bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung Ultrasound as a Screening Method for Interstitial Lung Disease in Patients With Systemic Sclerosis
Authors: Hassan Romina Isabel , Lubertino Lucia I. , Barth Maria Angeles , Quaglia Maria Fernanda , Montoya Sandra Fabiana , Kerzberg Eduardo , Binda Maria del Carmen 
Published: July 2018

Background
Patients with systemic sclerosis (SSc) undergo chest radiographs and high-resolution computed tomography (HRCT) of the thorax both for interstitial lung disease (ILD) detection and for disease progression monitoring.

Objective
The aim of this study was to assess whether lung ultrasound (LUS) is a useful screening tool for ILD in patients with SSc in comparison with HRCT.

Methods
This was a longitudinal cohort study carried out from December 2015 to April 2016. An LUS was performed to examine B-lines in 67 consecutive patients who met the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc and had a previous HRCT. B-lines were quantified and classified according to the score modified from Picano. Severity and extent of lung involvement on the HRCT were determined by means of the Warrick score.

Results
Twenty-nine patients had both abnormal HRCT (Warrick score >7) and abnormal LUS, 2 had a mild score (6–15 B-lines), and 27 had either moderate or severe scores (≥16 B-lines). Of the 38 patients with negative HRCT, 25 presented some degree of lung involvement on the LUS. Thus, LUS has a sensitivity of 100% and a specificity of 34%. Receiver operating characteristic curve analysis showed the analytic relation between the number of B-lines and the presence of ILD on the HRCT (area under the curve, 0.80; 95% confidence interval, 0.69–0.90).

Conclusions
Lung ultrasound may be a method to detect abnormal lung findings in a noninvasive manner in patients with SSc. Because of its high sensitivity, a low score almost rules out the need for an HRCT.
Pan-American League of Associations for Rheumatology–Central American, Caribbean and Andean Rheumatology Association Consensus-Conference Endorsements and Recommendations on the Diagnosis and Treatment of Chikungunya-Related Inflammatory Arthropathies in Latin America
Authors: Monge Pablo , Vega José Manuel , Sapag Ana María , Moreno Ilsa , Montúfar Rubén , Khoury Vianna , Camilo Pablo , Rivera Ruddy , Rueda Juan C. , Jaramillo-Arroyave Daniel , Londoño John , del Carmen Ruiz María , Fernández Félix , Quintero Maritza , Fuentes-Silva Yurilis , Aguilar José Luis , Vallejo-Flores Carlos , Caballero-Uribe Carlo V. , Sandoval Hugo , Pineda Carlos 
Published: July 2018

Background/Objective
Although mortality rates related with chikungunya (CHIK) outbreaks in Latin America's (LA's) dengue-endemic rural and new urban regions are low, dealing with symptoms and sequelae can both produce a significant burden of disease and diminish quality of life—from many months to years—after the acute phase of the infection, with a significant impact on public and individual health.
The aim of this work was to establish Pan-American League of Associations for Rheumatology–Central American, Caribbean and Andean Rheumatology Association (ACCAR) consensus-conference endorsements and recommendations on the diagnosis and treatment of CHIK-related inflammatory arthropathies transmitted by Aedes aegypti and Aedes albopictus in LA.

Methods
Based on the Consensus Development Conference format, a panel of ACCAR rheumatologist voting members (n = 10) took part in this Pan-American League of Associations for Rheumatology initiative. Experts voted from a previous content analysis of the medical literature on CHIK, 4 subsequent topic conferences, and a workshop. Consensus represents the majority agreement (≥80%) achieved for each recommendation.

Results
The experts' panel reached 4 overarching principles: (1) CHIK virus (CHIKV) is a re-emergent virus transmitted by 2 species of mosquitoes: A. aegypti and A. albopictus; (2) CHIKV caused massive outbreaks in LA; (3) chronic CHIKV infection produces an inflammatory joint disease that, in some cases, can last for several months to years, and (4) currently, there are no vaccines or antivirals licensed for CHIKV infections.

Recommendations
Pan-American League of Associations for Rheumatology–ACCAR achieved 13 endorsements and recommendations on CHIK categorized in 3 groups: (1) epidemiology and clinical manifestations, (2) diagnosis, and (3) treatment, representing the consensus agreement from the panel's members.
Clinical Associations of Uveitis in Axial Spondyloarthritis Group and Ankylosing Spondylitis Group
Authors: Wong Oi Man , Tsang Helen Hoi Lun , Chan Shirley Chiu Wai , Lee Kam Ho , Li Philip Hei , Lau Chak Sing , Chung Ho Yin 
Published: July 2018

Objective
The aim of this study was to determine the prevalence and associated factors for uveitis in ethnic Chinese patients with axial spondyloarthritis (SpA) and ankylosing spondylitis (AS).

Methods
This was a cross-sectional study. Patients fulfilling the Assessment of SpondyloArthritis international Society axial SpA criteria were recruited consecutively from 3 rheumatology centers in Hong Kong from March 2014 to July 2017. Clinical and biochemical parameters were collected. History of uveitis was inquired from both history and medical records. All patients received lumbosacral spine x-rays and whole-spine and sacroiliac joint magnetic resonance imaging. Patients were defined as axial SpA if they fulfilled the Assessment of SpondyloArthritis international Society criteria and AS if they fulfilled the modified New York criteria. Clinical and radiological findings were compared between patients with and without uveitis in the 2 groups. Factors associated with uveitis were identified with univariate analyses and multivariate logistic regression analyses.

Results
Among 252 patients, 67 patients (26.6%) had a history of uveitis. The male-to-female ratio was 55.4 to 44.6. Disease duration was 12.3 ± 11.7 years. In the axial SpA group, multivariate regression showed that older age (odds ratio [OR], 1.05; p = 0.01), human leukocyte antigen B27 positivity (OR, 11.79; p = 0.01), and history of inflammatory bowel disease (OR, 9.74; p = 0.04) were positively associated with uveitis. In the AS group, multivariate regression showed that back pain duration (OR, 1.05; p = 0.01) and male sex (OR, 3.46; p = 0.03) were associated with uveitis.

Conclusions
Axial SpA represents a spectrum of diseases. Its clinical associations with uveitis should be distinguished from those of traditional AS.
Celiac-like Enteropathy Associated With Mycophenolate Sodium in Renal Transplant Recipients
Authors: Filiopoulos Vassilis , Sakellariou Stratigoula , Papaxoinis Konstantinos , Melexopoulou Christina , Marinaki Smaragdi , Boletis John N. , Delladetsima Ioanna 
Published: July 2018

BackgroundAlthough colonic injury is a well-known complication of mycophenolic acid (MPA), the involvement of the upper gastrointestinal tract is less extensively documented. We present the occurrence of celiac-like duodenopathy manifested as a severe diarrhea syndrome in 2 renal transplant recipients on enteric-coated mycophenolate sodium.MethodsThe patients belong to a setting of 16 renal transplant recipients under MPA suffering from chronic diarrhea in the absence of MPA-related colitis.ResultsBoth patients had a history of persistent diarrhea with significant weight loss. Colonic mucosa was unremarkable, whereas duodenal biopsies revealed celiac-like changes with increased epithelial cell apoptosis. Clinical symptoms completely resolved, and follow-up biopsies demonstrated normalization of histology after enteric-coated mycophenolate sodium withdrawal and switching to azathioprine.ConclusionsCeliac-like enteropathy seems to represent a rare side effect of MPA-associated immunosuppressive therapy and should be taken into account in the differential diagnosis of diarrhea in transplant recipients treated with MPA particularly in the absence of MPA-related colitis. As macroscopic lesions are usually missing, blind duodenal biopsies are necessary to establish the diagnosis.
Liver Allograft Failure After Nivolumab Treatment—A Case Report With Systematic Literature Research
Authors: Gassmann Dimitri , Weiler Stefan , Mertens Joachim C. , Reiner Cäcilia S. , Vrugt Bart , Nägeli Mirjam , Mangana Joanna , Müllhaupt Beat , Jenni Fabienne , Misselwitz Benjamin 
Published: July 2018

Background
Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited.

Methods
We report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage.

Results
A systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss.

Conclusion
Experience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.
How useful is muscle ultrasound in the diagnostic workup of neuromuscular diseases?
Authors: van Alfen Nens , Gijsbertse Kaj , de Korte Chris L. 
Published: July 2018

Purpose of review
This review focuses on developments in muscle ultrasound as a noninvasive and accurate tool for the diagnosis and follow-up of neuromuscular disease. It discusses current muscle ultrasound applications with already proven clinical value, and highlights recent technical developments that may further advance muscle ultrasounds’ diagnostic qualities.

Recent findings
The sensitivity and specificity of muscle ultrasound for detecting a neuromuscular disorder are high (90–95%), and quantitative ultrasound is well suited to monitor disease progression in several disorders. Adding ultrasound to electromyography significantly improves diagnostic certainty in patients with suspected motor neuron disease, and ultrasound increases the detection of fasciculations with 30–50%. New developments include speckle tracking of tissue motion to quantify diaphragm excursions and diminished muscle contractility in dystrophy, and strain elastography to detect changes in muscle stiffness and anisotropy during contraction and in disease states. Deep learning algorithms are being developed to predict the presence of a muscle disease and differentiate between disorders.

Summary
Muscle ultrasound is excellent for screening, diagnosing, and follow-up of neuromuscular disease. New developments are underway to automate and objectify the diagnostic process, and to quantify tissue motion that can provide new insights in pathophysiology and serve as a biomarker.
Emerging antisense oligonucleotide and viral therapies for amyotrophic lateral sclerosis
Authors: Ly Cindy V. , Miller Timothy M. 
Published: July 2018

Purpose of reviewAmyotrophic lateral sclerosis (ALS) is a rapidly fatal disease for which there is currently no effective therapy. The present review describes the current progress of existing molecular therapies in the clinical trial pipeline and highlights promising future antisense oligonucleotide (ASO) and viral therapeutic strategies for treating ALS.Recent findingsThe immense progress in the design of clinical trials and generation of ASO therapies directed towards superoxide dismutase-1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) repeat expansion related disease have been propelled by fundamental work to identify the genetic underpinnings of familial ALS and develop relevant disease models. Preclinical studies have also identified promising targets for sporadic ALS (sALS). Moreover, encouraging results in adeno-associated virus (AAV)-based therapies for spinal muscular atrophy (SMA) provide a roadmap for continued improvement in delivery and design of molecular therapies for ALS.SummaryAdvances in preclinical and clinical studies of ASO and viral directed approaches to neuromuscular disease, particularly ALS, indicate that these approaches have high specificity and are relatively well tolerated.
Myasthenia gravis: from autoantibodies to therapy
Authors: Mantegazza Renato , Bernasconi Pia , Cavalcante Paola 
Published: July 2018

Purpose of reviewThe current article reviews the recent advances in the field of myasthenia gravis, which span from autoantibody profiling and pathogenic mechanisms to therapy innovation. The overview is highlighting specifically the data and the needs of targeted treatments in the light of precision medicine in myasthenia gravis.Recent findingsNovel data published recently further increased our knowledge on myasthenia gravis. The use of cell-based assays has greatly improved autoantibody detection in myasthenia gravis patients, and the mechanisms of action of these antibodies have been described. The role of Toll-like receptor activation in the generation of thymic alterations and anti-acetylcholine receptor autosensitization has been further investigated implementing our understanding on the relationships between innate immunity and autoimmunity. Additional studies have been focused on the alterations of T-cell/B-cell regulatory mechanisms in thymus and peripheral blood of myasthenia gravis patients. microRNAs and genetic factors are also emerging as key biomarkers in myasthenia gravis pathogenesis and prediction of drug efficacy in individual patients.SummaryThe recent immunological and pathological findings in myasthenia gravis promise to improve myasthenia gravis treatment, via the development of more precise and personalized therapies.
Activated αIIbβ3on platelets mediates flow-dependent NETosis via SLC44A2
Authors: Constantinescu-Bercu Adela , Grassi Luigi , Frontini Mattia , Salles-Crawley Isabelle I. , Woollard Kevin J , Crawley James T.B. 
Published: July 2018

AbstractPlatelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin αIIbβ3activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet αIIbβ3to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. A polymorphism inSLC44A2(rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated αIIbβ3and VWF-primed platelets. This was confirmed using neutrophils homozygous for theSLC44A2R154Q polymorphism. Taken together, these data reveal a previously unreported mode of platelet-neutrophil cross-talk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of theSLC44A2rs2288904-A polymorphism in venous thrombosis.SummaryPlatelets that are primed following interaction with von Willebrand factor under flow mediated direct interactions with neutrophils via activated platelet integrin, αIIbβ3, and SLC44A2 on neutrophils. This interaction initiates signaling in a mechanosensitive manner that promotes neutrophil extracellular trap formation.
Identification and characterization of yeast and human glycosphingolipid flippases
Authors: Roland Bartholomew P. , Naito Tomoki , Best Jordan T. , Arnaiz-Yépez Cayetana , Takatsu Hiroyuki , Yu Roger J. , Shin Hye-Won , Graham Todd R. 
Published: July 2018

AbstractLipid transport is an essential process with manifest importance to human health and disease. Phospholipid flippases (P4-ATPases) transport lipids across the membrane bilayer, and are involved in signal transduction, cell division, and vesicular transport. Mutations in flippase genes cause or contribute to a host of diseases such as cholestasis, neurological deficits, immunological dysfunction, and metabolic disease. Genome-wide association studies have shown thatATP10AandATP10Dvariants are associated with an increased risk of diabetes, obesity, myocardial infarction, and atherosclerosis; andATP10DSNPs are associated with elevated levels of glucosylceramide (GlcCer) in plasma from diverse European populations. Although sphingolipids are strong contributors to metabolic disease, little is known about how GlcCer is transported across cell membranes. We have identified an evolutionarily conserved clade of P4-ATPases fromSaccharomyces cerevisiae(Dnf1, Dnf2),Schizosaccharomyces pombe(Dnf2), andHomo sapiens(ATP10A, ATP10D) that transport GlcCer. Further, we establish the structural determinants necessary for the specific recognition of this sphingolipid substrate. Our molecular observations clarify the relationship between these flippases and human disease, and have fundamental implications for membrane organization and sphingolipid homeostasis.
Self-healing dyes for super-resolution microscopy
Authors: van der Velde Jasper H. M. , Smit Jochem , Punter Michiel , Cordes Thorben 
Published: July 2018

AbstractIn recent years optical microscopy techniques have emerged that allow optical imaging at unprecented resolution beyond the diffraction limit. Up to date, photostabilizing buffers are the method of choice to realize either photoswitching and/or to enhance the signal brightness and stability of the employed fluorescent probes. This strategy has, however, restricted applicability and is not suitable for live cell imaging. In this paper, we tested the performance of self-healing organic fluorophores with intramolecular photostabilization in super-resolution microscopy with targeted (STED) and stochastic readout (STORM). The overall goal of the study was to improve the spatial and temporal resolution of both techniques without the need for mixtures of photostabilizing agents in the imaging buffer. Due to its past superior performance we identified ATTO647N-photostabilizer conjugates as suitable candidates for STED microscopy. We characterize the photostability and resulting performance of NPA-ATTO647N oligonucleotide conjugates in STED microscopy. We find that the superior photophysical performance results in optimal STED imaging and demonstrate the possibility to obtain single-molecule fluorescent transients of individual fluorophores while illuminating with both the excitation- and STED-laser. Secondly, we show an analysis of photoswitching kinetics of self-healing Cy5 dyes (comprising TX, COT and NPA stabilizers) in the presence of TCEP- and cysteamine, which are typically used in STORM microscopy. In line with previous work, we find that intramolecular photostabilization strongly influences photoswitching kinetics and requires careful attention when designing STORM-experiments. In summary, this contribution explores the possibilities and limitations of self-healing dyes in super-resolution microscopy of differing modalities.
The structural basis for activation of voltage sensor domains in an ion channel TPC1
Authors: Kintzert Alexander F. , Green Evan M. , Dominik Pawel K. , Bridges Michael , Armache Jean-Paul , Deneka Dawid , Kim Sangwoo S. , Hubbell Wayne , Kossiakoff Anthony A. , Cheng Yifan , Stroud Robert M. 
Published: July 2018

AbstractVoltage sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured the first example of a resting-state VSD in an intact ion channel. To generate an activated state VSD in the same channel we removed the luminal inhibitory Ca2+-binding site (Cai2+), that shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side, but remains occluded on the luminal side and an intermediate activated state 2 in which the cytoplasmic solvent access to the gating charges closes, while luminal access partially opens. Activation can be thought of as moving a hydrophobic insulating region of the VSD from the external side, to an alternate grouping on the internal side. This effectively moves the gating charges from the inside potential to that of the outside. Activation also requires binding of Ca2+ to a cytoplasmic site (Caa2+). An X-ray structure with Caa2+ removed and a near-atomic resolution cryo-EM structure with Cai2+ removed define how dramatic conformational changes in the cytoplasmic domains may communicate with the VSD during activation. Together four structures provide a basis for understanding the voltage dependent transition from resting to activated state, the tuning of VSD by thermodynamic stability, and this channel’s requirement of cytoplasmic Ca2+-ions for activation.
High resolution AKT signaling in individual cells
Authors: Gross Sean M. , Dane Mark A. , Bucher Elmar , Heiser Laura M. 
Published: July 2018

AbstractCells sense and respond to their environment by activating distinct intracellular signaling pathways, however an individual cell’s ability to faithfully transmit and discriminate environmental signals is thought to be limited. To assess the fidelity of signal transmission in the PI3K-AKT signaling pathway, we first developed an optimized genetically encoded sensor that had an increased dynamic range and reduced variation under basal conditions. We then used this reporter to track responses to varying doses of IGF-I in live cells and found that signaling responses from individual cells overlapped across a wide range of IGF-I doses, suggesting limited transmission accuracy. However, further analysis of individual cell traces revealed that responses were constant over time without stochastic fluctuations. We devised a new information theoretic approach to calculate the channel capacity using variance of the single cell time course data‐‐rather than population-level variance as has been previously used—and predicted that cells were capable of discriminating multiple growth factor doses. We validated these predictions by tracking individual cell responses to multiple IGF-I doses and found that cells can accurately distinguish at least four different IGF-I concentrations, as demonstrated by their distinct responses. Furthermore, we found a similar discriminatory ability to pathway inhibition, as assessed by responses to the PI3K inhibitor alpelisib. Our studies indicate that cells can faithfully transmit an IGF-I input into a down-stream signaling response and that heterogeneous responses result from variation in the input-output relation across the population. These observations reveal the importance of viewing each cell as having its own communication channel and underscore the importance of understanding responses at the single cell level.