authors: S. Vari, A. Annovazzi, R. Pasqualoni, R. Sciuto, D. Giannarelli, F. Cognetti, V. Ferraresi
Journal: Annals of Oncology (2018)

Background: In previous reports it has been demonstrated that the 18F-FDG PET/CT performs better than contrast-enhanced CT in assessing the response to immunotherapy treatment in patients affected by metastatic melanomas. Aim of the present study was to evaluate if the first 18F-FDG PET/CT scan performed after the completion of 4 cycles of Ipilimumab treatment was predictive of patient clinical outcome. Methods: 26 patients who performed a PET/CT scan before treatment (PET0), after 4 cycles of Ipilimumab (PET1) and at least an additional later evaluation without starting new therapeutic regimen (PET2), were retrospectively evaluated. Response to treatment was evaluated according to PERCIST criteria for PET1 and PET2 and compared with patient clinical outcome. A total of 69 metastatic lesions were also singularly analyzed. Results: PET1 were performed after a mean of 6 weeks from the end of IPI and PET2 after a mean of 12 weeks from PET1. Patients were classified at PET1 as having progressive metabolic disease (PMD) in 15 cases, stable metabolic disease (SMD) in 6, partial metabolic response (PMR) in 2 and complete metabolic response (CMR) in 3. Discordant results between PET2 and PET1 were observed in 6 patients (from SMD to PMD in 4 cases, from SMD to CMR in 1 and from PMD to CMR in 1). Conclusions: The results showed that the first PET/CT evaluation after IPI was not always representative for the definitive response to treatment. The immediate start of a new therapeutic line can be proposed for PMD, in all other cases and in particular for SMD an early PET/CT restaging should be performed to confirm the patient clinical outcome. Legal entity responsible for the study: Ethical Committee. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Unresolved Splenomegaly in Recently Resettled Congolese Refugees ― Multiple States, 2015–2018
Authors: Laura D. Zambrano, Olivia Samson, Christina Phares, Emily Jentes, Michelle Weinberg, Matthew Goers, S. Patrick Kachur, Robert McDonald, Bozena Morawski, Henry Njuguna, Yasser Bakhsh, Rebecca Laws, Corey Peak, Sally Ann Iverson, Carla Bezold, Hayder Allkhenfr, Roberta Horth, Jun Yang, Susan Miller, Michael Kacka, Abby Davids, Margaret Mortimer, Nomana Khan, William Stauffer, Nina Marano
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Despite recommendations, most U.S.-bound Congolese refugees with splenomegaly did not have documented receipt of primaquine after resettlement. Most patients were clustered within families. Approximately 50% of patients with available medical records had persistent splenomegaly >6 months after arrival; 63% of patients with splenomegaly had a hematologic abnormality.
Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1+ regulatory B cell expansion
Authors: Linsen Ye, Qi Zhang, Yusheng Cheng, Xiaolong Chen, Guoying Wang, Mengchen Shi, Tong Zhang, Yingjiao Cao, Hang Pan, Liting Zhang, Genshu Wang, Yinan Deng, Yang Yang, Guihua Chen
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Regulatory B (Breg) cells represent one of the B cell subsets that infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, the phenotype, function and clinical relevance of Breg cells in human hepatocellular carcinoma (HCC) are presently unknown. <h3>Methods</h3> Flow cytometry analyses were performed to determine the levels, phenotypes and functions of TIM-1<sup>+</sup>Breg cells in samples from 51 patients with HCC. Kaplan-Meier plots for overall survival and disease-free survival were generated using the log-rank test. TIM-1<sup>+</sup>Breg cells and CD8<sup>+</sup> T cells were isolated, stimulated and/or cultured in vitro for functional assays. Exosomes and B cells were isolated and cultured in vitro for TIM-1<sup>+</sup>Breg cell expansion assays. <h3>Results</h3> Patients with HCC showed a significantly higher TIM-1<sup>+</sup>Breg cell infiltration in their tumor tissue compared with the paired peritumoral tissue. The infiltrating TIM-1<sup>+</sup>Breg cells showed a CD5<sup>high</sup>CD24<sup>−</sup>CD27<sup>−/+</sup>CD38<sup>+/high</sup> phenotype, expressed high levels of the immunosuppressive cytokine IL-10 and exhibited strong suppressive activity against CD8<sup>+</sup> T cells. B cells activated by tumor-derived exosomes strongly expressed TIM-1 protein and were equipped with suppressive activity against CD8<sup>+</sup> T cells similar to TIM-1<sup>+</sup>Breg cells isolated from HCC tumor tissue. Moreover, the accumulation of TIM-1<sup>+</sup>Breg cells in tumors was associated with advanced disease stage, predicted early recurrence in HCC and reduced HCC patient survival. Exosome-derived HMGB1 activated B cells and promoted TIM-1<sup>+</sup>Breg cell expansion via the Toll like receptor (TLR) 2/4 and mitogen-activated protein kinase (MAPK) signaling pathways. <h3>Conclusions</h3> Our results illuminate a novel mechanism of TIM-1<sup>+</sup>Breg cell-mediated immune escape in HCC and provide functional evidence for the use of these novel exosomal HMGB1-TLR2/4-MAPK pathways to prevent and to treat this immune tolerance feature of HCC.
Association Between Atopic Dermatitis and Suicidality
Authors: Jeena K. Sandhu, Kevin K. Wu, Thanh-Lan Bui, April W. Armstrong
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with numerous psychiatric comorbidities. However, the association between AD and suicidality has not been well established. <h3>Objective</h3> To synthesize the available literature to evaluate the association between AD and suicidality. <h3>Data Source</h3> The protocol was prospectively registered in the PROSPERO database (CRD42018105291). <h3>Study Selection</h3> Per PRISMA guidelines, PubMed, Embase, PsycINFO, and Cochrane databases were systematically searched for relevant articles published from 1946 to May 25, 2018. The search criteria for PubMed were as follows: (<i>dermatitis, atopic</i>[MeSH] OR<i>eczema</i>[MeSH]) AND (<i>suicidal ideation</i>[MeSH] OR<i>suicide, attempted</i>[MeSH] OR<i>suicide</i>[MeSH] OR<i>suicidality</i>OR<i>suicidal behavior</i>). The search criteria for Embase, PsycINFO, and Cochrane were as follows: (<i>atopic dermatitis</i>OR<i>eczema</i>) AND (<i>suicidal ideation</i>OR<i>suicide attempt</i>OR<i>suicide</i>OR<i>suicidality</i>OR<i>suicidal behavior</i>). <h3>Data Extraction and Synthesis</h3> This systematic review and meta-analysis performed in an academic medical setting included observational studies that evaluated suicidal ideation, suicide attempts, and completed suicide among patients with AD. <h3>Main Outcome and Measure</h3> The quality of included studies was assessed using the Newcastle-Ottawa Scale for observational studies. <h3>Results</h3> The analysis identified 15 studies with a total of 4 770 767 participants, of whom 310 681 were patients with AD (52.7% female) and 4 460 086 served as controls (50.9% female). In the meta-analyses, patients with AD were 44% more likely to exhibit suicidal ideation (pooled odds ratio, 1.44; 95% CI, 1.25-1.65) and 36% more likely to attempt suicide (pooled odds ratio, 1.36; 95% CI, 1.09-1.70) compared with patients without AD. Studies investigating completed suicides in patients with AD had inconsistent results. <h3>Conclusions and Relevance</h3> Results of this study suggest that patients with AD are at significantly increased risk of suicidal ideation and suicide attempts. It is important for dermatology providers to be aware of this risk, screen for suicidality in patients with AD, and make mental health referrals when necessary.
Оказание медицинской помощи в Екатеринославе в период Первой мировой войны
Authors: V.V. Haponov, Z.I. Shevtsova
Journal: GASTROENTEROLOGY (2020)

Изложено оказание медицинской помощи больным и раненым в период Первой мировой войны в Екатеринославе. Представлена история создания лазаретов, военных госпиталей, больницы Крас-ного Креста и церкви-памятника погибшим героям. Показана самоотверженная работа военных медиков. Даны биографические сведения о враче, общественном деятеле Ефиме Павловском.
Abstract 13516: Chronic inflammation, Albuminuria, and Hospital Admissions Among Adults With Hypertension: The National Health and Nutrition Examination Survey 2003-2012
Authors: Hsu-Ko Kuo, Joel M Gore
Journal: Circulation (2015)

Background: Although clinical factors such as advanced age, co-morbidities, or polypharmacy have been extensively documented as crucial predictors for hospitalizations, data examining the associations of preclinical disease indicators such as albuminuria and subclinical inflammation with hospitalization among people with hypertension are sparse. Methods: Data were from 5149 adults (&gt;20 years) with hypertension in the National Health and Nutrition and Examination Survey 2003-2012. Overnight hospitalization during the past 12 months (H) was ascertained by questionnaire. C-reactive protein (CRP) was quantified by latex-enhanced nephelometry. Urinary albumin-to-creatinine ratio (UACR) was categorized into normal, microalbuminuria (MiA), and macroalbuminuria (MaA). Results: Both MiA (UACR 30-300mg/g) and MaA (UACR&gt;300mg/g) were associated with H in patients with hypertension. In the full-adjusted model, odd ratios (ORs) of H were 1.74 (95% confidence interval [CI] 1.25-2.42) and 1.27 (95% CI 1.05-1.54), respectively, comparing participants with MaA and MiA to those without albuminuria. CRP&gt;0.3mg/dL was associated with increased odds of H comparing with normal CRP (OR 1.31; 95%CI 1.06-.162). Subjects with both albuminuria and elevated CRP had higher odds of H than individuals with no albuminuria and normal CRP (Figure). Conclusion: Albuminuria and inflammation were independent correlates for H among adults with hypertension. There was an interaction of albuminuria and elevated CRP on H, suggesting that the presence of subclinical inflammation may amplify the effect of albuminuria on hospitalization in adults living with hypertension. We provided new information on role of preclinical biomarkers in hospitalization among community-dwelling adults with hypertension where data currently are not available.
Tandom Autologous Transplantation and Combined Infusion of CD19 and Bcma-Specific Chimeric Antigen Receptor T Cells for High Risk MM: Initial Safety and Efficacy Report from a Clinical Pilot Study
Authors: Xiaolan Shi, Lingzhi Yan, Jingjing Shang, Su Qu, Liqing Kang, Jin Zhou, Song Jin, Weiqin Yao, Ying Yao, Shuang Yan, Yong Liu, Guanghua Chen, Ziling Zhu, Huirong Chang, Depei Wu, Lei Yu, ChengCheng Fu
Journal: Blood (2018)
Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1–1b study
Authors: Matthew S Davids, Haesook T Kim, Alyssa Nicotra, Alexandra Savell, Karen Francoeur, Jeffrey M Hellman, Josie Bazemore, Hari P Miskin, Peter Sportelli, Laura Stampleman, Rodrigo Maegawa, Jens Rueter, Adam M Boruchov, Jon E Arnason, Caron A Jacobson, Eric D Jacobsen, David C Fisher, Jennifer R Brown
Journal: The Lancet Haematology (2018)
Impact of Patient- and Clinician-Reported Cumulative Toxicity on Quality of Life in Patients With Metastatic Castration-Naïve Prostate Cancer
Authors: Claudia S.E.W. Schuurhuizen, Patricia Marino, Annemarie M.J. Braamse, Laurien M. Buffart, Florence Joly, Karim Fizazi, Muriel Habibian, Jean-Marie Boher, Michel Soulie, Stéphane Oudard, Inge R.H.M. Konings, Henk M.W. Verheul, Joost Dekker, Gwenaelle Gravis
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Current toxicity evaluation is primarily focused on high-grade adverse events (AEs) reported by clinicians. However, the cumulative effect of multiple lower-grade AEs may also impact patients' quality of life (QoL). Further, patient-reported toxicity may be more representative of patients' treatment experiences. This study aimed to determine whether cumulative toxicity comprising all-grade AEs is more associated with QoL than cumulative toxicity comprising high-grade AEs only, and whether patient-reported cumulative toxicity is more associated with QoL than clinician-reported cumulative toxicity. Methods: Patients with metastatic castration-naïve prostate cancer participating in the phase III GETUG-AFU 15 trial completed questionnaires on AEs (at 3 and 6 months) and QoL (at baseline and 3 and 6 months). Clinicians reported AEs during clinical visits. Cumulative toxicity scores were calculated for clinicians and patients in 3 ways: total number of high-grade AEs, total number of all-grade AEs, and total number of all AEs multiplied by their grade (severity score). Relationships between cumulative toxicity scores and QoL were studied using longitudinal regression analyses; unstandardized (B) and standardized regression coefficients (β) are reported. Results: Of 385 patients, 184 with complete QoL and toxicity data were included. Clinician-reported all-grade AEs (B, −2.2; 95% CI, −3.3 to −1.1; P<.01) and severity score (B, −1.4; 95% CI, −2.2 to −0.7; P<.01) were associated with deteriorated physical QoL, whereas the total number of high-grade AEs was not. All patient-reported scores were significantly (P<.01 for all) associated with deteriorated physical and global QoL. Standardized regression coefficients indicated that patient-reported toxicity scores were more associated with QoL outcomes than clinician-reported scores, with the strongest association found for the all-grade AEs and severity cumulative toxicity scores. Conclusions: Patient- and clinician-based cumulative toxicity scores comprising all-grade AEs better reflect impact on patient QoL than toxicity scores comprising high-grade AEs only. To assess the effect of toxicity on QoL, patient-reported cumulative toxicity scores are preferred.
Abstract 16975: Assessing the Relationship Between Neighborhood Social Capital and CPR Training Prevalence
Authors: Andrew D Murray, Shaun K McGovern, Marion Leary, Benjamin S Abella, Audrey L Blewer
Journal: Circulation (2016)

Introduction: CPR training rates across the US are varied and generally low. Neighborhood social capital (NSC) is an established means to study the impact of neighborhood conditions on health chara...
The Return of OTC Primatene Mist
Authors: Rebecca Voelker
Journal: JAMA (2018)

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Mussel-inspired injectable hydrogel and its counterpart for actuating proliferation and neuronal differentiation of retinal progenitor cells
Authors: Zhimin Tang, Fang Jiang, Yuanhao Zhang, Yi Zhang, None YuanYang, Xiaolin Huang, Yuyao Wang, Dandan Zhang, Ni Ni, Feng Liu, Min Luo, Xianqun Fan, Weian Zhang, Ping Gu
Journal: Biomaterials (2018)
PD-L1 microSPECT/CT imaging for longitudinal monitoring of PD-L1 expression in syngeneic and humanized mouse models for cancer
Authors: S. Heskamp, S.R. Verhoeff, P.J. Wierstra, J.D.M. Molkenboer-Kuenen, G.W. Sandker, S. Thordardottir, D. Olive, J. Bussink, O.C. Boerman, H. Dolstra, E.H.J.G. Aarntzen, W.A. Hobo
Journal: Annals of Oncology (2018)

Background: Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of cancer patient. PD-L1 expression in the tumor seems to be a pre-requisite for treatment response. However, it is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment. Imaging of PD-L1 could aid in patient selection. Methods: Previously, we showed the feasibility to image PD-L1 positive tumors in immunodeficient mice. However, PD-L1 is also expressed on immune cell subsets. Therefore, the aim of this study was to assess the potential of PD-L1 microSPECT/CT using radiolabeled anti-PD-L1 antibodies to 1) measure PD-L1 expression in two immunocompetent tumor models (syngeneic mice and humanized mice harboring PD-L1 expressing immune cells) and 2) monitor therapy induced changes in tumor PD-L1 expression levels. Results: We showed that radiolabeled anti-PD-L1 antibodies accumulated preferentially in PD-L1 positive tumors, despite considerable uptake in certain normal lymphoid tissues (spleen and lymph nodes) and non-lymphoid tissues (duodenum and brown fat). Moreover, PD-L1 microSPECT/CT imaging could distinguish between high and low PD-L1 expressing tumors. Notably, presence of PD-L1 positive immune cells did not compromise tumor uptake of the anti-human PD-L1 antibodies in humanized mice. Most importantly, we demonstrated that radiotherapy induced up-regulation of PD-L1 expression in murine tumors which could be monitored with microSPECT/CT imaging. Conclusions: Together, these data demonstrate that PD-L1 microSPECT/CT is a sensitive technique to detect varying levels of tumor PD-L1 expression and in the future, this technique may enable patient selection for PD-1/PD-L1 targeted therapy. Legal entity responsible for the study: Radboud UMC. Funding: Netherlands Organisation for Scientific Research and Dutch Cancer Society. Disclosure: All authors have declared no conflicts of interest.
Expression of Insulinoma-Associated Protein 1 (INSM1) and Orthopedia Homeobox (OTP) in Tumors with Neuroendocrine Differentiation at Rare Sites
Authors: Madhuchhanda Roy, Darya G. Buehler, Ranran Zhang, Michael L. Schwalbe, Rebecca M. Baus, M. Shahriar Salamat, Ricardo V. Lloyd, Jason N. Rosenbaum
Journal: Endocrine Pathology (2018)
Author Correction: Lipid management in patients with chronic kidney disease
Authors: Charles J. Ferro, Patrick B. Mark, Mehmet Kanbay, Pantelis Sarafidis, Gunnar H. Heine, Patrick Rossignol, Ziad A. Massy, Francesca Mallamaci, Jose M. Valdivielso, Jolanta Malyszko, Marianne C. Verhaar, Robert Ekart, Raymond Vanholder, Gerard London, Alberto Ortiz, Carmine Zoccali
Journal: Nature Reviews Nephrology (2018)