bluuebunny/crossref_metadata_2025 huggingface dataset:
Retroperitoneal Endometriotic Cyst Infiltrated in the Iliopsoas Incidentally Found in a Patient with Acute Back Pain
Authors: Tsukasaki Nanami , Yamamoto Takuro , Katayama Akihisa , Ogiso Nozomi , Okubo Tomoharu
Published: December 2017

We describe a rare case of retroperitoneal endometriotic cyst infiltrated in the iliopsoas incidentally found in a patient with acute back pain. Endometriosis at the pelvic peritoneum, including the Douglas pouch, has been reported often; there are few reports of cystic endometriosis in the retroperitoneal cavity. Today there are various theories regarding how endometriosis occurs. By pathological findings and lesion sites of the present case, we concluded that the endometrial tissues in the menstrual blood might metastasize lymphatically and implant and form the retroperitoneal cyst.
Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho
Authors: Gill Michelle M. , Hoffman Heather J. , Mokone Majoalane , Tukei Vincent J. , Nchephe Matsepeli , Phalatse Mamakhetha , Tiam Appolinaire , Guay Laura , Mofenson Lynne
Published: December 2017

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants’ HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January–June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems.
Pharmacological Hypotension as a Cause of Delirious Mania in a Patient with Bipolar Disorder
Authors: Carbone Manuel Glauco , Miniati Mario , Simoncini Marly , Tripodi Beniamino , Tagliarini Claudia , Carmassi Claudia , Dell’Osso Liliana
Published: December 2017

Delirious mania is a severe but often underrecognized syndrome characterized by rapid onset of delirium, mania, and psychosis, not associated with a prior toxicity, physical illness, or mental disorder. We discuss the case of a delirious mania potentially triggered and maintained by a systemic hypotension induced by antihypertensive drugs. Symptoms recovered completely after the discontinuation of antihypertensive medications and the normalization of blood pressure levels.
The Diagnostic Roles of Cytokines in Hepatobiliary Cancers
Authors: Koca Yavuz Savas , Bulbul Mahmut , Barut Ibrahim
Published: December 2017

Objectives. The aim of this study was to investigate the role of several cytokines including IL-2, IL-6, IL-8, IL-10, and TNF-α in the diagnosis of HPB cancers. Materials and Methods. The prospective study was performed between October 2007 and September 2014. The study included 226 patients who were divided into 5 groups depending on their postoperative and histopathologic diagnosis: Control group included 30 healthy volunteers. Hepatocellular cancer (HCC) group included 24 patients diagnosed with HCC. Gallbladder cancer (GBC) group included 36 patients diagnosed with GBC. Cholangiocellular carcinoma group included 64 patients diagnosed with cholangiocellular carcinoma. Pancreatic cancer group included 72 patients diagnosed with pancreatic cancer. Serum levels of IL-2, IL-6, IL-8, IL-10, and TNF-α were measured using an enzyme-linked immunosorbent assay kit in accordance with the guidelines of the producer. Results. Serum TNF-α concentration was significantly higher in the cholangiocellular carcinoma and pancreatic cancer groups compared to other groups. IL-6 and IL-10 were significantly increased in both the HCC and GBC groups, IL-2, IL-6, IL-10, and TNF-α in the cholangiocellular carcinoma group, and IL-2, IL-6, IL-8, and TNF-α in the pancreatic cancer group. Conclusion. We suggest that cytokines can be used as useful markers in the diagnosis of HPB cancers.
A Case of Midgut Volvulus Associated with a Jejunal Diverticulum
Authors: Gutowski Joseph , NeMoyer Rachel , Parker Glenn S.
Published: December 2017

Midgut volvulus in adults is a rare entity that may present with intermittent colicky abdominal pain mixed with completely asymptomatic episodes. This small bowel twist may result in complications of obstruction, ischemia, hemorrhage, or perforation. With a midgut volvulus, complications may be life-threatening, and emergent surgical intervention is the mainstay of treatment. This current case involves an 80-year-old woman with intermittent abdominal pain with increasing severity and decreasing interval of time to presentation. A CAT scan revealed mesenteric swirling with possible internal hernia. A diagnostic laparoscopy followed by laparotomy revealed a midgut volvulus, extensive adhesions involving the root of the mesentery, and a large jejunal diverticulum. The adhesions were lysed enabling untwisting of the bowel, allowing placement of the small bowel in the correct anatomic position and resection of the jejunal diverticulum. This is a rare case of midgut volvulus with intermittent abdominal pain, associated with jejunal diverticulum managed successfully. A midgut volvulus should be considered in the differential diagnosis of a patient who present with a small bowel obstruction secondary to an internal hernia, especially when a swirl sign is present on the CAT scan.
Unified Description of the Mechanical Properties of Typical Marine Soil and Its Application
Authors: Li Yongqiang , Wang Gang , Jing Liping , Zhang Lei , Cheng Xinjun
Published: December 2017

This study employed a modified elastoplastic constitutive model that can systematically describe the monotonic and cyclic mechanical behaviors of typical marine soils combining the subloading, normal, and superloading yield surfaces, in the seismic response analysis of three-dimensional (3D) marine site. New evolution equations for stress-induced anisotropy development and the change in the overconsolidation of soils were proposed. This model can describe the unified behaviour of unsaturated soil and saturated soil using independent state variables and can uniquely describe the multiple mechanical properties of soils under general stress states, without changing the parameter values using the transform stress method. An effective stress-based, fully coupled, explicit finite element–finite difference method was established based on this model and three-phase field theory. A finite deformation analysis was presented by introducing the Green-Naghdi rate tensor. The simulation and analysis indicated that the proposed method was sufficient for simulating the seismic disaster process of 3D marine sites. The results suggested that the ground motion intensity would increase due to the local uneven complex topography and site effect and also provided the temporal and spatial distribution of landslide and collapse at the specific location of the marine site.
Efficacy of a Rinse Containing Sea Salt and Lysozyme on Biofilm and Gingival Health in a Group of Young Adults: A Pilot Study
Authors: Hoover Jeyaraj , Tovar Eduardo , Zlatnik Trevor , Karunanayake Chandima
Published: December 2017

Objectives. To evaluate new mouth rinse containing sea salt, xylitol, and lysozyme on biofilm formation and gingival health in a group of young adults. Methods. The subjects were divided into two groups of 15 subjects each: control (A) and experimental group (B). The Turesky modification of Quigley-Hein plaque index was used to evaluate plaque scores while the presence or absence of gingival bleeding was used to determine gingival health. Measurements were done at baseline and at the end of the one-month trial period by one blinded examiner on six representative teeth. Group (A) maintained standardized oral health practices for the duration of the experiment. In addition, group (B) rinsed with a tablespoon of the provided sea salt mouth rinse for 30 seconds once in the morning and at night. After the 30-day trial period, subjects in both groups were reassessed as per baseline. Results. There were no statistically significant differences in the overall reduction from baseline in the mean plaque and gingivitis scores on all surfaces or on individual surfaces. Conclusion. Within the limitations of the study, rinsing with sea salt for thirty days did not affect the gingival and plaque scores in a group of young adults.
Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome
Authors: Manganelli Valeria , Capozzi Antonella , Truglia Simona , Alessandri Cristiano , Lococo Emanuela , Garofalo Tina , De Carolis Caterina , Conti Fabrizio , Valesini Guido , Sorice Maurizio , Longo Agostina , Misasi Roberta
Published: December 2017

Pregnancy problems are common in patients with rheumatic disease; indeed, autoimmune disorders and autoantibodies can affect pregnancy progress and lead to maternal complications. Recent studies have highlighted a close association between HMGB1, chronic inflammation, and autoimmune diseases. Thus, in this investigation, we analyzed serum levels of HMGB1, an alarmin which plays a pivotal role in inducing and enhancing immune cell function. Sera from 30 patients with antiphospholipid syndrome (11 primary and 19 secondary APS), 35 subjects with pregnancy morbidity, and 30 healthy women were analysed for HMGB1 and its putative receptor RAGE (sRAGE) by Western blot and for TNF-α by ELISA. Results revealed that APS patients showed significantly increased serum levels of HMGB1, sRAGE, and the proinflammatory cytokine TNF-α, as compared to healthy women. However, also, the pregnancy morbidity subjects showed significantly increased levels of HMGB1 and sRAGE as well as TNF-α compared to healthy women. Our findings suggest that in subjects with pregnancy morbidity, including obstetric APS, elevated levels of HMGB1/sRAGE may represent an alarm signal, indicating an increase of proinflammatory triggers. Further studies are needed to evaluate the role of HMGB1/sRAGE as a possible tool to evaluate the risk stratification of adverse pregnancy outcomes.
Evaluation of Predictive Factors for Successful Intravitreal Dexamethasone in Pseudophakic Cystoid Macular Edema
Authors: Kakkassery Vinodh , Schultz Tim , Wunderlich Marc Ilan , Schargus Marc , Dick H. Burkhard , Rehrmann Jörg
Published: December 2017

Purpose. To determine the efficacy, safety, and predictive outcome factors for intravitreal dexamethasone implant (DEX) in pseudophakic cystoid macular edema (PCME). Methods. Retrospective, interventional, controlled study. Patients included had to have clinically significant PCME and have been treated with the DEX between 2012 and 2015. Charts and one-year data were selected consecutively, and efficacy and safety were abstracted. Visual acuity (VA) and central foveal thickness (CFT) were analysed. Results. Nineteen patient data sets were analysed. After treatment with DEX, mean VA increased significantly by 0.2 logMAR (p=0.034), while the mean CFT was reduced significantly by 162.79 μm (p<0.001). Five patients receiving a combination of DEX/bevacizumab have not experienced a higher mean VA gain or CFT reduction compared to fourteen patients receiving DEX alone. Decision rules, when to combine DEX with bevacizumab, have not been defined before the study. Only posttreatment VA gains in the nonhypertensive subgroup (n=11) were significantly better (p=0.026). Analysis of data from diabetes patients (n=4) versus nondiabetics yielded no significant differences in efficacy. There have been no adverse events within follow-up time. Conclusion. The use of DEX in PCME showed significant improvements in VA and CFT. The VA seems to show greater improvements in patients without hypertension.
Guidance on Setup, Calibration, and Validation of Hydrodynamic, Wave, and Sediment Models for Shelf Seas and Estuaries
Authors: Williams Jon J. , Esteves Luciana S.
Published: December 2017

The paper is motivated by a present lack of clear model performance guidelines for shelf sea and estuarine modellers seeking to demonstrate to clients and end users that a model is fit for purpose. It addresses the common problems associated with data availability, errors, and uncertainty and examines the model build process, including calibration and validation. It also looks at common assumptions, data input requirements, and statistical analyses that can be applied to assess the performance of models of estuaries and shelf seas. Specifically, it takes account of inherent modelling uncertainties and defines metrics of performance based on practical experience. It is intended as a reference point both for numerical modellers and for specialists tasked with interpreting the accuracy and validity of results from hydrodynamic, wave, and sediment models.
Experiment Analysis of Concrete’s Mechanical Property Deterioration Suffered Sulfate Attack and Drying-Wetting Cycles
Authors: Tian Wei , Han Nv
Published: December 2017

The mechanism of concrete deterioration in sodium sulfate solution is investigated. The macroperformance was characterized via its apparent properties, mass loss, and compressive strength. Changes in ions in the solution at different sulfate attack periods were tested by inductively coupled plasma (ICP). The damage evolution law, as well as analysis of the concrete’s meso- and microstructure, was revealed by scanning electron microscope (SEM) and computed tomography (CT) scanning equipment. The results show that the characteristics of concrete differed at each sulfate attack period; the drying-wetting cycles generally accelerated the deterioration process of concrete. In the early sulfate attack period, the pore structure of the concrete was filled with sulfate attack products (e.g., ettringite and gypsum), and its mass and strength increased. The pore size and porosity decreased while the CT number increased. As deterioration progressed, the swelling/expansion force of products and the salt crystallization pressure of sulfate crystals acted on the inner wall of the concrete to accumulate damage and accelerate deterioration. The mass and strength of concrete sharply decreased. The number and volume of pores increased, and the pore grew more quickly resulting in initiation and expansion of microcracks while the CT number decreased.
Study on Transmission Characteristics of Vertical Rail Vibrations in Ballast Track
Authors: Sheng Xi , Zhao Caiyou , Wang Ping , Liu Dongya
Published: December 2017

A plane half‐track model and a periodic track‐substructure model are established. The spectral element method and spectral transfer matrix method are developed and applied to investigate the track decay rate (TDR) and transmission rate (TR) of the vertical rail vibrations, which can reflect the transmission characteristics in the longitudinal and downward directions, respectively. Furthermore, the effects of different track parameters on TDR and TR are investigated. The results show that the antiresonance frequency of the rail and the out‐of‐phase resonance frequency of the rail and sleeper form the boundary frequencies of the high‐attenuation zone for longwise vibration transmission, where the vibration absorption of the sleeper is significant. The downward transmissibility of vertical rail vibrations is greatest around the antiresonance frequency of the rail. Vertical rail vibrations are primarily transmitted in the downward direction at low frequencies, while they are mainly transmitted along the rail at high frequencies. Stiffer rail pads can make more vibrations transmitted downwards to the sleeper above the antiresonance frequency of the rail, while the changes of other track parameters have different effects on the transmission characteristics. Additionally, a field measurement is performed for verification, and the simulations are well consistent with measurements.
Distributed Optimal Day-Ahead Scheduling in a Smart Grid: A Trade-Off among Consumers, Power Suppliers, and Transmission Owners
Authors: Hu Xiong , Liu Zhi-Wei
Published: December 2017

To cope with the challenges due to increasing peak load, an optimal day-ahead scheduling problem for social welfare maximization is proposed, in which not only the comfort level of consumers and costs of power suppliers but also the power losses in transmission and operation costs of transmission owners are taken into account. Then this optimal day-ahead scheduling problem is reformulated and solved via the alternating direction method of multipliers (ADMM), by which fast convergence is guaranteed and the privacy of participants is ensured, in a distributed manner. Specifically, in the proposed distributed optimal day-ahead scheduling, the hourly prices for consumers are divided into hourly supply prices and hourly delivery prices, which will be updated by the independent system operator based on the hourly demand-supply situations and hourly demand-delivery situations, respectively. And the consumers, power suppliers, and transmission owners make their individual optimal day-ahead scheduling based on their individual hourly prices, hourly supply prices, and hourly delivery prices, respectively, until the hourly demand-supply balances and hourly demand-delivery balances are achieved. Effectiveness of the proposed distributed optimal day-ahead scheduling is verified by the cases studied.
Prediction of Skid Resistance Value of Glass Fiber-Reinforced Tiling Materials
Authors: Yildizel Sadik Alper , Tuskan Yesim , Kaplan Gökhan
Published: December 2017

This research focuses on the use of adaptive artificial neural network system for evaluating the skid resistance value (British Pendulum Number; BPN) of the glass fiber-reinforced tiling materials. During the creation of the neural model, four main factors were considered: fiber, calcium carbonate content, sand blasting, and polishing properties of the specimens. The model was trained, tested, and compared with the on-site test results. As per the comparison of the outcomes of the study, the analysis and on-site test results showed that there is a great potential for the prediction of BPN of glass fiber-reinforced tiling materials by using developed neural system.
Maximum Likelihood Estimation of Model Uncertainty in Predicting Soil Nail Loads Using Default and Modified FHWA Simplified Methods
Authors: Liu Huifen , Tang Liansheng , Lin Peiyuan
Published: December 2017

Accuracy evaluation of the default Federal Highway Administration (FHWA) simplified equation for prediction of maximum soil nail loads under working conditions is presented in this study using the maximum likelihood method and a large amount of measured lower and upper bound nail load data reported in the literature. Accuracy was quantitatively expressed as model bias where model bias is defined as the ratio of measured to predicted nail load. The maximum likelihood estimation was carried out assuming normal and lognormal distributions of bias. Analysis outcomes showed that, based on the collected data, the default FHWA simplified nail load equation is satisfactorily accurate on average and the spread in prediction accuracy expressed as the coefficient of variation of bias is about 30%, regardless of the distribution type. Empirical calibrations were proposed to the default FHWA simplified nail load equation for accuracy improvement. The Bayesian Information Criterion was adopted to perform a comparison of suitability between the competing normal and lognormal statistical models that were intended for description of model bias. Example of reliability‐based design of soil nail walls against internal pullout limit state of nails is provided in the end to demonstrate the benefit of performing model calibration and using calibrated model for design of soil nails.
Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells
Authors: Lunagariya Jignesh , Liao Xiaojian , Long Weili , Zhong Shenghui , Bhadja Poonam , Li Hangbin , Zhao Bingxin , Xu Shihai
Published: December 2017

Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation using flow cytometry in human breast cancer MCF‐7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF‐7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB‐MDA‐231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF‐7 cells. This galaxamide analogue significantly induced apoptosis in a dose‐dependent manner in MCF‐7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.
Evaluation of Chitosan-Microcrystalline Cellulose Blends as Direct Compression Excipients
Authors: Olorunsola Emmanuel O. , Akpan Grace A. , Adikwu Michael U.
Published: December 2017

This study was aimed at evaluating chitosan-microcrystalline cellulose blends as direct compression excipients. Crab shell chitosan, α-lactose monohydrate, and microcrystalline cellulose powders were characterized. Blends of the microcrystalline cellulose and chitosan in ratios 9 : 1, 4 : 1, 2 : 1, and 1 : 1 as direct compression excipients were made to constitute 60% of metronidazole tablets. Similar tablets containing blends of the microcrystalline cellulose and α-lactose monohydrate as well as those containing pure microcrystalline cellulose were also produced. The compact density, tensile strength, porosity, disintegration time, and dissolution rate of tablets were determined. Chitosan had higher moisture content (7.66%) and higher moisture sorption capacity (1.33%) compared to microcrystalline cellulose and lactose. It also showed better flow properties (Carr’s index of 18.9% and Hausner’s ratio of 1.23). Compact density of tablets increased but tensile strength decreased with increase in the proportion of chitosan in the binary mixtures. In contrast to lactose, the disintegration time increased and the dissolution rate decreased with increase in the proportion of chitosan. This study has shown that chitosan promotes flowability of powder mix and rapid disintegration of tablet. However, incorporation of equal proportions of microcrystalline cellulose and chitosan leads to production of extended-release tablet. Therefore, chitosan promotes tablet disintegration at low concentration and enables extended-release at higher concentration.
Learning and Using Abstract Words: Evidence from Clinical Populations
Authors: Lorusso Maria Luisa , Burigo Michele , Tavano Alessandro , Milani Anna , Martelli Sara , Borgatti Renato , Molteni Massimo
Published: December 2017

It has been shown that abstract concepts are more difficult to process and are acquired later than concrete concepts. We analysed the percentage of concrete words in the narrative lexicon of individuals with Williams Syndrome (WS) as compared to individuals with Down Syndrome (DS) and typically developing (TD) peers. The cognitive profile of WS is characterized by visual-spatial difficulties, while DS presents with predominant impairments in linguistic abilities. We predicted that if linguistic abilities are crucial to the development and use of an abstract vocabulary, DS participants should display a higher concreteness index than both Williams Syndrome and typically developing individuals. Results confirm this prediction, thus supporting the hypothesis of a crucial role of linguistic processes in abstract language acquisition. Correlation analyses suggest that a maturational link exists between the level of abstractness in narrative production and syntactic comprehension.
Chronic Pain and Sleep Disorders in Primary Care
Authors: Jank Robert , Gallee Alexander , Boeckle Markus , Fiegl Sabine , Pieh Christoph
Published: December 2017

Background. Chronic pain (CP) and sleep disorders (SD) are highly prevalent in the general population. However, comprehensive data regarding the prevalence and characteristics of pain and SD in primary care are rare. Methods. From N=578 patients N=570 were included within 8 weeks (mean age: 50.8±18.7 years, females: 289). Sociodemographic data, Insomnia Severity Index (ISI), and parts of a self-report questionnaire for pain (Multidimensional German Pain Questionnaire) were recorded and additional medical information (pain medication, sleep medication) was gathered from the patient charts. Results. Of the total sample, 33.2% (n=189) suffer from CP (pain ≥ 6 months) and 29.1% (n=166) from SD. 45.5% of the CP patients suffer from SD and 26.5% from clinical insomnia (ISI ≥ 15). SD (β = 0.872, SE = 0.191,  t = 4,572, p<0.001, CI [0.497; 1.246]) and older age (β = 0.025, SE = 0.005, t = 5.135, p<0.001, CI [0.015; 0.035]) were significantly associated with pain experience. Conclusion. About a quarter of CP patients suffer from clinical insomnia. The suggested bidirectional relation should be considered during comprehensive assessment and treatment of patients.
Topical Tranexamic Acid Reduces Blood Loss in Minimally Invasive Total Knee Arthroplasty Receiving Rivaroxaban
Authors: Yen Shih-Hsiang , Lin Po-Chun , Chen Bradley , Huang Chung-Chen , Wang Jun-Wen
Published: December 2017

Background. It is unclear whether topical (intra-articular) or intravenous TXA reduces blood loss in minimally invasive TKA patients receiving a direct oral anticoagulant for thromboprophylaxis. This study is to investigate whether TXA given intravenously or intra-articularly is effective in reducing blood loss in minimally invasive TKA patients using rivaroxaban for thromboprophylaxis.Methods. Ninety-three patients who underwent primary minimally invasive TKA were divided into placebo group (30 patients) that received saline both intravenously and intra-articularly, intravenous (IV) group (31 patients) that received 1 g TXA intravenously, and topical group (32 patients) that received 3 g TXA in 100 ml saline intra-articularly. All patients received oral rivaroxaban of 10 mg daily for 14 days postoperatively.Results.p<0.001andp=0.041. The mean total blood loss was 1131 mL (567–1845) in placebo, which was higher than that in the IV group (921 mL; range, 465–1495;p=0.014) and the topical group (795 mL; range, 336–1350;p<0.001). The total blood loss did not differ between the IV and the topical group (p=0.179).Conclusion. This prospective, randomized, controlled trial demonstrated an equal efficacy of TXA in blood conservation when administered intravenously or topically in minimally invasive TKA patients receiving rivaroxaban for thromboprophylaxis.
Inactivation of Cancer-Associated-Fibroblasts Disrupts Oncogenic Signaling in Pancreatic Cancer Cells and Promotes Its Regression
Authors: Dauer Patricia , Zhao Xianda , Gupta Vineet K. , Sharma Nikita , Kesh Kousik , Gnamlin Prisca , Dudeja Vikas , Vickers Selwyn M. , Banerjee Sulagna , Saluja Ashok
Published: December 2017

Resident fibroblasts that contact tumor epithelial cells (TEC) can become irreversibly activated as cancer-associated-fibroblasts (CAF) that stimulate oncogenic signaling in TEC. In this study, we evaluated the cross-talk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mut p53-induced pancreatic cancer (KPC mice). Transcriptomic profiling conducted after treatment with the anticancer compound Minnelide revealed deregulation of the TGFβ signaling pathway in CAF, resulting in an apparent reversal of their activated state to a quiescent, nonproliferative state. TEC exposed to media conditioned by drug-treated CAFs exhibited a decrease in oncogenic signaling, as manifested by downregulation of the transcription factor Sp1. This inhibition was rescued by treating TEC with TGFβ. Given promising early clinical studies with Minnelide, our findings suggest that approaches to inactivate CAF and prevent tumor–stroma cross-talk may offer a viable strategy to treat pancreatic cancer.

Significance: In an established mouse model of pancreatic cancer, administration of the promising experimental drug Minnelide was found to actively deplete reactive stromal fibroblasts and to trigger tumor regression, with implications for stromal-based strategies to attack this disease. Cancer Res; 78(5); 1321–33. ©2018 AACR.
Oncogenic RAS-Induced Perinuclear Signaling Complexes Requiring KSR1 Regulate Signal Transmission to Downstream Targets
Authors: Basu Sandip K. , Lee Sook , Salotti Jacqueline , Basu Srikanta , Sakchaisri Krisada , Xiao Zhen , Walia Vijay , Westlake Christopher J. , Morrison Deborah K. , Johnson Peter F.
Published: December 2017

The precise characteristics that distinguish normal and oncogenic RAS signaling remain obscure. Here, we show that oncogenic RAS and BRAF induce perinuclear relocalization of several RAS pathway proteins, including the kinases CK2 and p-ERK1/2 and the signaling scaffold KSR1. This spatial reorganization requires endocytosis, the kinase activities of MEK-ERK and CK2, and the presence of KSR1. CK2α colocalizes with KSR1 and Rab11, a marker of recycling endosomes, whereas p-ERK associates predominantly with a distinct KSR1-positive endosomal population. Notably, these perinuclear signaling complexes (PSC) are present in tumor cell lines, mouse lung tumors, and mouse embryonic fibroblasts undergoing RAS-induced senescence. PSCs are also transiently induced by growth factors (GF) in nontransformed cells with delayed kinetics (4–6 hours), establishing a novel late phase of GF signaling that appears to be constitutively activated in tumor cells. PSCs provide an essential platform for RAS-induced phosphorylation and activation of the prosenescence transcription factor C/EBPβ in primary MEFs undergoing senescence. Conversely, in tumor cells, C/EBPβ activation is suppressed by 3′UTR-mediated localization of Cebpb transcripts to a peripheral cytoplasmic domain distinct from the PSC region. Collectively, our findings indicate that sustained PSC formation is a critical feature of oncogenic RAS/BRAF signaling in cancer cells that controls signal transmission to downstream targets by regulating selective access of effector kinases to substrates such as C/EBPβ.

Significance: In addressing the long-standing question of the difference between normal and oncogenic RAS pathway signaling, this study shows that oncogenic RAS specifically triggers constitutive endocytosis-dependent movement of effector kinases to a perinuclear region, thereby creating connections to unique downstream targets such as the core prosenescence and the inflammatory regulatory transcription factor C/EBPβ. Cancer Res; 78(4); 891–908. ©2017 AACR.
Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans
Authors: Huang Xuelian , Browngardt Christopher M. , Jiang Min , Ahn Sang-Joon , Burne Robert A. , Nascimento Marcelle M.
Published: December 2017

Arginine metabolism via the arginine deiminase system (ADS) of oral bacteria generates ammonia, which can increase the pH of oral biofilms and decrease the risk for dental caries. Antagonistic interactions between ADS-positive and cariogenic bacteria in oral biofilms may be an important ecological determinant of caries. This study investigated the antagonistic potential and mechanisms of clinical isolates of arginolytic streptococci on and by Streptococcus mutans UA159, a well-characterized cariogenic human isolate. Low-passage isolates of Streptococcus gordonii, Streptococcus sanguinis, Streptococcus parasanguinis, Streptococcus australis, and Streptococcus cristatus inhibited the growth of S. mutans to various degrees when they were inoculated on growth media first or simultaneously with S. mutans. The antagonistic effects of arginolytic strains against S. mutans and the production of H2O2 by these strains were enhanced during growth in a less-rich medium or when galactose was substituted for glucose as the primary carbohydrate source. Pyruvate oxidase was the dominant pathway for H2O2 production by arginolytic strains, but lactate oxidase activity was also detected in some strains of S. gordonii and S. cristatus. UA159 inhibited the growth of all tested arginolytic strains when inoculated first, especially in aerobic conditions. However, the antagonistic effects of S. mutans on certain strains of S. gordonii and S. australis were not observed during anaerobic growth in the presence of arginine. Thus, arginolytic commensal streptococci may have a synergistically positive impact on the ecology of oral biofilms by moderating biofilm pH while antagonizing the growth and virulence of caries pathogens.
Systemic Therapy for Hepatocellular Carcinoma: 2017 Update
Authors: Kudo Masatoshi
Published: December 2017

Systemic therapy for hepatocellular carcinoma (HCC) changed drastically after the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib provides an additional therapeutic option for patients with extrahepatic spread or vascular invasion, resulting in improved survival even among patients with advanced HCC; however, the toxicity of sorafenib and its unsatisfactory antitumor effects remain unsolved issues. The development of novel molecular targeted agents as alternatives to sorafenib has been limited by difficulties unique to HCC. Recent studies have demonstrated the efficacy of two molecular targeted agents, the second-line agent regorafenib, which is used after sorafenib failure, and the first-line agent lenvatinib, which has been shown to be noninferior to sorafenib. Another category of agents that are attracting considerable interest are immune checkpoint inhibitors such as anti-PD-1/PD-L1 or CTLA-4 antibodies, which kill cancer cells via a unique mechanism. The therapeutic effects of some of these agents are currently under investigation in phase III studies. The most recent topics of interest are the combination of anti-PD-1/PD-L1 therapies with other immune checkpoint inhibitors, such as anti-CTLA-4 antibodies, or with a tyrosine kinase inhibitor, or with locoregional therapies such as resection, ablation, or transarterial chemoembolization.
Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature
Authors: Malinverni Andréa C.M. , Yamashiro Coelho Érika M. , Chen Kelin , Colovati Mileny E. , Soares Pinho Cernach Mirlene C. , Bragagnolo Silvia , Melaragno Maria Isabel
Published: December 2017

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.
Endoscopic Ultrasound-Guided Biliary Drainage in Two Patients with Difficult Biliary Access
Authors: Libânio Diogo , Giestas Sílvia , Martinez-Ares David , Ferreira Frederico , Canena Jorge , Certo Manuela , Lopes Luís
Published: December 2017

Introduction: Endoscopic retrograde cholangiopancreatography is the method of choice for biliary drainage, although in some cases standard biliary access is difficult or even impossible. Endoscopic ultrasound (EUS)-guided endoluminal procedures are an alternative in these cases, although experience with these techniques is still limited. Clinical Case: We present two cases of successful EUS-guided biliary drainage. In the first case, a hepaticogastrostomy was performed in a patient with stage IV gastric adenocarcinoma with obstructive jaundice due to compression of the hilum, where malignant gastric stenosis and previous palliative gastrojejunostomy precluded access to the second part of the duodenum. In the second case, a patient with a pancreatic head adenocarcinoma with duodenal invasion that precluded major papillae identification was submitted to a choledochoduodenostomy. Both procedures occurred without immediate or delayed adverse events, with technical and clinical success. Discussion: Although experience with EUS-guided biliary drainage is still limited, its efficacy and safety is favorable when compared with percutaneous and surgical drainage, and should be considered an alternative to these techniques where sufficient expertise exists.
Hand force symmetry during breaststroke swimming
Authors: Werlang Rafaela Grübel , Pereira Suzana Matheus , Ruschel Caroline , Pereira Gustavo Soares , Prado Ana Paula Moratelli , Schütz Gustavo Ricardo , Roesler Helio
Published: December 2017

Este trabalho teve como objetivo analisar a simetria da força aplicada durante a braçada do nado peito e a sua relação com o desempenho de nadadores. Participaram do estudo 17 nadadores especialistas em nado peito e medley (12 homens e 5 mulheres, 19,5 ± 5,2 anos, melhor tempo pessoal correspondente a 73,4 ± 7,0 % do recorde mundial dos 50 m peito). Cada sujeito realizou três repetições de 25 m peito em máxima velocidade. Sensores de pressão do Sistema Aquanex foram posicionados na mão direita e na mão esquerda dos nadadores, possibilitando a aquisição das variáveis Força Média (Fmed) e Força Máxima (Fmax). Calculou-se o índice de simetria conforme proposto por Sanders e utilizou-se o tempo de uma execução de 50 m peito em velocidade máxima (T50m) como indicador de desempenho. A comparação das variáveis entre a mão direita e a mão esquerda foi realizada através de testes para amostras dependentes, e a relação entre as variáveis foi investigada através da correlação de Spearman (p < 0,05). A Fmed aplicada foi de 47,9 ± 16,7 N e de 47,9 ± 14,5 N para as mãos direita e esquerda, respectivamente. A Fmax correspondeu a 120,7 ± 43,6 N e 112,8 ± 35,7 N para as mãos direita e esquerda, respectivamente. Não foram encontradas diferenças signifi cativas quando comparadas as mãos direita e esquerda. Uma análise individual e descritiva das variáveis permitiu observar assimetrias de até 30,6% para a Fmed e de até 35,9% para a Fmax. Entretanto, parece não haver relação entre os índices de simetria com o desempenho no nado peito em 50 m.
Poluição do ar e hospitalizações na maior metrópole brasileira
Authors: Gouveia Nelson , Corrallo Flavia Prado , Ponce de Leon Antônio Carlos , Junger Washington , Freitas Clarice Umbelino de
Published: December 2017

OBJETIVO: Avaliar o impacto da poluição do ar na maior metrópole brasileira sobre as internações por doenças respiratórias e cardiovasculares. MÉTODOS: Foi realizado estudo com dados das estações de monitoramento de nove municípios da Região Metropolitana de São Paulo, tendo o PM10 como indicador de poluição e as internações por doenças respiratórias e cardiovasculares como indicadores de efeito. Para cada município foi realizada uma análise de séries temporais usando modelos explicativos para contagens de internações ao longo do tempo via regressão de Poisson semi-paramétrica. Os resultados foram combinados em uma meta-análise de modo a estimar o risco global do PM10 na Região Metropolitana de São Paulo. RESULTADOS: Todos os municípios apresentaram estimativas estatisticamente significantes para as hospitalizações por doenças respiratórias com exceção de Santo André e Taboão da Serra. Os riscos relativos de admissão hospitalar para um aumento de 10 µg/m3 nos níveis de PM10 variaram de 1,011 (IC95% 1,009–1,013) para São Paulo a 1,032 (IC95% 1,024–1,040) em São Bernardo do Campo, para doenças respiratórias totais. O risco de internação por doenças respiratórias em crianças variou de 1,009 (IC95% 1,001–1,017) em Santo André a 1,077 (IC95% 1,056–1,098) em Mauá. Somente São Paulo e São Bernardo do Campo apresentaram resultados positivos e estatisticamente significantes para internações por doenças cardiovasculares. CONCLUSÕES: Esse é o primeiro estudo a estimar o risco de adoecimento devido à poluição do ar no conjunto de municípios da Região Metropolitana de São Paulo. As estimativas globais do efeito da exposição à poluição na região indicaram associações somente com as doenças respiratórias. Apenas São Paulo e de São Bernardo do Campo mostraram associação entre os níveis de PM10 e as internações por doenças cardiovasculares.
The Communist Party of China’s Approach to Human Rights and the Death Penalty
Authors: Gui Huang
Published: December 2017

Under the Constitution of China, the Communist Party (cpc) does not merely play a leadership role in the political field, but also in the legal arena. Legislation must reflect the Party’s outlook and achieve its policies, including any legal provisions governing particular systems, such as arrangements for the death penalty. After introducing the relationship between the cpc and legislation, this article will discuss the shift in the cpc’s approach to human rights and changes to the death penalty system in the Maoist, Deng Xiaoping and post-Deng eras. In the Maoist era, the government rejected human rights, but its policy on execution – at least on paper – was cautious and even stricter than during the other eras; the cpc recognised and accepted human rights in the Deng era, but emphasised national security and stability. As a result, individual human rights were not fully taken into account. Execution was considered an important measure to control crime and the scope of the relevant legislation was expanded. Post-Deng, human rights have developed gradually. Human rights protection has been incorporated into the Constitution and individual human rights have become more valued, but the cpc still focuses on state security, development and stability, and has not valued the right to life to the same extent as the right to subsistence. Although steps to reform the death penalty are being taken, 46 crimes are still punishable by death. The cpc should change its outlook and focus on the right to life, and abolish the death penalty de facto and de jure.
Moving Away From Paternalism: The New Law on Disability in Indonesia
Authors: Wardana Agung , Dewi Ni Putu Yogi Paramitha
Published: December 2017

In Indonesia, persons with disabilities have long been marginalised in mainstream development policies. The adoption of the United Nations Convention on the Rights of Persons with Disabilities (crpd), which was ratified by Indonesia in 2011, has opened new opportunities for persons with disabilities in the country to participate in the development process. In this regard, the first step toward the implementation of the convention domestically has been undertaken through the enactment of Law No. 8/2016 on Persons with Disabilities where the provisions of the convention are directly adopted. This article traces the development of the new law and how it differs from the previous legislation. We find that the new law is moving away from a long-standing paternalistic view toward disability in Indonesia by advancing a rights-based approach. Despite this substantial change, it remains to be seen how the new law would be able to change the challenging conditions of persons with disabilities in the country.
Achieving the Zenith of Education: Human Rights Based Transformation of Higher Education in Sri Lanka
Authors: Perera Binendri
Published: December 2017

As a country that has ratified core international human rights treaties, Sri Lanka has an international obligation to ensure that its higher education sector meets the standards set out in those treaties. However, due to a lack of normative recognition accorded at constitutional, legislative and policy levels, attempts at conformity with the aforementioned standards have been ad hoc and reactive. Consequently, whereas quality assurance mechanisms pertaining to state institutions are still in formative stages, private educational institutions have sprung up in the country without any effective scrutiny as to quality. The main method of challenging the standards of private institutions has been to reject the graduates from the said institutions.

This article explores the parameters of higher education as a state obligation under international human rights law, whereby the state is required simultaneously to be a provider of higher education and a facilitator of other providers to ensure that availability, accessibility, acceptability and adaptability of higher education are upheld. Establishment of a mechanism equipped to make human rights based transformations to the higher education sector of Sri Lanka is suggested to redress the deficiencies in setting standards for private higher educational institutions by the state.
A new and four known species of Diphtherophora (Nematoda: Diphtherophoridae) from Iran, with a diagnostic compendium of its species
Authors: GHADERI REZA , KASHI LEILA , KARANI HOSSEIN MIRBABAEI , KAREGAR AKBAR
Published: December 2017

A new and four known species of the genus Diphtherophora—D. geraerti sp. n., D. caudata, D. obesa, D. perplexans and D. tenera—were collected and identified from different plants and localities in Iran. Morphological and morphometric characters of Diphtherophora geraerti sp. n. are compared with those of closely-related species, including D. siddiqii, D. brevicollis, D. lata, D. obesa, D. citri, D. vasilevi and D. vitoshae. Females of the new species have a head continuous with the body contour, spear 11–14 µm in length, rod-shaped spermatozoa and conical tail with bluntly rounded to hemispherical terminus. Males have two ventromedian neck papillae located 22–25 and 52–60 µm from the anterior end, and two ventromedian supplements at 11–13 and 75–80 µm anterior from cloacal aperture, respectively. All Diphtherophora species recovered as part of the present study are new records for the Iranian nematode fauna. Finally, a diagnostic compendium is given, to assist with species identification in the genus.