bluuebunny/crossref_metadata_2025 huggingface dataset:
EndogenousClostridium perfringensPanophthalmitis with Potential Entry Port from Diverticulitis Exacerbated by Proliferative Diabetic Retinopathy
Authors: Neerukonda Vamsee , Cheng Anny M. S. , Dhanireddy Swetha , Alpert Samuel , Yin Han Y.
Published: March 2019

Purpose. To report a rapid endogenous fulminating panophthalmitis fromClostridium perfringensin a patient with diverticulitis and proliferative diabetic retinopathy.Methods. A 61-year-old female with poorly controlled diabetes mellitus, active proliferative diabetic retinopathy, and recent diverticulitis presented with conjunctival injection, ocular discharge, and sudden onset of painful vision loss of the left eye. Patient denied history of ocular trauma, intraocular surgery, or intravenous drug abuse. Examination revealed an erythematous, proptotic eye with restricted extraocular movements, mucopurulent discharge, diffuse corneal edema, and vitreous haze and cell. Orbital computed tomography (CT) confirmed no retained intraocular foreign body.Results. Despite 48 hours of treatment with systemic broad spectrum antimicrobial therapy (vancomycin, meropenem, and amphotericin B), patient underwent enucleation due to declined condition and progressive infection. Patient’s culture revealed gram-positive bacillus microbes (Clostridium perfringens). Patient’s subsequent CT abdomen showed resolved diverticulitis after antimicrobial therapy.Conclusion. Although rare,Clostridium perfringensinfection can be a cause of rapid loss of vision from fulminate endogenous panophthalmitis. Urgent extensive systemic work-up to identify potential port of entry from visceral pathology and rapid removal of source of infection are pivotal to avoid high rate of mortality.
iTRAQ-Based Proteomics to Reveal the Mechanism of Hypothalamus in Kidney-Yin Deficiency Rats Induced by Levothyroxine
Authors: Guan Wei , Liu Yan , Li Xiaomao , Yang Bingyou , Kuang Haixue
Published: March 2019

Kidney-yin deficiency syndrome (KYDS) is a typical syndrome encountered in traditional Chinese medicine (TCM) and is characterized by impaired lipid and glucose homeostasis. The hypothalamus acts as an important regulatory organ by controlling lipid and glucose metabolism in the body. Therefore, proteins in the hypothalamus could play important roles in KYDS development; however, the mechanisms responsible for KYDS remain unclear. Herein, iTRAQ-based proteomics was performed to analyze the protein expression in the hypothalamus of KYDS rats induced by levothyroxine (L-T4). Results revealed a total of 44 downregulated and 18 upregulated proteins in KYDS group relative to the control group. Gene Ontology (GO) analysis revealed that the differently expressed proteins (DEPs) were related to single-organism metabolism process under the biological process (BP), extracellular region part and organelle under the cellular component (CC), and oxidoreductase activity under the molecular function (MF). Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis showed that fatty acid degradation and pyruvate metabolism participated in the metabolism regulation in KYDS rats. RT-PCR validation of five distinctly expressed proteins related to the two pathways was consistent with the results of proteomics analysis. Taken together, the inhibition of fatty acid degradation and pyruvate metabolism in hypothalamus could potentially cause the dysfunction of the lipid and glucose metabolism in KYDS rats. This current study identified some novel potential biomarkers of KYDS and provided the basis for further research of KYDS.
Acute Efficacy of a Traditional Chinese Medicine for Treatment of Frequent Premature Ventricular Contractions in Patients with Concomitant Sinus Bradycardia: Results from a Double-Blind, Placebo-Controlled, Multicentre, Randomized Clinical Trial
Authors: Zhang Fengxiang , Zou Jiangang , Yu Hao , Li Xiaorong , Kojodjojo Pipin , Cai Xin , Zhang Shu , Huang Congxin , Hong Kui , Yu Bo , Li Guangping , Luo Suxin , Zhou Shenghua , Zheng Yang , Fan Jie , Cao Xuebin , Tao Guizhou , Sheng Guotai , Bai Zhisheng , Jiang Shan , Liu Xiaolin , Gu Weijuan , Chen Feng , Cao Kejiang
Published: March 2019

Pharmacological antiarrhythmic therapy such as beta-blockers in patients with frequent premature ventricular contractions (PVCs) and concomitant bradycardia is challenging. A traditional Chinese medicine, Shensong Yangxin (SSYX), has been effective in treatment of frequent PVCs and sinus bradycardia (SB) in separate patient cohorts. This double-blind, placebo-controlled, multicentre, randomized clinical trial investigates the acute efficacy of SSYX in reducing PVCs burden in patients with concomitant SB. Patients with symptomatic, frequent PVCs, and SB, defined as mean heart rate (MHR) of 45 to 59 beats per min (bpm), were recruited at 33 medical centres in mainland China and randomly assigned by computer to either SSYX or matching placebo for eight weeks. Patients, investigators, and trial personnel were masked to treatment allocation. Primary endpoints were changes in PVCs burden and MHR as assessed by 24-hour Holter monitoring relative to baseline. Secondary efficacy endpoints were subjective symptom score, ECG, and biochemical parameters. Analysis was based on intention-to-treat principles. 333 patients were randomized, of which 166 received SSYX and 167 placebo. Baseline characteristics did not differ. SSYX reduced PVCs burden by 68.2% (p< 0.001) and increased MHR by 10.9% (p< 0.001) compared to 32.2% and 4.7%, respectively, in the placebo group. SSYX group experienced greater symptomatic improvement (p< 0.001). No differences in reported adverse events were seen (20 versus 23). SSYX is an effective antiarrhythmic therapy for symptomatic, frequent PVCs uniquely suited patients with concomitant SB. Clinical trial number wasNCT01750775.
The Effect of Different Amounts of Cinnamon Consumption on Blood Glucose in Healthy Adult Individuals
Authors: Kizilaslan Nildem , Erdem Nihal Zekiye
Published: March 2019

Background. This study was aimed at investigating the effect of consumption of different amounts of cinnamon on preprandial blood glucose (PrBG), postprandial blood glucose (PoBG), glycosylated hemoglobin (HbA1c), and body mass index (BMI). Methods. This study was carried out on 41 healthy adult individuals. The individuals were divided into 3 groups and monitored for 40 days. The first, second, and third groups were given 1 g/day, 3 g/day, and 6 g/day cinnamon, respectively. Before the beginning of the consumption of cinnamon, HbA1c and PrBG blood tests of the individuals were examined on an empty stomach at family practice centers. Two hours after these tests were carried out and breakfast, PoBG tests were performed. Results. According to the findings of the study, the differences between the average weight measurements, BMI values, and HbA1c values before consumption on days 20 and 40 were not statistically significant in the individuals consuming 1 g, 3 g, and 6 g of cinnamon a day. The difference between the average PrBG measurements was found to be significant in the individuals consuming 6 g of cinnamon per day. The difference between the average PoBG measurements before consumption on days 20 and 40 was significant in the individuals consuming 1 g, 3 g, and 6 g of cinnamon per day. Conclusions. In particular a 3–6 g of cinnamon consumption was found to affect certain blood parameters of individuals positively. Therefore, it is considered to be beneficial to raise awareness of individuals to be conscious to regularly consume cinnamon.
Two Signs of Superfluid Liquid in a Suspension of CdSe/ZnS Quantum Dots at Room Temperature
Authors: Isaev A. A.
Published: March 2019

The paper presents experimental results of the interaction of a focused optical beam with a suspension of CdSe/ZnS quantum dots in toluene. Two autographs characteristic only of the behavior of a superfluid quantum liquid were experimentally observed. The first was the fountain effect from the region of local heating of the suspension with an optical beam; the second was the complete “creeping out” of the QDs suspension in the form of a thin film along the walls of the cuvette in which the suspension was located. The results of the work suggest that superfluid quantum liquid may arise at room temperature as a result of the functioning of many-particle quantum superposition. Bose-Einstein condensation of entangled quantum states is proposed as a physical mechanism for producing a superfluid liquid, regardless of temperature.
Can Occupational Therapy Address the Occupational Implications of Hoarding?
Authors: Clarke Cathy
Published: March 2019

Hoarding is often described as a medical disorder, defined by a persistent difficulty in discarding possessions and associated high levels of emotional distress when forced to part with these. This article will discuss how having a different view of hoarding, seeing hoarding as a daily occupation which provides value, purpose, and meaning and with a relationship to self-identity and life purpose, could offer alternate interventions to support an individual who hoards. The article will consider the components of hoarding activity and how these relate to health and wellbeing and doing, being, belonging, and becoming as understood by occupational therapists. The article will consider what occupational therapy, a profession which considers a person’s daily occupations, the things that occupy their time and which give meaning to their existence, could offer as an alternative to current hoarding interventions. Proposals for occupational therapy interventions will be suggested which would support occupational choice, support engagement in activities which have more positive outcomes on a person’s health, and seek to address barriers which limit engagement and occupational performance in activities within the person’s home environment.
Long Noncoding RNA ASB16-AS1 Promotes Proliferation, Migration, and Invasion in Glioma Cells
Authors: Zhang Delong , Zhou Huanggui , Liu Jun , Mao Jie
Published: March 2019

Glioma is a lethal, malignant intracranial tumor that becomes progressively common. It has been shown that long noncoding RNAs (lncRNAs) serve important roles in numerous diseases such as gliomas. lncRNAs can regulate the expression of targeted genes through various mechanisms. To identify a novel lncRNA that may be critical in glioma, the present study downloaded the RNA expression profiles of 171 glioma tissues and 5 normal tissues from The Cancer Genome Atlas (TCGA) database using the TCGAbiolinks package in R. Then, lncRNAs in the downloaded TCGA data were identified using the HUGO Gene Nomenclature Committee (HGNC). Based on the fragments per kilobase million value, differential expression analysis was conducted using the limma package in R. In addition, receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC) was evaluated using the ROCR package in R. A total of 178 lncRNAs corresponding to differentially expressed genes with an AUC >0.85 were selected. Upon identifying the differential lncRNAs, ceRNA networks were constructed with these differential lncRNAs using the starbase database. From these networks, the top 10% hub genes were selected. In addition, the present study randomly selected 4 lncRNAs for quantitative polymerase chain reaction validation in tissue samples. The results revealed that lncRNA ASB16-AS1 exhibited significantly differential expression in tissue samples and was significantly associated with tumor staging and grading. Furthermore, the proliferation, invasion, and migration of U87MG and U251 glioblastoma stem-like cells (U87GS, U251GS) were significantly inhibited upon inhibition of ASB16-AS1, and the expression of key proteins in the EMT signaling pathway was affected by knocking down ASB16-AS1. Overall, the present study revealed that lncRNA ASB16-AS1 improves the proliferation, migration, and invasion of glioma cells.
Weighted Endpoint Estimates for Commutators of Singular Integral Operators on Orlicz-Morrey Spaces
Authors: Qi Jinyun , Shi Hongxia , Li Wenming
Published: March 2019

In this paper, we obtain the weighted endpoint estimates for the commutators of the singular integral operators with the BMO functions and the associated maximal operators on Orlicz-Morrey Spaces. We also get the similar results for the commutators of the fractional integral operators with the BMO functions and the associated maximal operators.
Oral Health Status and Treatment Needs of Pregnant Women Attending Antenatal Clinics in KwaZulu-Natal, South Africa
Authors: Africa Charlene W. J. , Turton Mervyn
Published: March 2019

During pregnancy, the oral cavity is characterised by an acidic environment and an inflammatory response brought about by vomiting and changes in hormonal levels, respectively, thereby increasing the mother’s risk of developing caries. Although evidence exists to support an association between pregnancy-associated periodontal disease and adverse pregnancy outcomes, there is a paucity of studies which focus on the caries prevalence and other oral manifestations of pregnant women. The aim of this study was to assess the oral health status and treatment needs of pregnant women attending antenatal clinics in KwaZulu-Natal, South Africa. Randomly selected mothers (n=443) attending a maternal obstetrics unit participated in the study. A questionnaire elicited demographic information about the participants, while the measurement of decayed, missing, and filled indices (DMFT) determined their caries status. Oral lesions were noted if present. Descriptive statistics for independent variables described frequencies in the various categories of race, location, pregnancy stage, etc., with the association between 2 independent variables tested by chi-square. Dependent variables such as DMFT were expressed as means and standard deviations, and ANOVA was used to examine whether independent variables significantly influenced the DMFT. The mean DMFT was 7.18 (±4.22) with significant correlations observed between DMFT, D, M, and age. F scores differed significantly between races, location, and educational levels and showed a significant correlation with pregnancy stage. Pregnancy epulis was diagnosed in 38 (8.5%), oral lesions in 65 (14.7%), and tooth mobility in 26 (5.9%) mothers. Early oral health screening during pregnancy can ensure the overall well-being of both the mother and the foetus.
Solvability of Two Classes of Tensor Complementarity Problems
Authors: Xu Yang , Gu Weizhe , Huang He
Published: March 2019

In this paper, we first introduce a class of tensors, called positive semidefinite plus tensors on a closed cone, and discuss its simple properties; and then, we focus on investigating properties of solution sets of two classes of tensor complementarity problems. We study the solvability of a generalized tensor complementarity problem with a D‐strictly copositive tensor and a positive semidefinite plus tensor on a closed cone and show that the solution set of such a complementarity problem is bounded. Moreover, we prove that a related conic tensor complementarity problem is solvable if the involved tensor is positive semidefinite on a closed convex cone and is uniquely solvable if the involved tensor is strictly positive semidefinite on a closed convex cone. As an application, we also investigate a static traffic equilibrium problem which is reformulated as a concerned complementarity problem. A specific example is also given.
A Modified Anteromedial Approach for Exposure of Coronoid Fractures: An Anatomical Cadaver Study
Authors: Yang Fei , Feng Kai , Sun Yuehua , Dai Kerong , Wang Xiaoqing , Tang Jian
Published: March 2019

The previous anterior approach to the elbow provides a limited exposure of the coronoid process. The aim of this study was to identify the optimal exposure interval for coronoid fractures from the anterior aspect of elbow. We exposed the coronoid process on twelve fresh-frozen cadaveric elbows from the anteromedial aspect of the elbow. The dissection intervals used were the novel brachial artery-median nerve interval (B-M interval) and the previously reported biceps tendon-brachial artery interval (B-B interval). Access to key anatomic landmarks around the coronoid process was assessed and the exposed surface area of coronoid process was calculated in each specimen. The average exposed surface area of coronoid process was 2.26 times greater with the B-M interval (4.58 cm2) compared with the B-B interval (2.03 cm2) (p < 0.05). All key anatomic landmarks around the coronoid process were directly visualised via the B-M interval in each specimen. In conclusion, the anteromedial approach through the B-M interval provides a more extensive exposure of the coronoid process than the traditional B-B interval. This new approach can be useful for the fixation of coronoid fractures.
Serum Cystatin C Predicts Mortality in HBV-Related Decompensated Cirrhosis
Authors: Wu JianPing , Wu QianXia , Wu MinYi , Mao WeiLin
Published: March 2019

Background. Some studies have reported that renal dysfunction is associated with poor prognosis in cirrhotic patients. Serum cystatin C (CysC) is an accurate biomarker for early renal dysfunction. This study aimed to assess the prognostic value of serum CysC levels in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). Methods. This retrospective study included 75 subjects who had been diagnosed with HBV-DeCi. The association between serum CysC and prognosis was estimated by receiver operating characteristic curve analysis and a multivariable logistic regression model. Results. Serum CysC levels were higher in nonsurvivors than in survivors and were positively correlated with model for end-stage liver disease (MELD) scores. In multivariate analysis, CysC and the MELD score were independent prognostic factors in all HBV-DeCi patients. However, only serum CysC was an independent factor predicting mortality in patients with normal creatinine levels. Conclusions. These data suggest that high serum CysC levels can be considered an independent biomarker of 3-month mortality in patients with HBV-DeCi.
Randomized Comparison of Terumo® Coated Slender™ versus Terumo® Noncoated Traditional Sheath during Radial Angiography or Percutaneous Coronary Intervention
Authors: Sindberg Birthe , Aagren Nielsen Christel Gry , Hestbjerg Poulsen Marianne , Bøhme Rasmussen Martin , Carstensen Steen , Thim Troels , Jakobsen Lars , Thorsted Sørensen Jacob , Haastrup Benedicte , Maare Søndergaard Hanne , Mæng Michael , Juhl Terkelsen Christian
Published: March 2019

Background. The transradial approach is generally associated with few complications. However, periprocedural pain is still a common issue, potentially related to sheath insertion and/or arterial spasm, and may result in conversion to femoral access. Radial artery occlusion (RAO) following the procedure is also a potential risk. We evaluate whether the design of the sheath has any impact on these variables. Methods. A total of 1,000 patients scheduled for radial CAG or PCI were randomized (1:1) to the use of a Slender or a Standard sheath during the procedure. Randomization was stratified according to chosen sheath size (5, 6, 7 French) and gender. A radial band was used to obtain hemostasis after the procedure, employing a rapid deflation technique. A reverse Barbeau test was performed to evaluate radial artery patency after removal of the radial band, and level of pain was assessed using a numeric rating scale (NRS). Results. Use of the Slender sheath was associated with less pain during sheath insertion (median NRS 1 versus 2, p=0.02), whereas no difference was observed in pain during the procedure, radial procedural success rates, use of analgesics and sedatives during the procedure, and radial artery patency following the procedure. Rate of RAO was 1.5% with no difference between groups. Conclusion. The use of the hydrophilic coated Slender sheath during radial CAG or PCI was associated with less pain during sheath insertion, whereas no difference in other endpoints was observed. A rapid deflation technique was associated with RAO of only 1.5%.
Advanced Support Vector Machine- (ASVM-) Based Detection for Distributed Denial of Service (DDoS) Attack on Software Defined Networking (SDN)
Authors: Myint Oo Myo , Kamolphiwong Sinchai , Kamolphiwong Thossaporn , Vasupongayya Sangsuree
Published: March 2019

Software Defined Networking (SDN) has many advantages over a traditional network. The great advantage of SDN is that the network control is physically separated from forwarding devices. SDN can solve many security issues of a legacy network. Nevertheless, SDN has many security vulnerabilities. The biggest issue of SDN vulnerabilities is Distributed Denial of Service (DDoS) attack. The DDoS attack on SDN becomes an important problem, and varieties of methods had been applied for detection and mitigation purposes. The objectives of this paper are to propose a detection method of DDoS attacks by using SDN based technique that will disturb the legitimate user's activities at the minimum and to propose Advanced Support Vector Machine (ASVM) technique as an enhancement of existing Support Vector Machine (SVM) algorithm to detect DDoS attacks. ASVM technique is a multiclass classification method consisting of three classes. In this paper, we can successfully detect two types of flooding-based DDoS attacks. Our detection technique can reduce the training time as well as the testing time by using two key features, namely, the volumetric and the asymmetric features. We evaluate the results by measuring a false alarm rate, a detection rate, and accuracy. The detection accuracy of our detection technique is approximately 97% with the fastest training time and testing time.
Autosomal Dominant Hypophosphatemic Rickets Presenting in a Phenotypically Normal Adult Female
Authors: Mualla Hala , Bae Su Ah , Yaqub Abid
Published: March 2019

We describe a presentation of Autosomal Dominant Hypophosphatemic Rickets (ADHR) in a 22-year-old female with normal pubertal growth and development and a negative family history in first-degree relatives. The patient presented with a 2-year history of upper and lower extremity proximal muscle pain and weakness and bilateral femoral neck and pubic bone insufficiency fractures. She had a normal serum calcium but a low phosphate as well as 25-hydroxyvitamin D (25(OH)D) levels leading initially to a diagnosis of osteomalacia. Urine phosphate reabsorption was low confirming a phosphate wasting disorder. She had an elevated Fibroblast Growth Factor 23 (FGF23) level. After Tumor-Induced Osteomalacia was ruled out by extensive imaging, she was sent for genetic testing for hereditary rickets which showed a previously reported missense variant in FGF23. Subsequently, she found out that her father’s maternal aunt and grandfather had ‘bone disorder’ and were wheelchair-bound in adulthood. After replenishment of vitamin D, treatment with calcitriol and phosphate leads to complete resolution of patient’s symptoms and laboratory abnormalities.
A Robot Calibration Method Based on Joint Angle Division and an Artificial Neural Network
Authors: Wang Zhirong , Chen Zhangwei , Wang Yuxiang , Mao Chentao , Hang Qiang
Published: March 2019

Robot calibration is used to improve the accuracy of the kinematic model to achieve the higher positioning accuracy within the workspace. Due to some nongeometrical reasons such as joint and link flexibility, the errors are unevenly distributed in the workspace. In this case, it is difficult for the existing methods used to improve the absolute positioning accuracy to achieve good results in each region, especially for robots with large self‐weights. In this paper, a novel calibration method is proposed, which deals with joint deflection dependent errors to enhance the robot positioning accuracy in the whole workspace. Firstly, the joint angle workspace is divided into several local regions according to the mass distribution of the robot. Then, its geometric parameters are modeled and identified using the Denavit–Hartenberg (DH) model in each region and in the whole workspace separately. Since the nongeometric error sources are difficult to model correctly, an artificial neural network (ANN) is applied to compensate for the nongeometric errors. Finally, the experiments using an 8 degree‐of‐freedom (DOF) engineering robot are conducted to demonstrate the validity of the proposed method. The combination of the joint angle division and ANN could be an effective solution for the robot calibration, especially for one with a large self‐weight.
Rosmarinic Acid Enriched Fraction fromPerilla frutescensLeaves Strongly Protects Indomethacin-Induced Gastric Ulcer in Rats
Authors: Kangwan Napapan , Pintha Komsak , Lekawanvijit Suree , Suttajit Maitree
Published: March 2019

Gastric ulcers are a common problem in upper gastrointestinal tract (GI) disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most aggressive factors leading to inducing gastric ulcers. Natural products with lower toxicity and safety are currently sought as a potential source to minimize the effect of the gastric ulcers.Perilla frutescensor Nga-mon (in Thai) leaves are rich in rosmarinic acid (RA), which has antioxidant, anti-inflammatory, and anticancer effects. This study investigates the protective effect of ethanolic extract (EE) and aqueous fraction (AF) fromPerilla frutescensleaves, which are rich in RA, on indomethacin- (IND-) induced gastric ulcer in a rat model. The EE at the doses of 50 and 500 mg/kg body weight, AF at the doses of 50, 250, and 500 mg/kg body weight, or famotidine (a standard drug) were administered for 14 days prior to ulcer induction. The ulceration was performed by intragastric administration of IND. Gross gastric ulcers and biological and histological parameters were examined. The pretreatment with AF had more significant effects than EE, including reduced ulcer index, decreased gastric secretion volume and decreased acidity, but it had an elevated gastric pH relative to the IND-induced gastric ulcer. In a histopathological study, the EE and AF decreased mucosal ulcer, inflammatory infiltration, and degenerative lining cells. The IND-induced expression of inflammatory mediators was significantly attenuated with EE and AF. The experiment also remarkably showed the preservation of mucus and apoptosis protection of EE and AF on a gastric mucosal ulcer. The findings demonstrated that the EE and AF of perilla leaves were capable of protecting the stomach against gastric ulcers induced by IND through anti-inflammatory and antiapoptotic mechanisms that should be further investigated. It is suggested thatPerilla frutescensleaf could be a potential alternative source of RA as a therapeutic agent and food supplement for NSAID-induced gastric injuries.
Somatic Hypermutation of the YAP Oncogene in a Human Cutaneous Melanoma
Authors: Zhang Xiaomeng , Tang Jian Zhong , Vergara Ismael A. , Zhang Youfang , Szeto Pacman , Yang Lie , Mintoff Christopher , Colebatch Andrew , McIntosh Lachlan , Mitchell Katrina A. , Shaw Evangeline , Rizos Helen , Long Georgina V. , Hayward Nicholas , McArthur Grant A. , Papenfuss Anthony T. , Harvey Kieran F. , Shackleton Mark
Published: March 2019

Melanoma is usually driven by mutations in BRAF or NRAS, which trigger hyperactivation of MAPK signaling. However, MAPK-targeted therapies are not sustainably effective in most patients. Accordingly, characterizing mechanisms that co-operatively drive melanoma progression is key to improving patient outcomes. One possible mechanism is the Hippo signaling pathway, which regulates cancer progression via its central oncoproteins YAP and TAZ, although is thought to be only rarely affected by direct mutation. As YAP hyperactivation occurs in uveal melanoma, we investigated this oncogene in cutaneous melanoma. YAP protein expression was elevated in most benign nevi and primary cutaneous melanomas but present at only very low levels in normal melanocytes. In patient-derived xenografts and melanoma cell lines, we observed variable reliance of cell viability on Hippo pathway signaling that was independent of TAZ activity and also of classical melanoma driver mutations such as BRAF and NRAS. Finally, in genotyping studies of melanoma, we observed the first ever hyperactivating YAP mutations in a human cancer, manifest as seven distinct missense point mutations that caused serine to alanine transpositions. Strikingly, these mutate four serine residues known to be targeted by the Hippo pathway and we show that they lead to hyperactivation of YAP.

Implications:

Our studies highlight the YAP oncoprotein as a potential therapeutic target in select subgroups of melanoma patients, although successful treatment with anti-YAP therapies will depend on identification of biomarkers additional to YAP protein expression.
The Pioneering Role of GATA2 in Androgen Receptor Variant Regulation Is Controlled by Bromodomain and Extraterminal Proteins in Castrate-Resistant Prostate Cancer
Authors: Chaytor Lewis , Simcock Matthew , Nakjang Sirintra , Heath Richard , Walker Laura , Robson Craig , Jones Dominic , Gaughan Luke
Published: March 2019

The androgen receptor (AR) is a key driver of prostate cancer development. Antiandrogens effectively inactivate the AR, but subsequent AR reactivation progresses the disease to castrate-resistant prostate cancer (CRPC). Constitutively active AR splice variants (AR-V) that function unchallenged by current AR-targeted therapies are key drivers of CRPC. Currently, very little is known about the regulation of AR-Vs at the chromatin level. Here, we show that the pioneer factor GATA2 is a critical regulator of AR-Vs. Furthermore, we demonstrate that the GATA2 cistrome in CRPC shares considerable overlap with bromodomain and extraterminal (BET) proteins and is codependent for DNA binding. GATA2 activity is compromised by BET inhibitors, which attenuates the pioneering role of GATA2 in CRPC. In all, this study indicates that GATA2 is a critical regulator of AR-V–mediated transactivation and is sensitive to BET inhibitors, signifying these agents may be efficacious in patients with CRPC which overexpress GATA2.

Implications:

We have defined novel mechanisms of AR-V and GATA2 regulation in advanced prostate cancer that could be therapeutically exploited.
Association between Trimetazidine and Parkinsonism: A Population-Based Study
Authors: Kwon Jeongyoon , Yu Yun Mi , Kim Seungyeon , Jeong Kyeong Hye , Lee Euni
Published: March 2019

Background: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. Objectives: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. Methods: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. Results: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06–1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13– 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87–5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. Conclusions: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.
Diet-Induced Obesity Promotes Kidney Endothelial Stiffening and Fibrosis Dependent on the Endothelial Mineralocorticoid Receptor
Authors: Aroor Annayya R. , Habibi Javad , Nistala Ravi , Ramirez-Perez Francisco I. , Martinez-Lemus Luis A. , Jaffe Iris Z. , Sowers James R. , Jia Guanghong , Whaley-Connell Adam
Published: March 2019

Obesity is characterized by enhanced MR (mineralocorticoid receptor) activation, vascular stiffness, and associated cardiovascular and kidney disease. Consumption of a Western-style diet (WD), high in saturated fat and refined carbohydrates, by female mice, leads to obesity and vascular stiffening. Use of ECMR (endothelial cell–specific MR) knockout mice supports that ECMR activation is critical for development of vascular and cardiac fibrosis and stiffening. However, the role of ECMR activation in kidney inflammation and fibrosis remains unknown. We hypothesized that cell-specific deletion of ECMR would prevent WD-induced central aortic stiffness and protect the kidney from endothelial dysfunction and vascular stiffening. Four-week-old female ECMR KO and wild-type mice were fed either mouse chow or WD for 16 weeks. WD feeding increased body weight and fat mass, proteinuria, as well as vascular stiffness indices (pulse wave velocity and kidney artery stiffening) and impaired endothelial-dependent vasodilatation without blood pressure changes. The WD-induced kidney arterial stiffening was associated with attenuated eNOS (endothelial NO synthase) activation, increased oxidative stress, proinflammatory immune responses, alterations in extracellular matrix degradation pathways, and fibrosis. ECMR deletion prevented these abnormalities by improving eNOS activation and reducing macrophage proinflammatory M1 polarization, expression of TG2 (transglutaminase 2), and MMP (matrix metalloproteinase)-9. Our data support the concept that ECMR activation contributes to endothelial dysfunction, increased kidney artery fibrosis/stiffening, and impaired NOS (NO synthase) activation, processes associated with macrophage infiltration and polarization, inflammation, and oxidative stress, collectively resulting in tubulointerstitial fibrosis in females consuming a WD.
HIMF (Hypoxia-Induced Mitogenic Factor)-IL (Interleukin)-6 Signaling Mediates Cardiomyocyte-Fibroblast Crosstalk to Promote Cardiac Hypertrophy and Fibrosis
Authors: Kumar Santosh , Wang Gang , Zheng Na , Cheng Wanwen , Ouyang Kunfu , Lin Hairuo , Liao Yulin , Liu Jie
Published: March 2019

HIMF (hypoxia-induced mitogenic factor) is a secreted proinflammatory cytokine with a critical role in cardiac hypertrophy development. Loss of HIMF attenuates transverse aortic constriction-induced cardiac hypertrophy and fibrosis, but the underlying mechanisms are unknown. We show that IL (interleukin)-6 production increases following transverse aortic constriction in wild-type mice; this effect is inhibited in HIMF gene knockout (
Himf
−/−
) mice. IL-6 production also increases in cultured cardiac myocytes overexpressing HIMF and neutralizing IL-6 with an anti-IL-6 antibody prohibits HIMF-induced cardiomyocyte hypertrophy. HIMF expression in cardiac fibroblasts cannot be stimulated by transverse aortic constriction or exposure to prohypertrophic factors, including phenylephrine, Ang II (angiotensin II), TGF (transform growth factor)-β, and hypoxia. However, conditioned medium from cardiomyocytes overexpressing HIMF can increase IL-6 production, and cardiac fibroblast proliferation, migration, and myofibroblast differentiation to a similar level as exposure to exogenous rHIMF (recombinant HIMF). Again, neutralizing IL-6 prevented cardiac fibroblasts activation. Finally, the MAPK (mitogen-activated protein kinase) and CaMKII (Ca
2+
/calmodulin-dependent protein kinase II)–STAT3 (signal transducers and activators of transcription 3) pathways are activated in HIMF-overexpressing cardiomyocytes and rHIMF-stimulated cardiac fibroblasts; this effect can be inhibited on neutralizing IL-6. These data support that HIMF induces cardiac fibrosis via a cardiomyocyte-to-fibroblast paracrine effect. IL-6 is a downstream signal of HIMF and has a central role in cardiomyocyte hypertrophy and myocardial fibrosis that is mediated by activating the MAPK and CaMKII-STAT3 pathways.
Sudden Cardiac Death in Hypertensive Patients
Authors: Verdecchia Paolo , Angeli Fabio , Cavallini Claudio , Aita Adolfo , Turturiello Dario , De Fano Michelantonio , Reboldi Gianpaolo
Published: March 2019

In patients with hypertension, but without established cardiovascular disease, predictive factors for sudden cardiac death (SCD) remain undefined. We followed for an average of 10.3 years a cohort of 3242 initially untreated hypertensive patients without evidence of coronary or cerebrovascular heart disease at entry. All patients underwent a complete clinical examination which included ECG and 24-hour ambulatory blood pressure monitoring. At entry, the mean age of patients was 50.0 years, 45% were women, and 6.1% had type 2 diabetes mellitus. Average office blood pressure was 154/96 mm Hg, and average 24-hour ambulatory blood pressure was 136/86 mm Hg. Prevalence of left ventricular hypertrophy at ECG was 13.9%. During follow-up, SCD occurred in 33 patients at a rate of 0.10 per 100 patient-years (95% CI, 0.07–0.14). The rate of SCD was 0.07 and 0.30 per 100 patient-years, respectively, in the cohort of patients without and with ECG left ventricular hypertrophy (
P
<0.01). In a multivariable Cox model with Firth penalized maximum bias reduction method for rare outcome events, left ventricular hypertrophy almost tripled the risk of SCD (adjusted hazard ratio, 2.99; 95% CI, 1.47–6.09;
P
=0.002) after adjustment for age (
P
<0.0001), sex (
P
=0.019), diabetes mellitus (
P
<0.0001), and 24-hour ambulatory pulse pressure (
P
=0.036). For each 10 mm Hg increase in 24-hour ambulatory pulse pressure, the risk of SCD increased by 35%. The time-dependent area under the receiver operating characteristic curve was 0.85 (95% CI, 0.74–0.96). We conclude that in patients with hypertension without established cardiovascular disease, age, diabetes mellitus, ECG left ventricular hypertrophy, and 24-hour ambulatory pulse pressure are independent prognostic markers for SCD in the long-term.
Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5
Authors: Kaesmacher Johannes , Chaloulos-Iakovidis Panagiotis , Panos Leonidas , Mordasini Pasquale , Michel Patrik , Hajdu Steven D. , Ribo Marc , Requena Manuel , Maegerlein Christian , Friedrich Benjamin , Costalat Vincent , Benali Amel , Pierot Laurent , Gawlitza Matthias , Schaafsma Joanna , Mendes Pereira Vitor , Gralla Jan , Fischer Urs
Published: March 2019

Background and Purpose—

If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients.

Methods—

Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI.

Results—

Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results.

Conclusions—

In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.
A New Normal for Interest Rates? Evidence from Inflation-Indexed Debt
Authors: Christensen Jens H. E. , Rudebusch Glenn D.
Published: March 2019

The downtrend in U.S. interest rates over the past two decades may partly reflect a decline in the longer-run equilibrium real rate of interest. We examine this issue using dynamic term structure models that account for time-varying term and liquidity risk premiums and are estimated directly from prices of individual inflation-indexed bonds. Our finance-based approach avoids two potential pitfalls of previous macroeconomic analyses: structural breaks at the zero lower bound and misspecification of output and inflation dynamics. We estimate that the longer-run equilibrium real rate has fallen about 2 percentage points and appears unlikely to rise quickly.
Expectation Formation Following Large, Unexpected Shocks
Authors: Baker Scott R. , McElroy Tucker S. , Sheng Xuguang S.
Published: March 2019

By matching a large database of individual macroforecaster data with the universe of sizable natural disasters across 54 countries, we identify a set of new stylized facts: forecasters are persistently heterogeneous in how often they issue or revise a forecast; information rigidity declines significantly following large, unexpected natural disaster shocks; and disagreement decreases among inattentive agents while it might increase for attentive ones. We develop a learning model that captures the two channels through which natural disaster shocks affect expectation formation: attention effect—the visibly large shocks induce immediate and synchronized updating of information for inattentive agents—and uncertainty effect—attentive agents might increase their acquisition of private information to compensate for the higher uncertainty after shocks.
Exporting Sweatshops? Evidence from Myanmar
Authors: Tanaka Mari
Published: March 2019

This study investigates the impacts of exporting on working conditions in Myanmar by drawing on a new firm survey. For the identification, I use the rapid opening of Myanmar to trade alongside the firm's proximity to airports and products that have generated variations in access to foreign markets. The results show that exporting has significant positive impacts on working conditions regarding fire safety, health management, and freedom of negotiation; positive insignificant effects on wages; and negative insignificant effects on working hours. I also find that exporting positively affects firm size, management practices, and the likelihood of receiving a labor audit.
School Finance Reforms, Teachers' Unions, and the Allocation of School Resources
Authors: Brunner Eric , Hyman Joshua , Ju Andrew
Published: March 2019

School finance reforms caused some of the most dramatic increases in intergovernmental aid from states to local governments in U.S. history. We examine whether teachers' unions affected the fraction of reform-induced state aid that passed through to local spending and the allocation of these funds. Districts with strong teachers' unions increased spending nearly dollar-for-dollar with state aid and spent the funds primarily on teacher compensation. Districts with weak unions used aid primarily for property tax relief and spent remaining funds on hiring new teachers. The greater expenditure increases in strong union districts led to larger increases in student achievement.
New species of orchids and notes on Orchidaceae of Nepal

Authors: RASKOTI BHAKTA BAHADUR , ALE RITA
Published: March 2019

Two new species of orchids from Nepal, Calanthe himalaicum and Habenaria palpensis are described and illustrated. Notes on the diagnostic characters used to distinguish them from allied taxa are provided. Present paper also summarizes various taxonomic publications on orchids of Nepal and reveals that the known orchid flora of Nepal comprises 502 taxa from 108 genera.
Gundelia siirtica (Asteraceae), a new lactiferous species from Siirt (south-eastern Anatolia)
Authors: FIRAT MEHMET
Published: March 2019

Gundelia siirtica sp. nov. is described from Siirt Province, Turkey. The new species appears to be most similar to G. mesopotamica and G. armeniaca, from which it differs in plant height and indumentum, size and number of synflorescences, colour of corolla externally and internally, shape and size of fruit complex (disseminule). A comprehensive description of this species is provided, with detailed photographs, a distribution map, a habitat description, a vernacular name and an IUCN conservation status.
Colletotrichum yulongense sp. nov. and C. rhombiforme isolated as endophytes from Vaccinium dunalianum var. urophyllum in China
Authors: WANG QIUTONG , LIU XIAOTING , MA HAIYING , SHEN XIAOYE , HOU CHENGLIN
Published: March 2019

No species of Colletotrichum have been reported associated with Vaccinium dunalianum var. urophyllum, which is a significant medicinal plant in China. In this study, several endophytic strains were isolated from this host. Morphology and analysis of DNA sequences of nuc rDNA ITS1-5.8S-ITS2 (ITS barcode) and seven other gene regions (GAPDH, CAL, ACT, CHS-1, HIS, GS, TUB2) revealed a new species, Colletotrichum yulongense and a previously described species, C. rhombiforme. Both Colletotrichum species are described. The diversity and broad distribution of the host, suggest the likelihood of other endophytic Colletotrichum species in V. dunalianum var. urophyllum and this requires further investigation. The pathogenicity of the Colletotrichum species isolated from V. dunalianum var. urophyllum also needs testing.
Akemetopon, a new genus containing three new species of planthoppers (Hemiptera: Fulgoroidea: Delphacidae)
Authors: WEGLARZ KATHRYN M. , BARTLETT CHARLES R.
Published: March 2019

The new delphacid genus Akemetopon gen. n. (Delphacinae: Delphacini) is described and illustrated with 3 new species from Arizona and Mexico: Akemetopon inornatum sp. n., A. politum sp. n., and A. ainigma sp. n. A key to species is provided. The barcoding portion of the mitochondrial gene Cytochrome Oxidase I (COI) was sequenced for A. politum sp. n. A maximum likelihood analysis places this genus in the basal Delphacini.
Two new species of the genus Pison Jurine (Hymenoptera: Crabronidae) from China, with a key to the Chinese species
Authors: LI TINGJING , LI QIANG
Published: March 2019

Two new species, Pison irramulus n. sp. from Yunnan, China, and Pison liupanshanense n. sp. from Ningxia, China, are described. A key to the species of Pison from China is provided, along with illustrations of the new species. Type specimens of the new species are deposited in Yunnan Agricultural University.