bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of systemic inflammation to permanence of KATP-induced neonatal diabetes in mice
Authors: Emfinger Christopher H. , Yan Zihan , Welscher Alecia , Hung Peter , McAllister William , Hruz Paul W. , Nichols Colin G. , Remedi Maria S.
Published: September 2018

Gain-of-function (GOF) mutations in the ATP-sensitive potassium (KATP) channels cause neonatal diabetes. Despite the well-established genetic root of the disease, pathways modulating disease severity and treatment effectiveness remain poorly understood. Patient phenotypes can vary from severe diabetes to remission, even in individuals with the same mutation and within the same family, suggesting that subtle modifiers can influence disease outcome. We have tested the underlying mechanism of transient vs. permanent neonatal diabetes in KATP-GOF mice treated for 14 days with glibenclamide. Some KATP-GOF mice show remission of diabetes and enhanced insulin sensitivity long after diabetes treatment has ended, while others maintain severe insulin-resistance. However, insulin sensitivity is not different between the two groups before or during diabetes induction, suggesting that improved sensitivity is a consequence, rather than the cause of, remission, implicating other factors modulating glucose early in diabetes progression. Leptin, glucagon, insulin, and glucagon-like peptide-1 are not different between remitters and nonremitters. However, liver glucose production is significantly reduced before transgene induction in remitter, relative to nonremitter and nontreated, mice. Surprisingly, while subsequent remitter animals exhibited normal serum cytokines, nonremitter mice showed increased cytokines, which paralleled the divergence in blood glucose. Together, these results suggest that systemic inflammation may play a role in the remitting versus non-remitting outcome. Supporting this conclusion, treatment with the anti-inflammatory meloxicam significantly increased the fraction of remitting animals. Beyond neonatal diabetes, the potential for inflammation and glucose production to exacerbate other forms of diabetes from a compensated state to a glucotoxic state should be considered.
An Uncommon Meridional Globe Rupture due to Blunt Eye Trauma
Authors: Kumar Krishan , Figurasin Rick , Kumar Swati , Waseem Muhammad
Published: September 2018

Open globe injury (OGI) is a severe form of eye trauma. It is an important cause of monocular blindness worldwide. Ruptures from blunt trauma are most common at the sites where the sclera is thinnest, at the insertions of the extraocular muscles, and at the limbus. Most often, rupture is equatorial. We present a unique case of open globe injury due to blunt ocular trauma from a thrown rock that resulted in a meridional rupture of the eye. The pertinent literature is reviewed.
Approach to Online Defect Monitoring in Fused Deposition Modeling Based on the Variation of the Temperature Field
Authors: He Ketai , Wang Huan , Hu Huaqing
Published: September 2018

According to the surface state of the product, a process quality monitoring technology based on a Qualitative Trend Analysis method is proposed. The construction of the product surface defect knowledge base provides a basis for online monitoring of the nozzle status of the fused deposition modeling (FDM) machine. Ten workpieces are designed in all, and each one conducts two prints which are normal and abnormal, respectively. An infrared thermal imager is used to obtain the temperature image of each layer of the workpiece surface; the feature values are extracted, and the difference between the feature values in the two kinds of printing is calculated. The Qualitative Trend Analysis method is used to analyze the difference in order to obtain the corresponding sensitive feature parameters corresponding to the starting points in different phases of the product printing. The change rules of the sensitive feature values are summarized, and the threshold of each starting point is solved. Base on that, the knowledge rules are defined and the defect knowledge base is constructed. Finally, a new experiment is designed to obtain the theoretical starting point of each state of the product surface in the building process. By comparing the theoretical starting point with the actual starting point, the feasibility of the knowledge rules in monitoring the nozzle working state is verified.
Phytochemical Composition of Solanum retroflexum Analysed with the Aid of Ultra-Performance Liquid Chromatography Hyphenated to Quadrupole-Time-of-Flight Mass Spectrometry (UPLC-qTOF-MS)
Authors: Daji Grace , Steenkamp Paul , Madala Ntakadzeni , Dlamini Bhekisisa
Published: September 2018

Solanum retroflexum (nightshade) is an edible plant that is consumed in some regions of South Africa. Its leaves are a good source of vitamins, proteins, and minerals. It appears that there is no scientific report about the phytochemical composition of S. retroflexum. Here, ultra-performance liquid chromatography coupled to quadruple-time-of-flight mass spectrometry (UPLC-qTOF-MS) technique was use to achieve an untargeted metabolite fingerprinting of this plant. A total of 30 phytochemicals, including alkaloids, flavonoids, and cinnamic acids derivatives, were identified from the methanolic leaf extracts. The concentration of solvent did not affect the type of compounds extracted. The extraction resulted in qualitative yields of molecules such as quercetin-3-rutinoside, kaempferol-3-0-rutinoside, kaempferol-3-0-glucoside, 3-caffeoylquinic acid, 5-caffeoylquinic acid, and 3, 4-di-caffeoylquinic acid. The present study confirms the presence of phytochemical compounds in S. retroflexum similar to other Solanum plants.
Dynamic Strategies on Firm Production and Platform Advertisement in Crowdfunding considering Investor’s Perception
Authors: Ji Ying , Wei Ju , Wu Zhong , Qu Shaojian , Zhang Baojun
Published: September 2018

Taking investor’s perception into account, the optimal decisions about the product quality and platform advertisement are investigated in a dynamic model in the context of crowdfunding. Researches in the literature, however, usually set investor’s perception as a fixed value and rarely consider the important phenomenon that the online information has some influences on investor’s perception. Considering the effects of information about product quality and platform advertisement on the investor’s perception, a dynamic decision model is proposed. Firstly, investment desire and reference price of the investor are introduced in two dynamic settings to describe investor’s perception. Then, the optimal decisions about the product quality and platform advertisement are formulated under two circumstances: the sponsor and the platform make decisions independently and they cooperate as a system. Finally, the influences of reference price and cost-sharing ratio on the optimal results are compared and the data simulation experiment verifies the necessity of the study. Some new insights can be drawn for the operations management of the firm in crowdfunding as follows: (i) it is more profitable for the firm to cooperate with the platform when investors pay more attention to their reference price; (ii) it is optimal for the firm to share a larger proportion of platform cost when the profit-sharing ratio is low.
Treatment of Chronic Hepatitis C Can Improve Glycemic Control in Patients with Type 2 Diabetes
Authors: Okuroglu Nalan , Sertbas Meltem , Ozdemir Ali
Published: September 2018

A 73-year-old female patient with a history of type 2 DM for seven years was admitted to our out-patient clinic with a complaint of frequent hypoglycemic episodes. She was receiving basal- bolus insulin treatment. She underwent liver transplantation 20 months ago due to end stage liver disease caused by HCV infection genotype 1b. While she was still on tacrolimus for liver transplantation, she received direct acting antiviral agents including fix dose ledipasvir-sofosbuvir with ribavirin. Biochemical analysis showed fasting plasma glucose of 105 mg/dl and postprandial glucose of 200 mg/dl, glycosylated hemoglobin A1c of 4.8%, and c-peptide of 3.17 ng/ml. After achieving successfully virologic response with antiviral therapy, the patient stayed euglycemic and was no longer in need to any medication including insulin and the patient was followed only by dietary regulation. Achievement of the virological response in treatment of HCV infection can improve not only the liver status, but also the extrahepatic manifestations including type 2 DM.
Antioxidant and Tyrosinase Inhibitory Activities of Seed Oils from Torreya grandis Fort. ex Lindl.
Authors: Cui Hong-Xin , Duan Fang-Fang , Jia Shan-Shan , Cheng Fang-Rong , Yuan Ke
Published: September 2018

Torreya grandis Fort. ex Lindl. is a plant belonging to the Taxaceae family and Torreya grandis cv. Merrillii is the only grafted and thoroughbred species belonging to this species. In this study, we extracted five different seed oils, including T. grandis seed oil (TGSO), T. grandis “Xiangyafei” seed oil (XYSO), T. grandis “Zhimafei” seed oil (ZMSO), T. grandis “Majus”seed oil (TGMSO), and T. grandis “cunguangfei” seed oil (CGSO) using physical pressure. The resulting extracts were analyzed to determine their fatty acid composition, antioxidant activity, and inhibitory activity towards tyrosinase. The results of the antioxidant activity assays revealed that XYSO and ZMSO exhibited much greater DPPH radical scavenging activity and ferric reducing power than TGSO. Notably, all five of the seed oils showed dose-dependent inhibitory activity towards tyrosinase. XYSO and TGSO gave the highest activities of all of the seed oils tested in the current study against monophenolase and diphenolase, with IC50 values of 227.0 and 817.5μg/mL, respectively. The results of this study show that wild TGSOs exhibit strong antioxidant and tyrosinase inhibition activities. These results therefore suggest that wild TGSOs could be used as a potential source of natural antioxidant agents and tyrosinase inhibitors.
Raloxifene Has No Efficacy in Reducing the High Bone Turnover and the Risk of Spontaneous Vertebral Fractures after Denosumab Discontinuation
Authors: Gonzalez-Rodriguez Elena , Stoll Delphine , Lamy Olivier
Published: September 2018

At denosumab discontinuation, an antiresorptive agent is prescribed to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report the case of a woman treated with aromatase inhibitors and denosumab for 5 years. Raloxifene was then prescribed to prevent the rebound effect. Raloxifene was ineffective to reduce the high bone turnover and to avoid spontaneous clinical vertebral fractures. We believe that among the antiresorptive treatments, the most powerful bisphosphonates should be favored, and their administration adapted according to the serial follow-up of bone markers.
Difference of Liver and Kidney Metabolic Profiling in Chronic Atrophic Gastritis Rats between Acupuncture and Moxibustion Treatment
Authors: He Qi-da , Huang Yuan-peng , Zhu Li-bing , Shen Jia-cheng , Lian Lin-yu , Zhang Yuan , Zhang Long-bin , Qian Lin-chao , Meng Xian-jun , Liu Mi , Liu Cai-chun , Yang Zong-bao
Published: September 2018

Acupuncture and moxibustion proved to be very effective in chronic atrophic gastritis (CAG). According to the Chinese traditional medicine theory, chronic diseases have an influence on the function of liver and kidney. However, there is little research to demonstrate this theory. This study is aimed at assessing the 1H NMR‐based metabolic profiling in liver and kidney of CAG rats and comparing the difference between electroacupuncture and moxibustion treatment. Male SD rats were subjected to CAG modeling by intragastric administration of mixture of 2% sodium salicylate and 30% alcohol coupled with compulsive sporting and irregular fasting for 12 weeks and then treated by electroacupuncture or moxibustion at Liangmen (ST 21) and Zusanli (ST 36) acupoints for 2 weeks. A 1H NMR analysis of liver and kidney samples along with histopathological examination and molecular biological assay was employed to assess and compare the therapeutic effects of electroacupuncture and moxibustion. CAG brought characterization of metabolomic signatures in liver and kidney of rats. Both electroacupuncture and moxibustion treatment were found to normalize the CAG‐induced changes by restoring energy metabolism, neurotransmitter metabolism, antioxidation metabolism, and other metabolism, while the moxibustion treatment reversed more metabolites related to energy metabolism in liver than electroacupuncture treatment. CAG did have influence on liver and kidney of rats. Both of these treatments had good effects on CAG by reversing the CAG‐induced perturbation in liver and kidney. For regulating the energy metabolism in liver, the moxibustion played more important role than electroacupuncture treatment.
Cohort and Rhyme Priming Emerge from the Multiplex Network Structure of the Mental Lexicon
Authors: Stella Massimo
Published: September 2018

Complex networks recently opened new ways for investigating how language use is influenced by the mental representation of word similarities. This work adopts the framework of multiplex lexical networks for investigating lexical retrieval from memory. The focus is on priming, i.e., exposure to a given stimulus facilitating or inhibiting retrieval of a given lexical item. Supported by recent findings of network distance influencing lexical retrieval, the multiplex network approach tests how the layout of hundreds of thousands of word‐word similarities in the mental lexicon can lead to priming effects on multiple combined semantic and phonological levels. Results provide quantitative evidence that phonological priming effects are encoded directly in the multiplex structure of the mental representation of words sharing phonemes either in their onsets (cohort priming) or at their ends (rhyme priming). By comparison with randomised null models, both cohort and rhyming effects are found to be emerging properties of the mental lexicon arising from its multiplexity. These priming effects are absent on individual layers but become prominent on the combined multiplex structure. The emergence of priming effects is displayed both when only semantic layers are considered, an approximated representation of the so‐called semantic memory, and when semantics is enriched with phonological similarities, an approximated representation of the lexical‐auditory nature of the mental lexicon. Multiplex lexical networks can account for connections between semantic and phonological information in the mental lexicon and hence represent a promising modelling route for shedding light on the interplay between multiple aspects of language and human cognition in synergy with experimental psycholinguistic data.
Intranasal Lobular Capillary Hemangioma with Multiple Sites of Origin during Pregnancy: A Case Report and Literature Review
Authors: Alalula Lama S. , Arafat Abdullah S. , Alhedaithy Riyadh A. , Elkrim Mohammed
Published: September 2018

In the present case report, we describe a 33-year-old pregnant woman in the third trimester with a history of recurrent epistaxis leading to frequent visits to the emergency department. Each episode of epistaxis was managed by anterior nasal packing. During endoscopic examination, a left nasal mass was seen. She was admitted and managed conservatively until she delivered her baby without complication. After delivery, a CT scan was taken, which showed an enhancing mass in the middle and lower meatus of the nasal cavity with no bony erosions. For symptomatic relief and tissue diagnosis, endoscopic surgical removal was advised. An intraoperative examination revealed a red, smooth, and well-circumscribed mass occupying the left nasal cavity and originating from the medial surface of the inferior turbinate and the inferior surface of the posterior part of the middle turbinate. A complete en bloc resection of the mass was performed endoscopically. The mass was sent for histologic analysis, which confirmed the diagnosis of lobular capillary hemangioma. Eventually, upon follow-up at two weeks, one month, three months, and six months postsurgery, no evidence of recurrence was detected.
Quality Investing and Pricing Strategies by Startups: Impacts of Demand Uncertainties and Capital Constraint
Authors: Xia Bing , Fung Richard Y. K. , Guo Ju'e
Published: September 2018

Investing in product quality for future growths or conserving cash flow to avoid bankruptcy is an important trade-off faced by many capital-constrained startups. Focusing on the trade-off, this paper proposes a two-stage model where a startup firm must earn profit above the survival threshold by the end of every stage. Considering impacts of the uncertainty of demand responsiveness to quality (DRQ), market shocks, and survival threshold, a hedge with price setting and quality investing is established against the bankruptcy risk. Besides, this paper stresses the necessity of identifying the operational decisions of startups under both profit-seeking and survival-seeking objectives. Results illustrate that, under stochastic environment, the profit-seeking startup makes conservative (aggressive) investment on quality by setting lower (higher) price and investing in lower (higher) quality than the deterministic case, while the survival-seeking startup always sets its price linked to quality in positive direction. In addition, the profit-seeking startup always improves its investment on quality when either the mean or the variance of DRQ increase, while the survival-seeking startup reduces its investment when either the mean of DRQ increases to a certain level or the variance of DRQ increases. Other factors are also examined. Finally, this paper provides the startup managers some guidance on the quality investing strategy under capital constraints.
Rheological and Nutritional Properties and Sensory Evaluation of Bread Fortified with Natural Sources of Calcium
Authors: Alsuhaibani Amnah M. A.
Published: September 2018

By-products of oyster shell and egg shell are new candidates for use as calcium supplements. The effect of the fortification of bread with natural sources of calcium such as skim milk powder, egg shell powder, and oyster shell powder at levels of 10%, 2%, and 2%, respectively, on the rheological, nutritional, and sensory properties was determined. Compared to the control bread, breads fortified with egg and oyster shells had a higher water absorption (%), dough development time, dough stability, mixing time, heat of transition, and setback viscosity but a lower weakening index. Skim milk-fortified bread had the lowest levels of carbohydrates and energy of the bread formulations tested. Oyster shell-fortified bread showed significantly higher contents of protein, ash, fibre, and carbohydrates. Sensory evaluation revealed that the breads fortified with egg and oyster shells showed lower scores for odour and general acceptability compared with the control bread and the bread fortified with skim milk powder. Higher levels of minerals and amino acids except proline were estimated in the tested breads. These results indicate that the addition of natural sources of calcium to bread could positively impact its technological and nutritional properties.
An Improved Time‐Frequency Analysis Method for Instantaneous Frequency Estimation of Rolling Bearing
Authors: Ma Zengqiang , Ruan Wanying , Chen Mingyi , Li Xiang
Published: September 2018

Instantaneous frequency estimation of rolling bearing is a key step in order tracking without tachometers, and time‐frequency analysis method is an effective solution. In this paper, a new method applying the variational mode decomposition (VMD) in association with the synchroextracting transform (SET), named VMD‐SET, is proposed as an improved time‐frequency analysis method for instantaneous frequency estimation of rolling bearing. The SET is a new time‐frequency analysis method which belongs to a postprocessing procedure of the short‐time Fourier transform (STFT) and has excellent performance in energy concentration. Considering nonstationary broadband fault vibration signals of rolling bearing under variable speed conditions, the time‐frequency characteristics cannot be obtained accurately by SET alone. Thus, VMD‐SET method is proposed. Firstly, the signal is decomposed into several intrinsic mode functions (IMFs) with different center frequency by VMD. Then, effective IMFs are selected by mutual information and kurtosis criteria and are reconstructed. Next, the SET method is applied to the reconstructed signal to generate the time‐frequency representation with high resolution. Finally, instantaneous frequency trajectory can be accurately extracted by peak search from the time‐frequency representation. The proposed method is free from time‐varying sidebands and is robust to noise interference. It is proved by numerical simulated signal analysis and is further validated by lab experimental rolling bearing vibration signal analysis. The results show this method can estimate the instantaneous frequency with high precision without noise interference.
Application of Nonlinear Time-Fractional Partial Differential Equations to Image Processing via Hybrid Laplace Transform Method
Authors: Jacobs B. A. , Harley C.
Published: September 2018

This work considers a hybrid solution method for the time-fractional diffusion model with a cubic nonlinear source term in one and two dimensions. Both Dirichlet and Neumann boundary conditions are considered for each dimensional case. The hybrid method involves a Laplace transformation in the temporal domain which is numerically inverted, and Chebyshev collocation is employed in the spatial domain due to its increased accuracy over a standard finite-difference discretization. Due to the fractional-order derivative we are only able to compare the accuracy of this method with Mathematica’s NDSolve in the case of integer derivatives; however, a detailed discussion of the merits and shortcomings of the proposed hybridization is presented. An application to image processing via a finite-difference discretization is included in order to substantiate the application of this method.
Association of p16 as Prognostic Factors for Oropharyngeal Cancer: Evaluation of p16 in 1470 Patients for a 16 Year Study in Northeast China
Authors: Meng Hong-xue , Miao Su-sheng , Chen Kexin , Li Hui-ning , Yao Guodong , Geng Jiashi , Wang Hongmei , Shi Qing-tao , He Jing , Mao Xionghui , Tong Fang-jia , Wei Lan-Lan , Sun Ji , Tan Dongfeng , You Qi , Li Xiaomei , Geng Jing-shu
Published: September 2018

Human papillomavirus (HPV) is an etiological risk factor for oropharyngeal squamous cell carcinomas (OPSCC). Our study investigates the prevalence, prognostic, and clinicopathologic features of HPV-related oropharyngeal cancer in Northeast China and elucidates the involvement of p16 in the tumorigenesis and progression of OPSCC. Specimens from 1470 OPSCC patients collected from 2000 to 2016 were analyzed using the status of HPV by polymerase chain reaction (PCR) and p16 immunohistochemistry. Overexpression of p16 was observed in 81 (5.51%) of the 1470 cases, and HPV positive was present in 78 cases (5.31%) of the 1470 cases. HPV positive and p16 overexpression have a good concordance. However, we found that the etiological fraction of HPV in cancers of the OPSCCs was obviously lower in Northeast China than other cohorts previously reported. Interestingly, nearly 89% of patients with p16 expression were smokers, and nearly 70% of patients with p16 expression had a history of alcohol. Our study also demonstrates that p16 expression is significantly associated with early stage primary OPSCCs and the patients with p16 expression tend to show better survival following surgery and radiotherapy.
Multiscale Study on the Effect of Nano-Organic Montmorillonite on the Performance of Rubber Asphalt
Authors: Tian Xiaoge , Zhang Ren , Yang Zhen , Chu Yantian , Xu Yichao , Zhang Qisen
Published: September 2018

In order to improve the high-temperature performance, antiaging performance, and storage stability of rubber asphalt, nano-organic montmorillonite (NOMMT) was mixed with rubber asphalt. Macroscopic influences of NOMMT on rubber asphalt were measured through penetration, softening point, ductility, rotational viscosity tests, dynamic shear rheology test, and bending beam rheology test at low temperature and were conducted on rubber asphalt with different contents of NOMMT. Then, the microscopic mechanism of NOMMT on the microscopic performance of rubber asphalt was studied through using scanning electron microscopy (SEM), infrared spectroscopy (IR), and differential scanning calorimetry (DSC). The results showed that the rubber particles were smoother, uniform, and dispersed after NOMMT was introduced, and the compatibility between NOMMT and crumbed rubber powder was good. Some stable structures were formed in the composite modified asphalt. The disappearance of alcohol phenol and the increase in related groups such as alkane, benzene, and hydrocarbon indicated that chemical reaction occurred between NOMMT and rubber asphalt, resulting in the changes of the performance of the composite modified system, so that high-temperature stability, antiaging properties, and storage stability were improved but its low-temperature performance was decreased.
Appendiceal Perforation due to Migration of a Dental Instrument
Authors: Tsukamoto Ryoichi , Miyano Shozo , Machida Michio , Kitabatake Toshiaki , Fujisawa Minoru , Kojima Kuniaki
Published: September 2018

A 40-year-old male without any past medical history accidentally swallowed a titanium dental instrument (reamer) for root canal treatment. A cathartic was prescribed at a local hospital, and the course was observed. However, since the reamer was not excreted in feces, he was referred to our hospital. After admission, CT, lower gastrointestinal endoscopy, and barium enema revealed the migration of a foreign body into the appendix and its protrusion into the intraperitoneal cavity. As an emergency operation, laparoscopic appendectomy including the foreign body was performed. The following course was favorable without postoperative complications, and he was discharged on the 2nd hospital day. We report a patient with appendiceal perforation due to a foreign body (dental instrument for root canal treatment) in the appendix.
Maximizing the Use of Scoring Systems in the Prediction of Outcomes in Acute Pancreatitis
Authors: Gray Rachel , Cagliani Joaquin , Amodu Leo I. , Nauka Peter , Villacres Benjamin , Santos Tabia , Castenada Alex , Fishbein Joanna , Ahmed Nibras , Coppa Gene , Rodriguez Rilo Horacio L.
Published: September 2018

Background/Aims: No single classification system has so far effectively predicted the severity for Acute Pancreatitis (AP). This study compares the effectiveness of classification systems: Original Atlanta (OAC), Revised Atlanta (RAC), Determinant based classification (DBC), PANC 3, Harmless AP Score (HAPS), Japanese Severity Score (JSS), Symptoms Nutrition Necrosis Antibiotics and Pain (SNNAP), and Beside Index of Severity for AP (BISAP) in predicting outcomes in AP. Methods: Scores for BISAP, Panc 3, HAPS, SNNAP, OAC, RAC, and DBC were calculated for 221 adult patients hospitalized for AP. Receiver Operating Characteristic curve analysis and Akaike Information Criteria were used to compare the effectiveness of predicting need for surgery, intensive care unit (ICU) admission, readmission within 30 days, and length of hospital stay. Results: Both the RAC and the DBC strongly predict the length of hospital stay (p < 0.0001 for both) and ICU admission (p < 0.0001 for both). Additionally, both BISAP and PANC 3 showed weak predictive capacity at identifying length of stay and ICU admission. Conclusions: We suggest that BISAP and PANC3 be obtained within the initial 24 h of hospitalization to offer an early prediction of length of stay and ICU admission. Subsequently, RAC and DBC can offer further information later in the course of the disease.
Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and Prognostic Biomarkers for Waldenström Macroglobulinemia
Authors: Xu Haitao , Yao Fusheng
Published: September 2018

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.
Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience
Authors: Giona Fiorina , Santopietro Michelina , Menna Giuseppe , Putti Maria Caterina , Micalizzi Concetta , Santoro Nicola , Ziino Ottavio , Mura Rosamaria , Ladogana Saverio , Iaria Grazia , Sau Antonella , Burnelli Roberta , Vacca Nadia , Bernasconi Sayla , Consarino Caterina , Petruzziello Fara , Moleti Maria Luisa , Biondi Andrea , Locatelli Franco , Foà Robin
Published: September 2018

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.
Treatment Effects in Retinal Angiomatous Proliferation Imaged with OCT Angiography
Authors: de Jong Jan H. , Braaf Boy , Amarakoon Sankha , Gräfe Maximilian , Yzer Suzanne , Vermeer Koenraad A. , Missotten Tom , de Boer Johannes F. , van Velthoven Mirjam E.J.
Published: September 2018

Purpose: This prospective case series is aimed at exploring optical coherence tomographic angiography (OCT-A) as a treatment monitoring tool in patients treated for retinal angiomatous proliferation (RAP). Methods: Twelve treatment-naïve RAP patients were included, with a median age of 79 years (range 65–90). Patients were imaged with an experimental 1,040-nm swept-source phase-resolved OCT-A instrument before and after treatment. Treatment consisted of either intravitreal bevacizumab or triamcinolone injections with or without photodynamic therapy (PDT). Abnormal blood flow after treatment was graded as increased, unchanged, decreased, or resolved. Results: OCT-A images before and after treatment could be obtained in 9 patients. The median follow-up period was 10 weeks (range 5–19). After various treatments, the RAP lesion resolved in 7 patients, in 1 patient the OCT-A depicted decreased flow in the lesion, and 1 patient showed unchanged abnormal blood flow. Monotherapy with intravitreal bevacizumab injections resolved RAP in 1 out of 2 patients. Combined therapy of bevacizumab with PDT resolved RAP in 6 out of 7 patients. Conclusions: OCT-A visualized resolution of abnormal blood flow in 7 out of 9 RAP patients after various short-term treatment sequences. OCT-A may become an important noninvasive monitoring tool for optimizing treatment strategies in RAP patients.
Hepatocyte Growth Factor Facilitates Esophageal Mucosal Repair and Inhibits the Submucosal Fibrosis in a Rat Model of Esophageal Ulcer
Authors: Komaki Yuga , Kanmura Shuji , Sasaki Fumisato , Maeda Hidehito , Oda Kohei , Arima Shiho , Tanoue Shiroh , Nasu Yuichiro , Hashimoto Shinichi , Mawatari Seiichi , Tsubouchi Hirohito , Ido Akio
Published: September 2018

Background/Aims: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer. Methods: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 µg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined. Results: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF. Conclusion: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.
Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature
Authors: Luo Yeping , Li Zhuoying , Huang Lihua , Tian Jing , Xiong Menglong , Yang Zuocheng
Published: September 2018

Background/Aims: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. Methods: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. Results: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. Conclusion: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.
The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study
Authors: Reininghaus Eva Z. , Wetzlmair Lisa-Christin , Fellendorf Frederike T. , Platzer Martina , Queissner Robert , Birner Armin , Pilz Rene , Hamm Carlo , Maget Alexander , Koidl Christoph , Riedrich Karin , Klampfer Kerstin , Ferk Kerstin , Dalkner Nina
Published: September 2018

Introduction: Cognitive dysfunction is prevalent in depressive as well as manic episodes in individuals with Bipolar Disorder (BD). Even more, after symptom remission, many individuals with BD experience persisting cognitive impairment also in euthymic periods, leading to high illness burden and low quality of life. According to a recent research in animals and healthy humans, microbiota may influence cognitive processes via the brain-gut axis. A strategy to examine the role of the microbiota in different diseases is the intake of supplements that modulate the gut microbiome. The aim of this pilot study was to analyze the impact of probiotic supplements on cognitive parameters in a cohort of euthymic individuals with BD, receiving daily probiotic treatment over a time period of 3 months. Methods: A total of 20 euthymic individuals with BD received probiotic supplement over a time period of 3 months and completed a cognitive test battery at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3 months of probiotic intake). Results: We found a significant improvement of performance concerning attention and psychomotor processing speed measured with the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment (F = 8.60; η2 = 0.49, p < 0.01). Furthermore, executive function measured with the TMT-B, increased significantly over 3 months (F = 3.68; η2 = 0.29, p < 0.05). Conclusion: The results confirm the hypotheses that probiotic supplement might help stable individuals with BD to improve the cognitive function, which in turn might lead to better psychosocial, occupational, work and financial functioning. Nevertheless, the idea of this potential new treatment is challenging because of the variety of the human’s gut microbiota.
Blood Pressure Variability in Acute Ischemic Stroke: The Role of Early Recanalization
Authors: Martins Ana Inês , Sargento-Freitas João , Jesus-Ribeiro Joana , Correia Inês , Cardoso Leila , Gomes João Pedro , Gonçalves Mariana , Costa Rui , Silva Fernando , Galego Orlando , Nunes César , Beato-Coelho José , Varela Ricardo , Machado Cristina , Rodrigues Bruno , Santo Gustavo C. , Cunha Luís
Published: September 2018

We performed a retrospective study with the aim of investigating the association between blood pressure (BP) variability in the first 24 h after ischemic stroke and functional outcome, regarding arterial recanalization status. A total of 674 patients diagnosed with acute stroke and treated with revascularization therapies were enrolled. Systolic and diastolic BP values of the first 24 h after stroke were collected and their variation quantified through standard deviation. Recanalization state was evaluated at 6 h and clinical outcome at 3 months was assessed by modified Rankin Scale. In multivariate analyses systolic BP variability in the first 24 h post-stroke showed an association with 3 months clinical outcome in the whole population and non-recanalyzed patients. In recanalyzed patients, BP variability did not show a significant association with functional outcome.
Are There Differences in Toxicity and Efficacy between Various Bacillus Calmette-Guerin Strains in Bladder Cancer Patients? Analysis of 844 Patients
Authors: Krajewski Wojciech  , Matuszewski Michal , Poletajew Sławomir , Grzegrzółka Jędrzej , Zdrojowy Romuald , Kołodziej Anna
Published: September 2018

Purpose: To evaluate if there are differences in toxicity and efficacy between different Bacillus Calmette-Guerin (BCG) stains used for intravesical immunotherapy in patients with non-muscle invasive bladder cancer. Methods: We retrospectively analysed a group of 844 patients who received TICE, RIVM and Moreau BCG strains. The allocation of the strain to each patient was random, stemming from differences in supply and distribution. The patients were analysed in terms of toxicity, recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS) and overall survival (OS). Results: In the survival analysis, statistical significance was not reached in any tumour group for any clinical event. TICE caused more local and mild adverse effects and severe complications were mainly associated with RIVM strain. In a group in which the strain was changed during the course of the therapy, significantly more severe complications were observed and, in most of these cases, complications appeared right after the strain change. Conclusions: There were no differences in terms of RFS, PFS, CSS and OS after use of TICE, RIVM and Moreau strains. The complication profile differed statistically between used strains with TICE causing mostly mild complications. Also, strain change during the therapy course was associated with the increased risk of moderate to severe toxicity occurrence.
Differences in Clinical Course of Intraprocedural and Delayed Perforation Caused by Endoscopic Submucosal Dissection for Colorectal Neoplasms: A Retrospective Study
Authors: Iwatsubo Taro , Takeuchi Yoji , Yamasaki Yasushi , Nakagawa Kentaro , Arao Masamichi , Ohmori Masayasu , Iwagami Hiroyoshi , Matsuno Kenshi , Inoue Shuntaro , Nakahira Hiroko , Matsuura Noriko , Shichijo Satoki , Maekawa Akira , Kanesaka Takashi , Yamamoto Sachiko , Higashino Koji , Uedo Noriya , Ishihara Ryu
Published: September 2018

Background: Although the use of endoscopic submucosal dissection (ESD) as a minimally invasive treatment for large superficial colorectal neoplasms is increasing, colorectal ESD remains technically challenging. As perforation in the colorectum is generally considered to be associated with a higher risk of complications, the aim of this study was to investigate the characteristics of perforation caused by colorectal ESD. Methods: This retrospective study included 635 lesions treated with colorectal ESD, between February 2011 and December 2015, in a tertiary cancer center. We evaluated and compared the clinical course and short-term outcomes of the intraprocedural perforation group with those of the delayed perforation and no perforation groups. Results: Perforation occurred in 45 (7.1%) of the 635 cases. Thirty-six cases were intraprocedural perforation (5.7%), all of which were successfully closed with endoclips during the procedure. Nine cases of delayed perforation occurred (1.4%). No emergency surgery was performed in the intraprocedural perforation group; however, 5 of 9 cases underwent emergency surgery in the delayed perforation group (56%, p < 0.0001). There were statistically significant differences between the intraprocedural and delayed perforation groups with regard to the hospitalization period, fasting period, abdominal pain scale, peak white blood cell (WBC) count, and peak C-reactive protein (CRP), and between the intraprocedural and no perforation groups with regard to the location of the lesion, hospitalization period, fasting period, abdominal pain scale, peak WBC, peak CRP, and en bloc resection rate. Conclusions: While intraprocedural perforation due to colorectal ESD can be managed conservatively, delayed perforation can lead to serious adverse events.
How to Define Acute Liver Failure Patients with Pre-Existing Liver Disease without Signs of Cirrhosis
Authors: Gottlieb Aline , Kottmann Maren , Manka Paul , Bedreli Sotiria , Hadem Johannes , Bechmann Lars , Sowa Jan-Peter , Gerken Guido , Canbay Ali
Published: September 2018

Background: The definition of acute liver failure (ALF) usually implies no previous liver injury. Though, some patients admitted to liver transplantation centers with the diagnosis of ALF are obese or have diabetes. Elevated liver enzymes were not recorded previously, and no signs of cirrhosis or prior decompensation of the liver function were ever present. Still, these patients differ from the “typical” ALF-patient. Goals: In this study, we aimed to confirm acute-on-chronic-liver failure (AOCLF) in patients diagnosed with ALF and to identify possible differences between ALF and AOCLF. Study: Patients were retrospectively recruited from all patients admitted to the University Hospital Essen with diagnosis of ALF between 2008 and 2015. Data of 163 patients were evaluated, resulting in a reclassification of 32 patients as AOCLF (remaining ALF: 131). Demographic and clinical data as well as serum parameters, including cell death markers, were correlated with clinical outcome. Results: Patients with AOCLF were significantly older, had a higher body mass index (BMI), and were more often male. The cause for liver failure in these patients differed significantly from patients who had an actual ALF. Significant differences were also found for serum liver enzymes. Outcome of patients did not differ between AOCLF and ALF. Though, lower BMI and MELD and higher AST and GLDH were predictors for a beneficial outcome. Conclusion: AOCLF is still commonly misdiagnosed as ALF. While clinical outcome does not significantly differ between ALF and AOCLF, risk factors for adverse outcome may significantly differ between these entities.
Rare Cause of Infantile Hypercalcemia: A Novel Mutation in the SLC34A1 Gene
Authors: Kurnaz Erdal , Savaş Erdeve Şenay , Çetinkaya Semra , Aycan Zehra
Published: September 2018

Background: Under physiological conditions, proximal tubular phosphate reabsorption via NaPi-IIa (and NaPi-IIc) ensures the maintenance of phosphate homeostasis. Impairment of NaPi-IIa, encoded by SLC34A1, is associated with various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi’s syndrome with chronic kidney disease, and idiopathic infantile hypercalcemia and nephrocalcinosis. Methods: A patient was referred to our hospital due to hyponatremia, hyperkalemia, and hypophosphatemia, as well as persistent hypercalcemia after fluid therapy and sodium replacement. At admission to our hospital, potassium and sodium values were normal. After initiation of phosphorus therapy, hypokalemia and metabolic alkalosis were observed. Renal sonography showed bilateral medullary nephrocalcinosis. Analyses of the SLC34A1 gene were performed due to hypercalcemia and hypophosphatemia. Results: Gene analyses identified a novel homozygous c.682T>C (p.W228R) (p.Trp228Arg) mutation. There are no previous reports of patients with SLC34A1 gene mutations presenting with hypokalemia and metabolic alkalosis. Conclusion: Herein, we present a case of infantile hypercalcemia 2 with a very different phenotype from that of previously described patients. Our findings provide further evidence for the wide range of phenotypic heterogeneity associated with NaPi-IIa impairment.