bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the cerebellum shape the spatiotemporal organization of muscle patterns? Insights from subjects with cerebellar ataxias
Authors: Berger Denise J. , Masciullo Marcella , Molinari Marco , Lacquaniti Francesco , d’Avella Andrea
Published: March 2020

In recent studies, the decomposition of muscle activity patterns has revealed a modular organization of the motor commands. We show, for the first time, that muscle patterns of subjects with cerebellar damage share with healthy controls spatial, but not temporal and spatiotemporal, modules. Moreover, changes in spatiotemporal organization characterize the severity of the subject’s impairment. These results suggest that the cerebellum has a specific role in shaping the spatiotemporal organization of the muscle patterns.
A Prediction Model of Cutting Force about Ball End Milling for Sculptured Surface
Authors: Mou Wenping , Zhu Shaowei , Zhu Menghao , Han Lei , Jiang Lei
Published: March 2020

Cutting force prediction is very important to optimize machining parameters and monitor machining state. In order to predict cutting force of sculptured surface machining with ball end mill accurately, tool posture, cutting edge, contact state between cutter, and workpiece are studied. Firstly, an instantaneous motion model of ball end mill for sculptured surface is established. The instantaneous milling coordinate system and instantaneous tool coordinate system are defined to describe the position and orientation of tool, and the transformation matrix between coordinate systems is derived. Secondly, by solving three boundaries around engagement of cutter and workpiece, a cutter-workpiece engagement model related to tool posture, milling parameters, and tool path is established. It has good adaptability to the variable tool axis relative to the machining surface. Finally, an algorithm of thickness about an instantaneous undeformed chip is researched, and a prediction model of cutting force is realized with microelement cutting theory. Also, the model is suitable for sculptured surface machining with arbitrary tool posture and feed direction. The accuracy of the proposed prediction model was verified by a series of experiments.
A Distributed Conjugate Gradient Online Learning Method over Networks
Authors: Xu Cuixia , Zhu Junlong , Shang Youlin , Wu Qingtao
Published: March 2020

In a distributed online optimization problem with a convex constrained set over an undirected multiagent network, the local objective functions are convex and vary over time. Most of the existing methods used to solve this problem are based on the fastest gradient descent method. However, the convergence speed of these methods is decreased with an increase in the number of iterations. To accelerate the convergence speed of the algorithm, we present a distributed online conjugate gradient algorithm, different from a gradient method, in which the search directions are a set of vectors that are conjugated to each other and the step sizes are obtained through an accurate line search. We analyzed the convergence of the algorithm theoretically and obtained a regret bound of OT, where T is the number of iterations. Finally, numerical experiments conducted on a sensor network demonstrate the performance of the proposed algorithm.
Bilateral Femoral Neuropathy: A Rare Complication of Drug Overdose due to Prolonged Posturing in Lithotomy Position
Authors: Tsiptsios D. , Daud D. , Tsamakis K. , Rizos E. , Anastadiadis A. , Cassidy A.
Published: March 2020

Background. Bilateral femoral neuropathy is an uncommon complication of various surgical and nonsurgical procedures, such as pelvic/abdominal surgery or vaginal delivery. Case Report. We report a case of a 41-year-old male who was found unresponsive against the wall in a “lithotomy-type” position with both knees flexed at approximately 90 degrees and both hips flexed and externally rotated at approximately 90 and 60 degrees, respectively, 24–48 hours after a drug overdose (combination of dihydrocodeine, paracetamol, diazepam, and amitriptyline). During his recovery, he complained of severe bilateral proximal lower limb weakness and bilateral distal lower limb pain and allodynia. His symptoms were initially attributed to critical illness myopathy/neuropathy (CIMN). However, thorough clinical and neurophysiological evaluation revealed that his symptoms were due to severe bilateral femoral neuropathies. Conclusions. To our knowledge, this is the first reported case of bilateral femoral nerve palsy due to prolonged posturing in a “lithotomy-type” position in the context of a drug overdose.
Organoids as a Powerful Model for Respiratory Diseases
Authors: Li Yu , Wu Qi , Sun Xin , Shen Jun , Chen Huaiyong
Published: March 2020

Insults to the alveoli usually lead to inefficient gas exchange or even respiratory failure, which is difficult to model in animal studies. Over the past decade, stem cell-derived self-organizing three-dimensional organoids have emerged as a new avenue to recapitulate respiratory diseases in a dish. Alveolar organoids have improved our understanding of the mechanisms underlying tissue homeostasis and pathological alterations in alveoli. From this perspective, we review the state-of-the-art technology on establishing alveolar organoids from endogenous lung epithelial stem/progenitor cells or pluripotent stem cells, as well as the use of alveolar organoids for the study of respiratory diseases, including idiopathic pulmonary fibrosis, tuberculosis infection, and respiratory virus infection. We also discuss challenges that need to be overcome for future application of alveolar organoids in individualized medicine.
The Effects and Safety of Chinese Oral Herbal Paste on Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Zeng Yan , Li Yu , Wei Hua , Xiong Chan , Liao Li , Miao Ti-wei , Mao Bing , Fu Juan-juan
Published: March 2020

Background. Chinese oral herbal paste has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the treatment effects of herbal paste were controversial and lack evidence to support its clinical use. This study aims to systematically assess the efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD. Methods. PubMed, Web of Science, CENTRAL, EMBASE, CNKI, VIP, CBM, and WANFANG database in addition to two websites of clinical trial registry were searched from respective inception to August 2019. Only randomized controlled trials (RCTs) studying Chinese herbal paste for the treatment of stable COPD were included. Methodological quality was assessed based on Cochrane risk of bias and GRADE approach. Data were analyzed using RevMan 5.3. Results. A total of 19 RCTs with 1303 individuals compared Chinese oral herbal paste and Western medicine (WM) with WM alone were included for meta‐analysis. The review showed compared with WM alone, the combination of herbal paste and WM reduced exacerbation frequency. Subgroup analyses showed that after two to three months of treatment, compared with WM alone, Chinese herbal paste plus WM significantly decreased the St George’s Respiratory Questionnaire (SGRQ) scores, COPD assessment test (CAT) scores, and scores of traditional Chinese medicine (TCM) syndrome, and improved clinical effective rates, lung function, and 6‐minute walk distance. No serious adverse events related to herbal paste were reported. Conclusion. Current evidence showed that Chinese oral herbal paste may be an effective and well‐tolerated adjuvant therapy for stable COPD. Considering the risks of bias and heterogeneity, more high‐quality, well‐designed RCTs are still needed.
Quantitative Nondestructive Testing of Broken Wires for Wire Rope Based on Magnetic and Infrared Information
Authors: Li Xi , Zhang Juwei , Shi Jingzhuo
Published: March 2020

The lifetime of wire rope is crucial in industry manufacturing, mining, and so on. The damage can be detected by using appropriate nondestructive testing techniques or destructive tests by cutting the part. For broken wires classification problems, this work is aimed at improving the recognition accuracy. Facing the defects at the exterior of the rope, a novel method for recognition of broken wires is firstly developed based on magnetic and infrared information fusion. A denoising method, which is adopted for magnetic signal, is proposed for eliminating baseline signal and wave strand. An image segmentation method is employed for parting the defects of infrared images. Characteristic vectors are extracted from magnetic images and infrared images, then kernel extreme learning machine network is applied to implement recognition of broken wires. Experimental results show that the denoising method and image segmentation are effective and the information fusion can improve the classification accuracy, which can provide useful information for estimating the residual lifetime of wire rope.
Effects of Plant and Animal Natural Products on Mitophagy
Authors: Shakeri Farzaneh , Bianconi Vanessa , Pirro Matteo , Sahebkar Amirhossein
Published: March 2020

Mitophagy is a protected cellular process that is essential for autophagic removal of damaged mitochondria and for preservation of a healthy mitochondrial population. In the last years, a particular interest has been devoted in studying the effects of natural compounds on mitophagy. Different natural compounds may modulate mitochondrial oxidative phosphorylation, the production of mitochondrial reactive oxygen species, the expression of mitophagy- and autophagy-related genes, and the activities of transcription factors which regulate the expression of mitochondrial proteins, thereby controlling mitochondrial damage and mitophagy. Remarkably, since mitochondrial function has a crucial role in the pathogenesis of various diseases (e.g., cancer, atherosclerosis, Duchenne muscular dystrophy, diabetes complications, Alzheimer’s disease, and hepatic steatosis), these effects might have important therapeutic implications. In this review, preclinical studies investigating the role of different natural compounds in the modulation of mitophagy will be discussed.
Pseudodifferential Operators on Weighted Hardy Spaces
Authors: Deng Yu-long , Long Shun-chao
Published: March 2020

We study two sufficient conditions for the boundedness of a class of pseudodifferential operators T with symbols in the Hölmander class Sρ,δmℝn on weighted Hardy spaces Hω1ℝn, where ω belongs to Muckenhoupt class Ap. The first one is an estimate from Hω1ℝn into Lω1ℝn. We get a better range of admissible p and m. The second one is a weighted version bounded for the operators T on Hω1ℝn, and it is an addition to the literature.
Facile Synthesis of Hollow Carbon Nanospheres by Using Microwave Radiation
Authors: Chen Jiareng , Lin Jiaqi , Cui Bin , Liu Yang
Published: March 2020

Carbon-based nanomaterials have attracted much research interest in recent years due to their excellent chemical and physiological properties such as chemical stability, low cytotoxicity, and biocompatibility. The traditional methods to prepare hollow carbon nanospheres require complicated instrumentation and harsh chemicals, including high-temperature furnace, gas inlets, and hydrogen fluoride etching. Herein, we propose a new strategy to prepare hollow carbon nanospheres in a simple and fast manner by using microwave radiation. Polypyrrole-coated silica core-shell nanoparticles (SiO2@PPy NPs) were firstly prepared and subsequently processed by microwave radiation and aqueous alkaline solution to obtain the hollow carbon nanospheres. This facile method has potent potential to be utilized in the preparation of different types of hollow carbon nanospheres with various microstructure and elemental composition.
Instability Mechanism of Cavity‐Bearing Formation under Tunnel Excavation Disturbance
Authors: Liu Tao , Wang Haotong , Su Xiuting , Li Kexian , Liu Shiqun , Guo Fengsong
Published: March 2020

Urban subway construction inevitably causes disturbances to the rock strata. It can even cause ground collapse accidents when construction encounters a bad geological body in the stratum. To verify the influence of cavities on surface settlement and the mechanism of formation instability, the instability mechanism of cavity‐bearing strata under tunnel excavation disturbance was herein studied by tests using self‐designed indoor models and numerical simulations. This study was based on the concrete project case of Qingdao Metro. Two groups of experiments (with and without cavities) were designed to simulate the four‐step excavation by staged unloading of an airbag. The results show that the settlement value in the cavity state was about twice as much as that in the nonvoid state at the same stage. Besides the first step of excavation, in the numerical simulation, the settlement value of the same stage is about 1.3 times that of the model test. Simulating the deformation process of the surrounding rock in model tests shows that, in the excavation of the tunnel, the collapse surface of the tunnel arch roof will be connected with the sliding surface of the formation cavity. The cavity will gradually change from a regular circle to an ellipse or may even close, resulting in a sudden increase in land subsidence or even ground collapse. This indicates that disturbance during tunnel excavation would cause greater instability in a stratum when bad geological bodies, such as cavities, exist in the stratum.
Scalability of OpenFOAM Density-Based Solver with Runge–Kutta Temporal Discretization Scheme
Authors: Li Sibo , Paoli Roberto , D’Mello Michael
Published: March 2020

Compressible density-based solvers are widely used in OpenFOAM, and the parallel scalability of these solvers is crucial for large-scale simulations. In this paper, we report our experiences with the scalability of OpenFOAM’s native rhoCentralFoam solver, and by making a small number of modifications to it, we show the degree to which the scalability of the solver can be improved. The main modification made is to replace the first-order accurate Euler scheme in rhoCentralFoam with a third-order accurate, four-stage Runge-Kutta or RK4 scheme for the time integration. The scaling test we used is the transonic flow over the ONERA M6 wing. This is a common validation test for compressible flows solvers in aerospace and other engineering applications. Numerical experiments show that our modified solver, referred to as rhoCentralRK4Foam, for the same spatial discretization, achieves as much as a 123.2% improvement in scalability over the rhoCentralFoam solver. As expected, the better time resolution of the Runge–Kutta scheme makes it more suitable for unsteady problems such as the Taylor–Green vortex decay where the new solver showed a 50% decrease in the overall time-to-solution compared to rhoCentralFoam to get to the final solution with the same numerical accuracy. Finally, the improved scalability can be traced to the improvement of the computation to communication ratio obtained by substituting the RK4 scheme in place of the Euler scheme. All numerical tests were conducted on a Cray XC40 parallel system, Theta, at Argonne National Laboratory.
A Retrospective Analysis of the Role of Single-Session Gamma Knife Stereotactic Radiosurgery in Sporadic Vestibular Schwannomas with Tumor Volumes Greater Than 10 cm3: Is It Worth Stretching the Boundaries?
Authors: Mezey Geza , Cahill Julian , Rowe Jeremy G. , Yianni John , Bhattacharyya Debapriya , Walton Lee , Rodgers Joanne , Radatz Matthias W.R.
Published: March 2020

Objective: To evaluate the role of single-session Gamma Knife stereotactic radiosurgery (GK-SRS) in the treatment of vestibular schwannomas (VSs) with volumes of greater 10 cm3. Methods: A retrospective analysis was performed of 103 patients treated with single-session GK-SRS between 1993 and 2011 with a mean follow-up of 6.2 years ± 4.4 SD. Treatment, clinical and outcome details were recorded and assessed. Results: Eighty-one (78.6%) patients achieved radiological control with slow progression in a further 5 (4.9%) patients, who did not require further treatment. Linear measurements did not correlate well with volume, which can predict outcome following treatment more precisely. 2.9% of patients developed a new facial paresis, 5.8% trigeminal numbness and 2.9% facial pain. In all, 26 (25.2%) patients who were tested preserved some level of hearing following treatment. Conclusions: The overall radiological control rate in this study was 78.6%, while tumor volumes less than 20 cm3 can be safely treated with single-stage GK-SRS with an expected control rate of 83.2% without unacceptable morbidity rates. GK-SRS can be utilized as a first-line treatment option in patients with large-volume VSs especially in whom surgery is unattractive.
Development and Validation of a Nomogram for Patients with Nonmetastatic BCLC Stage C Hepatocellular Carcinoma after Stereotactic Body Radiotherapy
Authors: Huang Wen-Yen , Tsai Chiao-Ling , Que Jenny Y. , Lo Cheng-Hsiang , Lin Yu-Ju , Dai Yang-Hong , Yang Jen-Fu , Shen Po-Chien , Lee Mei-Hsuan , Cheng Jason Chia-Hsien
Published: March 2020

Background: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for hepatocellular carcinoma (HCC) with promising outcome. However, appropriate survival prediction models are scarce. This study aimed to develop a simple and clinically useful prognostic nomogram for patients with nondistant metastatic Barcelona Clinic Liver Cancer (BCLC) stage C HCC undergoing SBRT. Methods: The data were based on a prospective multi-institutional registry enrolling 246 patients with nondistant metastatic BCLC stage C HCC treated with SBRT between January 1, 2008 and December 31, 2016. They were randomly divided into two subsets: 164 into the development cohort and 82 into the validation cohort. We identified and included prognostic factors for survival to derive a nomogram in the development cohort. The predictability of the nomogram was evaluated in the validation cohort. The area under the receiver operating characteristic curve (AUROC) and the calibration plot were used to evaluate the performance of the nomogram. Results: The median survival was 13.5 months, with 1- and 2-year overall survival (OS) rates of 55.0 and 32.9%, respectively. Number of tumors, largest tumor size, macrovascular invasion, Child-Turcotte-Pugh class, and biologically effective dose were significantly associated with OS (p < 0.05). These predictors were included to develop a nomogram with an AUROC of 0.77 (0.73–0.87). The prediction model was well calibrated in the validation cohort. The OS for patients who were divided by their risk scores differed significantly (p < 0.001). Conclusions: The nomogram we generated had discriminatory and satisfactory predictability for OS among nonmetastatic BCLC stage C HCC patients treated with SBRT. It demands further validations with cross-country data to confirm its worldwide usefulness.
Clinical Benefit Derived from Decitabine Therapy for Advanced Phases of Myeloproliferative Neoplasms
Authors: Zhou Selena , Tremblay Douglas , Hoffman Ronald , Kremyanskaya Marina , Najfeld Vesna , Li Lihua , Moshier Erin , Mascarenhas John
Published: March 2020

Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8–29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP.
Turning to Thyroid Disease in Pregnant Women
Authors: Andersen Stine Linding , Andersen Stig
Published: March 2020

Thyroid disease in pregnant women needs attention from a clinical and scientific standpoint due to the potential severe adverse consequences. It is well-established that overt thyroid disease in pregnant women should be treated to prevent maternal and fetal complications, but routine testing for overt thyroid function test abnormalities has not been implemented. In contrast, the scientific focus has shifted towards smaller aberrations in maternal thyroid function including subclinical thyroid disease and isolated deviations in maternal thyroxine. In this focused review, we touch upon the assessment of maternal thyroid function in pregnancy and how the historical advancements in thyroid function tests parallel with the thyroid function test abnormalities described. Furthermore, we discuss how the scientific focus has evolved and how the field could turn in view of the existing discrepancies between results of observational studies and randomized controlled trials.
Assessing Physiological Stress Responses to Word Retrieval in Individuals with Aphasia: A Preliminary Study
Authors: Chih Yu-Chun , Tsai Meng-Ju , Stierwalt Julie A.G. , LaPointe Leonard L.
Published: March 2020

Objective: Word retrieval difficulty can be distressing for individuals with aphasia. However, physiological stress responses to word retrieval are relatively unstudied. This study aims to measure the physiological response (i.e., heart rate and respiratory rate) and perceived stress in individuals with aphasia during a naming task to understand whether word retrieval may be a stressor to them. Method: An aphasia group (n = 7) and a healthy group (n = 38) participated in 4 experimental conditions, including rest, counting, and high-frequency and low-frequency word conditions, while their physiological parameters were measured throughout the sessions. Stress ratings were also obtained for each condition. Results: Significant differences in heart rate were found while participants were engaged in speech and/or language tasks, compared to the rest condition, for both groups. Significant differences in respiratory rate were found between the rest and low-frequency word conditions in the aphasia group. No significant difference was found in heart rate between 2 groups, but a difference in respiratory rate was found between 2 groups in the low-frequency word condition. There were some discrepancies between stress level and physiological parameters. Conclusions: Individuals with aphasia perceived greater stress in the naming tasks, however, the perceived stress was not necessarily parallel to the physiological parameters.
The Efficacy of Topical Basil Essential Oil on Relieving Migraine Headaches: A Randomized Triple-Blind Study
Authors: Ahmadifard Mahdieh , Yarahmadi Sajad , Ardalan Arash , Ebrahimzadeh Farzad , Bahrami Parviz , Sheikhi Elham
Published: March 2020

Objective: Complementary therapies have been increasingly used for the prevention and treatment of migraine so that there is a need for studies in this setting. This study sought to determine the effects of basil essential oil on the severity and frequency of migraine attack headaches. Methods: A triple-blind clinical trial study was performed on 144 patients diagnosed with migraine. Patients were randomly allocated by a stratified method to four groups of 36 titled basil essential oil 2, 4, 6%, and placebo groups. Medications were used topically every 8 h for 3 successive months. In addition, each individual received 325 mg of acetaminophen every 12 h. The severity and frequency of migraine attacks were measured prior to the study, at weeks 2, 4, 8, and 12. The visual analog scale was used to measure pain intensity. The marginal model and generalized estimation equations were used to compare changes in the intensity and frequency of pain over time. Results: The interaction of the dose and time factors was significant on both pain intensity (p < 0.001) and frequency of attack (p < 0.001). The odds ratio of higher pain intensity and rate ratio of higher frequency of attack in the intervention groups compared to the placebo group were decreased over the study time. Conclusion: Time lapse and higher doses of basil essential oil would reduce both the intensity and frequency of migraine attacks.
Association between Genetic and Immunological Background of Hepatocellular Carcinoma and Expression of Programmed Cell Death-1
Authors: Nishida Naoshi , Sakai Kazuko , Morita Masahiro , Aoki Tomoko , Takita Masahiro , Hagiwara Satoru , Komeda Yoriaki , Takenaka Mamoru , Minami Yasunori , Ida Hiroshi , Ueshima Kazuomi , Nishio Kazuto , Kudo Masatoshi
Published: March 2020

Background and Aim: Immune checkpoint inhibitors are promising agents for the treatment of hepatocellular carcinomas (HCC) refractory to conventional therapies. To enhance the efficacy of this treatment, immunological and molecular characteristics of HCC with programmed cell death ligand 1 (PD-L1) should be explored. Methods: Clinical backgrounds, PD-L1 expression, and the amount of CD8+ tumor-infiltrating mononuclear cells (TIMCs) were analyzed in 154 HCCs. The expression of 3 stem cell markers and co-inhibitory receptors on tumor cells and TIMCs, respectively, were examined by immunohistochemical analysis. Somatic mutations in the 409 cancer-associated genes and TERT promoter were determined; HCCs were classified based on the presence of gene alterations affecting the 8 oncogenic pathways. The results were validated using the dataset from the Cancer Genome Atlas. Results: The expression of PD-L1 in the HCCs was positively correlated with progressive tumor features, the presence of cytokeratin 19 (CK19), Sal-like protein 4 (SALL4), and the mutations of genes involving the phosphatidyl inositol 3-kinase (PI3K)-Akt pathway. Although CD8+ cells were densely infiltrated in PD-L1-positive tumors, these TIMCs frequently expressed multiple co-inhibitory receptors. However, a subset of PD-L1-positive tumors characterized by activating mutations of the PI3K-Akt pathway showed a low degree of TIMCs. Conversely, PD-L1-negative HCCs were associated with mutations in the β-catenin pathway and a small number of TIMCs, although the expression of co-inhibitory receptors was rare. Conclusions: PD-L1-positive HCCs frequently showed an inflamed phenotype with stem cell features; a subset of PD-L1-positive HCCs with mutations in the PI3K-Akt pathway showed a non-inflamed phenotype. In HCCs with dense infiltration of TIMCs, CD8+ cells expressed multiple co-inhibitory receptors, suggesting T cell exhaustion. On the other hand, PD-L1-negative HCCs showed mutations leading to β-catenin activation and exhibited a non-inflamed background. These characteristics should be taken into consideration for developing novel combination therapies using immune checkpoint inhibitors.
A Case of Large Sarcoid Choroidal Granuloma Treated with Steroid Pulse Therapy
Authors: Kobayashi Takatoshi , Takai Nanae , Sato Takaki , Tada Rei , Maruyama Eri , Shouda Hiromi , Okamoto Takako , Maruyama Kohichi , Ikeda Tsunehiko
Published: March 2020

Purpose: To report a case of large sarcoid choroidal granuloma that was successfully treated with steroid pulse therapy. Case Report: A 38-year-old man presented with the primary complaint of decreased visual acuity (VA) in his left eye. Upon examination, a large white protruding lesion of 10 × 8 papilla diameter in size was observed in the macular region, and slightly temporal to it, in the patient’s left eye. Whole-body contrast-enhanced computed tomography performed for differential diagnosis detected numerous enlarged lymph nodes throughout the body, including the bilateral hilar regions. Sarcoidosis was diagnosed by biopsy of the right cervical lymph nodes showing noncaseating epithelioid cell granuloma. The fundus lesion was found to be a choroidal granuloma caused by sarcoidosis, and steroid pulse therapy was started. The granuloma was considerably decreased, and the VA in the left eye improved to 0.7 after 2 months. Conclusion: Steroid pulse therapy was found to be effective as an initial treatment for a large sarcoid choroidal granuloma.
Whole-Exome Sequencing Identifies Three Candidate Homozygous Variants in a Consanguineous Iranian Family with Autism Spectrum Disorder and Skeletal Problems
Authors: Farajzadeh Valilou Saeed , Alavi Afagh , Pashaei Mahdiyeh , Ghasemi Firouzabadi Saghar , Shafeghati Yousef , Nozari Ahoura , Hadipour Fatemeh , Hadipour Zahra , Maghsoodlou Estrabadi Bijan , Gholamreza Noorazar Seyed , Banihashemi Susan , Karimian Javad , Fattahi Mahshid , Behjati Farkhondeh
Published: March 2020

Autism spectrum disorder (ASD) is characterized by 3 core symptoms with impaired social communication, repetitive behavior, and/or restricted interests in early childhood. As a complex neurodevelopmental disorder (NDD), the phenotype and severity of autism are extremely heterogeneous. Genetic factors have a key role in the etiology of autism. In this study, we investigated an Azeri Turkish family with 2 ASD-affected individuals to identify probable ASD-causing variants. First, the affected individuals were karyotyped in order to exclude chromosomal abnormalities. Then, whole-exome sequencing was carried out in one affected sibling followed by cosegregation analysis for the candidate variants in the family. In addition, SNP genotyping was carried out in the patients to identify possible homozygosity regions. Both proband and sibling had a normal karyotype. We detected 3 possible causative variants in this family: c.5443G>A; p.Gly1815Ser, c.1027C>T; p.Arg343Trp, and c.382A>G; p.Lys128Glu, which are in the FBN1, TF, and PLOD2 genes, respectively. All of the variants cosegregated in the family, and SNP genotyping revealed that these 3 variants are located in the homozygosity regions. This family serves as an example of a multimodal polygenic risk for a complex developmental disorder. Of these 3 genes, confluence of the variants in FBN1 and PLOD2 may contribute to the autistic features of the patient in addition to skeletal problems. Our study highlights the genetic complexity and heterogeneity of NDDs such as autism. In other words, in some patients with ASD, multiple rare variants in different loci rather than a monogenic state may contribute to the development of phenotypes.
Histopathological Revision for Gastroenteropancreatic Neuroendocrine Neoplasms in Expert Centers: Does It Make the Difference?
Authors: Merola Elettra , Zandee Wouter , de Mestier Louis , Klümpen Heinz Josef , Makulik Karolina , Geboes Karen , van Velthuysen Marie Louise , Couvelard Anne , Cros Jérôme , van Eeden Susanne , Hoorens Anne , Stephenson Timothy , Zajęcki W. , de Herder Wouter , Munir Alia
Published: March 2020

Background: The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. Objectives: To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. Methods: Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. Results: 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. Conclusions: Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.
Systematic and Multidisciplinary Evaluation of Fibromuscular Dysplasia Patients Reveals High Prevalence of Previously Undetected Fibromuscular Dysplasia Lesions and Affects Clinical Decisions
Authors: Warchol-Celinska Ewa , Prejbisz Aleksander , Dobrowolski Piotr , Klisiewicz Anna , Kadziela Jacek , Florczak Elzbieta , Michalowska Ilona , Jozwik-Plebanek Katarzyna , Kabat Marek , Kwiatek Pawel , Nazarewski Slawomir , Madej Krzysztof , Rowinski Olgierd , Swiatlowski Lukasz , Peczkowska Mariola , Hanus Katarzyna , Talarowska Paulina , Smolski Mikołaj , Kowalczyk Katarzyna , Kurkowska-Jastrzebska Iwona , Stefanczyk Ludomir , Wiecek Andrzej , Widecka Krystyna , Tykarski Andrzej , Stryczynski Lukasz , Litwin Mieczyslaw , Hoffman Piotr , Witkowski Adam , Szczerbo-Trojanowska Malgorzata , Januszewicz Magdalena , Januszewicz Andrzej
Published: March 2020

Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia–Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.
Blood Pressure Variability and the Risk of Dementia
Authors: Yoo Jung Eun , Shin Dong Wook , Han Kyungdo , Kim Dahye , Lee Seung-Pyo , Jeong Su-Min , Lee Jinkook , Kim SangYun
Published: March 2020

To investigate the association between visit-to-visit variability in blood pressure and the incidence of dementia and its subtypes in a general population, we conducted a population-based retrospective cohort study using the Korean National Health Insurance System database. We identified 7 844 814 subjects without a history of any dementia who underwent ≥3 health examinations from 2005 to 2012 in the Korean National Health Insurance System cohort. Blood pressure variability (BPV) was measured using the variability independent of the mean, coefficient of variation, and SD. During the median follow-up of 6.2 years, there were 200 574 cases of all-cause dementia (2.8%), 165 112 cases of Alzheimer’s disease (2.1%), and 27 443 cases of vascular dementia (0.3%). There was a linear association between higher BPV and outcome measures. In the multivariable adjusted model, the hazard ratios and 95% CIs of all-cause dementia were 1.06 (1.04–1.07) for the highest quartile of variability independent of the mean of diastolic blood pressure only, 1.09 (1.08–1.11) for that of systolic blood pressure only, and 1.18 (1.16–1.19) for that of both systolic and diastolic blood pressure compared with subjects having no highest quartile for BPV. Consistent results were noted for Alzheimer’s disease and vascular dementia using other indices of variability and in various sensitivity and subgroup analyses. BPV is an independent predictor for developing dementia and its subtypes. A dose-response relationship was noted between higher BPV and dementia incidence. Reducing BPV may be a target for preventing dementia in the general population.
Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy
Authors: Deliyanti Devy , Alrashdi Saeed F. , Touyz Rhian M. , Kennedy Christopher R. , Jha Jay C. , Cooper Mark E. , Jandeleit-Dahm Karin A. , Wilkinson-Berka Jennifer L.
Published: March 2020

Hypertension is a risk factor for the vascular permeability and neovascularization that threatens vision in diabetic retinopathy. Excess reactive oxygen species derived from the Nox (NADPH oxidase) isoforms, Nox1 and Nox4, contributes to vasculopathy in diabetic retinopathy; however, if Nox1/4 inhibition is beneficial in hypertensive diabetic retinopathy is unknown. Here, we determined that diabetic spontaneously hypertensive rats had exacerbated retinal vascular permeability and expression of angiogenic and inflammatory factors, compared with normotensive diabetic Wistar Kyoto rats. GKT136901, a specific dual inhibitor of Nox1 and Nox4, prevented these events in diabetic Wistar Kyoto rats and spontaneously hypertensive rats. Retinal neovascularization does not develop in diabetic rodents, and therefore, the oxygen-induced retinopathy model is used to evaluate this pathology. We previously demonstrated that Nox1/4 inhibition reduced retinal neovascularization in oxygen-induced retinopathy. However, although Nox5 is expressed in human retina, its contribution to retinopathy has not been studied in vivo, largely due to its absence from the rodent genome. We generated transgenic mice with inducible human Nox5 expressed in endothelial cells (vascular endothelial-cadherin
+
Nox5
+
mice). In vascular endothelial-cadherin
+
Nox5
+
mice with oxygen-induced retinopathy, retinal vascular permeability and neovascularization, as well as the expression of angiogenic and inflammatory factors, were increased compared with wild-type littermates. In bovine retinal endothelial cells, which express Nox1, Nox4, and Nox5, Nox1/4 inhibition, as well as Nox5 silencing RNA, reduced the high glucose–induced upregulation of oxidative stress, angiogenic, and inflammatory factors. Collectively, these data indicate the potential of Nox1, Nox4, and Nox5 inhibition to reduce vision-threatening damage to the retinal vasculature.
Risk Score for Predicting 2‐Year Mortality in Patients With Chagas Cardiomyopathy From Endemic Areas: SaMi‐Trop Cohort Study
Authors: Di Lorenzo Oliveira Claudia , Nunes Maria Carmo P. , Colosimo Enrico Antonio , de Lima Emilly Malveira , Cardoso Clareci S. , Ferreira Ariela Mota , de Oliveira Lea Campos , Moreira Carlos Henrique Valente , Bierrenbach Ana Luiza , Haikal Desireé Sant′Ana , Peixoto Sérgio Viana , Lima‐Costa Maria Fernanda , Sabino Ester Cerdeira , Ribeiro Antonio Luiz P.
Published: March 2020

Background

Risk stratification of Chagas disease patients in the limited‐resource setting would be helpful in crafting management strategies. We developed a score to predict 2‐year mortality in patients with Chagas cardiomyopathy from remote endemic areas.

Methods and Results

This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi‐Trop cohort (The São Paulo‐Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and
NT
‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all‐cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow‐up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person‐years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points),
QRS
duration ≥150 ms (15 points), and abnormal
NT
‐pro
BNP
adjusted by age (55 points). The observed mortality rates in the low‐, intermediate‐, and high‐risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71).

Conclusions

In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.
Soluble CD14, Ischemic Stroke, and Coronary Heart Disease Risk in a Prospective Study: The REGARDS Cohort
Authors: Olson Nels C. , Koh Insu , Reiner Alex P. , Judd Suzanne E. , Irvin Marguerite R. , Howard George , Zakai Neil A. , Cushman Mary
Published: March 2020

Background

Soluble
CD
14 (
sCD
14), a circulating pattern recognition receptor, has been suggested as a cardiovascular disease risk factor. Prospective studies evaluating
sCD
14 with incident cardiovascular disease events are limited, particularly among racially diverse populations.

Methods and Results

Between 2003 and 2007, the
REGARDS
(
Re
asons for Geographic and Racial Differences in Stroke) study recruited 30 239 black and white participants across the United States. In a nested case–cohort study,
sCD
14 was measured in baseline serum from 548 cases of incident ischemic stroke, 612 cases of incident coronary heart disease (
CHD
), and a cohort random sample (n=1039). Cox models estimated hazards ratios (
HR
) of incident ischemic stroke or
CHD
per 1
SD
higher
sCD
14, adjusting for cardiovascular disease risk factors. There was a differential association of
sCD
14 with ischemic stroke and
CHD
risk by race. Among blacks, the adjusted
HR
of stroke per
SD
increment of
sCD
14 was 1.42 (95%
CI
: 1.12, 1.80), with no association among whites (
HR
1.02 [95%
CI
: 0.82, 1.27]). Higher
sCD
14 was associated with increased
CHD
risk in blacks but not whites, and relationships between
sCD
14 and
CHD
were stronger at younger ages. Adjusted for risk factors, the
HR
of
CHD
per
SD
higher
sCD
14 among blacks at age 45 years was 2.30 (95%
CI
: 1.45, 3.65) compared with 1.56 (95%
CI
: 0.94, 2.57) among whites. At age 65 years, the
CHD HR
was 1.51 (95%
CI
: 1.20, 1.91) among blacks and 1.02 (95%
CI
: 0.80, 1.31) among whites.

Conclusions

sCD
14 may be a race‐specific stroke and
CHD
risk marker.
Non-Proliferation Treaty and Nuclear Disarmament
Authors: Hayashi Mika
Published: March 2020

A few final documents adopted by the Review Conferences of the Nuclear Non-Proliferation Treaty (‘NPT’) include important references to nuclear disarmament and to Article VI of the NPT. It is frequently assumed or claimed that these references amount to subsequent agreements as to the interpretation of Article VI. However, such a view is difficult to maintain. With the help of the 2018 Draft Conclusions on subsequent agreements and practice, this article seeks to establish two conditions that such final documents ought to satisfy if they are to be treated as subsequent agreements under Article 31 of the Vienna Convention on the Law of Treaties (‘VCLT’). The analysis suggests that the final documents in question do not satisfy such conditions. Based on this evaluation, the article also explores other theoretical frameworks both within and without treaty interpretation rules, that can adequately take into account the final documents of the NPT Review Conferences in discussing nuclear disarmament in international law.
Phyllopentas schimperi comb. nov. (Rubiaceae), a replacement name for the illegitimate combination Phyllopentas schimperiana

Authors: ZHOU YA-DONG , MWANGI BRIAN NJOROGE , MUSILI PAUL MUTUKU , HU GUANG-WAN , WANG QING-FENG
Published: March 2020

The new combination Phyllopentas schimperi (Hochstetter) Y.D. Zhou & Q.F. Wang is here proposed to replace the two illegitimate combinations Phyllopentas schimperiana (Vatke) Kårehed & B. Bremer and Phyllopentas schimperiana (A. Richard) Kårehed & B. Bremer of this species, which is found in Tropical Africa, and was formerly positioned in Pentas.
Megarthrus of China. Part 1. Description of a new species resembling M. antennalis Cameron, 1941 (Coleoptera: Staphylinidae: Proteininae)
Authors: LIU ZHIPING , CUCCODORO GIULIO
Published: March 2020

Megarthrus chujiao Liu and Cuccodoro sp. nov., from Sichuan and Yunnan provinces in China is described and illustrated. It is the third record of the genus in the Hengduan Mountains, and the first endemic Megarthrus species from this temperate biodiversity hotspot. Megarthrus chujiao strongly resembles M. antennalis Cameron, 1941, from Nepal and North India, with which they form a new complex of species—the M. antennalis-complex within the predominantly Holactic and African M. depressus-supergroup of species.
Coccygidium transcaspicum (Kokujev) (Hymenoptera: Braconidae) parasitizing larvae of invasive pest Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) in India
Authors: GUPTA ANKITA , SOUJANYA P. LAKSHMI , VAN ACHTERBERG CORNELIS , SEKHAR J.C.
Published: March 2020

The parasitoid Coccygidium transcaspicum (Kokujev) (Hymenoptera: Braconidae: Agathidinae) was reared from fall armyworm or Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) in maize fields in South India (Telangana) during 2019. It is the first report of a host for C. transcaspicum and the first report of C. transcaspicum as a parasitoid of S. frugiperda across the globe. The present study contains the first report from India and the Oriental region, provides morphological identification details of C. transcaspicum and comparison notes from its closely allied species C. melleum (Roman) which is basically an Afrotropical species.