bluuebunny/crossref_metadata_2025 huggingface dataset:
Locating Errors in Faulty Formulas
Authors: Kannan Sampath , Tian Kevin T.
Published: June 2019

Given a drawing of a read-once formula (called the blueprint), and a blackbox implementation with the same topology as the blueprint that purports to compute the formula, can we tell if it does? Under a fault model, where the only faults in the implementation are gates that complement their outputs, we show that there is an efficient algorithm that makes a linear number of probes to the blackbox implementation and determines if the blueprint and implementation are identical. We also show a matching lower bound. We further ask whether we can diagnose where the faults are, using blackbox testing. We prove that if the implementation has a property called
polynomial balance
, then it is possible to do this efficiently. To complement this result, we show that even if the
blueprint
is polynomially balanced and there are only logarithmically many errors in the implementation, the implementation could be unbalanced and the diagnosis problem provably requires super-polynomially many tests. We point out that this problem is one instance of a general class of problems of learning deviations from a blueprint, which we call
conformance learning
. Conformance learning seems worthy of further investigation in a broader context.
A Survey of Parallel Sequential Pattern Mining
Authors: Gan Wensheng , Lin Jerry Chun-Wei , Fournier-Viger Philippe , Chao Han-Chieh , Yu Philip S.
Published: June 2019

With the growing popularity of shared resources, large volumes of complex data of different types are collected automatically. Traditional data mining algorithms generally have problems and challenges including huge memory cost, low processing speed, and inadequate hard disk space. As a fundamental task of data mining, sequential pattern mining (SPM) is used in a wide variety of real-life applications. However, it is more complex and challenging than other pattern mining tasks, i.e., frequent itemset mining and association rule mining, and also suffers from the above challenges when handling the large-scale data. To solve these problems, mining sequential patterns in a parallel or distributed computing environment has emerged as an important issue with many applications. In this article, an in-depth survey of the current status of parallel SPM (PSPM) is investigated and provided, including detailed categorization of traditional serial SPM approaches, and state-of-the art PSPM. We review the related work of PSPM in details including partition-based algorithms for PSPM, apriori-based PSPM, pattern-growth-based PSPM, and hybrid algorithms for PSPM, and provide deep description (i.e., characteristics, advantages, disadvantages, and summarization) of these parallel approaches of PSPM. Some advanced topics for PSPM, including parallel quantitative/weighted/utility SPM, PSPM from uncertain data and stream data, hardware acceleration for PSPM, are further reviewed in details. Besides, we review and provide some well-known open-source software of PSPM. Finally, we summarize some challenges and opportunities of PSPM in the big data era.
Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases
Authors: Chaix Amandine , Manoogian Emily N.C. , Melkani Girish C. , Panda Satchidananda
Published: June 2019

Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity–rest and feeding–fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8–12 h. This paradigm has pervasive benefits on multiple organ systems.
Detection of Total Aflatoxins in Groundnut and Soybean Samples in Yemen Using Enzyme-Linked Immunosorbent Assay
Authors: Ahmed Abdullah Murshed Safwan , Bacha Nafees , Alharazi Talal
Published: June 2019

Aflatoxins are fungal toxins that have mutagenic and carcinogenic effects, especially hepatocellular carcinoma effect. This work aimed to investigate the presence of aflatoxins in groundnuts and soybeans that are consumed in Yemen. The samples were collected from three different regions in Yemen (Sana’a, al-Hodeida, and Aden), and they were divided into two groups. The concentration of total aflatoxins was analyzed by enzyme-linked immunosorbent assay (ELISA). Aflatoxins were determined in 89 groundnut and 65 soybean samples. The results showed that 85.39% (76/89) of groundnut and 72.3% (45/65) of soybean samples were contaminated with aflatoxins. In addition, in 49.44% and 27.6% of the groundnut and soybean samples, total aflatoxins exceed the acceptable level of European Commission (4 μg/kg), while in only 6.2% of soybean samples and 22.47% of groundnut samples, total aflatoxins were beyond the maximum limit of FDA/Yemen standards (20 μg/kg). The results showed that the aflatoxin contamination in the groundnut and soybean samples may be considered a significant risk for public health. The present study is the first to report the data on the presence of aflatoxins in groundnut and soybean samples in Yemen.
New Stability Criteria for Event‐Triggered Nonlinear Networked Control System with Time Delay
Authors: Lu Hongqian , Hu Yue , Guo Chaoqun , Zhou Wuneng
Published: June 2019

This note focuses on the stability and stabilization problem of nonlinear networked control system with time delay. To alleviate the burden of transformation channel and shorten the dynamic process simultaneously, an improved event‐triggered scheme is proposed. This paper employs an improved time delay method to enhance the performance and reduce the delay upper bound conservatism. Less conservative stability criteria related to the order N are derived by establishing an augmented Lyapunov‐Krasovskii functional manufactured for the use of Bessel‐Legendre inequality. In addition, an event‐triggered controller is designed for nonlinear networked control system with time delay. At last, numerical examples are proposed to verify the effectiveness of the new method.
Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo (Citrus grandisL. Osbeck) in Long Evan Rats
Authors: Ali Md. Yousuf , Rumpa Nur-E Noushin , Paul Sudip , Hossen Md. Sakib , Tanvir E. M. , Hossan Tareq , Saha Moumoni , Alam Nadia , Karim Nurul , Khalil Md. Ibrahim , Gan Siew Hua
Published: June 2019

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandisL. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%),γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli’s risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.
Recent Advances on Renewable and Biodegradable Cellulose Nanopaper Substrates for Transparent Light-Harvesting Devices: Interaction with Humid Environment
Authors: Operamolla Alessandra
Published: June 2019

Cellulose nanopaper (CNP) has attracted much interest during the last decade as a new fascinating renewable and biodegradable substrate for printed electronics and solar cells. Its outstanding optical and mechanical properties make CNP the ideal substrate for the preparation of photovoltaic devices, since its high transparency and haze favour the absorption of light from the active layer of the solar cell. However, some advances need to be done in the direction of increasing CNP stability in humid environment without compromising its remarkable advantages. This review critically points at these aspects, presenting an overview of state-of-art solutions to enhance nanopaper stability in a humid environment.
Inherent Geometry Correction for Diffusion EPI Using the Reference Echoes as Navigators
Authors: van den Brink Johan S. , Koonen Jos J.
Published: June 2019

Diffusion-weighted EPI has become an indispensable tool in body MRI. Geometric distortions due to field inhomogeneities are more prominent at large field–of–view and require correction for comparison with T2W TSE. Several known correction methods require acquisition of additional lengthy scans, which are difficult to apply in body imaging. We implement and evaluate a geometry correction method based on the already available non phase-encoded EPI reference data used for Nyquist ghost removal. The method is shown to provide accurate and robust global geometry correction in the absence of strong, local phase offsets. It does not require additional time for calibrations and is directly compatible with parallel imaging methods. The resulting images can serve as improved starting point for additional geometry correction methods relying on feature extraction and registration.
Decision Support Systems in Prostate Cancer Treatment: An Overview
Authors: van Wijk Y. , Halilaj I. , van Limbergen E. , Walsh S. , Lutgens L. , Lambin P. , Vanneste B. G. L.
Published: June 2019

Background. A multifactorial decision support system (mDSS) is a tool designed to improve the clinical decision-making process, while using clinical inputs for an individual patient to generate case-specific advice. The study provides an overview of the literature to analyze current available mDSS focused on prostate cancer (PCa), in order to better understand the availability of decision support tools as well as where the current literature is lacking. Methods. We performed a MEDLINE literature search in July 2018. We divided the included studies into different sections: diagnostic, which aids in detection or staging of PCa; treatment, supporting the decision between treatment modalities; and patient, which focusses on informing the patient. We manually screened and excluded studies that did not contain an mDSS concerning prostate cancer and study proposals. Results. Our search resulted in twelve diagnostic mDSS; six treatment mDSS; two patient mDSS; and eight papers that could improve mDSS. Conclusions. Diagnosis mDSS is well represented in the literature as well as treatment mDSS considering external-beam radiotherapy; however, there is a lack of mDSS for other treatment modalities. The development of patient decision aids is a new field of research, and few successes have been made for PCa patients. These tools can improve personalized medicine but need to overcome a number of difficulties to be successful and require more research.
Patients with Incompetent Valves in Chronic Venous Insufficiency Show Increased Systematic Lipid Peroxidation and Cellular Oxidative Stress Markers
Authors: Ortega Miguel A. , Romero Beatriz , Asúnsolo Ángel , Sola Mayte , Álavrez-Rocha María J. , Sainz Felipe , Álavrez-Mon Melchor , Buján Julia , García-Honduvilla Natalio
Published: June 2019

Chronic venous insufficiency (CVI) is a disease that impacts cellular homeostasis. CVI may occur with a valvular destruction process known as venous reflux or valvular incompetence. One of the cellular processes that may be triggered as a consequence of these events is the production of reactive oxygen species (ROS), which may trigger the production of different cellular markers and cell damage processes, such as lipid peroxidation. Therefore, the present study performed an observational, analytical, and prospective cohort study by reviewing 110 patients with CVI, and the activities and plasma levels of iNOS, eNOS, NOX1, and NOX2 were determined using immunohistochemistry and RT-qPCR. Lipid peroxidation (MDA) was also measured. Patients were distributed according to the presence or absence of valvular incompetence-venous reflux, which was diagnosed clinically as the absence of venous reflux (NR=29) or presence of venous reflux (R=81). Each group was divided according to age, with a cutoff point of fifty years (NR<50=13, NR≥50=16, R<50=32, and R≥50=49). The results showed that R patients exhibited significantly increased plasma MDA levels, and R<50 patients exhibited the highest statistically significant increase. iNOS, NOX1, and NOX2 exhibited the highest gene and protein expression in R patients. The increased expression was maintained in the R<50 patients. Our data suggest that young patients with valvular incompetence (venous reflux) show higher levels of lipid peroxidation and oxidative stress, which reflects the characteristics of an aged patient.
Successful Clearance of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia with Daptomycin, Linezolid, and Meropenem Salvage Therapy
Authors: Shaddix Grant , Patel Kalindi , Simmons Matthew , Burner Kelsie
Published: June 2019

Staphylococcus aureus is one of the most virulent Gram-positive organisms responsible for a multitude of infections, including bacteremia. Methicillin-resistant Staphylococcus aureus (MRSA) is of special concern in patients with bacteremia. Due to its associated poor clinical outcomes, morbidity, and mortality, the superlative salvage regimen for persistent MRSA bacteremia remains uncertain. An 85-year-old white female presented with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Empiric antibiotic therapy with linezolid was initiated prior to blood culture results. Once MRSA bacteremia was confirmed, alternative antibiotic therapy with daptomycin was initiated. Blood cultures remained positive for MRSA despite three days of daptomycin therapy after which ceftaroline was added to the antibiotic regimen. Blood cultures remained positive for MRSA despite seven days of combination therapy with daptomycin and ceftaroline. Salvage therapy was then initiated with daptomycin, linezolid, and meropenem. One day following initiation of salvage therapy, blood cultures revealed no bacterial growth for the remainder of the length of stay. This report supports the effectiveness of salvage therapy consisting of daptomycin, linezolid, and meropenem in patients with persistent MRSA bacteremia.
A Giant Primary Mediastinal Teratocarcinoma in a Male Adult
Authors: Al-Khalifa Muneera , Alsaad Sara , Al-Tareef Habib , Arekat Zaid , Darwish Abdulla
Published: June 2019

Germ cell tumors (GCTs) arise along the midline, in which 50-70% of extragonadal GCTs occur in the mediastinum. Malignant GCTs are more common in males, while benign GCTs occur equally in both males and females. This report presents a case of a giant primary mediastinal nonseminomatous GCT resected from a 35-year-old male who presented with dyspnoea and tightness in the chest. Thorough investigations including a chest MRI were done. It showed a 21×19×15 cm tumor. Thus, surgical resection of the tumor through a midline sternotomy was done. Histopathological analysis diagnosed the tumor as a primary mediastinal teratocarcinoma with a sarcomatous component. Eighteen-month follow-up showed no tumor recurrence. Mediastinal teratocarcinoma is a rare and life-threatening germ cell tumor. Studies recommend the use of chemotherapy prior to resection as an important step in its management. Close and regular follow-up postsurgical resection is advised.
TFAP4 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating the PI3K/AKT Signaling Pathway
Authors: Huang Tao , Chen Qi-Feng , Chang Bo-Yang , Shen Lu-Jun , Li Wang , Wu Pei-Hong , Fan Wei-Jun
Published: June 2019

Transcription factor activating enhancer binding protein 4 (TFAP4) is established as a regulator of human cancer genesis and progression. Overexpression of TFAP4 indicates poor prognosis in various malignancies. The current study was performed to quantify TFAP4 expression as well as to further determine its potential prognostic value and functional role in patients with hepatocellular carcinoma (HCC). We identified that the expression of TFAP4 mRNA in 369 tumor tissues was higher than that in 160 normal liver tissues. Upregulated TFAP4 expressions were discovered in HCC cell lines compared to the healthy liver cell line, and similarly, the levels of TFAP4 were higher in tumor tissues than its expression in paratumor tissues. High mRNA and protein expression of TFAP4 was associated with worse overall survival (OS) and disease-free survival (DFS). Additionally, TFAP4 expression emerged as a risk factor independently affecting both OS and DFS of HCC patients. Functional studies demonstrated that TFAP4 increased HCC cell migration and invasion. Further investigations found that TFAP4 promotes invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) and regulating MMP-9 expression via activating the PI3K/AKT signaling pathway in HCC. In conclusion, our study demonstrated that TFAP4 is a valuable prognostic biomarker in determining the likelihood of tumor metastasis and recurrence, as well as the long-term survival rates of HCC patients. Exploring the regulatory mechanism of TFAP4 will also contribute to the development of new prevention and treatment strategies for HCC.
Neutrophilic Dermatoses and Their Implication in Pathophysiology of Asthma and Other Respiratory Comorbidities: A Narrative Review
Authors: Salem Iman , Kimak Mark , Conic Rosalynn , Bragazzi Nicola L. , Watad Abdulla , Adawi Mohammad , Bridgewood Charlie , Pacifico Alessia , Santus Pierachille , Rizzi Maurizio , Petrou Stephen , Colombo Delia , Fiore Marco , Pigatto Paolo D. M. , Damiani Giovanni
Published: June 2019

Neutrophilic dermatoses (ND) are a polymorphous group of noncontagious dermatological disorders that share the common histological feature of a sterile cutaneous infiltration of mature neutrophils. Clinical manifestations can vary from nodules, pustules, and bulla to erosions and ulcerations. The etiopathogenesis of neutrophilic dermatoses has continuously evolved. Accumulating genetic, clinical, and histological evidence point to NDs being classified in the spectrum of autoinflammatory conditions. However, unlike the monogenic autoinflammatory syndromes where a clear multiple change in the inflammasome structure/function is demonstrated, NDs display several proinflammatory abnormalities, mainly driven by IL-1, IL-17, and tumor necrosis factor-alpha (TNF-a). Additionally, because of the frequent association with extracutaneous manifestations where neutrophils seem to play a crucial role, it was plausible also to consider NDs as a cutaneous presentation of a systemic neutrophilic condition. Neutrophilic dermatoses are more frequently recognized in association with respiratory disorders than by chance alone. The combination of the two, particularly in the context of their overlapping immune responses mediated primarily by neutrophils, raises the likelihood of a common neutrophilic systemic disease or an aberrant innate immunity disorder. Associated respiratory conditions can serve as a trigger or may develop or be exacerbated secondary to the uncontrolled skin disorder. Physicians should be aware of the possible pulmonary comorbidities and apply this knowledge in the three steps of patients’ management, work-up, diagnosis, and treatment. In this review, we attempt to unravel the pathophysiological mechanisms of this association and also present some evidence for the role of targeted therapy in the treatment of both conditions.
Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity
Authors: Paschke L. , Lincke T. , Mühlberg K. , Lindner Tom H. , Paschke R.
Published: June 2019

TKIs including anti-VEGF receptor activity have been approved for the treatment of patients with radioiodine resistant thyroid carcinomas. For lenvatinib arterial thromboembolic events are listed as adverse events of special interest with lenvatinib. In the phase III study, arterial thromboembolic events were reported in 3% of lenvatinib-treated patients and 1% in the placebo group. Most of the patients had predisposing factors. Only one myocardial infarct was reported in the lenvatinib phase III study. We report a 73-year-old female patient with metastatic thyroid papillary carcinoma who was treated with total thyroidectomy. The operation was followed by four radioiodine therapies over a period of 6 years. At 6 years she developed lung metastasis without radioiodine uptake, one solitary liver metastasis and one solitary right renal metastasis. One year after the first diagnosis of radioiodine resistant lung metastasis the lung metastasis showed progression according to RECIST criteria. This treatment was resulting in prolonged partial response with disappearance of a hepatic and renal metastasis. A myocardial infarction occurred after 39 months of lenvatinib treatment resulting in implantation of 3 stents and a two chamber pacemaker. The treatment was discontinued. Except for well controlled hypertension there were neither predisposing diseases like diabetes nor symptoms of cardiac ischemia on exertion. However, the family history for cardiovascular diseases was positive for cardiac infarction reported for one brother. Another brother was treated for hypertension and the patient’s mother suffered from a cerebral infarction at the age of 60. While only one myocardial infarct was reported in the lenvatinib phase III study with 392 patients this case suggests that long-term treatment with lenvatinib may be associated with an increased risk for myocardial infarct also in patients with no predisposing diseases except well controlled hypertension and positive family history for cardiovascular diseases.
High Concentration of Low-Density Lipoprotein Results in Disturbances in Mitochondrial Transcription and Functionality in Endothelial Cells
Authors: Gonnissen Stefanie , Ptok Johannes , Goy Christine , Jander Kirsten , Jakobs Philipp , Eckermann Olaf , Kaisers Wolfgang , von Ameln Florian , Timm Jörg , Ale-Agha Niloofar , Haendeler Judith , Schaal Heiner , Altschmied Joachim
Published: June 2019

Concentrations of low-density lipoprotein (LDL) above 0.8 mg/ml have been associated with increased risk for cardiovascular diseases and impaired endothelial functionality. Here, we demonstrate that high concentrations of LDL (1 mg/ml) decreased NOS3 protein and RNA levels in primary human endothelial cells. In addition, RNA sequencing data, in particular splice site usage analysis, showed a shift in NOS3 exon-exon junction reads towards those specifically assigned to nonfunctional transcript isoforms further diminishing the functional NOS3 levels. The reduction in NOS3 was accompanied by decreased migratory capacity, which depends on intact mitochondria and ATP formation. In line with these findings, we also observed a reduced ATP content. While mitochondrial mass was unaffected by high LDL, we found an increase in mitochondrial DNA copy number and mitochondrial RNA transcripts but decreased expression of nuclear genes coding for respiratory chain proteins. Therefore, high LDL treatment most likely results in an imbalance between respiratory chain complex proteins encoded in the mitochondria and in the nucleus resulting in impaired respiratory chain function explaining the reduction in ATP content. In conclusion, high LDL treatment leads to a decrease in active NOS3 and dysregulation of mitochondrial transcription, which is entailed by reduced ATP content and migratory capacity and thus, impairment of endothelial cell functionality.
A Robust Online Identification of Sustained Low Frequency Oscillation in Steady‐State Power Systems
Authors: Chu Zhaobi , Wang Yan , Zhu Min , Dong Xueping , Li Hua
Published: June 2019

For sustained low frequency oscillations in steady‐state power systems, an algorithm is proposed for precise online identification of oscillation frequency, oscillation amplitude, and fundamental amplitude. The algorithm consists of a robust low frequency estimator and a notch filter in parallel. The asymptotical convergence property is analyzed by slow integral manifold, averaging method, and Lyapunov stability theorem sequentially. The steady‐state antinoise property is investigated by perturbed system theorem. The robust advantages of the proposed algorithm are embodied in the following aspects: the fundamental amplitude identification is little influenced by oscillation frequency and oscillation amplitude, both oscillation frequency identification and oscillation amplitude identification have small steady‐state errors under high order harmonics or bounded noises, the ramp variations of both fundamental amplitude and oscillation amplitude are also significantly tracked, and three design parameters have different effects on identification performance of oscillation frequency, oscillation amplitude, and fundamental amplitude, respectively. Simulation results verify the validity.
Effect of Linearization in a WNT Signaling Model
Authors: Ciușdel C. F. , Coman S. , Boldișor Cr. , Kessler T. , Muradyan A. , Kovachev A. , Lehrach H. , Wierling C. , Itu L. M.
Published: June 2019

A nonlinear model consisting of a system of coupled ordinary differential equations (ODE), describing a biological process linked with cancer development, is linearized using Taylor series and tested against different magnitudes of input perturbations, in order to investigate the extent to which the linearization is accurate. The canonical wingless/integrated (WNT) signaling pathway is considered. The linearization procedure is described, and special considerations for linearization validity are analyzed. The analytical properties of nonlinear and linearized systems are studied, including aspects such as existence of steady state and initial value sensitivity. Linearization is a useful tool for speeding up drug response computations or for providing analytical answers to problems such as required drug concentrations. A Monte Carlo-based error testing workflow is employed to study the errors introduced by the linearization for different input conditions and parameter vectors. The deviations between the nonlinear and the linearized system were found to increase in a polynomial fashion w.r.t. the magnitude of tested perturbations. The linearized system closely followed the original one for perturbations of magnitude within 10% of the base input vector which yielded the state-space fixed point used for the linearization.
Effect of Bletilla striata on the Prevention of Postoperative Peritoneal Adhesions in Abrasion-Induced Rat Model
Authors: Liu BoTong , Zhang QiuHua , Wu Xiao , Fu YanJun , Wang Hui , Guan YunXia , Yang ShiCheng , Liu YiLan , Cao WenCong , Wang Jian
Published: June 2019

Postoperative peritoneal adhesions (PPAs) constitute a common complication of abdominal surgery with a high incidence. Bletilla striata (BS) is an important hemostatic drug used in China for nearly 2000 years. The purpose of this study was to investigate the effect of Bletilla striata on postoperative intestinal adhesion in rats. PPA was induced by cecal wall abrasion, and Bletilla striata was injected to observe its effect on adhesion in rats. The adhesion and inflammation score were assessed through visual observation and histopathologic evaluation. The levels of interleukin-1 (IL-1β), tumor necrosis factor (TNF-α), and interleukin-17F (IL-17F) in abdominal cavity and interleukin-6 (IL-6) in plasma were measured by enzyme-linked immunosorbent assay (ELISA) at 6 hours, 12 hours, 24 hours, and 1 week after operation. The tissue level of transforming growth factor beta-1 (TGF-β1) was also determined by ELISA on the seventh day after surgery. The expressions of collagen and TNF-α were, respectively, detected by Masson trichrome staining and immunohistochemical staining. The expression of TGF-β1 and alpha smooth muscle actin (α-SMA) was detected by Western blot. The result showed that Bletilla striata has obvious preventive effect on PPAs and celiac inflammation of PPAs. Bletilla striata could significantly reduce the level of IL-17F abdominal cavity and IL-6 in plasma. Masson trichrome staining and immunohistochemical staining results showed that Bletilla striata also decreased the expression of TNF-α and collagen. Western blot results showed that Bletilla striata decreased the expression of α-SMA and TGF-β1. Our results suggest that Bletilla striata decreased the development of abdominal adhesion in abrasion-induced model of rats and reduced the expression of the important substance which increased in PPAs. Bletilla striata can be further studied as a new and cheaper antiadhesive substance.
Analysis of Nutritional Quality of Black Fungus Cultivated with Corn Stalks
Authors: Yao Hongwei , Liu Yang , Ma Zheng Feei , Zhang Hongxia , Fu Tingting , Li Zunqiang , Li Yuanjing , Hu Wei , Han Shuchang , Zhao Fengchen , Wu Hongjun , Zhang Xueyi
Published: June 2019

Black fungus is a homologous fungus of medicine and food. Its nutrient content determines the health value, and the accumulation of nutrients is easily affected by the substitute materials. The aim of this study was to analyze the effect of corn stalks as a cultivation substitution material for sawdust on macronutrients, micronutrients, and functional components of black fungus. The results reported that corn stalks could significantly increase the content of ash, protein, copper, and iron in black fungus, but reduce the content of zinc, magnesium, manganese, and colloidal substances; corn stalks had less effect on melanin and polyphenols; its effect on water, total sugar, reducing sugar, crude fiber, and total flavonoids was insignificant. Therefore, the study provided a theoretical basis for the cultivation of black fungus with corn stalks.
The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents
Authors: Spriano Filippo , Chung Elaine Yee Lin , Gaudio Eugenio , Tarantelli Chiara , Cascione Luciano , Napoli Sara , Jessen Katti , Carrassa Laura , Priebe Valdemar , Sartori Giulio , Graham Garrett , Selvanathan Saravana P. , Cavalli Andrea , Rinaldi Andrea , Kwee Ivo , Testoni Monica , Genini Davide , Ye B. Hilda , Zucca Emanuele , Stathis Anastasios , Lannutti Brian , Toretsky Jeffrey A. , Bertoni Francesco
Published: June 2019

Purpose:

Transcription factors are commonly deregulated in cancer, and they have been widely considered as difficult to target due to their nonenzymatic mechanism of action. Altered expression levels of members of the ETS-transcription factors are often observed in many different tumors, including lymphomas. Here, we characterized two small molecules, YK-4-279 and its clinical derivative, TK-216, targeting ETS factors via blocking the protein–protein interaction with RNA helicases, for their antilymphoma activity.

Experimental Design:

The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination; validation experiments on in vivo models; and transcriptome and coimmunoprecipitation experiments.

Results:

YK-4-279 and TK-216 demonstrated an antitumor activity across several lymphoma cell lines, which we validated in vivo. We observed synergistic activity when YK-4-279 and TK-216 were combined with the BCL2 inhibitor venetoclax and with the immunomodulatory drug lenalidomide. YK-4-279 and TK-216 interfere with protein interactions of ETS family members SPIB, in activated B-cell–like type diffuse large B-cell lymphomas, and SPI1, in germinal center B-cell–type diffuse large B-cell lymphomas.

Conclusions:

The ETS inhibitor YK-4-279 and its clinical derivative TK-216 represent a new class of agents with in vitro and in vivo antitumor activity in lymphomas. Although their detailed mechanism of action needs to be fully defined, in DLBCL they might act by targeting subtype-specific essential transcription factors.
Clinical and Angiographic Outcomes With a Novel Radiopaque Sirolimus-Eluting Bioresorbable Vascular Scaffold
Authors: Chevalier Bernard , Abizaid Alexandre , Carrié Didier , Frey Norbert , Lutz Matthias , Weber-Albers Joachim , Dudek Darius , Weng Shu-Chuan , Akodad Mariama , Anderson Jeffrey , Stone Gregg W. ,   on behalf of the FANTOM II Clinical Investigators
Published: June 2019

Background:

A novel bioresorbable scaffold, the sirolimus-eluting Fantom, incorporates a radiopaque polymer, struts with a thickness of 125 µm, and a crossing profile of 1.35 mm. The purpose of this study was to evaluate the 9-month angiographic and 12-month clinical outcomes of the FANTOM scaffold in a larger patient population.

Methods and Results:

The FANTOM II study (Safety & Performance Study of the Fantom Sirolimus-Eluting Bioresorbable Coronary Scaffold – First Report on Initial 24 Month Outcomes) was a prospective, multicenter trial which enrolled 240 patients with single de novo coronary stenosis with reference vessel diameter 2.5 to 3.5 mm diameter and lesion length ≤20 mm. Major adverse cardiac events through 12-month follow-up were assessed. Angiographic follow-up was performed in consecutive patient cohorts at 6 months (n=117) and 9 months (n=123). Acute delivery success, acute technical success, acute procedural success, and clinical procedural success rates as defined in the clinical protocol were 97.9% (235/240), 95.8% (230/240), 99.1% (228/230), and 99.6% (227/228), respectively. The mean in-stent late lumen loss at 6 months and 9 months were 0.25±0.40 mm and 0.33±0.36 mm, respectively, and in-segment binary restenosis occurred in 2.0% and 7.6% of patients, respectively. Major adverse cardiac events and target lesion failure through 12 months occurred in 4.2% of 240 patients; scaffold thrombosis developed in only one patient (0.4%).

Conclusions:

The Fantom sirolimus-eluting bioresorbable coronary scaffold demonstrated favorable safety and effectiveness performance at 12-month follow-up. Longer-term follow-up is ongoing to examine the late outcomes with this novel device.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02539966.
Antipsychotic Use Among 1144 Patients After Aneurysmal Subarachnoid Hemorrhage
Authors: Paavola Juho T. , Väntti Nelli , Junkkari Antti , Huttunen Terhi J. , von und zu Fraunberg Mikael , Koivisto Timo , Kämäräinen Olli-Pekka , Lång Maarit , Meretoja Atte , Räikkönen Katri , Viinamäki Heimo , Jääskeläinen Juha E. , Huttunen Jukka , Lindgren Antti E.
Published: June 2019

Background and Purpose—

At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population–based cohort with long-term follow-up.

Methods—

We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data.

Results—

In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use.

Conclusions—

The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.
Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials
Authors: Godolphin Peter J. , Bath Philip M. , Algra Ale , Berge Eivind , Brown Martin M. , Chalmers John , Duley Lelia , Eliasziw Misha , Gregson John , Greving Jacoba P. , Hankey Graeme J. , Hosomi Naohisa , Johnston S. Claiborne , Patsko Emily , Ranta Annamarei , Sandset Per Morten , Serena Joaquín , Weimar Christian , Montgomery Alan A. , Knipp S.C. , Giugliano R.P. , Bonati L.H. , Nagai Y. , Matsumoto M. , Barnett H.J.M. , Fox A.J. , Farrant M. , Easton J.D. , Elm J.J. , Neal B. , Arima H. , Dávalos A. , Amarenco P. , Evans S. , Sprigg N. , Dineen R. , Eikelboom J.W. , Chen C.
Published: June 2019

Background and Purpose—

In randomized stroke trials, central adjudication of a trial’s primary outcome is regularly implemented. However, recent evidence questions the importance of central adjudication in randomized trials. The aim of this review was to compare outcomes assessed by central adjudicators with outcomes assessed by site investigators.

Methods—

We included randomized stroke trials where the primary outcome had undergone an assessment by site investigators and central adjudicators. We searched MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, and Google Scholar for eligible studies. We extracted information about the adjudication process as well as the treatment effect for the primary outcome, assessed both by central adjudicators and by site investigators. We calculated the ratio of these treatment effects so that a ratio of these treatment effects >1 indicated that central adjudication resulted in a more beneficial treatment effect than assessment by the site investigator. A random-effects meta-analysis model was fitted to estimate a pooled effect.

Results—

Fifteen trials, comprising 69 560 participants, were included. The primary outcomes included were stroke (8/15, 53%), a composite event including stroke (6/15, 40%) and functional outcome after stroke measured on the modified Rankin Scale (1/15, 7%). The majority of site investigators were blind to treatment allocation (9/15, 60%). On average, there was no difference in treatment effect estimates based on data from central adjudicators and site investigators (pooled ratio of these treatment effects=1.02; 95% CI, [0.95–1.09]).

Conclusions—

We found no evidence that central adjudication of the primary outcome in stroke trials had any impact on trial conclusions. This suggests that potential advantages of central adjudication may not outweigh cost and time disadvantages in stroke studies if the primary purpose of adjudication is to ensure validity of trial findings.
Circulating Multiple Metals and Incident Stroke in Chinese Adults
Authors: Xiao Yang , Yuan Yu , Liu Yiyi , Yu Yanqiu , Jia Ningning , Zhou Lue , Wang Hao , Huang Suli , Zhang Yanwei , Yang Handong , Li Xiulou , Hu Frank B. , Liang Liming , Pan An , Zhang Xiaomin , He Meian , Cheng Jinquan , Wu Tangchun
Published: June 2019

Background and Purpose—

Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke.

Methods—

We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model.

Results—

The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13–1.46], 1.19 [95% CI, 1.05–1.35], and 1.30 [95% CI, 1.07–1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50–0.87] and 0.68 [95% CI, 0.51–0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20–1.56] and 1.53 [95% CI, 1.16–2.01]).

Conclusions—

Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.
Polystachya danielana (Orchidaceae: Polystachyinae), a new species from Kenya
Authors: TIAN JING , HUANG WEI-CHANG , MBUNI YUVENALIS MORARA , KAMAU PERIS , MWACHALA GEOFFREY , MALOMBE ITAMBO , HU GUANG-WAN , WANG QING-FENG
Published: June 2019

Polystachya danielana, a new species from Kenya based on evidence from morphology and molecular phylogenetics is described and illustrated here. It is closely related to P. spatella and P. kermesina, but distinguished from these two species mainly by its pseudobulbs mostly arising from the nodes near the base of the previous growth with only a few from the middle or upper nodes, leaves narrowly oblong or narrowly obovate-lanceolate, 2–8 × 1–2 cm, bracts oblong, ca. 4 × 3 mm, apex emarginate with a caudate tip, ovary purple, dorsal sepal subovate, 5.0–7.0 × 3.0–4.5 mm, column ca. 2 mm long. Its position in P. sect. Superpositae is discussed.
A new species of Dollfusentis Golvan, 1969 (Palaeacanthocephala: Illiosentidae) in the striped mojara, Eugerres plumieri (Perciformes: Actinoptergii), from Bahia de Chetumal, Quintana Roo, Mexico
Authors: MONKS SCOTT , ALEMÁN-GARCÍA BERENICE , PULIDO-FLORES GRISELDA
Published: June 2019

A new species, Dollfusentis salgadoi n. sp., is described from Eugerres plumieri, Bahía de Chetumal, Quintana Roo, México. The new species is most similar to D. bravoae, but has 17–19 hooks per longitudinal row on the proboscis (excluding the ventral crescent), longer lemnisci (2250±391, n=44), testes that are longer and wider (322±38, n= 25 long and 176±29, n= 25 wide), and a uterine bell that is smaller (289±61, n= 23 long and 80±24, n= 23 wide). Dollfusentis bravoae has 16–17 hooks per longitudinal row on the proboscis, shorter lemnisci (2015±516, n=9), testes that are shorter and not as wide (218±46, n= 6 long and 136±24, n= 6), and a uterine bell that is larger (321±64, n= 4 long and 78±33, n= 4 wide). Adults of all other known species of the genus inhabit the intestine of their host, but adults of D. salgadoi n. sp. inhabit the rectum of its host.
New Venezuelan genus of Hubardiidae (Arachnida: Schizomida)
Authors: MANZANILLA OSVALDO VILLARREAL , DE LEÃO GIUPPONI ALESSANDRO PONCE , TOURINHO ANA LÚCIA
Published: June 2019

A new Amazonian genus and species of Schizomida is described from Tobogán de la Selva, Amazonas state in Venezuela. Piaroa virichaj n. gen. and n. sp is the seventh species of the order described for Venezuela. Piaroa virichaj gen. and n. sp. is distinguished by having the metapeltidium entire; abdominal segment IX – XII elongated in the male; male without posterodorsal abdominal process on segment XII; male flagellum flattened dorsoventrally, very elongated, with two small dorsomedian depressions; pedipalps not sexually dimorphic; spermathecae with lateral lobes slender and curved, with the base swollen, ending in slightly trifid bulbs; medial lobes absent; gonopod absent. The locality where the species was collected is shown in a map, a discussion on the taxonomic characters of the new genus and species, the relationships of the new genus and the interrelationship of some species in Hubardiidae are provided.
Pupal cases of Nearctic robber flies (Diptera: Asilidae)
Authors: DENNIS D. STEVE , BARNES JEFFREY K. , KNUTSON LLOYD
Published: June 2019

The literature on robber fly pupae published primarily since 1972 is reviewed. Terminology used in morphological descriptions of pupal cases is compared and standardized, and some new terminology is used. A general description of asilid pupal cases is presented. Diagnostically useful characters are identified, and a consistent format for descriptions is presented. Pupal cases of 24 species are described for the first time, those of 13 species are redescribed, and additional comments are made on the pupal cases of 12 other species. Keys to species, genera, and higher categories are presented. Asilus lecythus Walker is transferred to the genus Machimus (new combination).