bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitral valve papillary fibroelastoma as a cause of acute coronary syndrome
Authors: Gonçalves Mariana , Tralhão António , Trabulo Marisa , Madeira Márcio
Published: December 2018

A 37-year-old man presented with acute chest pain, an unremarkable ECG and mildly elevated cardiac troponin. Coronary CT angiography showed a calcium score of 0 together with the absence of atherosclerotic plaques and normal origin and course of the coronary arteries. Transthoracic and transoesophageal echocardiography revealed an infracentimetric round-shaped mobile mass attached to a secondary tendinous chord of the anterior mitral valve leaflet. Cardiac magnetic resonance further evidenced localised contrast uptake supporting vascular irrigation, making thrombus unlikely. After surgical excision, the patient had an uneventful postoperative course. Histopathology disclosed the typical collagenous matrix covered by a single cell layer. Although mostly benign, cardiac tumours are prone to embolisation and can thus mimic an acute coronary syndrome. Multimodality imaging has an important role in unmasking the true mechanism, revealing less common aetiologies and elucidating the possibility of curative surgical resection.
Meropenem-induced liver injury and beta-lactam cross-reactivity
Authors: Tattersall Timothy , Wright Hugh , Redmond Andrew
Published: December 2018

A 63-year-old man admitted to hospital for the management of a frontal lobe abscess developed elevated liver enzymes within 48 hours of receiving meropenem. Liver enzymes reached a maximum at 5 days postadministration of meropenem, with alanine aminotransferase 1160 U/L, aspartate aminotransferase 787 U/L, alkaline phosphatase 297 U/L and gamma-glutamyltransferase 252 U/L. Meropenem was ceased and liver function normalised. Meropenem was administered for a second time later in the patient’s admission and again the patient developed rapidly increasing liver enzymes, with a mixed hepatocellular/cholestatic pattern. Other possible causes of liver injury were excluded following extensive investigations, and the patient’s liver enzymes continued to normalise following meropenem discontinuation. The patient was asymptomatic during the admission and was transferred to a rehabilitation facility. This case demonstrates that meropenem can cause severe liver injury and that early recognition of drug-induced liver injury is important.
Acute retinal necrosis (ARN) following chickenpox in a patient of Vogt-Koyanagi-Harada (VKH) syndrome using immunosuppressants
Authors: Gupta Rajan , Tyagi Mudit , Balakrishnan Divya , Rani Padmaja Kumari
Published: December 2018

A 36-year-old woman presented with diminution of vision and floaters in both the eyes. Both eyes had disc oedema, multiple pockets of neurosensory detachments along with vitritis. Fluorescein angiography and optical coherence tomography showed characteristic features of Vogt-Koyanagi-Harada (VKH) syndrome (figure 1). She was started on corticosteroid pulse therapy and immunosuppressants following which her VKH lesions resolved. However, she developed chickenpox after 2 weeks and after 1 month she developed discrete yellowish white retinitis patches in the periphery of the right eye which were consistent with a diagnosis of acute retinal necrosis. She was started on oral antivirals for the same and immunosuppressants were withheld in view of immunocompromised state potentially acting as a trigger for reactivation of latent virus. Retinitis patches started to resolve and showed a favourable response to the treatment.
Anaphylaxis after treatment with recombinant factor VIII: investigation and therapeutic challenge
Authors: Pires Sofia , Sevivas Teresa , Loureiro Carla Chaves , Bartholomé Borja
Published: December 2018

We report a 10-year-old patient with haemophilia A developing anaphylaxis to recombinant factor VIII (octocog alfa). Allergic reactions, and especially anaphylactic events, are rare in patients with haemophilia A. The nature of these reactions is not fully understood. Here, we demonstrate a type I hypersensitivity reaction using sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting assay. This test revealed itself as an essential diagnostic tool, as it allowed us to choose an alternative treatment (moroctocog alfa). Its safety was later confirmed by an uneventful challenge test.
Prescribing lessons from an ocular chemical injury: Vitaros inadvertently dispensed instead of VitA-POS
Authors: Edington Magdalena , Connolly Julie , Lockington David
Published: December 2018

We wish to report an ocular chemical injury caused by inadvertent dispensing and administration of an erectile dysfunction cream (Vitaros) instead of an ocular lubricant (VitA-POS) to highlight this potential source of error. Prescribing errors are common, and medications with similar names/packaging increase risk. However, it is unusual in this case that no individual (including the patient, general practitioner or dispensing pharmacist) questioned erectile dysfunction cream being prescribed to a female patient, with ocular application instructions. The patient was treated for a mild ocular chemical injury with topical antibiotics, steroids and lubricants, with good response. However, we believe this to be an important issue to report to enhance awareness and promote safe prescribing skills.
Neck–tongue syndrome
Authors: Chu Eric Chun Pu , Lin Andy Fu Chieh
Published: December 2018

Neck–tongue syndrome (NTS) is a rarely reported disorder characterised by paroxysmal episodes of intense pain in the upper cervical or occipital areas associated with ipsilateral hemiglossal dysaesthesia brought about by sudden neck movement. The most likely cause of this clinical entity is a temporary subluxation of the lateral atlantoaxial joint with impaction of the C2 ventral ramus against the articular processes on head rotation. NTS is an under-recognised condition that can be debilitating for patients and challenging for the treating physicians. Here, we report a 47-year-old man who fulfilled the International Classification of Headache Disorders, third edition criteria for a diagnosis of NTS was treated successfully with a chiropractic approach. There are currently no consensus guidelines for dealing with this disorder. Reassuringly, chiropractic care for uncomplicated NTS appears highly effective.
Multiple cystic lung lesions and autoimmune thrombocytopaenia developing after chemotherapy for pulmonary indolent B-cell lymphoma with plasmacytic differentiation
Authors: Tanaka Hiroaki , Kuwabara Chihiro , Isshiki Yusuke , Suzuki Yoshio
Published: December 2018

Among lung malignancies, primary pulmonary lymphoma is rare and many of them are indolent B-cell lymphomas. We describe a case of primary pulmonary indolent B-cell lymphoma with plasmacytic differentiation, which exacerbated with the manifestation of macroglobulinaemia and was successfully treated using chemotherapy. The patient subsequently developed pulmonary cysts and thrombocytopaenia due to autoimmune pathology and was successfully treated using prednisolone. This case suggests that in indolent B-cell lymphoma with plasmacytic differentiation, immunoglobulin M level should be carefully followed even if it is within the normal range at lymphoma onset. Additionally, new cystic pulmonary infiltrates that develop during the post-treatment follow-up of an indolent pulmonary B-cell lymphoma may indicate pulmonary lymphoma recurrence, but there is also a possibility of an immunological complication.
Ethical issues in nursing home palliative care: a cross-national survey
Authors: Muldrew Deborah H. L. , Kaasalainen Sharon , McLaughlin Dorry , Brazil Kevin
Published: December 2018

Objectives

With an increased dependency on nursing homes to provide care to the ageing population, it is likely that ethical issues will also increase. This study aimed to identify the type of ethical issues and level of associated distress experienced by nurses providing palliative care in nursing homes in the UK and Canada, and pilot the Ethical issues in Palliative Care for Nursing Homes (EPiCNH) instrument in Canada.

Methods

A cross-sectional survey design was used. One hundred and twenty-three nurses located in 21 nursing homes across the UK and Canada completed the EPiCNH instrument.

Results

Frequent ethical issues include upholding resident autonomy, managing family distress, lack of staff communication and lack of time in both countries. Higher levels of distress resulted from poor communication, insufficient training, lack of time and family disagreements. Nurses in Canada experienced a greater frequency of ethical issues (p=0.022); however, there was no statistical difference in reported distress levels (p=0.53). The survey was positively rated for ease of completion, relevance and comprehensiveness.

Conclusions

Nurses’ reported comparable experiences of providing palliative care in UK and Canadian nursing homes. These findings have implications on the practice of care in nursing homes, including how care is organised as well as capacity of staff to care for residents at the end of life. Training staff to take account of patient and family values during decision-making may address many ethical issues, in line with global policy recommendations. The EPiCNH instrument has demonstrated international relevance and applicability.
Dietary flaxseed: what we know and don’t know about its effects on cardiovascular disease
Authors: Parikh Mihir , Pierce Grant N.
Published: December 2018

Flaxseed (Linum usitatissimum) is composed of a unique combination of bioactive components that appear to generate, through either an isolated or a synergistic action, a significant beneficial effect on the cardiovascular system. With a significant increase in the generation of data on the dietary impact of flaxseed on the cardiovascular system, a review of where we stand — what we know and what we still need to understand about these effects on the heart and the vasculature — was thought to be of value and the rationale for this paper. For example, although we now know how to deliver the bioactives most efficiently (oil versus ground seed versus whole seed), we do not know how different foods can influence that delivery. Further, we know flaxseed has anti-arrhythmic, anti-atherogenic, anti-hypertensive, and cholesterol-lowering actions in animal studies and some selected human trials but much more needs to be learned, particularly in human trials. These results have justified further commitment of resources to the initiation of human trials. Because of the impact of nutrition on many chronic diseases, this may not only be true for the effects of flaxseed on cardiovascular disease but may be just as relevant for many other disease conditions.
Molecular evidence for multiple introductions of the banded grove snail (Cepaea nemoralis) in North America
Authors: Layton K.K.S. , Warne C.P.K. , Nicolai A. , Ansart A. , deWaard J.R.
Published: December 2018

Global identification and monitoring programs for invasive species aim to reduce imminent impacts to biodiversity, ecosystem services, agriculture, and human health. This study employs a 658 base pair fragment of the cytochrome c oxidase subunit I (COI) gene to identify and categorize clades of the banded grove snail (Cepaea nemoralis (Linnaeus, 1758)) from native (European) and introduced (North American) ranges using a maximum-likelihood phylogeny and haplotype networks. This work corroborates the existence of eight clades within C. nemoralis and further identified three clades that were common to both Europe and North America (A, D, O). Clades A and D were found in eastern Canada, Ontario (Canada), and British Columbia (Canada), whereas clade O was restricted to Ontario, possibly introduced from Poland or central Europe. Haplotype networks suggest clade A was introduced from northern Europe, whereas clade D was introduced from western and central Europe. Networks contained many private haplotypes and a lack of haplotype sharing, suggesting strong genetic structure in this system, possibly resulting from reduced dispersal in this species. This study describes the contemporary distribution of C. nemoralis in Canada and demonstrates the efficacy of DNA barcoding for monitoring the spread of invasive species, warranting its widespread adoption in management policies.
Analytic approximations in GR and gravitational waves
Authors: Blanchet Luc
Published: December 2018

Analytic approximation methods in general relativity play a very important role when analyzing the gravitational wave signals recently discovered by the LIGO and Virgo detectors. In this contribution, we present the state of the art and some recent developments in the famous post-Newtonian (PN) or slow-motion approximation, which has successfully computed the equations of motion and the early inspiral phase of compact binary systems. We discuss also some interesting interfaces between the PN and the gravitational self-force (GSF) approach based on black-hole perturbation theory, and between PN and the post-Minkowskian (PM) approximation, namely a nonlinearity expansion valid for weak field and possibly fast-moving sources.
A New Non-Parametric Subspace-Based Approach for Unit Root Test
Authors: Farahikia Mehran , Yarmohammadi Masoud , Hassani Hossein
Published: December 2018

A new non-parametric subspace-based approach is introduced for unit root test in AR(1) process. The proposed approach contains block-bootstrap and spectrum properties of a time series as well as statistical testing methodology. The simulation result validates the proposed test and indicates its superiority compared with other existent procedures.
Quantum distance-based classifier with distributed knowledge and state recycling
Authors: Sadowski Przemysław
Published: December 2018

In this work, we examine a recently proposed distance-based classification method designed for near-term quantum processing units with limited resources. We study possibilities to reduce the quantum resources without any efficiency decrease. We show that only a part of the information undergoes coherent evolution and this fact allows us to introduce an algorithm with significantly reduced quantum system size requirements. Additionally, considering only partial information at a time, we propose a classification protocol with information distributed among a number of agents. Finally, we show that the information evolution during a measurement can lead to a better solution and that the accuracy of the algorithm can be improved by harnessing the state after the final measurement.
GOLAP: Graph-Based Online Analytical Processing
Authors: Chou Chung-Hsien , Hayakawa Masahiro , Kitazawa Atsushi , Sheu Phillip
Published: December 2018

Graph-based Online Analytical Processing (GOLAP) extends Online Analytical Processing (OLAP) to address graph-based problems that involve object attributes. Based on graph data, GOLAP can answer user queries related to combinatorial optimization, structural analytics, and influence analytics. Besides, since a GOLAP system is an online interactive system that requires fast response time, the execution time for graph-problem queries is essentially critical. Thus, how to speed up the execution time of specific graph problems becomes a challenge in GOLAP. In this paper, we show several methods to speed up the running time, including graph data reduction and approximation. In this paper, we survey classes of graph-based queries, challenges for GOLAP, and solutions that GOLAP provides.
A Modified Artificial Bee Colony Algorithm with Firefly Algorithm Strategy for Continuous Optimization Problems
Authors: Panniem Amnat , Puphasuk Pikul
Published: December 2018

Artificial Bee Colony (ABC) algorithm is one of the efficient nature-inspired optimization algorithms for solving continuous problems. It has no sensitive control parameters and has been shown to be competitive with other well-known algorithms. However, the slow convergence, premature convergence, and being trapped within the local solutions may occur during the search. In this paper, we propose a new Modified Artificial Bee Colony (MABC) algorithm to overcome these problems. All phases of ABC are determined for improving the exploration and exploitation processes. We use a new search equation in employed bee phase, increase the probabilities for onlooker bees to find better positions, and replace some worst positions by the new ones in onlooker bee phase. Moreover, we use the Firefly algorithm strategy to generate a new position replacing an unupdated position in scout bee phase. Its performance is tested on selected benchmark functions. Experimental results show that MABC is more effective than ABC and some other modifications of ABC.
Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise
Authors: Liu Wenfeng , Li Li , Kuang Heyu , Xia Yan , Wang Zhiyuan , Liu Shaopeng , Yin Dazhong
Published: December 2018

To research carbonylated proteins and screen molecular targets in the rat striatum on regular aerobic exercise, male Sprague-Dawley rats (13 months old, n = 24) were randomly divided into middle-aged sedentary control (M-SED) and aerobic exercise (M-EX) groups (n = 12 each). Maximum oxygen consumption (VO2max) gradually increased from 50%–55% to 65%–70% for a total of 10 weeks. A total of 36 carbonylated proteins with modified oxidative sites were identified by Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometer (ESI-Q-TOF-MS), including 17 carbonylated proteins unique to the M-SED group, calcium/calmodulin-dependent protein kinase type II subunit beta (CaMKIIβ), and heterogeneous nuclear ribonucleoprotein A2/B1 (Hnrnpa2b1), among others, and 19 specific to the M-EX group, ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), and malic enzyme, among others. Regular aerobic exercise improved behavioral and stereological indicators, promoted normal apoptosis (P < 0.01), alleviated carbonylation of the CaMKIIβ and Hnrnpa2b1, but induced carbonylation of the UCH-L1, and significantly upregulated the expression levels of CaMKIIβ, CaMKIIα, and Vdac1 (p < 0.01) and Hnrnpa2b1 and UCH-L1 (p < 0.01), as well as the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways (PI3K/Akt/mTOR) pathway-related genes Akt and mTOR. Regular aerobic exercise for 10 weeks (incremental for the first 6 weeks followed by constant loading for 4 weeks) enhanced carbonylation of CaMKIIβ, Hnrnpa2b1, and modulated apoptosis via activation of CaMK and phosphoinositide 3-kinase/protein kinase B/mTOR signaling. It also promoted normal apoptosis in the rat striatum, which may have protective effects in neurons.
A Unique Conjunction: Evidence for Gynogenesis Accompanying Haplodiploid Sex Determination in the Australian Ant Myrmecia impaternata Taylor
Authors: Taylor Robert W. , Imai Hirotami T. , Hasegawa Eisuke , Beaton Colin D.
Published: December 2018

Myrmecia impaternata is an allodiploid all-female species of hybrid origin. Its parental taxa are confirmed here to be M. banksi and M. pilosula. We suggest that its queens produce diploid female offspring by gynogenetic parthenogenesis, a process which requires interaction between unreduced maternal oocytes and allospecific sperm cells obtained by copulation with another related species. We propose that impaternata queens almost certainly mate for this purpose with males reared in impaternata nests from eggs laid by impaternata females. Because sex in ants is determined by haplodiploidy (males haploid, females diploid), we posit that these males would in fact not be technically conspecific with the females in whose reproductive systems they developed, since they would each carry the haploid genome of one or other of the hybridic parental species. They would therefore be individually identical karyologically to males of either M. banksi or M. pilosula and appropriately allospecific to M. impaternata. We postulate that, unlike all other known gynogens, M. impaternata would have no need to maintain parasitic affiliation or sympatry with free-living sperm-donor host species. Its queens are arguably able to produce the required allospecific males by accessing their own genomes. M. impaternata apparently originated by instantaneous speciation when individuals of its parental species first successfully hybridized.
Multiple Injuries to the Lower Urinary Tract: Two Cases and Comparison with the EAU Guidelines
Authors: Lumen N. , Sharma D. , Abu-Ghanem Y. , Djakovic N. , Kuehhas F. , Serafetinidis E. , Sujenthiran A. , Waterloos M. , Hallscheidt P. , Kitrey N. D.
Published: December 2018

Blunt trauma to the lower urinary tract is usually associated with pelvic fractures. The European Association of Urology (EAU) provides guidelines to diagnose and treat these injuries. The guidelines summarise the available evidence and provide recommendations on diagnosis and treatment of these patients. Therefore, these guidelines are important adjuncts to the urologist and emergency physician in the clinical decision-making. However, strict adherence to the guidelines is not always easy or possible because of concomitant injuries obscuring the clinical picture. This is illustrated by two case reports of concomitant injuries of the lower urinary tract (bladder with urethral injury). The clinical decisions will be discussed point by point and should serve as a practical teaching moment for the reader.
Pharmacokinetics of Eight Flavonoids in Rats Assayed by UPLC-MS/MS after Oral Administration of Drynariae rhizoma Extract
Authors: Xu Zhan-Ling , Xu Ming-Yue , Wang Hai-Tao , Xu Qing-Xuan , Liu Ming-Yang , Jia Chun-Peng , Geng Fang , Zhang Ning
Published: December 2018

As a traditional Chinese medicine, Drynariae rhizoma (Kunze ex Mett.) J. Sm. has been used to treat osteoporosis and bone resorption for 2500 years. Based on the previous study and literature references, flavonoids were proved to be the most abundant and main active compounds of Drynariae rhizoma for osteoporosis treatment. In order to make good and rational use of Drynariae rhizoma in future, a rapid, sensitive, and selective ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics of eight main flavonoids in rat plasma after oral administration of the Drynariae rhizoma extract, including neoeriocitrin, luteolin-7-O-β-D-glucoside, astragalin, naringin, eriodictyol, luteolin, naringenin, and kaempferol. Plasma samples’ pretreatment involved a solid-phase extraction column. The separation was performed on an ACQUITY UPLCTM BEH C18 column with a gradient mobile-phase system of acetonitrile and 1% acetic acid in water. The detection was performed using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface (ESI) by multiple reaction monitoring (MRM) in the positive ion mode. All calibration curves exhibited good linearity (r2 > 0.9990) over the measured ranges. The intraday and interday precisions (RSD) were within 13.87%, and the accuracy (RE) ranged from −14.57% to −0.25% at three quality control levels. Extraction recovery, matrix effect, and stability were satisfactory. The pharmacokinetic characteristics of the eight flavonoids of interest were clearly elucidated.
Evaluation of Chickpea Varieties and Fungicides for the Management of Chickpea Fusarium Wilt Disease (Fusarium oxysporum f.sp. ciceris) at Adet Sick Plot in Northwest Ethiopia
Authors: Mengist Yigrem , Sahile Samuel , Sintayehu Assefa , Singh Sanjay
Published: December 2018

A 2-year experiment was conducted at wilt sick plot infested with natural occurring Fusarium oxysporum f.sp. ciceris at Adet Agricultural Research Center in northwestern Ethiopia with an aim to evaluate effective chickpea varieties and fungicides for the management of chickpea fusarium wilt in order to integrate chickpea varieties and fungicides. Four varieties, namely, Shasho, Arerti, Marye, and local, two fungicides, namely, Apron Star and mancozeb, and untreated local chickpea were used as treatments. Treatments were arranged in a factorial combination in randomized complete block design in three replications. There were significant differences at p<0.05 in the overall mean of fusarium wilt disease incidence, area under disease progress curve %-day, yield and yield components among varieties and fungicides treatments. Data were analyzed using SAS system version 9.2. The results indicated that the maximum disease incidence and area under disease progress curve values 65.62% and 578.5%-day, respectively, were recorded from untreated local chickpea, while the minimum disease incidence and area under disease progress curve values 23.41% and 147%-day, respectively, were recorded from Shasho variety treated with Apron Star. The maximum biomass and grain yield of 6.71 t/ha and 4.6 t/ha, respectively, were recorded from Shasho variety treated with Apron Star while the minimum biomass and grain yield of 0.62 t/ha and 0.21 t/ha, respectively, were recorded from untreated local chickpea. Thus, the experiment results suggested that the variety of Shasho treated with fungicide Apron Star caused significant reduction in chickpea fusarium wilt incidence leading to a corresponding increase in grain yield of chickpea.
QoE Evaluation: The TRIANGLE Testbed Approach
Authors: Díaz Zayas Almudena , Panizo Laura , Baños Janie , Cárdenas Carlos , Dieudonne Michael
Published: December 2018

This paper presents the TRIANGLE testbed approach to score the Quality of Experience (QoE) of mobile applications, based on measurements extracted from tests performed on an end‐to‐end network testbed. The TRIANGLE project approach is a methodology flexible enough to generalize the computation of the QoE for any mobile application. The process produces a final TRIANGLE mark, a quality score, which could eventually be used to certify applications.
New Extension of Beta Function and Its Applications
Authors: Chand Mehar , Hachimi Hanaa , Rani Rekha
Published: December 2018

In the present paper, new type of extension of classical beta function is introduced and its convergence is proved. Further it is used to introduce the extension of Gauss hypergeometric function and confluent hypergeometric functions. Then we study their properties, integral representation, certain fractional derivatives, and fractional integral formulas and application of these functions.
Fracture Toughness Improvement of Poly(lactic acid) Reinforced with Poly(ε‐caprolactone) and Surface‐Modified Silicon Carbide
Authors: Chen Jie , Zhang Tian-Yi , Jin Fan-Long , Park Soo-Jin
Published: December 2018

In this study, bio‐based poly(lactic acid) (PLA)/polycaprolactone (PCL) blends and PLA/PCL/silicon carbide (SiC) composites were prepared using a solution blending method. The surface of the SiC whiskers was modified using a silane coupling agent. The effects of the PCL and SiC contents on the flexural properties, fracture toughness, morphology of PLA/PCL blends, and PLA/PCL/SiC composites were investigated using several techniques. Both the fracture toughness and flexural strength of PLA increased by the introduction of PCL and were further improved by the formation of SiC whiskers. Fracture surfaces were observed by scanning electron microscopy, which showed that the use of PCL as a reinforcing agent induces plastic deformation in the PLA/PCL blends. The SiC whiskers absorbed external energy because of their good interfacial adhesion with the PLA matrix and through SiC‐PLA debonding in the PLA/PCL/SiC composites.
Probabilistic Prediction of Mine Dynamic Disaster Risk Based on Multiple Factor Pattern Recognition
Authors: Lan Tianwei , Fan Chaojun , Li Sheng , Zhang Hongwei , Batugin Andrian Sergaevich
Published: December 2018

Rock burst and coal and gas outburst are the most serious dynamic disasters in coal mine and are affected by many factors, such as mining engineering environment. In order to accurately predict the risk area of mine dynamic disasters, a series of impact factors and events are classified, and the spatial data of these factors are managed on the basis of identifying the internal relationship between the impact factors and the disasters. A multifactor pattern recognition model is established by artificial intelligence. The risk probability prediction criteria of mine dynamic disasters and the risk probability values of each unit in the prediction area are determined by using the method of neural network and fuzzy mathematics. The dangerous area, threat area, and safety area of mine dynamic disasters are divided to evaluate the dangerous degree. The corresponding control measures for different dangerous areas are also put forward. Application of the prediction method of mine dynamic disaster factors based on pattern recognition, to improve the implementation of mine dynamic disaster prediction and controlling measures, guarantees the safe production of the coal mine.
Inhibitor of Differentiation-1 Sustains Mutant KRAS-Driven Progression, Maintenance, and Metastasis of Lung Adenocarcinoma via Regulation of a FOSL1 Network
Authors: Román Marta , López Inés , Guruceaga Elisabeth , Baraibar Iosune , Ecay Margarita , Collantes María , Nadal Ernest , Vallejo Adrián , Cadenas Silvia , Miguel Marta Echavarri-de , Jang Jae Hwi , Martin-Uriz Patxi San , Castro-Labrador Laura , Vilas-Zornoza Amaia , Lara-Astiaso David , Ponz-Sarvise Mariano , Rolfo Christian , Santos Edgardo S. , Raez Luis E. , Taverna Simona , Behrens Carmen , Weder Walter , Wistuba Ignacio I. , Vicent Silvestre , Gil-Bazo Ignacio
Published: December 2018

Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G2–M arrest and apoptosis in mutant KRAS LUAD cells. In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in downregulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD.

Significance:

These findings highlight the prognostic significance of the transcriptional regulator Id1 in KRAS-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.
YAP1-Mediated CDK6 Activation Confers Radiation Resistance in Esophageal Cancer – Rationale for the Combination of YAP1 and CDK4/6 Inhibitors in Esophageal Cancer
Authors: Li Fan , Xu Yan , Liu Bovey , Singh Pankaj Kumar , Zhao Wei , Jin Jiankang , Han Guangchun , Scott Ailing W. , Dong Xiaochuan , Huo Longfei , Ma Lang , Pizzi Melissa Pool , Wang Ying , Li Yuan , Harada Kazuto , Xie Min , Skinner Heath D. , Ding Sheng , Wang Linghua , Krishnan Sunil , Johnson Randy L. , Song Shumei , Ajani Jaffer A.
Published: December 2018

Purpose:

Esophageal cancer is a lethal disease that is often resistant to therapy. Alterations of YAP1 and CDK6 are frequent in esophageal cancer. Deregulation of both molecules may be responsible for therapy resistance.

Experimental Design:

Expressions of YAP1 and CDK6 were examined in esophageal cancer cells and tissues using immunoblotting and immunohistochemistry. YAP1 expression was induced in esophageal cancer cells to examine YAP1-mediated CDK6 activation and its association with radiation resistance. Pharmacologic and genetic inhibitions of YAP1 and CDK6 were performed to dissect the mechanisms and assess the antitumor effects in vitro and in vivo.

Results:

YAP1 expression was positively associated with CDK6 expression in resistant esophageal cancer tissues and cell lines. YAP1 overexpression upregulated CDK6 expression and transcription, and promoted radiation resistance, whereas treatment with the YAP1 inhibitor, CA3, strongly suppressed YAP1 and CDK6 overexpression, reduced Rb phosphorylation, as well as sensitized radiation-resistant/YAP1high esophageal cancer cells to irradiation. CDK4/6 inhibitor, LEE011, and knock down of CDK6 dramatically inhibited expression of YAP1 and sensitized resistant esophageal cancer cells to irradiation indicating a positive feed-forward regulation of YAP1 by CDK6. In addition, suppression of both the YAP1 and CDK6 pathways by the combination of CA3 and LEE011 significantly reduced esophageal cancer cell growth and cancer stem cell population (ALDH1+ and CD133+), sensitized cells to irradiation, and showed a strong antitumor effect in vivo against radiation-resistant esophageal cancer cells.

Conclusions:

Our results document that a positive crosstalk between the YAP1 and CDK6 pathways plays an important role in conferring radiation resistance to esophageal cancer cells. Targeting both YAP1 and CDK6 pathways could be a novel therapeutic strategy to overcome resistance in esophageal cancer.
A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO)
Authors: Turner Nicholas C. , Telli Melinda L. , Rugo Hope S. , Mailliez Audrey , Ettl Johannes , Grischke Eva-Maria , Mina Lida A. , Balmaña Judith , Fasching Peter A. , Hurvitz Sara A. , Wardley Andrew M. , Chappey Colombe , Hannah Alison L. , Robson Mark E.
Published: December 2018

Purpose:

To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer.

Patients and Methods:

ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment.

Results:

We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31–75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10–35; cohort 1] and 37% [95% CI, 22–55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor–positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval <8 weeks; 47% ORR with interval >6 months).

Conclusions:

Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation.
Antidermatophyte Activity of the Gentiopicroside-Rich n-Butanol Fraction from Gentiana siphonantha Maxim. Root on a Guinea Pig Model of Dermatophytosis
Authors: Zhou Wenna , Ouyang Jian , Wang HongLun , Wang XiaoYan
Published: December 2018

Background:Gentiana siphonantha Maxim. is a traditional medicine for the treatment of rheumarthritis, icterepatitis, pain and hypertension; it is rich in gentiopicroside with anti-inflammatory, antibacterial, and free radical-scavenging activities. This study was to evaluate the antidermatophyte activity of G. siphonantha on a guinea pig model in vitro and in vivo. Material andMethods: The antidermatophyte activities of 10 plants were tested by the broth microdilution method. Fractions and an extract of G. siphonantha were tested against Trichophyton mentagrophytes by the disc diffusion method. The morphological changes of T. mentagrophytes were observed. Component analysis of the n-butanol (n-BuOH) fraction was made by HPLC. Finally, the antifungal activity in an in vivo guinea pig model of dermatophytosis was examined. Results:G. siphonantha had strong antidermatophyte activity with MIC50 values of 32-64 μg/mL. The n-BuOH fraction of G. siphonantha showed the most potent activity compared to the other fractions. After being exposed to the n-BuOH fraction at 80 and 160 μg/mL, the hyphae were distorted and collapsed. Gentiopicroside is the main active ingredient in the n-BuOH fraction of G. siphonantha. The lesion scores of the guinea pig model of dermatophytosis significantly declined in the 10% and 30% extract and positive control groups in comparison with the untreated control group. Periodic acid-Schiff and hematoxylin/eosin staining displayed similar results. Conclusion: The n-BuOH fraction of G. siphonantha demonstrated antidermatophyte efficacy in experimental dermatophytosis.
Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins
Authors: Shi Yuanyuan , Tian Huajun , Wang Yifeng , Shen Yue , Zhu Qiuyu , Ding Feng
Published: December 2018

Background and Objectives: While trying to optimize the dialysis clearances of protein-bound uremic toxins (PBUTs), their percentage protein binding (% PB) is an important parameter. We evaluated the effects of ionic strength, pH change and chemical displacers on the dissociation of PBUTs from albumin in vitro. Methods: PBUTs, such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresylsulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA), were spiked with human serum albumin (HSA) solution prepared with different Nacl concentrations and pH values or in the presence of a series of chemical displacers. Ultrafiltration was performed to separate the free and bound fractions, and the % PB of each PBUT was calculated. Results: For all 4 compounds, their % PB decreased with increasing ionic strength, while only slight changes occurred when the pH of the test solution increased from pH 6.0 to pH 8.5; PCS, IS and 3-IAA were relatively easily dissociated from albumin by drug displacement, while CMPF was released from HSA by all studied drugs with difficulty; the PB % for CMPF, PCS, IS and 3-IAA decreased most remarkably in the presence of free fatty acids, such as oleic acid (41.73% for CMPF, 29.9% for PCS, 23.22% for IS, and 20.34% for 3-IAA) and linoleic acid (43.12% for CMPF, 16.65% for PCS, 29.99% for IS, and 16.29% for 3-IAA). Conclusion: The protein binding of PBUTs can be decreased by higher ionic strength, increased pH and the presence of some chemical displacers, including free fatty acids. Effective dialytic removal of PBUTs may be achieved by applying these methods jointly to blood-purification techniques.
The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells
Authors: Wang Jing , Liu Guangnan , Liu Mengwei , Xiang Li , Xiao Yizhi , Zhu Huiqiong , Wu Xiaosheng , Peng Ying , Zhang Wenjing , Jiang Ping , Li Aimin , Nan Qingzhen , Chen Ye , Chen Chudi , Cheng Tianming , Liu Side , Wang Jide
Published: December 2018

Background/Aims: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. Methods: The functional role of CCDC43 and FOXK1 in epithelial-mesenchymal transition (EMT) was determined using immunohistochemistry, flow cytometry, western blot, EdU incorporation, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. Results: The CCDC43 gene was overexpressed in human CRC. High expression of CCDC43 protein was associated with tumor progression and poor prognosis in patients with CRC. Moreover, the induction of EMT by CCDC43 occurred through TGF-β signaling. Furthermore, a positive correlation between the expression patterns of CCDC43 and FOXK1 was observed in CRC cells. Promoter assays demonstrated that FOXK1 directly bound and activated the human CCDC43 gene promoter. In addition, CCDC43 was necessary for FOXK1- mediated EMT and metastasis in vitro and vivo. Taken together, this work identified that CCDC43 promoted EMT and was a direct transcriptional target of FOXK1 in CRC cells. Conclusion: FOXK1-CCDC43 axis might be helpful to develop the drugs for the treatment of CRC.
Garcinia Multiflora Inhibits FPR1-Mediated Neutrophil Activation and Protects Against Acute Lung Injury
Authors: Tsai Yung-Fong , Yang Shun-Chin , Chang Wen-Yi , Chen Jih-Jung , Chen Chun-Yu , Chang Shih-Hsin , Hwang Tsong-Long
Published: December 2018

Background/Aims: Formyl peptide receptors (FPRs) recognize different endogenous and exogenous molecular stimuli and mediate neutrophil activation. Dysregulation of excessive neutrophil activation and the resulting immune responses can induce acute lung injury (ALI) in the host. Accordingly, one promising approach to the treatment of neutrophil-dominated inflammatory diseases involves therapeutic FPR1 inhibition. Methods: We extracted a potent FPR1 antagonist from Garcinia multiflora Champ. (GMC). The inhibitory effects of GMC on superoxide anion release and elastase degranulation from activated human neutrophils were determined with spectrophotometric analysis. Reactive oxygen species (ROS) production and the FPR1 binding ability of neutrophils were assayed by flow cytometry. Signaling transduction mediated by GMC in response to chemoattractants was assessed with a calcium influx assay and western blotting. A lipopolysaccharide (LPS)-induced ALI mouse model was used to determine the therapeutic effects of GMC in vivo. Results: GMC significantly reduced superoxide anion release, the reactive oxidants derived therefrom, and elastase degranulation mediated through selective, competitive FPR1 blocking in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF)-stimulated human neutrophils. In cell-free systems, GMC was unable to scavenge superoxide anions or suppress elastase activity. GMC produced a right shift in fMLF-activated concentration-response curves and was confirmed to be a competitive FPR1 antagonist. GMC binds to FPR1 not only in neutrophils, but also FPR1 in neutrophil-like THP-1 and hFPR1-transfected HEK293 cells. Furthermore, the mobilization of calcium and phosphorylation of mitogen-activated protein kinases and Akt, which are involved in FPR1-mediated downstream signaling, was competitively blocked by GMC. In an in vivo study, GMC significantly reduced pulmonary edema, neutrophil infiltration, and alveolar damage in LPS-induced ALI mice. Conclusion: Our findings demonstrate that GMC is a natural competitive FPR1 inhibitor, which makes it a possible anti-inflammatory treatment option for patients critically inflicted with FPR1-mediated neutrophilic lung damage.
High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival
Authors: Li Chao , Bu Juyuan , Liao Yifeng , Zhang Jin , Han Jun , Zhang Han , Xing Hao , Li Zhenli , Wu Han , Liang Lei , Wang Mingda , Qin Wenxing , Yang Tian
Published: December 2018

Background/Aims: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. Methods: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. Results: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. Conclusion: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.
Effects of Ca2+-Activated Cl- Channel ANO1inhibitors on Pacemaker Activity in Interstitial Cells of Cajal
Authors: Choi Seok , Kang Hyun Goo , Wu Mei Jin , Jiao Han Yi , Shin Dong Hoon , Hong Chansik , Jun Jae Yeoul
Published: December 2018

Background/Aims: Anoctamin1 (Ca2+-activated Cl- channel, ANO1) is a specific marker of the interstitial cells of Cajal (ICC) in the gastrointestinal tract, and are candidate proteins that can function as pacemaker channels. Recently, novel selective ANO1 inhibitors were discovered and used to study Ca2+-activated Cl- channels. Therefore, to investigate whether ANO1 channels function as pacemaker channels, selective ANO1 inhibitors were tested with respect to the pacemaker potentials in ICC. Methods: Whole-cell patch-clamp recording, RT-PCR, and intracellular Ca2+ ([Ca2+]i) imaging were performed in cultured ICC obtained from mice. Results: Though CaCCinh-A01 (5 µM), T16Ainh-A01 (5 µM), and MONNA (5 µM) (selective ANO1 inhibitors) blocked the generation of pacemaker potentials in colonic ICC, they did not do so in small intestinal ICC. Though nifulmic acid (10 µM) and DIDS (10 µM) (classical Ca2+-activated Cl- channel inhibitors) also had no effect in small intestinal ICC, they suppressed the generation of pacemaker potentials in colonic ICC. In addition, knockdown of ANO1 reduced the pacemaker potential frequency in colonic ICC alone. Though ANO1 inhibitors suppressed [Ca2+]i oscillations in colonic ICC, they did not do so in small intestinal ICC. T-type Ca2+ channels were expressed in the both the small intestinal and colonic ICC, but mibefradil (5 µM) and NiCl2 (30 µM) (T-type Ca2+ channel inhibitors) inhibited the generation of pacemaker potentials in colonic ICC alone. Conclusion: These results indicate that though ANO1 and T-type Ca2+ channels participate in generating pacemaker potentials in colonic ICC, they do not do so in small intestinal ICC. Therefore, the mechanisms underlying pacemaking in ICC might be different in the small intestine and the colon.