bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral Cerebrovascular Stroke as an Initial Presenting Symptom of Moyamoya Disease
Authors: Ilyayeva Ester , Nada Khaled , Farahi Far Roxane , Albright Kamal , Gujral Manmeet Kaur , Gold Menachem
Published: November 2018

Moyamoya disease is a rare condition affecting the circle of Willis and its branching arteries. While the pathogenesis is unclear, it causes progressive occlusion of multiple cerebral vessels leading to severe strokes. We report a case of a 47-year-old Hispanic woman with HTN presented with altered mental status and bilateral upper and lower extremity weakness with dystonic-like upper extremity movement. Serial brain CTs and angiography were performed which showed massive frontal and parietal cerebral infarcts with radiological evidence of moyamoya disease.
Influence of Nanofiber Orientation on Morphological and Mechanical Properties of Electrospun Chitosan Mats
Authors: Nitti Paola , Gallo Nunzia , Natta Lara , Scalera Francesca , Palazzo Barbara , Sannino Alessandro , Gervaso Francesca
Published: November 2018

This work explored the use of chitosan (Cs) and poly(ethylene oxide) (PEO) blends for the fabrication of electrospun fiber-orientated meshes potentially suitable for engineering fiber-reinforced soft tissues such as tendons, ligaments, or meniscus. To mimic the fiber alignment present in native tissue, the CS/PEO blend solution was electrospun using a traditional static plate, a rotating drum collector, and a rotating disk collector to get, respectively, random, parallel, circumferential-oriented fibers. The effects of the different orientations (parallel or circumferential) and high-speed rotating collector influenced fiber morphology, leading to a reduction in nanofiber diameters and an improvement in mechanical properties.
Improving POI Recommendation via Dynamic Tensor Completion
Authors: Liao Jinzhi , Tang Jiuyang , Zhao Xiang , Shang Haichuan
Published: November 2018

POI recommendation finds significant importance in various real-life applications, especially when meeting with location-based services, e.g., check-ins social networks. In this paper, we propose to solve POI recommendation through a novel model of dynamic tensor, which is among the first triumphs of its kind. In order to carry out timely recommendation, we predict POI by utilizing a completion algorithm based on fast low-rank tensor. Particularly, the dynamic tensor structure is complemented by the fast low-rank tensor completion algorithm so as to achieve prediction with better performance, where the parameter optimization is achieved by a pigeon-inspired heuristic algorithm. In short, our POI recommendation via the dynamic tensor method can take advantage of the intrinsic characteristics of check-ins data due to the multimode features such as current categories, subsequent categories, and temporal information as well as seasons variations are all integrated into the model. Extensive experiment results not only validate the superiority of our proposed method but also imply the application prospect in large-scale and real-time POI recommendation environment.
Pedestrian Patterns at Railway Platforms during Boarding: Evidence from a Case Study in Switzerland
Authors: Dell’Asin Giulia , Hool Johannes
Published: November 2018

The boarding/alighting process at railway platforms is an important determinant of the railway system performance and depends on the characteristics of passengers, the layout of the platform, and the rolling stock. This research aims to increase the understanding of the process, providing a methodological approach to model the passengers’ behaviour when boarding at railway platforms. Adequate criteria were selected to define the so called “boarding cluster” and an easy mechanism was developed to select the boarding clusters. Passenger flow data collected at Bern railway station in Switzerland was used to test the proposed approach. The results show that (a) the clusters near the doors grow in the longitudinal direction with a rate of 6:1 between the length and width of clusters, and that (b) the growth curves rise quickly when clusters are still small, i.e., at the beginning of the boarding/alighting activity. Further research is needed to extend the validation of the model, considering other variables, such as critical pedestrian densities which occur at specific hot spots near obstacles at platforms.
Anaesthetic Considerations in a Patient with Pycnodysostosis undergoing Caesarean Delivery
Authors: Hansen Niklas S. , Dalgaard Karoline S. , Jensen Troels B.
Published: November 2018

Pycnodysostosis is a rare congenital disorder with several implications, which might complicate anesthesia. Patients are more prone to fractures and have an anticipated difficult airway. We report a case of a 34-year-old woman with pycnodysostosis who underwent elective caesarean delivery under epidural blockade.
Exploring Epidemiological Aspects, Distribution of WHO Maternal Near Miss Criteria, and Organ Dysfunction Defined by SOFA in Cases of Severe Maternal Outcome Admitted to Obstetric ICU: A Cross-Sectional Study
Authors: Oliveira Neto Antonio Francisco , Parpinelli Mary Angela , Costa Maria Laura , Souza Renato Teixeira , Ribeiro do Valle Carolina , Cecatti José Guilherme
Published: November 2018

Objective. To explore the epidemiological aspects, to describe the frequency and distribution of WHO maternal near miss (MNM) criteria and the presence of organ dysfunction and failure measured by the maximum SOFA (Sequential Organ Failure Assessment) score (SOFA max) in cases of severe maternal outcome (SMO). Methods. In an observational cross-sectional study performed between January 2013 and December 2015, 279 pregnant or postpartum women were admitted to an obstetric ICU (intensive care unit) in Brazil. MNM, maternal death (grouped as SMO), and potentially life-threatening conditions (PLTC) were defined according to WHO criteria. For categorical variables, a descriptive analysis was carried out. Frequency and distribution of WHO criteria, organ dysfunction, or failure defined by SOFA max were performed. Results. WHO criteria identified 65 SMO and 214 PLTC. Management criteria were present in 58/65 (89.2%) while 61/65 (93.8%) of SMO cases had dysfunction or failure by SOFA. Conclusions. The systematic evaluation of the organic function by SOFA max score identified the presence of organic dysfunction or failure in almost all SMO cases. Management criteria were present in all MD cases. Our results indicate the need for new studies evaluating the parameterization of the WHO laboratory criteria for values compatible with the definition of organic dysfunction by the SOFA to identify MNM.
Using Multiple Criteria Optimization and Two‐Stage Genetic Algorithms to Select a Population Management Strategy with Optimized Reliability
Authors: Chapman Jessica L. , Lu Lu , Anderson-Cook Christine M.
Published: November 2018

An important aspect of good management of inventory for many single‐use populations or stockpiles is to develop an informed consumption strategy to use a collection of single‐use units, with varied reliability as a function of age, during scheduled operations. We present a two‐phase approach to balance multiple objectives for a consumption strategy to ensure good performance on the average reliability, consistency of unit reliability over time, and least uncertainty of the reliability estimates. In the first phase, a representative subset of units is selected to explore the impact of using units at different time points on reliability performance and to identify beneficial consumption patterns using a nondominated sorting genetic algorithm based on multiple objectives. In the second phase, the results from the first phase are projected back to the full stockpile as a starting point for determining best consumption strategies that emphasize the priorities of the manager. The method can be generalized to other criteria of interest and management optimization strategies. The method is illustrated with an example that shares characteristics with some munition stockpiles and demonstrates the substantial advantages of the two‐phase approach on the quality of solutions and efficiency of finding them.
Rapid Disaster Data Dissemination and Vulnerability Assessment through Synthesis of a Web‐Based Extreme Event Viewer and Deep Learning
Authors: Crawford P. Shane , Al-Zarrad Mohammad A. , Graettinger Andrew J. , Hainen Alexander M. , Back Edward , Powell Lawrence
Published: November 2018

Infrastructure vulnerability has drawn significant attention in recent years, partly because of the occurrence of low‐probability and high‐consequence disruptive events such as 2017 hurricanes Harvey, Irma, and Maria, 2011 Tuscaloosa and Joplin tornadoes, and 2015 Gorkha, Nepal, and 2017 Central Mexico earthquakes. Civil infrastructure systems support social welfare, thus viability and sustained operation is critical. A variety of frameworks, models, and tools exist for advancing infrastructure vulnerability research. Nevertheless, providing accurate vulnerability measurement remains challenging. This paper presents a state‐of‐the‐art data collection and information extraction methodology to document infrastructure at high granularity to assess preevent vulnerability and postevent damage in the face of disasters. The methods establish a baseline of preevent infrastructure functionality that can be used to measure impacts and temporal recovery following a disaster. The Extreme Events Web Viewer (EEWV) presented as part of the methodology is a GIS‐based web repository storing spatial and temporal data describing communities before and after disasters and facilitating data analysis techniques. This web platform can store multiple geolocated data formats including photographs and 360° videos. A tool for automated extraction of photography from 360° video data at locations of interest specified in the EEWV was created to streamline data utility. The extracted imagery provides a manageable data set to efficiently document characteristics of the built and natural environment. The methodology was tested to locate buildings vulnerable to flood and storm surge on Dauphin Island, Alabama. Approximately 1,950 buildings were passively documented with vehicle‐mounted 360° video. Extracted building images were used to train a deep learning neural network to predict whether a building was elevated or nonelevated. The model was validated, and methods for iterative neural network training are described. The methodology, from rapidly collecting large passive datasets, storing the data in an open repository, extracting manageable datasets, and obtaining information from data through deep learning, will facilitate vulnerability and postdisaster analyses as well as longitudinal recovery measurement.
Mitochondrial DNA D-Loop Diversity of the Helmeted Guinea Fowls in Kenya and Its Implications on HSP70 Gene Functional Polymorphism
Authors: Murunga Philip , Kennedy Grace Moraa , Imboma Titus , Malaki Phillista , Kariuki Daniel , Ndiema Emmanuel , Obanda Vincent , Agwanda Bernard , Lichoti Jacqueline Kasiiti , Ommeh Sheila Cecily
Published: November 2018

We analyzed variations in 90 mitochondrial DNA (mtDNA) D-loop and heat shock protein 70 (HSP70) gene sequences from four populations of domesticated helmeted Guinea fowls (70 individuals) and 1 population of wild helmeted Guinea fowls (20 individuals) in Kenya in order to get information about their origin, genetic diversity, and traits associated with heat stress. 90 sequences were assigned to 25 distinct mtDNA and 4 HSP70 haplotypes. Most mtDNA haplotypes of the domesticated helmeted Guinea fowls were grouped into two main haplogroups, HgA and HgB. The wild population grouped into distinct mtDNA haplogroups. Two mtDNA haplotypes dominated across all populations of domesticated helmeted Guinea fowls: Hap2 and Hap4, while the dominant HSP70 haplotype found in all populations was CGC. Higher haplotype diversities were generally observed. The HSP70 haplotype diversities were low across all populations. The nucleotide diversity values for both mtDNA and HSP70 were generally low. Most mtDNA genetic variations occurred among populations for the three hierarchical categories considered while most variations in the HSP70 gene occurred among individuals within population. The lack of population structure among the domestic populations could suggest intensive genetic intermixing. The differentiation of the wild population may be due to a clearly distinct demographic history that shaped its genetic profile. Analysis of the Kenyan Guinea fowl population structure and history based on mtDNA D-loop variations and HSP70 gene functional polymorphisms complimented by archaeological and linguistic insight supports the hypothesis that most domesticated helmeted Guinea fowls in Kenya are related to the West African domesticated helmeted Guinea fowls. We recommend more molecular studies on this emerging poultry species with potential for poverty alleviation and food security against a backdrop of climate change in Africa.
Paroxysmal Cold Hemoglobinuria in an Adult with Respiratory Syncytial Virus
Authors: Leibrandt Ryan , Angelino Kenneth , Vizel-Schwartz Monique , Shapira Ilan
Published: November 2018

Paroxysmal cold hemoglobinuria (PCH) is a rare form of cold autoimmune hemolytic anemia first discovered in the early 20th century in adults with tertiary syphilis. Today, it is more commonly seen in children as a life-threatening anemia during a viral upper respiratory tract infection (URI). Although respiratory syncytial virus (RSV) has previously been reported to cause PCH in a child, herein we present the first documented case in an adult. The Donath–Landsteiner (DL) test, the diagnostic test for PCH, was positive on two separate occasions. The patient was treated successfully with warming and avoidance of cold temperatures. To facilitate identification of this rare entity by clinicians, we include a discussion about the pathophysiology, diagnosis, and treatment of PCH.
Encoding Longer‐Term Contextual Information with Predictive Coding and Ego‐Motion
Authors: Zhong Junpei , Cangelosi Angelo , Ogata Tetsuya , Zhang Xinzheng
Published: November 2018

Studies suggest that, within the hierarchical architecture, the topological higher level possibly represents the scenarios of the current sensory events with slower changing activities. They attempt to predict the neural activities on the lower level by relaying the predicted information after the scenario of the sensorimotor event has been determined. On the other hand, the incoming sensory information corrects such prediction of the events on the higher level by the fast‐changing novel or surprising signal. From this point, we propose a predictive hierarchical artificial neural network model that examines this hypothesis on neurorobotic platforms. It integrates the perception and action in the predictive coding framework. Moreover, in this neural network model, there are different temporal scales of predictions existing on different levels of the hierarchical predictive coding architecture, which defines the temporal memories in recording the events occurring. Also, both the fast‐ and the slow‐changing neural activities are modulated by the motor action. Therefore, the slow‐changing neurons can be regarded as the representation of the recent scenario which the sensorimotor system has encountered. The neurorobotic experiments based on the architecture were also conducted.
Chemocatalytic Production of Lactates from Biomass-Derived Sugars
Authors: Zhang Heng , Hu Yulin , Qi Liying , He Jian , Li Hu , Yang Song
Published: November 2018

In recent decades, a great deal of attention has been paid to the exploration of alternative and sustainable resources to produce biofuels and valuable chemicals, with aims of reducing the reliance on depleting confined fossil resources and alleviating serious economic and environmental issues. In line with this, lignocellulosic biomass-derived lactic acid (LA, 2-hydroxypropanoic acid), to be identified as an important biomass-derived commodity chemical, has found wide applications in food, pharmaceuticals, and cosmetics. In spite of the current fermentation of saccharides to produce lactic acid, sustainability issues such as environmental impact and high cost derived from the relative separation and purification process will be growing with the increasing demands of necessary orders. Alternatively, chemocatalytic approaches to manufacture LA from biomass (i.e., inedible cellulose) have attracted extensive attention, which may give rise to higher productivity and lower costs related to product work-up. This work presents a review of the state-of-the-art for the production of LA using homogeneous, heterogeneous acid, and base catalysts, from sugars and real biomass like rice straw, respectively. Furthermore, the corresponding bio-based esters lactate which could serve as green solvents, produced from biomass with chemocatalysis, is also discussed. Advantages of heterogeneous catalytic reaction systems are emphasized. Guidance is suggested to improve the catalytic performance of heterogeneous catalysts for the production of LA.
The Effect of Chlorhexidine and Listerine® Mouthwashes on the Tensile Strength of Selected Absorbable Sutures: An In Vitro Study
Authors: Alsarhan Mohammed , Alnofaie Hourya , Ateeq Rawan , Almahdy Ahmed
Published: November 2018

Background. Suturing plays a critical role in the healing of surgical wounds. The tensile strength of suture materials indicates the ability of the material to withstand stress during knotting and protect the wound during an extended period of healing. Objective. An in vitro study was conducted to determine the effect of two commercially available mouthwashes on the tensile strength and breakage mode of two absorbable intraoral sutures. Materials and Methods. Two common absorbable sutures, Vicryl® and Monocryl®, both with 4-0 and 5-0 gauges were used. A total of 400 specimens were sutured around rubber rods and immersed in three thermostatically controlled experimental conditions: artificial saliva, 0.2% chlorhexidine gluconate (Parodontax® extra), and essential oils-based rinse (Listerine® Zero™), and these were compared to a nonimmersed dry condition. All specimens were stored in an incubator at 37°C. Tensile strengths were assessed after days 1, 3, 7, 10, and 14 of immersion using a universal Instron® testing machine. The maximum load for suture breakage and the location of the point of breakage were assessed. Results. Unlike Monocryl® 4-0, the tensile strength of both gauges of Vicryl® sutures significantly increased in chlorhexidine and Listerine®. There was a significant decrease in the strength for all suture types after day 10, regardless of the immersion solution. Listerine® significantly reduced the tensile strength of Monocryl® 5-0. Conclusion. Oral surgeons and periodontists should be cautious when prescribing commercial mouthwashes for patients relative to their selection of suture materials. However, further studies are needed to understand the molecular changes in sutures when exposed to chemical solutions found in mouthwashes.
Evaluating the Efficacy and Adverse Effects of Clearing Heat and Removing Dampness Method of Traditional Chinese Medicine by Comparison with Western Medicine in Patients with Gout
Authors: Xiao Nan , Chen Hao , He Shi-Yong , Xue Chong-Xiang , Sui Hua , Chen Jing , Qu Jia-Lin , Liang Li-Na , Zhang Lin
Published: November 2018

Objective. In China, the method of clearing heat and removing dampness medicine of Chinese traditional medicine has been widely used on gout. However, the clinical effects are various and not summarized systematically. Methods. In this study, a large number of randomized controlled clinical trials were reviewed and analyzed and the clinical efficacy and adverse reactions of traditional Chinese medicine with clearing heat and removing dampness effects for the treatment of gout were systematically evaluated. A comprehensive search of databases including pubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, Wanfang Data, and SinoMed was performed. Results. There are 69 randomized controlled trials with 5915 sample sizes meeting the criteria in the study. The results of the meta‐analysis indicate that the effects of clearing heat and removing dampness medicine were slightly better than western medicine in the treatment of gout based on the following parameters: serum uric acid (standardized mean difference (SMD):‐62.14, 95% confidence interval (CI): ‐78.12 to‐46.15), C reactive protein (SMD: ‐4.21, 95% CI: ‐6.19 to ‐2.23), erythrocyte sedimentation rate (SMD: ‐6.23, 95% CI: ‐8.39 to‐4.06), and overall clinical response (relative risk (RR): 1.11, 95% CI: 1.08 to 1.15) and, in the profile of adverse drug reactions, the clearing heat and removing dampness medicine showed less adverse reactions than traditional Western medicine (RR: 0.18, 95% CI: 0.10 to 0.32). Conclusions. Through a systemic evaluation of the clinical efficacy of the clearing heat and removing dampness medicine of traditional Chinese medicine and western medicine on gout, the clearing heat and removing dampness medicine and western medicine possessed similar clinical efficacy, but traditional Chinese medicine treatments are superior to western medicine in controlling adverse reactions.
Speciation Analysis of Arsenic Compounds by HPLC-ICP-MS: Application for Human Serum and Urine
Authors: Nguyen Manh Ha , Pham Tien Duc , Nguyen Thi Lien , Vu Hai Anh , Ta Thi Thao , Tu Minh Binh , Nguyen Thi Hong Yen , Chu Dinh Binh
Published: November 2018

A high-performance liquid chromatography (HPLC) in combination with inductively coupled plasma mass spectrometry (ICP-MS) as an elemental specific detector was used for the speciation analysis of arsenic compounds in urine and serum samples from Vietnam. Five arsenic species including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB) were studied. A gradient elution of ammonium carbonate ((NH4)2CO3), ethylenediaminetetraacetic acid disodium salt (Na2EDTA), and methanol at pH 9.0 utilizing Hamilton PRP-X100 strong anion-exchange column allowed the chromatographic separation of five arsenic species. In this study, urine and serum samples were prepared by dilution in solvent and protein precipitation by trichloroacetic acid, respectively. The extraction efficiency was greater than 91% for urine matrix, and recoveries from spiked samples were in the range of 94–139% for the arsenic species in human serum. The method limit of detection (MDL) and limit of quantification (MQL), which were calculated by signal to noise ratio, were found to be 0.3–1.5 and 1.0–5.0 ng·mL−1, respectively. The concentration of arsenic species in 17 pairs of urine and serum samples from Vietnam was also quantified and evaluated. The major species of arsenic in the urine and serum samples were AsB and DMA.
Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors
Authors: Hong David S. , LoRusso Patricia , Hamid Omid , Janku Filip , Kittaneh Muaiad , Catenacci Daniel V.T. , Chan Emily , Bekaii-Saab Tanios , Gadgeel Shirish M. , Loberg Robert D. , Amore Benny M. , Hwang Yuying C. , Tang Rui , Ngarmchamnanrith Gataree , Kwak Eunice L.
Published: November 2018

Purpose:

This first-in-human, open-label phase I study evaluated AMG 337, an oral, highly selective small-molecule inhibitor of MET in advanced solid tumors.

Patients and Methods: Patients enrolled into dose-escalation cohorts received AMG 337 up to 400 mg once daily or up to 250 mg twice daily, following a modified 3+3+3 design. Dose expansion was conducted in MET-amplified patients at the maximum tolerated dose (MTD). Primary endpoints included assessment of adverse events (AEs), establishment of the MTD, and pharmacokinetics; clinical response was a secondary endpoint.

Results:

The safety analysis set included 111 patients who received ≥1 dose of AMG 337. Thirteen patients had ≥1 AE qualifying as dose-limiting toxicity. The MTD was determined to be 300 mg once daily; the MTD for twice-daily dosing was not reached. Most frequent treatment-related AEs were headache (63%) and nausea (31%). Grade ≥3 treatment-related AEs occurred in 23 patients (21%), most commonly headache (n = 6) and fatigue (n = 5). Maximum plasma concentration occurred at 3.0 hours following 300-mg once-daily dosing, indicating AMG 337 absorption soon after treatment. Objective response rate was 9.9% (11/111; 95% CI, 5.1%–17.0%) in all patients and 29.6% (8/27; 95% CI, 13.8%–50.2%) in MET-amplified patients; median (range) duration of response was 202 (51–1,430+) days in all patients and 197 (64–1,430+) days in MET-amplified patients.

Conclusions:

Oral AMG 337 was tolerated with manageable toxicities, with an MTD and recommended phase II dose of 300 mg once daily. The promising response rate observed in patients with heavily pretreated MET-amplified tumors warrants further investigation.

See related commentary by Ma, p. 2375
Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma
Authors: Hogan Sabrina A. , Courtier Anaïs , Cheng Phil F. , Jaberg-Bentele Nicoletta F. , Goldinger Simone M. , Manuel Manuarii , Perez Solène , Plantier Nadia , Mouret Jean-François , Nguyen-Kim Thi Dan Linh , Raaijmakers Marieke I.G. , Kvistborg Pia , Pasqual Nicolas , Haanen John B.A.G. , Dummer Reinhard , Levesque Mitchell P.
Published: November 2018

Many metastatic melanoma patients experience durable responses to anti-PD1 and/or anti-CTLA4; however, a significant proportion (over 50%) do not benefit from the therapies. In this study, we sought to assess pretreatment liquid biopsies for biomarkers that may correlate with response to checkpoint blockade. We measured the combinatorial diversity evenness of the T-cell receptor (TCR) repertoire (the DE50, with low values corresponding to more clonality and lack of TCR diversity) in pretreatment peripheral blood mononuclear cells from melanoma patients treated with anti-CTLA4 (n = 42) or anti-PD1 (n = 38) using a multi-N-plex PCR assay on genomic DNA (gDNA). A receiver operating characteristic curve determined the optimal threshold for a dichotomized analysis according to objective responses as defined by RECIST1.1. Correlations between treatment outcome, clinical variables, and DE50 were assessed in multivariate regression models and confirmed with Fisher exact tests. In samples obtained prior to treatment initiation, we showed that low DE50 values were predictive of a longer progression-free survival and good responses to PD-1 blockade, but, on the other hand, predicted a poor response to CTLA4 inhibition. Multivariate logistic regression models identified DE50 as the only independent predictive factor for response to anti-CTLA4 therapy (P = 0.03) and anti-PD1 therapy (P = 0.001). Fisher exact tests confirmed the association of low DE50 with response in the anti-CTLA4 (P = 0.041) and the anti-PD1 cohort (P = 0.0016). Thus, the evaluation of basal TCR repertoire diversity in peripheral blood, using a PCR-based method, could help predict responses to anti-PD1 and anti-CTLA4 therapies.
High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions
Authors: Blaha Dylan T. , Anderson Scott D. , Yoakum Daniel M. , Hager Marlies V. , Zha Yuanyuan , Gajewski Thomas F. , Kranz David M.
Published: November 2018

Mutated peptides (neoantigens) from a patient's cancer genome can serve as targets for T-cell immunity, but identifying which peptides can be presented by an MHC molecule and elicit T cells has been difficult. Although algorithms that predict MHC binding exist, they are not yet able to distinguish experimental differences in half-lives of the complexes (an immunologically relevant parameter, referred to here as kinetic stability). Improvement in determining actual neoantigen peptide/MHC stability could be important, as only a small fraction of peptides in most current vaccines are capable of eliciting CD8+ T-cell responses. Here, we used a rapid, high-throughput method to experimentally determine peptide/HLA thermal stability on a scale that will be necessary for analysis of neoantigens from thousands of patients. The method combined the use of UV-cleavable peptide/HLA class I complexes and differential scanning fluorimetry to determine the Tm values of neoantigen complexes. Measured Tm values were accurate and reproducible and were directly proportional to the half-lives of the complexes. Analysis of known HLA-A2–restricted immunogenic peptides showed that Tm values better correlated with immunogenicity than algorithm-predicted binding affinities. We propose that temperature stability information can be used as a guide for the selection of neoantigens in cancer vaccines in order to focus attention on those mutated peptides with the highest probability of being expressed on the cell surface.
Mapping the MHC Class I–Spliced Immunopeptidome of Cancer Cells
Authors: Liepe Juliane , Sidney John , Lorenz Felix K.M. , Sette Alessandro , Mishto Michele
Published: November 2018

Anticancer immunotherapies demand optimal epitope targets, which could include proteasome-generated spliced peptides if tumor cells were to present them. Here, we show that spliced peptides are widely presented by MHC class I molecules of colon and breast carcinoma cell lines. The peptides derive from hot spots within antigens and enlarge the antigen coverage. Spliced peptides also represent a large number of antigens that would otherwise be neglected by patrolling T cells. These antigens tend to be long, hydrophobic, and basic. Thus, spliced peptides can be a key to identifying targets in an enlarged pool of antigens associated with cancer.
Challenging the Use of Bandage Compression as the Baseline for Evaluating the Healing Outcomes of Venous Leg Ulcer-Related Compression Therapies in the Community and Outpatient Setting: An Integrative Review
Authors: Asaf Maryam , Salim Nezar , Tuffaha Mohammed
Published: November 2018

Background: Venous ulcers have considerable human and financial costs. Bandage compression is the most common type of compression used to enhance healing. Ulcer size, pretreatment ulcer duration, and the consistency of pressure (depending on the competency of the bandager) significantly affect the healing process. Summary: The aim of this review is to explore whether the variability in bandage-related baselines contributes to the differences in healing outcomes among the empirical studies designed to evaluate bandage compression for treating venous ulcers in community and outpatient settings. Two health-related databases were searched: Medline and the Cumulative Index for Nursing and Allied Health. A manual search of relevant reviews and publication reference lists was also undertaken. Fourteen studies were included. The most common study design was a randomized controlled trial. Only one study used a cohort design. This review focused on two variables: healing rate and healing time. The ulcer features, the consistency of the pressure level, and the competency of the bandager were the main factors within the reviewed studies that affect the baselines and healing outcomes. Key Messages: This integrative review confirms that the large variability in the baselines results from differences in the ulcer size, duration, competency level, and amount of pressure that led to differing healing outcomes. Future research designs need to pay attention to make the baselines consistent by ensuring that the ulcer size, duration, competency of the nurses, and level of compression are comparable and consistent within the studies’ design.
The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension
Authors: Brunelli Steven M. , Cohen Dena E. , Marlowe Gilbert , Van Wyck David
Published: November 2018

Background: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis, and is associated with significant morbidity and mortality. Off-label use of the alpha-1 andrenergic receptor agonist midodrine to reduce the frequency and severity of IDH is common. However, limited data exist to support this practice. This study sought to examine real-world efficacy of midodrine with respect to relevant clinical and hemodynamic outcomes. Methods: Here, we compared a variety of clinical and hemodynamic outcomes among adult patients who were prescribed midodrine (n = 1,046) and matched controls (n = 2,037), all of whom were receiving in-center hemodialysis treatment at dialysis facilities in the United States (July 2015 – September 2016). Mortality, all-cause hospitalization, cardiovascular hospitalization, and hemodynamic outcomes were considered from the month following the initiation of midodrine (or corresponding month for controls) until censoring for discontinuation of dialysis, transplant, loss to follow-up, or study end (September 30, 2016). Rate outcomes were compared using Poisson models and quantitative outcomes using linear mixed models; all models were adjusted for imbalanced patient characteristics. Results: Compared to non-use, midodrine use was associated with higher rates of death (adjusted incidence rate ratio 1.37, 95% CI 1.15–1.62), all-cause hospitalization (1.31, 1.19–1.43) and cardiovascular hospitalization (1.41, 1.17–1.71). During follow-up, midodrine use tended to be associated with lower pre-dialysis systolic blood pressure (SBP), lower nadir SBP, greater fall in SBP during dialysis, and a greater proportion of treatments affected by IDH. Conclusion: Although residual confounding may have influenced the results, the associations observed here are not consistent with a potent beneficial effect of midodrine with respect to either clinical or hemodynamic outcomes.
High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits
Authors: Carraro Michela , Checchetto Vanessa , Sartori Geppo , Kucharczyk Roza , di Rago Jean-Paul , Minervini Giovanni , Franchin Cinzia , Arrigoni Giorgio , Giorgio Valentina , Petronilli Valeria , Tosatto Silvio C.E. , Lippe Giovanna , Szabó Ildikó , Bernardi Paolo
Published: November 2018

Background/Aims: The permeability transition pore (PTP) is an unselective, Ca2+-dependent high conductance channel of the inner mitochondrial membrane whose molecular identity has long remained a mystery. The most recent hypothesis is that pore formation involves the F-ATP synthase, which consistently generates Ca2+-activated channels. Available structures do not display obvious features that can accommodate a channel; thus, how the pore can form and whether its activity can be entirely assigned to F-ATP synthase is the matter of debate. In this study, we investigated the role of F-ATP synthase subunits e, g and b in PTP formation. Methods: Yeast null mutants for e, g and the first transmembrane (TM) α-helix of subunit b were generated and evaluated for mitochondrial morphology (electron microscopy), membrane potential (Rhodamine123 fluorescence) and respiration (Clark electrode). Homoplasmic C23S mutant of subunit a was generated by in vitro mutagenesis followed by biolistic transformation. F-ATP synthase assembly was evaluated by BN-PAGE analysis. Cu2+ treatment was used to induce the formation of F-ATP synthase dimers in the absence of e and g subunits. The electrophysiological properties of F-ATP synthase were assessed in planar lipid bilayers. Results: Null mutants for the subunits e and g display dimer formation upon Cu2+ treatment and show PTP-dependent mitochondrial Ca2+ release but not swelling. Cu2+ treatment causes formation of disulfide bridges between Cys23 of subunits a that stabilize dimers in absence of e and g subunits and favors the open state of wild-type F-ATP synthase channels. Absence of e and g subunits decreases conductance of the F-ATP synthase channel about tenfold. Ablation of the first TM of subunit b, which creates a distinct lateral domain with e and g, further affected channel activity. Conclusion: F-ATP synthase e, g and b subunits create a domain within the membrane that is critical for the generation of the high-conductance channel, thus is a prime candidate for PTP formation. Subunits e and g are only present in eukaryotes and may have evolved to confer this novel function to F-ATP synthase.
miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1
Authors: Wang Xuesong , Peng Lei , Gong Xiaojin , Zhang Xiugong , Sun Ruifu , Du Jinlong
Published: November 2018

Background/Aims: Increasing evidences suggest that dysregulated expression of miRNAs contributes to the progression of various tumors. However, the underlying function of miR-423-5p in osteosarcoma remains unexplored. Methods: The expression of miR-423-5p and STMN1 were determined in osteosarcoma samples and cell lines via quantitative real-time PCR. Colony formation and Cell Counting Kit-8 (CCK-8) assays were performed to measure cell proliferation ability and transwell analysis was used to detect cell invasion, and dual luciferase reporter assay was perform to analysis the interaction between the miR-423-5p and STMN1. Results: The expression levels of miR-423-5p and STMN1 in the osteosarcoma tissues and cell lines were measured by qRT-PCR. Cell viability was determined using the clone formation and CCK-8 assays. A dual-luciferase reporter and Western blot were performed to stdudy the target gene of miR-423-5p. Here, we showed that miR-423-5p expression was downregulated in osteosarcoma tissues and cell lines. However, the expression of stathmin1 (STMN1) was downregulated in osteosarcoma tissues and cell lines. Moreover, STMN1 expression level was negatively correlated with the miR-423-5p expression in the osteosarcoma tissues. We identified STMN1 was a direct target gene of miR-423-5p in osteosarcoma cell. Overexpression of miR-423-5p inhibited osteosarcoma cell proliferation, colony formation and invasion. Furthermore, we demonstrated that STMN1 was involved in miR-423-5p-mediated cell behavior such as cell proliferation, colony formation and invasion in the osteosarcoma cell. Conclusion: Our present study indicated that miR-423-5p acted as a tumor suppressor gene in osteosarcoma partly through inhibiting STMN1 expression.
MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice
Authors: Liu Ying  , Miao Yi , Gao Xin , Wang Yuan-Yuan , Wang Huan , Zheng Ya-Wen , Zhao Zhi-Yuan
Published: November 2018

Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.
Genome-Wide Analysis of mRNAs and lncRNAs of Intramuscular Fat Related to Lipid Metabolism in Two Pig Breeds
Authors: Huang Wanlong , Zhang Xiuxiu , Li Ai , Xie Lingli , Miao Xiangyang
Published: November 2018

Background/Aims: Long non-coding RNAs (lncRNAs) can regulate adipogenesis and lipid accumulation. Intramuscular fat deposition appears to vary in different pig breeds, and the regulation mechanism has not yet been fully elucidated at molecular level. Moreover, little is known about the function and profile of lncRNAs in intramuscular fat deposition and metabolism in pig. The aim of this study was thus to explore the regulatory functions of lncRNAs in intramuscular fat deposition. Methods: In this study, Laiwu (LW) pig and Large White (LY) pig with significant difference in fat deposition were selected for use. RNA-seq technology and bioinformatics methods were used to comparatively analyze the gene expression profiles of intramuscular fat between LW and LY pigs to identify key mRNAs and lncRNAs associated with lipid metabolism and adipogenesis. Real-time fluorescence-based quantitative PCR was applied to verify the expression level of the differentially expressed mRNAs and lncRNAs. Results: A total of 513 mRNAs and 55 lncRNAs were differentially expressed between two pig breeds. By co-expression network construction as well as cis- and trans-regulated target gene analysis, 31 key lncRNAs were identified. Gene Ontology and KEGG pathway analyses revealed that differentially expressed genes and lncRNAs were mainly involved in the biological processes and pathways related to adipogenesis and lipid metabolism. Conclusion: XLOC_046142, XLOC_004398 and XLOC_015408 may target MAPKAPK2, NR1D2 and AKR1C4, respectively, and play critical regulatory roles in intramuscular adipogenesis and lipid accumulation in pig. XLOC_064871 and XLOC_011001 may play a role in lipid metabolism-related disease via regulating TRIB3 and BRCA1. This study provides a valuable resource for lncRNA study and improves our understanding of the biological roles of lipid metabolism- related genes and molecular mechanism of intramuscular fat metabolism and deposition.
ДЕЯКІ АСПЕКТИ КОРЕКЦІЇ ЛІПІТЕНЗІЇ – НОВОЇ ПРОБЛЕМИ У СУЧАСНІЙ КАРДІОЛОГІЇ
Authors: Radetska L. V. , Yarema N. I. , Smachylo I. V. , Bob A. O. , Mandzii Z. P. , Khomitska A. I. , Savchenko I. P. , Naumova L. V.
Published: November 2018

Ліпітензія – це сучасний термін, що описує адитивний вплив артеріальної гіпертензії та гіперхолестеринемії на ризик серцево-судинних захворювань (ССЗ). Згідно з епідеміологічними дослідженнями, понад 50 % пацієнтів з артеріальною гіпертензією (АГ) мають гіперліпідемію.

Мета дослідження – оцінити ефективність сучасної антигіпертензивної терапії у поєднанні зі статинотерапією та урсодезоксихолевою кислотою (УДХК) у хворих із ліпітензією (АГ та гіперхолестеринемією).

Матеріали і методи. Обстежено 36 пацієнтів із гіпертонічною хворобою (ГХ) ІІ стадії 2–3 ступенів та гіперхолестеринемією, яким на тлі потрійної антигіпертензивної терапії (валсартан, амлодипін, тіазидний діуретик), аторвакору, урсохолу проводили комплексне клінічне дослідження, моніторування артеріального тиску (АТ) та ліпідного метаболізму.

Результати досліджень та їх обговорення. Результати моніторування АТ свідчать про сприятливий вплив лікування на добовий профіль АТ: через 2 місяці терапії зареєстровано достовірне зниження середньодобового систолічного та діастолічного артеріального тиску. Під впливом аторвастатину та урсохолу відбулось поліпшення показників ліпідного обміну, що проявлялось достовірним зниженням рівня загального холестерину та холестерину ліпопротеїнів низької щільності, зростанням вмісту ліпопротеїнів високої щільності.

Висновки. У статті обґрунтовано поєднане використання потрійної антигіпертензивної терапії, статинотерапії та урсохолу в пацієнтів із ліпітензією, особливо у клінічних випадках, при яких необхідно обмежити дозування статинів з точки зору поліпшення прогнозу хворих на ГХ за рахунок синергізму антигіпертензивного та ліпідознижувального потенціалів і плейотропних ефектів цих препаратів, дія яких направлена на сповільнення прогресування ГХ і атеросклерозу.
ДОСЛІДЖЕННЯ ВИМОГ ДО ІНСТРУМЕНТА ДЛЯ ОТРИМАННЯ ЕЛЕКТРОЗВАРНОГО З’ЄДНАННЯ СТІНОК КИШЕЧНИКА В ЕКСПЕРИМЕНТІ
Authors: Podpriatov S. S. , Podpryatov S. E. , Gichka S. G. , Makarov A. V. , Marinsky G. S. , Tkachenko V. A. , Chernets O. V. , Tarnavsky D. V. , Lopatkina K. G.
Published: November 2018

Створення електрозварного міжкишкового анастомозу є очікуваною новою технологією. Упровадження результатів досліджень у спеціалізованому інструменті вимагає попереднього вивчення змін у місці електрозварювання.

Мета досліджень – на основі стендових досліджень із прототипом спеціалізованого інструмента установити вимоги до інструментів для створення електрозварного з’єднання в міжкишковому анастомозі для клінічних випробувань.

Матеріали і методи. В умовах гострого експерименту на свині та лабораторних досліджень на органокомплексах виконали 98 серій досліджень із лінійними та циркулярними електродами. Джерелом електрозварювальних імпульсів були адаптовані клінічні апарати ЕК-300М1 та ЕКВЗ-300 “Патонмед”. Тиск втрати герметичності порівнювали з тиском, який визначали ми раніше, для скобкового анастомозу – (24,2±3,2) мм рт. ст.

Результати досліджень та їх обговорення. Моделювали розташування кишки в циркулярному анастомозі та стискали електродами в діапазоні від 2,0 до 3,0 Н/мм2. Застосовували напругу до 140 В, струм – до 5 А. У 32,4 % спостережень виявлено ділянки від 1/3 до 1/4 довжини кола, із менш щільним з’єднанням, або розрізали струмом. Середня міцність анастомозу в дослідженні склала (36,2±12,3) мм рт. ст., діапазон міцності нещільних ділянок – 12–34 мм рт. ст. При тиску 3,0 Н/мм2 розподіл ефектів електрозварного струму в тканинах був рівномірним.

Висновки. Розміри електродів, величина та межі стиснення тканини, функціональний стан стінки кишки, відведення пари та фіксація від розмикання є чинниками стабільної щільності тканини між електродами, перебігу електрозварного струму та досягнення характеристик електрозварного міжкишкового з’єднання, прийнятних для клінічного впровадження.