bluuebunny/crossref_metadata_2025 huggingface dataset:
Inpatient and Emergency Room Ophthalmology Consultations at a Tertiary Care Center
Authors: Oh Daniel J. , Kanu Levi N. , Chen Judy L. , Aref Ahmad A. , Mieler William F. , MacIntosh Peter W.
Published: February 2019

Background. An ophthalmology consultation service is of significant benefit to patients in the hospital and is an instructive component of a residency education program. Ophthalmology consultations in a hospital present unique challenges to those seen in an outpatient clinic, for which the consulting ophthalmologist should be prepared. The purpose of this study was to profile the emergency room and inpatient ophthalmology consultations seen at an academic institution. Methods. A prospective study of 581 patients was conducted on inpatient and emergency room ophthalmology consultations at the University of Illinois at Chicago over twelve months. Characteristics such as the consulting service, type of and reason for consultation, subspecialty staffing service, diagnosis, and suitability for in-hospital evaluation were recorded. Results. Consultations were received from either inpatient wards (59.4%) or the Emergency Department (40.6%). The most common inpatient consulting services were internal medicine (22%), followed by neurosurgery (16%) and neurology (7%). All the consultations were categorized as acute (72.3%), chronic (6.0%), or screening (21.7%). Consultations categorized as screening included papilledema (31.0%), fungemia (20.6%), syndromic evaluation (19.8%), visual field evaluation (17.5%), and miscellaneous evaluation (11.1%). We classified the ophthalmic diagnoses into 63 unique diagnoses. Amongst the ophthalmic subspecialties, neuro-ophthalmologic diagnoses were the most common (32.0%), followed by retina (20.1%) and cornea (19.4%). Neuro-ophthalmology had the highest proportion of screening consultations (36.6%), while glaucoma had the least overall number of consultations (10.1%), and the least proportion of screening consultations (3.6%). A significant proportion of nonacute consultations (19.0%) was deemed to be more suitable for outpatient evaluation. Discussion. Consultation databases can be useful in preparing trainees for in-hospital clinical care. A wide range of ocular pathologies may present to the ophthalmology consultant, from acute trauma to screening for systemic syndromes. Some consultations may be more suitable for outpatient evaluation which may help optimize patient care.
Nonlinear Transient Thermal Modeling and Analysis of a Convective-Radiative Fin with Functionally Graded Material in a Magnetic Environment
Authors: Sobamowo M. G. , Oguntala G. A. , Yinusa A. A.
Published: February 2019

Nonlinear transient thermal analysis of a convective-radiative fin with functionally graded materials (FGMs) under the influence of magnetic field is presented in this study. The developed nonlinear thermal models of linear, quadratic, and exponential variation of thermal conductivity are solved approximately and analytically using the differential transformation method (DTM). In order to verify the accuracies of the nonlinear solutions, exact analytical solutions are also developed with the aids of Bessel, Legendre, and modified Bessel functions. Good agreements are established between the exact and the approximate analytical solutions. In the parametric studies, effects of heat enhancement capacity of fin with functionally graded material as compared to fin with homogeneous material are investigated. Also, influence of the Lorentz force and radiative heat transfer on the thermal performance of the fin are analyzed. From the results, it is shown that increase in radiative and magnetic field parameters as well as the in-homogeneity index improve the thermal performance of the fin. Also, the transient responses reveal that the FGM fin with quadratic-law and exponential-law function shows the slowest and fasted thermal responses, respectively. This study will provide a very good platform for the design and optimization of an improved heat transfer enhancement in thermal systems, where the surrounding fluid is influenced by a magnetic field.
Corrosion Inhibition Mechanism of Mild Steel by Amylose-Acetate/Carboxymethyl Chitosan Composites in Acidic Media
Authors: Erna Maria , Herdini Herdini , Futra Dedi
Published: February 2019

This article details an investigation on the mechanism of corrosion inhibition of mild steel using amylose-acetate-blended carboxymethyl chitosan (AA-CMCh) in acidic media in the context of kinetic and thermodynamic parameters. The surface of mild steel was exposed to test solutions and evaluated using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The activation energy (Ea), free energy of adsorption (ΔG), enthalpy of activation (ΔHads), and entropy of activation (ΔSads) were determined in order to elucidate the mechanism of corrosion inhibition. The results confirmed that AA could be improved using CMCh as a corrosion inhibitor. The corrosion rate decreased from 1109.00 to 229.70 mdd (79.29%), while corrosion inhibition increased from 35.13 to 89.72%. Sulfate acid (H2SO4) of 0.25 M also helped in decreasing the corrosion rate from 2664.4 to 1041.67 mdd (60.9%) while also in increasing corrosion inhibition from 56.94 to 68.31%. The calculated values for ΔG, ΔHads, and ΔSads were −33.22 kJ·mol−1, −48.56 kJ·mol−1, and 0.0495 kJ·mol−1·K−1, respectively. The mechanism of corrosion inhibition of mild steel in the acidic condition is dominated and precipitated by the formation of the Fe-chelate compound, which was confirmed by the SEM/EDS spectrum. The reactions were spontaneous, exothermic, and irregular and takes place on the surface of mild steel.
Optimizing Train-Set Circulation Plan in High-Speed Railway Networks Using Genetic Algorithm
Authors: Wang Yun , Zhou Yu , Yan Xuedong
Published: February 2019

As a sustainable transportation mode, high-speed railway (HSR) has been developing rapidly during the past decade in China. With the formation of dense HSR network, how to improve the utilization efficiency of train-sets (the carrying tools of HSR) has been a new research hotspot. Moreover, the emergence of railway transportation hubs has brought great challenges to the traditional train-sets’ utilization mode. Thus, in this paper, we address the issue of train-sets’ utilization problem with the consideration of railway transportation hubs, which consists of finding an optimal Train-set Circulation Plan (TCP) to complete trip tasks in a given Train Diagram (TD). An integer programming TCP model is established to optimize the train-set utilization scheme, aiming to obtain the one-to-one correspondence relationship among sets of train-sets, trip tasks, and maintenances. A genetic algorithm (GA) is designed to solve the model. A case study based on Nanjing and Shanghai HSR transportation hubs is made to demonstrate the practical significance of the proposed method. The results show that a more efficient TCP can be formulated by introducing train-sets being dispatched among different stations in the same hub.
Models of Collapsing and Expanding Cylindrical Source in f(R,T) Theory
Authors: Sharif M. , Siddiqa Aisha
Published: February 2019

We discuss the collapsing and expanding solutions of anisotropic charged cylinder in the context of f(R,T) theory (R represents the Ricci scalar and T denotes the trace of energy-momentum tensor). For this purpose, we take an auxiliary solution of Einstein-Maxwell field equations and evaluate expansion scalar whose negative values lead to collapse and positive values give expansion. For both cases, the behavior of density, pressure, anisotropic parameter, and mass is explored and the effects of charge as well as model parameter on these quantities are examined. The energy conditions are found to be satisfied for both solutions.
Approximating Betweenness Centrality to Identify Key Nodes in a Weighted Urban Complex Transportation Network
Authors: Liu Weiyan , Li Xin , Liu Tao , Liu Bin
Published: February 2019

The key nodes in a complex transportation network have a significant influence on the safety of traffic operations, connectivity reliability, and the performance of the entire network. However, the identification of key nodes in existing urban transportation networks has mainly focused on nonweighted networks and the network information of the nodes themselves, which do not accurately reflect their global status. Thus, the present study proposes a key node identification algorithm that combines traffic flow features and is based on weighted betweenness centrality. This study also uses weighted roads to construct an L-space weighted transportation network and an approximate algorithm for betweenness centrality in order to reduce the complexity of the calculations. The results of the simulation indicate that the proposed algorithm is not only capable of identifying the key nodes in a relatively short amount of time, but it does so with high accuracy. The findings of this study can be used to provide decision-making support for road network management, planning, and urban traffic construction optimization.
A Case Report of Melanoma as Acute Mastoiditis in a 10-Month-Old Female Child
Authors: Chrysouli Konstantina , Tsakanikos Michael , Stamataki Sofia
Published: February 2019

We present a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the pregnancy of a 34-year-old woman. She was diagnosed with a melanoma at the age of 25, for which she was treated with chemotherapy. During her pregnancy, she presented with a recurrence of the disease and died 3 months after delivery. The 10-month-old female child presented with a recurrent retroauricular oedema on the left side. A trephination of mastoid apophysis followed. Multiple fragments of dark-coloured tissue were sent for histological examination, and the immunophenotype showed a melanocytic tumour in the mastoid. A full radiological assessment showed no sign of metastasis. The child remained without treatment. Complete remission of bone metastatic lesion has been confirmed by follow-up; now, the child is 4 years old, alive, and without evidence of disease.
Cytochrome c Deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer
Authors: Kumar Rahul , Bhat Tariq A. , Walsh Elise M. , Chaudhary Ajay K. , O'Malley Jordan , Rhim Johng S. , Wang Jianmin , Morrison Carl D. , Attwood Kristopher , Bshara Wiam , Mohler James L. , Yadav Neelu , Chandra Dhyan
Published: February 2019

Although African-American (AA) patients with prostate cancer tend to develop greater therapeutic resistance and faster prostate cancer recurrence compared with Caucasian-American (CA) men, the molecular mechanisms of this racial prostate cancer disparity remain undefined. In this study, we provide the first comprehensive evidence that cytochrome c deficiency in AA primary tumors and cancer cells abrogates apoptosome-mediated caspase activation and contributes to mitochondrial dysfunction, thereby promoting therapeutic resistance and prostate cancer aggressiveness in AA men. In AA prostate cancer cells, decreased nuclear accumulation of nuclear respiration factor 1 (Nrf1) and its subsequent loss of binding to the cytochrome c promoter mediated cytochrome c deficiency. The activation of cellular Myc (c-Myc) and NF-κB or inhibition of AKT prevented nuclear translocation of Nrf1. Genetic and pharmacologic inhibition of c-Myc and NF-κB or activation of AKT promoted Nrf1 binding to cytochrome c promoter, cytochrome c expression, caspase activation, and cell death. The lack of p-Drp1S616 in AA prostate cancer cells contributed to defective cytochrome c release and increased resistance to apoptosis, indicating that restoration of cytochrome c alone may be insufficient to induce effective apoptosis. Cytochrome c deficiency promoted the acquisition of glycolytic phenotypes and mitochondrial dysfunction, whereas cytochrome c restoration via inhibition of c-Myc and NF-κB or activation of AKT attenuated glycolysis in AA prostate cancer cells. Inhibition of c-Myc and NF-κB enhanced the efficacy of docetaxel in tumor xenografts. Therefore, restoring cytochrome c may overcome therapeutic resistance and prostate cancer aggressiveness in AA men. Overall, this study provides the first comprehensive experimental, mechanistic, and clinical evidence for apoptosome and mitochondrial dysfunction in prostate cancer racial disparity.

Significance:

Mechanistic insights on prostate cancer health disparity among American men provide novel approaches to restore mitochondrial function, which can address therapeutic resistance and aggressiveness in African-American men with prostate cancer.
MDH1 and MPP7 Regulate Autophagy in Pancreatic Ductal Adenocarcinoma
Authors: New Maria , Van Acker Tim , Sakamaki Jun-Ichi , Jiang Ming , Saunders Rebecca E. , Long Jaclyn , Wang Victoria M.-Y. , Behrens Axel , Cerveira Joana , Sudhakar Padhmanand , Korcsmaros Tamas , Jefferies Harold B.J. , Ryan Kevin M. , Howell Michael , Tooze Sharon A.
Published: February 2019

Pancreatic ductal adenocarcinoma (PDAC) is driven by metabolic changes in pancreatic cells caused by oncogenic mutations and dysregulation of p53. PDAC cell lines and PDAC-derived xenografts grow as a result of altered metabolic pathways, changes in stroma, and autophagy. Selective targeting and inhibition of one of these may open avenues for the development of new therapeutic strategies. In this study, we performed a genome-wide siRNA screen in a PDAC cell line using endogenous autophagy as a readout and identified several regulators of autophagy that were required for autophagy-dependent PDAC cell survival. Validation of two promising candidates, MPP7 (MAGUK p55 subfamily member 7, a scaffolding protein involved in cell–cell contacts) and MDH1 (cytosolic Malate dehydrogenase 1), revealed their role in early stages of autophagy during autophagosome formation. MPP7 was involved in the activation of YAP1 (a transcriptional coactivator in the Hippo pathway), which in turn promoted autophagy, whereas MDH1 was required for maintenance of the levels of the essential autophagy initiator serine–threonine kinase ULK1, and increased in the activity upon induction of autophagy. Our results provide a possible explanation for how autophagy is regulated by MPP7 and MDH1, which adds to our understanding of autophagy regulation in PDAC.

Significance:

This study identifies and characterizes MPP7 and MDH1 as novel regulators of autophagy, which is thought to be responsible for pancreatic cancer cell survival.
BRAF Targeting Sensitizes Resistant Melanoma to Cytotoxic T Cells
Authors: Atay Cigdem , Kwak Taekyoung , Lavilla-Alonso Sergio , Donthireddy Laxminarasimha , Richards Allison , Moberg Valerie , Pilon-Thomas Shari , Schell Michael , Messina Jane L. , Rebecca Vito W. , Xiao Min , Tan Jiufeng , Zhang Gao , Weber Jeffrey S. , Herlyn Meenhard , Sarnaik Amod A. , Gabrilovich Dmitry I.
Published: February 2019

Purpose:

BRAF and MEK inhibitors (BRAFi and MEKi) are actively used for the treatment of metastatic melanoma in patients with BRAFV600E mutation in their tumors. However, the development of resistance to BRAFi and MEKi remains a difficult clinical challenge with limited therapeutic options available to these patients. In this study, we investigated the mechanism and potential therapeutic utility of combination BRAFi and adoptive T-cell therapy (ACT) in melanoma resistant to BRAFi.

Experimental Design:

Investigations were performed in vitro and in vivo with various human melanoma cell lines sensitive and resistant to BRAFi as well as patient-derived xenografts (PDX) derived from patients. In addition, samples were evaluated from patients on a clinical trial of BRAFi in combination with ACT.

Results:

Herein we report that in human melanoma cell lines, senstitive and resistant to BRAFi and in PDX from patients who progressed on BRAFi and MEKi therapy, BRAFi caused transient upregulation of mannose-6-phosphate receptor (M6PR). This sensitized tumor cells to CTLs via uptake of granzyme B, a main component of the cytotoxic activity of CTLs. Treatment of mice bearing resistant tumors with BRAFi enhanced the antitumor effect of patients' TILs. A pilot clinical trial of 16 patients with metastatic melanoma who were treated with the BRAFi vemurafenib followed by therapy with TILs demonstrated a significant increase of M6PR expression on tumors during vemurafenib treatment.

Conclusions:

BRAF-targeted therapy sensitized resistant melanoma cells to CTLs, which opens new therapeutic opportunities for the treatment of patients with BRAF-resistant disease.

See related commentary by Goff and Rosenberg, p. 2682
A Variant of a Killer Cell Immunoglobulin-like Receptor Is Associated with Resistance to PD-1 Blockade in Lung Cancer
Authors: Trefny Marcel P. , Rothschild Sacha I. , Uhlenbrock Franziska , Rieder Dietmar , Kasenda Benjamin , Stanczak Michal A. , Berner Fiamma , Kashyap Abhishek S. , Kaiser Monika , Herzig Petra , Poechtrager Severin , Thommen Daniela S. , Geier Florian , Savic Spasenija , Jermann Philip , Alborelli Ilaria , Schaub Stefan , Stenner Frank , Früh Martin , Trajanoski Zlatko , Flatz Lukas , Mertz Kirsten D. , Zippelius Alfred , Läubli Heinz
Published: February 2019

Purpose:

PD-(L)1–blocking antibodies have clinical activity in metastatic non–small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways.

Experimental Design:

Peripheral blood mononuclear cells were collected from 35 patients with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels, gene expression, and polymorphisms were compared between responders and nonresponders to treatment. Findings were confirmed in additional cohorts of patients with NSCLC receiving immune checkpoint blockade.

Results:

We identified a genetic variant of a killer cell immunoglobulin-like receptor (KIR) KIR3DS1 that is associated with primary resistance to PD-1 blockade in patients with NSCLC. This association could be confirmed in independent cohorts of patients with NSCLC. In a multivariate analysis of the pooled cohort of 135 patients, the progression-free survival was significantly associated with presence of the KIR3DS1 allele (HR, 1.72; 95% confidence interval, 1.10–2.68; P = 0.017). No relationship was seen in cohorts of patients with NSCLC who did not receive immunotherapy. Cellular assays from patients before and during PD-1 blockade showed that resistance may be due to NK-cell dysfunction.

Conclusions:

We identified an association of the KIR3DS1 allelic variant with response to PD-1–targeted immunotherapy in patients with NSCLC. This finding links NK cells with response to PD-1 therapy. Although the findings are interesting, a larger analysis in a randomized trial will be needed to confirm KIRs as predictive markers for response to PD-1–targeted immunotherapy.
Phase I Trial of Inducible Caspase 9 T Cells in Adult Stem Cell Transplant Demonstrates Massive Clonotypic Proliferative Potential and Long-term Persistence of Transgenic T Cells
Authors: Zhang Ping , Raju Jyothy , Ullah Md Ashik , Au Raymond , Varelias Antiopi , Gartlan Kate H. , Olver Stuart D. , Samson Luke D. , Sturgeon Elise , Zomerdijk Nienke , Avery Judy , Gargett Tessa , Brown Michael P. , Coin Lachlan J. , Ganesamoorthy Devika , Hutchins Cheryl , Pratt Gary R. , Kennedy Glen A. , Morton A. James , Curley Cameron I. , Hill Geoffrey R. , Tey Siok-Keen
Published: February 2019

Purpose:

Inducible caspase 9 (iCasp9) is a cellular safety switch that can make T-cell therapy safer. The purpose of this phase I trial was to investigate the use of iCasp9-transduced T-cell addback in adult patients undergoing haploidentical stem cell transplantation for high-risk hematologic malignancies.

Patients and Methods:

Patients undergoing myeloablative, CD34-selected haploidentical stem cell transplantation were treated with 0.5−1.0 × 106/kg donor-derived iCasp9-transduced T cells on day +25 or 26 post-transplant, with additional doses allowed for disease relapse, infection, or mixed chimerism.

Results:

Three patients were enrolled. iCasp9-transduced T cells were readily detectable by 4 weeks post-infusion in all patients and remained at high level (114 cells/μL, 11% of T cells) in 1 patient alive at 3.6 years. One patient developed donor-derived Epstein–Barr virus-associated post-transplant lymphoproliferative disease (EBV-PTLD), which was followed by a marked expansion of iCasp9 T cells and cytokine release syndrome (CRS). These iCasp9-transduced T cells infiltrated the affected lymph nodes and secreted IFNγ and IL-10. They peaked at 1,848 cells/μL and were found to be monoclonal by T-cell receptor (TCR) clonotype and oligoclonal by viral integrant analysis, representing a 6-log in vivo expansion of the dominant T-cell clone. These T cells were not autonomous and contracted with the resolution of EBV-PTLD, which did not recur.

Conclusions:

iCasp9-transduced T cells could persist long-term. They retained very high in vivo clonotypic proliferative capacity and function, and could cause CRS in response to de novo lymphoma development.
Panax notoginseng Saponins Ameliorate Leukocyte Adherence and Cerebrovascular Endothelial Barrier Breakdown upon Ischemia-Reperfusion in Mice
Authors: Wu Ting , Jia Zhanhong , Dong Shifen , Han Bing , Zhang Rong , Liang Yaoyue , Zhang Shuofeng , Sun Jianning
Published: February 2019

Panax notoginseng saponins (PNS) are known as clinical anti-stroke herbal medicines. The aim of this study is to describe the impact of PNS on ischemia-reperfusion-induced cerebral microvasculature barrier dysfunction which has not been investigated yet. Mice were subjected to transient middle cerebral artery occlusion and PNS were administrated to mice 3 days before and 2 days after surgery. Leukocyte adhesion, albumin leakage, tight junctions and other parameters in the cortex were measured. The PNS 45 mg/kg intervention alleviated leukocyte adhesion, inhibited endothelial barrier alterations evidenced by reduced albumin leakage and tight junction degradations, and ultimately ameliorated infarct volumes and neurological deficits subsequent to ischemia-reperfusion. Taken together, P. notoginseng saponins are able to attenuate leukocyte-mediated microvascular disturbance at the onset of ischemic stroke.
One-Year Risk of Recurrent Stroke and Death Associated with Vertebrobasilar Artery Stenosis and Occlusion in a Cohort of 10,515 Patients
Authors: Qureshi Adnan I. , Qureshi Mushtaq H. , Lien Li-Ming , Lee Jiunn-Tay , Jeng Jiann-Shing , Hu Chaur-Jong , Lai Ta-Chang , Liu Chung-Hsiang , Chen Chih-Hung , Chen Po-Lin , Chen Tsang-Shan , Li Jie-Yuan , Lin Cheng-Li , Hsu Chung Y. ,   Taiwan Stroke Registry Investigators
Published: February 2019

Background: The natural history of vertebrobasilar artery (VBA) stenosis or occlusion remains understudied. Methods: Patients with diagnosis of ischemic stroke or transient ischemic attack (TIA) who were noted to have VBA stenosis based on computed tomography or magnetic resonance imaging or catheter-based angiogram were selected from Taiwan Stroke Registry. Cox proportional hazards model was used to determine the hazards ratio (HR) of recurrent stroke and death within 1 year of index event in various groups based on severity of VBA stenosis (none to mild: 0–49%; moderate to severe: 50–99%: occlusion: 100%) after adjusting for differences in demographic and clinical characteristics between groups at baseline evaluation. Results: None to mild or moderate to severe VBA stenosis was diagnosed in 6972 (66%) and 3,137 (29.8%) among 10,515 patients, respectively, and occlusion was identified in 406 (3.8%) patients. Comparing with patients who showed none to mild stenosis of VBA, there was a significantly higher risk of recurrent stroke (HR 1.21, 95% CI 1.01–1.45) among patients with moderate to severe VBA stenosis. There was a nonsignificantly higher risk of recurrent stroke (HR 1.49, 95% CI 0.99–2.22) and significantly higher risk of death (HR 2.21, 95% CI 1.72–2.83), among patients with VBA occlusion after adjustment of potential confounders. Conclusions: VBA stenosis or occlusion was relatively prevalent among patients with TIA or ischemic stroke and associated with higher risk of recurrent stroke and death in patients with ischemic stroke or TIA who had large artery atherosclerosis.
Effectiveness of Scleral Buckling with a Wide-Field Surgical Microscope and Chandelier Illumination in Retinal Detachment Repair
Authors: Jeon Gang Seok , Han Jae Ryong
Published: February 2019

Purpose: To assess treatment efficacy of scleral buckling surgery with wide-field surgical microscope and 27-gauge (G) chandelier illumination for rhegmatogenous retinal detachment (RRD). Methods: This study is a retrospective chart review of 29 eyes in 29 patients with RRD who underwent scleral buckling surgery with a wide-field surgical microscope and 27-G chandelier illumination fiber inserted into the sclera at the pars plana. Results are expressed as mean ± standard deviation. Data were analyzed using the paired sample t test. Statistical significance was considered if p value was less than 0.05. Results: The mean age of patients was 43.5 ± 3.5 years, and the mean follow-up time was 10.4 ± 2.5 months. Retinal reattachment was achieved in 27 of 29 eyes at initial surgery. The mean best corrected visual acuity improved from 0.38 ± 0.29 (logMAR) preoperatively to 0.19 ± 0.21 at 6 months after surgery. Two eyes underwent vitrectomy with silicone oil tamponade because of development of proliferative vitreoretinopathy. There was no complication such as choroidal hemorrhage, hypotony, or vitreous herniation at the end of surgery. Conclusion: Scleral buckling with a wide-field surgical microscope and 27-G chandelier illumination has the advantage of offering exact identification of retinal tears and determination of the adequacy of buckle height and position in retinal detachment surgery compared to conventional scleral buckling surgery.
Development of HiSQOL: A Hidradenitis Suppurativa-Specific Quality of Life Instrument
Authors: Thorlacius Linnea , Esmann Solveig , Miller Iben , Vinding Gabrielle , Jemec Gregor B.E.
Published: February 2019

Background: Hidradenitis suppurativa (HS) is a chronic and painful skin disease. In addition, HS lesions may be associated with pus and odour, potentially leading to significant stigma and, consequently, greatly affected quality of life (QOL). QOL is a multidimensional construct, which can be measured in various ways. However, generic or dermatologic QOL measures may not capture changes in QOL particularly affected in HS. Accordingly, patients and experts included in the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) agreed that future clinical HS trials should measure HS-specific QOL. Objectives: To develop an HS-specific QOL instrument (HiSQOL, Hidradenitis Suppurativa Quality of life). Method: The initial phases of the questionnaire development, described in this study, included item generation by patient interviews, development of a pilot questionnaire, questionnaire refinement, and pilot testing. Results: For item generation, 21 patients were interviewed individually or in focus groups. Analysis of the interviews identified 105 candidate items and, next, a pilot questionnaire was developed. Finally, item reduction and two rounds of pilot testing resulted in a 23-item questionnaire representing physical, psychological, and social QOL dimensions. Conclusions: We have comprehensively explored on HS’s possible effect on the QOL of the affected individuals and identified a 23-item HS-specific QOL questionnaire. The questionnaire proved to be feasible, acceptable, and comprehensible in the second round of pilot testing. With HiSQOL, researchers can measure HS-specific QOL in future clinical trials, potentially enabling them to discover more effective treatment options. It is envisaged, that after thorough validation in a trial setting, a streamlined version of HISQOL may also become available for clinical use in daily practice.
Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population
Authors: Kim Tae-Joon , Yoon Jee Eun , Park Jung A , Lee Seung Ku , Chu Min Kyung , Yang Kwang Ik , Kim Won-Joo , Park Seong-Ho , Thomas Robert J. , Shin Chol , Yun Chang-Ho
Published: February 2019

Background: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in ­Korean adults is mostly 4.5–12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries. Methods: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19–79 years) and (2) community-based cohort (n = 2,685; age 47–79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings. Results: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented. Conclusions: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.
Liver Fibrosis, Not Steatosis, Associates with Long-Term Outcomes in Ischaemic Stroke Patients
Authors: Baik Minyoul , Kim Seung Up , Kang Sungwoo , Park Hyung Jong , Nam Hyo Suk , Heo Ji Hoe , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Han Kwang-Hyub , Lee Hye Sun , Kim Young Dae
Published: February 2019

Background: To investigate whether there are differences in long-term all-cause and cardiovascular mortality according to the burden of liver fibrosis or steatosis in patients with ischaemic stroke or transient ischaemic attack (TIA). ­Methods: Consecutive patients with acute ischaemic stroke or TIA who underwent transient elastography (TE) from January 2014 to December 2014 were considered eligible. The influence of liver fibrosis or steatosis, assessed via TE, on long-term outcomes was investigated using Cox proportional hazard models. Results: Among 395 patients included in this study, there were 37 (9%) patients with significant fibrosis (> 8.0 kPa) and 164 (41.5%) patients with fatty liver (> 250 dB/m). During the follow-up period (median 2.7 years), all-cause and cardiovascular mortality occurred in 28 (7.1%) and 20 (5.1%) patients. On multivariate analyses, significant liver fibrosis was independently associated with increased risk of all-cause (hazard ratio [HR] 8.14, 95% CI 3.03–21.90, p < 0.001) and cardiovascular (HR 4.29, 95% CI 1.10–16.73, p = 0.036) mortality, whereas fatty liver was not (all p > 0.05). Conclusions: This study found that the burden of liver fibrosis but not that of steatosis, assessed via TE, was an independent predictor of all-cause and cardiovascular mortality during long-term follow-up in patients with ischaemic stroke.
Misplacement of Tunneled Hemodialysis Catheter into Azygos Vein: Left or Right Jugular Insertion Has Similar Susceptibility
Authors: Li Xiang-Yang , Ye Jin-Bao , Zhang Long-Guang , Jia Yi-Zhen , Zhou Ru-Ming , Pai Pearl
Published: February 2019

Background: Central venous catheter (CVC) is commonly used to provide access for hemodialysis (HD) when arteriovenous access is not available. The misplacement of CVC into azygos vein (AV) is a rare but a potential serious complication. Previous reports communicated the opinion that left-sided catheterization predisposed to AV misplacement, but these reports concentrated on peripherally inserted CVCs, placed for indications rather than HD. Unintended AV misplacement of HD catheters (HDCs) has not been well studied. We seek to investigate factors associated with inadvertent AV miscannulation during HDC placement. Methods: We are to present a case of unintentional misplacement of a tunneled HD catheter (tHDC) into the azygos arch from right internal jugular vein (RIJV) despite real-time fluoroscopy guidance. Additionally, we have undertaken a systematic literature search in Pubmed to study the anatomical and other factors related to unintended AV misposition in HD setting. Results: From 2005 to August 31, 2018, a total of 11 articles containing 16 cases of misplacement of HDCs into AV were identified. Of the 17 cases of unintentional AV misposition including ours, the majority of the misguided HDCs (94.1%, 16/17) were tHDCs and only 1 case was related to a temporary (non-tunneled) catheter. Most catheter misplacements (88.2%, 15/17) were performed without real-time radiological guidance. The reported incidence of inadvertent AV cannulation from different institutions varied between 0.6% and 3.8%. Among the 16 misplaced tHDCs, the rates of AV misposition that arose from RIJV and left internal jugular vein (LIJV) insertion are even at 50%. Conclusions: Based upon anatomical and case studies, we have found that AV may join posterior aspect of superior vena cava at different directions and levels. Hence, this might explain why AV misplacement might occur whether an HDC is inserted from the LIJV or RIJV approach. By raising the awareness of this potential complication and how we may minimize it, we hope to reduce the future complication of AV misposition.
Loss of RUNX3 Immunoreactivity in Non-Neoplastic Rectal Mucosa May Predict the Occurrence of Ulcerative Colitis-Associated Colorectal Cancer
Authors: Shinagawa Takahide , Hata Keisuke , Morikawa Teppei , Matsunaga Keigo , Emoto Shigenobu , Murono Koji , Kaneko Manabu , Sasaki Kazuhito , Nishikawa Takeshi , Tanaka Toshiaki , Kawai Kazushige , Nozawa Hiroaki , Fukayama Masashi , Ishihara Soichiro
Published: February 2019

Background/Aims: Runt-related transcription factor (RUNX) 3 is a tumor suppressor whose expression is reduced in non-neoplastic rectal mucosa of patients with ulcerative colitis (UC) with coexisting colitis-associated cancer (CAC). We aimed to evaluate RUNX3 utility as a predictive marker for CAC using immunohistochemistry (IHC) for non-neoplastic UC mucosa. Methods: We retrospectively compared the RUNX3 expression detected by IHC between non-neoplastic rectal biopsy specimens from 20 cases with invasive cancer (CAC group) and 20 cases selected from 138 patients without CAC (non-CAC group) that were treated during the same period (2006–2017) and were matched for sex, duration, extension, and age. We validated the results using tissue microarrays (TMA) of 44 operated cases with CAC. The RUNX3 expression level was determined by calculating the percentage of RUNX3-positive-cells. Results: The RUNX3 expression was lower in the CAC than that in the non-CAC group (35.6 vs. 70.7%, p = 0.03). For a cutoff value of 58%, the sensitivity and specificity for predicting CAC were 75.0 and 70.0% respectively. The immunostaining results for the TMA showed the same trend; 74% of cases with CAC were negative for the RUNX3 expression. Conclusion: RUNX3 immunostaining of non-neoplastic mucosa is useful for identifying UC patients at a high risk of developing CAC.
Fraseamento prosódico em português
Authors: Fernandes-Svartman Flaviane Romani , Santos Vinícius Gonçalves dos , Braga Gabriela
Published: February 2019

Este trabalho tem como objetivo a análise do fraseamento prosódico de sentenças declarativas neutras na ordem de estrutura sujeito-verbo-objeto (sentenças SVO) em sintagmas entoacionais (Is) nas variedades brasileiras de português faladas em Salvador (Bahia) e Florianópolis (Santa Catarina) e nas variedades africanas de português faladas em São Tomé (República Democrática de São Tomé e Príncipe) e no Libolo (Angola). O intuito desse estudo é a investigação de semelhanças e diferenças entre essas variedades quanto ao fraseamento prosódico. Os resultados obtidos revelaram que (SVO)I é o padrão de fraseamento prosódico preferencial em todas as variedades de português. Padrões de fraseamento diferentes também são encontrados para as variedades brasileiras de português, ainda que com baixa frequência e levando em conta a ramificação e a extensão dos constituintes sujeito e objeto. Já para as variedades africanas, só são encontrados outros padrões de fraseamento quando são considerados dados de fala espontânea ou semiespontânea. Esses resultados contribuem para o conhecimento de um tópico que merece ser melhor explorado para as variedades brasileiras e africanas do português e para uma maior compreensão sobre as características prosódicas gerais da língua portuguesa e sobre aquelas que singularizam suas diferentes variedades.
Apresentação
Authors: Fernandes-Svartman Flaviane Romani
Published: February 2019

O volume 20(especial) da revista Filologia e Linguística Portuguesa publica um conjunto de oito trabalhos que tratam de temas concernentes aos estudos sobre prosódia de variedades da língua portuguesa, particularmente, as faladas no Brasil e no continente africano.
O estudo sobre a prosódia de variedades de português, de um ponto de vista comparativo ou não, tem sido tema de grande interesse de pesquisas recentes, principalmente no tocante às variedades ainda pouco ou mesmo inexploradas linguisticamente, como as africanas. Assim, os artigos deste volume, ao abordarem dados de produção e de percepção da fala, dados de escrita e aspectos metodológicos de construção de corpus e de tratamento de dados de prosódia, trazem contributos significativos para os estudos gramaticais do português, seja no que diz respeito à metodologia de constituição de base de dados e de tratamento desses, seja para o conhecimento de características prosódicas inexploradas das diferentes variedades do português e ainda para uma maior compreensão da gramática fonológica dessa língua.
Novel Antiplatelet Therapies for Atherothrombotic Diseases
Authors: Majithia Arjun , Bhatt Deepak L.
Published: February 2019

Antiplatelet therapies are an essential tool to reduce the risk of developing clinically apparent atherothrombotic disease and are a mainstay in the therapy of patients who have established cardiovascular, cerebrovascular, and peripheral artery disease. Strategies to intensify antiplatelet regimens are limited by concomitant increases in clinically significant bleeding. The development of novel antiplatelet therapies targeting additional receptor and signaling pathways, with a focus on maintaining antiplatelet efficacy while preserving hemostasis, holds tremendous potential to improve outcomes among patients with atherothrombotic diseases.
Stem Cell and Left Ventricular Assist Device Combination Therapy
Authors: Poglajen Gregor , Gregoric Igor D. , Radovancevic Rajko , Vrtovec Bojan
Published: February 2019

Ventricular assist device (VAD) technology has evolved significantly over the past decades and currently represents one of the most important treatment strategies for patients with advanced chronic heart failure. There is increasing evidence that in selected patients undergoing long-term VAD support, improvement of myocardial structure and function may occur. However, there seems to be a significant discrepancy between structural and functional recovery of the failing myocardium, as only a small fraction of VAD-supported patients demonstrate reverse structural remodeling and eventually reach clinically significant and stable, functional improvement. More recently, cell therapy has gained a growing interest in the heart failure community because of its potential to augment reverse remodeling of the failing myocardium. Although theoretically the combination of long-term VAD support and cell therapy may offer significant advantages over using these therapeutic modalities separately, it remains largely unexplored. This review aims to summarize the current state of the art of the effects of VAD support and cell therapy on the reverse remodeling of the failing myocardium and to discuss the rationale for using a combined treatment strategy to further promote myocardial recovery in patients with advanced chronic heart failure.
Genetics of Thoracic and Abdominal Aortic Diseases
Authors: Pinard Amélie , Jones Gregory T. , Milewicz Dianna M.
Published: February 2019

Dissections or ruptures of aortic aneurysms remain a leading cause of death in the developed world, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Genetic variants predispose individuals to these aortic diseases. In the case of thoracic aortic aneurysm and dissections (thoracic aortic disease), genetic data can be used to identify some at-risk individuals and dictate management of the associated vascular disease. For abdominal aortic aneurysms, genetic associations have been identified, which provide insight on the molecular pathogenesis but cannot be used clinically yet to identify individuals at risk for abdominal aortic aneurysms. This compendium will discuss our current understanding of the genetic basis of thoracic aortic disease and abdominal aortic aneurysm disease. Although both diseases share several pathogenic similarities, including proteolytic elastic tissue degeneration and smooth muscle dysfunction, they also have several distinct differences, including population prevalence and modes of inheritance.
Pharmacologic Management of Aneurysms
Authors: Lindeman Jan H. , Matsumura Jon S.
Published: February 2019

Current management of aortic aneurysms relies exclusively on prophylactic operative repair of larger aneurysms. Great potential exists for successful medical therapy that halts or reduces aneurysm progression and hence alleviates or postpones the need for surgical repair. Preclinical studies in the context of abdominal aortic aneurysm identified hundreds of candidate strategies for stabilization, and data from preoperative clinical intervention studies show that interventions in the pathways of the activated inflammatory and proteolytic cascades in enlarging abdominal aortic aneurysm are feasible. Similarly, the concept of pharmaceutical aorta stabilization in Marfan syndrome is supported by a wealth of promising studies in the murine models of Marfan syndrome–related aortapathy. Although some clinical studies report successful medical stabilization of growing aortic aneurysms and aortic root stabilization in Marfan syndrome, these claims are not consistently confirmed in larger and controlled studies. Consequently, no medical therapy can be recommended for the stabilization of aortic aneurysms. The discrepancy between preclinical successes and clinical trial failures implies shortcomings in the available models of aneurysm disease and perhaps incomplete understanding of the pathological processes involved in later stages of aortic aneurysm progression. Preclinical models more reflective of human pathophysiology, identification of biomarkers to predict severity of disease progression, and improved design of clinical trials may more rapidly advance the opportunities in this important field.
Temporal Patterns of 14 Blood Biomarker candidates of Cardiac Remodeling in Relation to Prognosis of Patients With Chronic Heart Failure—The Bio‐SHiFT Study
Authors: Bouwens Elke , Brankovic Milos , Mouthaan Henk , Baart Sara , Rizopoulos Dimitris , van Boven Nick , Caliskan Kadir , Manintveld Olivier , Germans Tjeerd , van Ramshorst Jan , Umans Victor , Akkerhuis K. Martijn , Kardys Isabella
Published: February 2019

Background

Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure (
CHF
) patients. However, temporal patterns during the course of
CHF
, and especially the trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio‐SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study.

Methods and Results

In 263
CHF
patients, we performed trimonthly blood sampling during a median follow‐up of 2.2 years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point (
PE
), or the last sample available for end point–free patients. Thus, in 567 samples, we measured suppression of tumorigenicity‐2, galectin‐3, galectin‐4, growth differentiation factor‐15, matrix metalloproteinase‐2, 3, and 9, tissue inhibitor metalloproteinase‐4, perlecan, aminopeptidase‐N, caspase‐3, cathepsin‐D, cathepsin‐Z, and cystatin‐B. The
PE
was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and
HF
hospitalization. Associations between repeatedly measured biomarker candidates and the
PE
were investigated by joint modeling. Median age was 68 (interquartile range: 59–76) years with 72% men; 70 patients reached the
PE
. Repeatedly measured suppression of tumorigenicity‐2, galectin‐3, galectin‐4, growth differentiation factor‐15, matrix metalloproteinase‐2 and 9, tissue inhibitor metalloproteinase‐4, perlecan, cathepsin‐D, and cystatin‐B levels were significantly associated with the
PE
, and increased as the
PE
approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity‐2 was the strongest predictor (hazard ratio: 7.55 per
SD
difference, 95%
CI
: 5.53–10.30), followed by growth differentiation factor‐15 (4.06, 2.98–5.54) and matrix metalloproteinase‐2 (3.59, 2.55–5.05).

Conclusions

Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in
CHF
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01851538.