tbuckley/cabot-search huggingface dataset:
OP0062 IDENTIFICATION OF SIX DERMATOMYOSITIS SUBGROUPS USING PRINCIPAL COMPONENT ANALYSIS-BASED CLUSTER ANALYSIS
Authors: Huiyi Zhu, Chanyuan Wu, Nan Jiang, Yanhong Wang, Jiuliang Zhao, Dong Xu, Xiaofeng Zeng, LI Mengtao
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Dermatomyositis (DM) is a heterogeneous disease with a wide range of clinical manifestations. Bohan and Peter suggested four subtypes of DM: idiopathic DM, juvenile DM, DM associated with cancer, and DM associated with other connective tissue diseases. Different DM subtypes have distinct clinical manifestations, responses to therapy and prognoses. <h3>Objectives</h3> The aim of the present study was to identify the clinical subtypes of DM by applying cluster analysis. <h3>Methods</h3> We retrospectively reviewed the medical records of 720 DM patients and selected 21 variables for analysis, including clinical characteristics, laboratory findings, and comorbidities. Principal component analysis (PCA) was first conducted to transform the 21 variables into independent principal components. Patient classification was then performed using cluster analysis based on the PCA-transformed data. The relationships among the clinical variables were also assessed. <h3>Results</h3> We transformed the 21 clinical variables into 9 independent principal components by PCA and identified 6 distinct subgroups. Cluster A was composed of two sub-clusters of patients with classical or moderate DM. Cluster-B patients were older and had malignancies. Cluster C was characterized by interstitial lung disease (ILD), skin ulcer, and minimal muscle involvement. Cluster D included patients with prominent lung, muscle, and skin involvement. Cluster E contained DM patients with other connective tissue diseases. Cluster F included all patients with myocarditis and prominent myositis and ILD. We found significant differences in treatment across the six clusters, with clusters C, D, and E being more likely to receive aggressive immunosuppressive therapy. <h3>Conclusion</h3> We applied cluster analysis to a large group of DM patients and identified six clinical subgroups, underscoring the need for better phenotypic characterization to help develop individualized treatments and improve prognosis. <h3>References</h3> [1] Bohan, A. and J.B. Peter, Polymyositis and dermatomyositis (first of two parts). N Engl J Med, 1975. 292(7): p. 344-7. [2] Bohan, A. and J.B. Peter, Polymyositis and dermatomyositis (second of two parts). N Engl J Med, 1975. 292(8): p. 403-7. [3] Marie, I., Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep, 2012. 14(3): p. 275-85. [4] Callen, J.P., Dermatomyositis. The Lancet, 2000. 355(9197): p. 53-57. <h3>Disclosure of Interests</h3> None declared
Comment on Kim et al. The Effect of a Smartphone-Based, Patient-Centered Diabetes Care System in Patients With Type 2 Diabetes: A Randomized, Controlled Trial for 24 Weeks. Diabetes Care 2019;42:3–9
Authors: Xiqian Huo, Rury R. Holman, Jane Armitage
Journal: Diabetes Care (2019)

We read with interest the article by Kim et al. (1), which demonstrated the potential benefits of a smartphone-based, patient-centered diabetes care system (mDiabetes) for improving glycemic control among patients with type 2 diabetes. We commend the substantial achievement of completing this trial but would like to add some comments concerning the interpretation of the results.

Intention-to-treat analyses are recommended for avoiding bias when estimating treatment effects, particularly when not all participants complete a …
Hierarchical Heterogeneity across Human Cortex Shapes Large-Scale Neural Dynamics
Authors: Murat Demirtaş, Joshua B. Burt, Markus Helmer, Jie Lisa Ji, Brendan D. Adkinson, Matthew F. Glasser, David C. Van Essen, Stamatios N. Sotiropoulos, Alan Anticevic, John D. Murray
Journal: Neuron (2019)

The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from magnetic resonance imaging (MRI)-derived T1- to T2-weighted (T1w/T2w) mapping and fit the model using multimodal neuroimaging data. We found that incorporating hierarchical heterogeneity substantially improves the model fit to functional MRI (fMRI)-measured resting-state functional connectivity and captures sensory-association organization of multiple fMRI features. The model predicts hierarchically organized higher-frequency spectral power, which we tested with resting-state magnetoencephalography. These findings suggest circuit-level mechanisms linking spatiotemporal levels of analysis and highlight the importance of local properties and their hierarchical specialization on the large-scale organization of human cortical dynamics.
AB1005 THE UNUSUAL ADVERSE EVENTS INCLUDING MULTIPLE SCLEROSIS DEVELOPED UNDER ABATACEPT THERAPY IN A PATIENT WITH JIA
Authors: Alia Latypova, Anna Shapovalenko, Irina Nikishina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Biological therapy in patients with pediatric rheumatology disease may be associated with adverse events up to demyelinative lesion of CNS including multiple sclerosis (MS). It is a rare condition in the pediatric practice. <h3>Objectives</h3> to describe the clinical case of newly diagnosed psoriasis and subsequently developing of multiple sclerosis in pediatric patient revealed in JIA who has been followed-up in Pediatric department of V.A. Nasonova Research Institute of Rheumatology for 8 years. <h3>Methods</h3> Description of clinical case of 13 y.o. male Caucasian pts presented with polyarthritis variant of juvenile idiopathic arthritis (JIA) since 2006. <h3>Results</h3> The first symptoms (at the age of 1,5) were polyarthritis with fever, morning stiffness and inflammatory activity in laboratory tests in chronological link of DTP – re-vaccination. The patient admitted to the regional hospital where JIA was diagnosed and he received traditional therapy including NSAIDS, methotrexate, numerous of intraarticular injections, methylprednisolone pulse therapy with initial response. By the 2012 the child deteriorated with progressive polyarthritis, deformation of wrist joints, bilateral camptodactylia with progressive destruction on X-ray. Under the administration of abatacept therapy in our clinic in 2012 the significant improvement (70-90% ACR response) was achieved. 2 years later the plaque psoriasis developed. The cutaneous changes were impaired by the regular local application of GC so infusions of abatacept were continued. In 4th years of regular therapy (in the age of 13) sudden neurological symptoms such as headache, loss of sensitivity, ataxia, visual field defect appeared. He was admitted to neurological clinic. Multiple sclerosis was diagnosed based on the presenting signs and symptoms supporting cranial MRI – multiple focal areas of demyelination. <h3>Conclusion</h3> We presented a patient with JIA who developed two different immunological related adverse events under long-term abatacept using: psoriasis "de novo" appeared as a native origin of juvenile arthritis and CNS – multiple sclerosis. This is the first case of developing MS under the abatacept therapy among the 1118 pts (2002-2018) who receive biological therapy in our clinic. <h3>Disclosure of Interests</h3> None declared
Результаты обсервационного перекрестного исследования PRELID 2 (2015–2016). Часть 2. Факторы риска неалкогольной жировой болезни печени и методы лечения болезни у пациентов, обращающихся к терапевтам и гастроэнтерологам в Украине
Authors: Yu.M. Stepanov
Journal: GASTROENTEROLOGY (2019)

Цель: оценить наличие у больных с подтвержденным и неподтвержденным диагнозом НАЖБП факторов риска и фоновых состояний; преимущества практикующих врачей относительно фармакологических и нефармакологических методов лечения НАЖБП в условиях реальной клинической практики. Материалы и методы. В исследование включено 5000 пациентов (в среднем по 50 пациентов из 100 исследовательских центров), среди них 2450 женщин (49,00 %) и 2550 мужчин (51,00 %), средний возраст — (52,83 ± 12,33) года. Для проведения исследования в Украине было отобрано 100 гастроэнтерологических отделений. В список исследовательских центров включались отделения с квалифицированным персоналом, обеспеченые надлежащими материалами и техническим оборудованием, с обязательным наличием местного Комитета по вопросам этики. В исследовании применены данные, полученые во время одного обычного визита пациента в центр, включенный в исследование. Во время визита регистрировались основные исходные данные пациента, данные инструментальных методов обследования (ультразвуковое исследование печени), результаты лабораторных анализов, данные относительно применения методик лечения (фармакологических и нефармакологических). Диагноз НАЖБП устанавливался или исключался на основании результатов лабораторных и инструментальных данных, внесенных в медицинские карты. Результаты. В целом факторы риска НАЖБП обнаружены у 4650 (93,00 %) пациентов. Чаще всего отмечались избыточный вес (91,90 %), гиперхолестеринемия (61,44 %), гиперлипидемия (41,23 %). Частота выявления практически всех исследуемых факторов риска (за исключением гиперхолестеринемии) достоверно выше (p &lt; 0,05) в группе пациентов с подтвержденным диагнозом НАЖБП, чем в группе пациентов с неподтвержденным диагнозом НАЖБП. Нефармакологические и фармакологические методы лечения применяли большинство пациентов (90,44 и 93,82 % соответственно). Большинство как нефармакологических, так и фармакологических методов лечения достоверно чаще применялись у пациентов с подтвержденным диагнозом НАЖБП (p &lt; 0,05). Выводы. По результатам исследования определены наиболее значимые факторы риска НАЖБП. Частота выявления практически всех исследуемых факторов риска (за исключением гиперхолестеринемии) достоверно выше (p &lt; 0,05) в группе пациентов с подтвержденным диагнозом НАЖБП, чем в группе пациентов с неподтвержденным диагнозом НАЖБП. Исследование также позволило оценить фармакологические и нефармакологические методы, наиболее часто применяющиеся в лечении больных НАЖБП в Украине.
A tandem simulation framework for predicting mapping quality
Authors: Ben Langmead
Journal: Genome biology (2017)

Read alignment is the first step in most sequencing data analyses. Because a read's point of origin can be ambiguous, aligners report a mapping quality, which is the probability that the reported alignment is incorrect. Despite its importance, there is no established and general method for calculating mapping quality. I describe a framework for predicting mapping qualities that works by simulating a set of tandem reads. These are like the input reads in important ways, but the true point of origin is known. I implement this method in an accurate and low-overhead tool called Qtip, which is compatible with popular aligners.
PB2282 REASSESSING THE EFFICACY OF LOW DOSE RASBURICASE FOR MANAGEMENT OF TUMOR LYSIS SYNDROME IN HIGH RISK HEMATOLOGIC MALIGNANCIES
Authors: G. Heering, R. Loebstein, H. Rotem Rabinovitch, A. Avigdor, D. Merkel, O. Benjamini, Y. Volchek, A. Nagler, J. Canaani
Journal: HemaSphere (2019)

Background: Tumor lysis syndrome (TLS) is a potentially life‐threatening metabolic derangement seen in aggressive hematologic malignancies which is characterized by the massive release of toxic metabolic byproducts and consequent kidney damage. Whereas rasburicase is an established standard of care for management of TLS, the high cost of administering standard dosing of rasburicase has led to exploring lower doses of rasburicase. Aims: Assess our center's experience with lower dosing of rasburicase for management of TLS in aggressive hematologic malignancies. Methods: We studied all adult patients with hematologic malignancies who were treated with rasburicase in our institution between the years 2011‐2018. Charts were reviewed and demographic, clinical, and laboratory data were collected. Subjects were defined to be at high risk for TLS if they had any of the following features: acute leukemia, elevated uric acid levels at baseline (&gt;7.5 mg/dL) or aggressive lymphoma. Results: Fifty‐five patients were evaluated. The median age of patients was 67 years (range 22‐92) consisting of 20 patients with acute leukemia, 21 with aggressive lymphoma, 11 with multiple myeloma, and 3 with other hematologic cancers. Nearly all analyzed patients (98%) were considered to be at high risk for TLS and 44 patients did meet criteria for clinical TLS. Twenty‐six patients (47%) received allopurinol prophylaxis. The median dose of rasburicase administered was 3 mg (range 1.5‐9) with 10 patients being given a second dose of rasburicase. The median baseline levels of uric acid and creatinine were 13.9 mg/dL (range 6.5‐42.8) and 2.18 mg/dL (range 0.63‐8.15), respectively. At 24 hours post administration of rasburicase the median uric acid levels were 7.9 mg/dL (range 0.8‐17.5) while at 48 hours they were 4.9 mg/dL (range 0.8‐13.5). Notably, 54 patients (98%) experienced a decrease in uric acid levels of at least 10% within the first 24 hours following rasburicase administration and 40% of patients had normal uric levels by that time. Within the initial 24 hours, creatinine levels were significantly improved in only a minority of patients with only 10 patients (18%) experiencing a decrease of more than 10% compared to baseline levels. Of note, 15 patients required dialysis during their admission and 26 patients died during the index hospitalization. Summary/Conclusion: The majority of subjects in our analysis of a high‐risk patient population responded favorably to low dose rasburicase in terms of rapid uric acid reduction although rates of dialysis and early mortality were substantial. Our data illustrate and confirm the feasibility of lower dosing of rasburicase to patients with aggressive hematologic malignancies.
The Use and Abuse of Growth Hormone in Sports
Authors: Richard I G Holt, Ken K Y Ho
Journal: Endocrine Reviews (2019)

Abstract GH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes’ biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.
PB2030 COMBINATION OF INVASIVE ASPERGILLOSIS AND INVASIVE CANDIDIASIS IN ONCOHEMATOLOGICAL PATIENTS
Authors: E. Shagdileeva, O. Shadrivova, T. Shneyder, S. Ermolova, T. Bogomolova, S. Ignatyeva, N. Klimko
Journal: HemaSphere (2019)

Background: Candida spp. and Aspergillus spp. are the most common fungal pathogen an oncohematological patients. Publications about combination of invasive aspergillosis (IA) and invasive candidiasis (IC) are limited. Aims: To investigate the frequency, risk factors, treatment outcome in patients with combination of IA and IC. Methods: Retrospective analysis of 800 adult patients with proven and probable IA in 1998 ‐ 2017 yy. For the IA and IC diagnosis criteria EORTS/MSG, 2008 were used. Results: IC was detected in 10 patients, 1.25% of all IA patients. The patients’ age was from 18 to 59 years (median ‐ 37), men ‐ 60%. Among the underlying conditions acute leukemia prevailed ‐ 60%, lymphoma ‐ 10%, aplastic anemia ‐ 10%, and hemolytic uremic syndrome – 10%. Main risk factors were prolonged neutropenia – 90% (median – 10 days), lymphocytopenia ‐ 70% (median – 19 days), ICU stay – 50%, and glucocorticosteroid therapy – 40%. The main clinical variant of IC was candidemia (100%) with liver (10%) or spleen (10%) involvement. The main sites of IA were lungs (100%) and sinuses (20%). Diagnosis of IC was confirmed with blood culture in all patients: C. krusei – 40%, C. parapsilosis – 30%, Candida spp. – 30%. Positive galactomannan test in bronchoalveolar lavage (BAL) was in 80% patients. Microscopy of BAL revealed septated mycelium in 20% patients, BAL culture was positive ( A.flavus ) in 20% cases. All patients received antifungal therapy (voriconazole ‐ 60%, amphotericin B deoxycholate ‐ 60%, fluconazole – 30%, lipid amphotericin B – 20%, posaconazole – 20%). In patients with IA and IC 30‐days overall survival rate was 60%, 12‐weeks overall survival rate – 40%. Summary/Conclusion: Invasive candidiasis was detected in 1,25 % of patients with invasive aspergillosis. Main risk factors were prolonged neutropenia and lymphocytopenia, ICU stay, and glucocorticosteroid therapy. The main agents of invasive candidiasis were C. krusei ‐ 40% and C. parapsilosis – 30%. The main clinical variant of invasive candidiasis was candidemia (100%) with liver (10%) or spleen (10%) involvement. In patients with invasive aspergillosis and invasive candidiasis 30‐days overall survival rate was 60%, 12‐weeks overall survival rate – 40%.
AB1423-HPR ELICITING THE AGENDA OF PATIENTS WITH MUSCULOSKELETAL DISORDERS; THE PHYSIOTHERAPIST-PATIENT INTERACTION
Authors: Sercan Yilli, Serkan Kalmaz, Faruk Altay, Elif Turgut
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Eliciting main concerns via interviewing is important for patient-centered care and for planning individualized rehabilitation program (1, 2). Recently, it has been shown that clinicians often fail to elicit the patients agenda and, when they do, they interrupt the patients discourse (3). However, the prevalence of agenda setting in physiotherapist as a health care provider and the physiotherapist-patient interaction remains relatively unexplored. <h3>Objectives</h3> The aim of this study was to describe agenda elicitation in rehabilitation, to determine the frequency of encounters in which physiotherapists elicited the patients with musculoskeletal disorders agenda, the proportion and timing of interrupted answers. <h3>Methods</h3> An audio-recording analysis of 52 clinical encounters recorded during first physiotherapist-patient interaction were performed. The elicitation of the patient agenda characteristics as the time to interruption or to complete statement were analyzed. <h3>Results</h3> Physiotherapists elicited the patients agenda in all (96.1%) clinical encounters. Interestingly, in those encounters in which physiotherapists elicited patient concerns, the clinician interrupted the patient after a median of 15 seconds (interquartile range 6 to 22 seconds). In the un-interrupted encounters in which physiotherapists elicited patient concerns, the patients with musculoskeletal disorders was state their agenda in 2414.5 seconds. <h3>Conclusion</h3> Physiotherapist emphasize to elicit the patients agenda, however, they interrupt expression very sooner. Eventually, the failure to elicit the patients agenda inhibits the physiotherapists-patient communication and this would lead to failure to plan rehabilitation program based on the needs of each patient. <h3>References</h3> [1] Dyche L, Swiderski DJJogim. The effect of physician solicitation approaches on ability to identify patient concerns. 2005;20(3):267-70. [2] Marvel MK, Epstein RM, Flowers K, Beckman HBJJ. Soliciting the patient's agenda: have we improved?1999;281(3):283-7. [3] Ospina NS, Phillips KA, Rodriguez-Gutierrez R, Castaneda-Guarderas A, Gionfriddo MR, Branda ME, et al. Eliciting the patients agenda-secondary analysis of recorded clinical encounters. 2019;34(1):36-40. <h3>Disclosure of Interests</h3> None declared
Treatment Outcomes of Immune-Related Cutaneous Adverse Events
Authors: Gregory S. Phillips, Jennifer Wu, Matthew D. Hellmann, Michael A. Postow, Naiyer A. Rizvi, Azael Freites-Martinez, Donald Chan, Stephen Dusza, Robert J. Motzer, Jonathan E. Rosenberg, Margaret K. Callahan, Paul B. Chapman, Larisa Geskin, Adriana T. Lopez, Vanessa A. Reed, Gabriella Fabbrocini, Maria Carmela Annunziata, Oluwaseun Kukoyi, Aliyah Pabani, Chih-Hsun Yang, Wen-Hung Chung, Alina Markova, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2019)

The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics.
Identification of Novel RAS Signaling Therapeutic Vulnerabilities in Diffuse Intrinsic Pontine Gliomas
Authors: Robert F. Koncar, Brittany R. Dey, Ann-Catherine J. Stanton, Nishant Agrawal, Michelle L. Wassell, Lauren H. McCarl, Abigail. L. Locke, Lauren Sanders, Olena Morozova-Vaske, Max I. Myers, Ronald L. Hamilton, Angel M. Carcaboso, Gary Kohanbash, Baoli Hu, Nduka M. Amankulor, James Felker, Madhuri Kambhampati, Javad Nazarian, Oren J. Becher, C. David James, Rintaro Hashizume, Alberto Broniscer, Ian F. Pollack, Sameer Agnihotri
Journal: Cancer Research (2019)

Diffuse intrinsic pontine gliomas (DIPG) are incurable brain tumors with an aggressive onset. Apart from irradiation, there are currently no effective therapies available for patients with DIPG, who have a median survival time of less than one year. Most DIPG cells harbor mutations in genes encoding histone H3 (H3K27M) proteins, resulting in a global reduction of H3K27 trimethylation and activation of oncogenic signaling pathways. Here we show that the H3K27M mutations contribute to RAS pathway signaling, which is augmented by additional RAS activators including PDGFRA. H3K27M mutation led to increased expression of receptor tyrosine kinases (RTK). A RAS pathway functional screen identified ERK5, but not ERK1/2, as a RAS pathway effector important for DIPG growth. Suppression of ERK5 decreased DIPG cell proliferation and induced apoptosis in vitro and in vivo. In addition, depletion or inhibition of ERK5 significantly increased survival of mice intracranially engrafted with DIPG cells. Mechanistically, ERK5 directly stabilized the proto-oncogene MYC at the protein level. Collectively, our data demonstrate an underappreciated role of H3K27M in RAS activation and reveal novel therapeutic targets for treating DIPG tumors. SIGNIFICANCE: These findings identify the H3K27M mutation as an enhancer of RAS activation in DIPG and ERK5 as a novel, immediately actionable molecular target. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/16/4026/F1.large.jpg.