bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Low Intensity Pulsed Ultrasound on Proliferation of Rat Condylar Cartilage Cells in Hypoxia Culture
Authors: Li Qiong , Geng Wei , Li Jun , Liang Chao , Bao Chaolumen
Published: November 2019

Temporomandibular disorder (TMD) is a common and frequently-occurring oral and maxillofacial disease. Restoration of the joint's cartilage and subchondral bone tissue is the key to treat TMD. Low intensity pulsed ultrasound (LIPUS) has been proved to be effective in facilitating chondrocyte's
proliferation, which inspired us to probe its treatment effect on TMD. With an isolated and hypoxic cultured mandibular condylar chondrocytes (MCC), we established a model for TMD. HIF-1α and VEGF's mRNA level was increased in hypoxic cultured MCC, which indicates our model simulated
the cell's status caused by TMD pathology. When stimulated with LIIPUS at 45 mW/cm2, the MCC's apoptosis rate was inhibited and its proliferation was improved with best efficiency. Further experiment revealed that LIPUS restored MCC's Metalloproteinase's (MMP) up-regulation and
collagen II's downregulation in hypoxic cultured MCC, respectively, which might be related to LIPUS's improvement effect on MCC.
The Protective Role of Inhibition of Keratin on Rheumatoid Arthritis
Authors: Zhao Yan , Yang Lanxiu , Pan Jihong , Zhang Huan , Sun Guodong , Zhang Lei
Published: November 2019

Objective: Rheumatoid arthritis (RA) is a common inflammatory disease. Studies showed that keratin type II cuticular Hb4 (KRT84) was highly expressed in the synovial membrane of patients with RA. However, the function and mechanism of KRT84 in RA is still unclear. Methods:
In this study, we isolated fibroblast-like synoviocytes (FLS) from the mixed knee joint synovial tissues from five patients with RA and the cells were treated with KRT84 siRNA. After transfection of 24 h and 36 h, the knockdown efficiency and expression of relevant genes was detected by RT-PCR.
MTT assay, transwell assay, wound scratch assays, flow cytometric analysis and ELISA were used to assess cell proliferation, invasive and migratory capacity. Results: We found that the invasion and migration of RAFLS were significantly decreased after transfection of KRT84 siRNA. ELISA
showed a remarkably decrease in TNF-α secretion after KRT84 knockdown. We also explore stimulatory factors for high expression of KRT84 in RA. The inhibitors of ERK, STAT3 and NF-κ B pathways were employed. Our results showed that the expression of KRT84 in RAFLS
was evidently increased after treatment with ERK and STAT3 pathway inhibitor. Conclusions: These results imply a protective role of KRT84 knockdown on RA and lay a foundation for further studies on the pathogenetic mechanisms of RA.
An Emphasis of Digital Wallets for E-Commerce Transactions
Authors: Raghavendra R. , Niranjanamurthy M. , Nachappa M. N. , Shalini K. B.
Published: November 2019

Payment is one of the main parts of the business. Since from the last decade, the use of mobile devices for electronic payment has increased significantly. The current generation of individual payment systems that is replaced the traditional smart cards by mobile devices supplied with
E-wallet and M-wallet functions. The spread of such E-wallet systems will depend on their security, functionality ease of use and the effectiveness of realization. E-wallet is a utility which offers users to save their money and make payments anywhere and all time. Many banks and nonbanks
organizations are contesting to develop new on this filed. As customers adopt E-wallet and M-wallet. As customers adopt E-wallet and M-wallet, they becoming a cybercrime target. E-wallet provides a monetary action through smartphones which is fruitful freedom for electronic crimes. Quality
of the system, quality of service and quality of information has to improve by the mobile wallet service providers for their M-wallet applications.
An Efficient Approach to Secure Mobile Wireless Sensor Network from Node Replication Attack
Authors: Gupta Kavita , Garg Atul , Singh Aarti
Published: November 2019

Security of Mobile Wireless Sensor Network (MWSN) is the most sensitive issue that needs attention of researchers. Node replication attack is the most dangerous type of security attack. In this paper key based centralized security mechanism is proposed, where pair the keys of generated
for each node at the time of registration. The proposed scheme (EESRP) proposes promising solution for handling node replication attack.
An Efficient Method to Detect Outliers in High Dimensional Data
Authors: Garg Atul , Kaur Kamaljeet
Published: November 2019

In this era, detection of outliers or anomalies from high dimensional data is really a great challenge. Normal data is distinguished from data containing anomalies using Outlier detection techniques which classifies new data as normal or abnormal. Different Outlier Detection algorithms
are proposed by many researchers for high dimensional data and each algorithm has its own benefits and limitations. In the literature the researchers proposed different algorithms. For this work few algorithms such as Dice-Coefficient Index (DCI), Mapreduce Function and Linear Discriminant
Analysis Algorithm (LDA) are considered. Mapreduce function is used to overcome the problem of large datasets. LDA is basically used in the reduction of the data dimensionality. In the present work a novel Hybrid Outlier Detection Algorithm (HbODA) is proposed for efficiently detection of
outliers in high dimensional data. The important parameters efficiency, accuracy, computation cost, precision, recall etc. are focused for analyzing the performance of the novel hybrid algorithm. Experimental results on real large sets show that the proposed algorithm is better in detecting
outliers than other traditional methods.
Development and investigation on transmission efficiency of functionally graded material-based polybutylene terephthalate spur gears
Authors: Singh Akant K , Siddhartha
Published: November 2019

Application of polymer composite gears is increasing due to their superior properties. They have lower inertia, less weight, and run much quieter than their metal counterparts. In the present work, functionally graded material-based glass fiber reinforced polybutylene terephthalate gears are fabricated with a novel horizontal centrifugal casting technique using an injection molding machine. Conventional technique is used to fabricate homogeneous polybutylene terephthalate gears. Polybutylene terephthalate reinforced with 15 and 30 wt% glass fibers is used to fabricate gears. Unfilled polybutylene terephthalate gear is also manufactured for comparative study. Gradation in functionally graded material gear is verified by scanning electron microscope analysis, and Shore D hardness is measured in three different locations of the fabricated functionally graded material gears. Gradation in functionally graded material gear is also verified by ignition loss test method. Continuous gradation is observed in functionally graded material gear by scanning electron microscope and confirmed by hardness test and ignition loss test. The objective of present work is to investigate and compare the transmission efficiency of homogeneous and functionally graded material gears during operation. A polymer gear test rig is used for the experimental work. Experiments are conducted at various torque and speed combinations for 0.2 million cycles. Life span of fabricated gear is also tested for 10 million cycles. The range of the torque is 0.8–2.6 N m and the range for rotational speed is 500–1400 r/min. The transmission efficiency of the fabricated gears is found to be sensitive to the operating torque.
Lateral ventilation performance for removal of pulsating buoyant jet under the influence of high-temperature plume
Authors: Wang Yi , Cao Lei , Huang Yanqiu , Cao Yingxue
Published: November 2019

Lateral exhaust systems have commonly been applied to capture polluted buoyant jets in many industrial processes, such as casting and metallurgy. Compared with the normal conditions of design manuals, the capture efficiency of a lateral exhaust hood (LEH) is often weakened by two factors in actual processes: the unsteady buoyant jet released from the operating surface, and the plume formed above a high-temperature workpiece placed between the LEH and the operating surface. In this study, through experiments and numerical simulations, a pulsatile phenomenon was found in the velocity and concentration distribution of the unsteady buoyant jet. Results show that the contaminate escape ratio is pulsatile; it rises with the instantaneous increase in the buoyant jet velocity and gradually decreases to a constant value. This study not only reveals the air distribution of pulsating buoyant jet but also analyses the effect of the pulsating buoyant jet and high-temperature plume on lateral ventilation system capture efficiency and provides a possible guidance for future design of new building ventilation technologies.
OmicsARules: a R package for integration of multi-omics datasets via association rules mining
Authors: Chen Danze , Zhang Fan , Zhao Qianqian , Xu Jianzhen
Published: November 2019

Background

The improvements of high throughput technologies have produced large amounts of multi-omics experiments datasets. Initial analysis of these data has revealed many concurrent gene alterations within single dataset or/and among multiple omics datasets. Although powerful bioinformatics pipelines have been developed to store, manipulate and analyze these data, few explicitly find and assess the recurrent co-occurring aberrations across multiple regulation levels.

Results

Here, we introduced a novel R-package (called OmicsARules) to identify the concerted changes among genes under association rules mining framework. OmicsARules embedded a new rule-interestingness measure, Lamda3, to evaluate the associated pattern and prioritize the most biologically meaningful gene associations.

As demonstrated with DNA methlylation and RNA-seq datasets from breast invasive carcinoma (BRCA), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD), Lamda3 achieved better biological significance over other rule-ranking measures. Furthermore, OmicsARules can illustrate the mechanistic connections between methlylation and transcription, based on combined omics dataset. OmicsARules is available as a free and open-source R package.

Conclusions

OmicsARules searches for concurrent patterns among frequently altered genes, thus provides a new dimension for exploring single or multiple omics data across sequencing platforms.
Genome-wide association study of milk and reproductive traits in dual-purpose Xinjiang Brown cattle
Authors: Zhou Jinghang , Liu Liyuan , Chen Chunpeng James , Zhang Menghua , Lu Xin , Zhang Zhiwu , Huang Xixia , Shi Yuangang
Published: November 2019

Background

Dual-purpose cattle are more adaptive to environmental challenges than single-purpose dairy or beef cattle. Balance among milk, reproductive, and mastitis resistance traits in breeding programs is therefore more critical for dual-purpose cattle to increase net income and maintain well-being. With dual-purpose Xinjiang Brown cattle adapted to the Xinjiang Region in northwestern China, we conducted genome-wide association studies (GWAS) to dissect the genetic architecture related to milk, reproductive, and mastitis resistance traits. Phenotypic data were collected for 2410 individuals measured during 1995–2017. By adding another 445 ancestors, a total of 2855 related individuals were used to derive estimated breeding values for all individuals, including the 2410 individuals with phenotypes. Among phenotyped individuals, we genotyped 403 cows with the Illumina 150 K Bovine BeadChip.

Results

GWAS were conducted with the FarmCPU (Fixed and random model circulating probability unification) method. We identified 12 markers significantly associated with six of the 10 traits under the threshold of 5% after a Bonferroni multiple test correction. Seven of these SNPs were in QTL regions previously identified to be associated with related traits. One identified SNP, BovineHD1600006691, was significantly associated with both age at first service and age at first calving. This SNP directly overlapped a QTL previously reported to be associated with calving ease. Within 160 Kb upstream and downstream of each significant SNP identified, we speculated candidate genes based on functionality. Four of the SNPs were located within four candidate genes, including CDH2, which is linked to milk fat percentage, and GABRG2, which is associated with milk protein yield.

Conclusions

These findings are beneficial not only for breeding through marker-assisted selection, but also for genome editing underlying the related traits to enhance the overall performance of dual-purpose cattle.
Mining and genomic characterization of resistance to tan spot, Stagonospora nodorum blotch (SNB), and Fusarium head blight in Watkins core collection of wheat landraces
Authors: Halder Jyotirmoy , Zhang Jinfeng , Ali Shaukat , Sidhu Jagdeep S. , Gill Harsimardeep S. , Talukder Shyamal K. , Kleinjan Jonathan , Turnipseed Brent , Sehgal Sunish K.
Published: November 2019

Background

In the late 1920s, A. E. Watkins collected about 7000 landrace cultivars (LCs) of bread wheat (Triticum aestivumL.) from 32 different countries around the world. Among which 826 LCs remain viable and could be a valuable source of superior/favorable alleles to enhance disease resistance in wheat. In the present study, a core set of 121 LCs, which captures the majority of the genetic diversity of Watkins collection, was evaluated for identifying novel sources of resistance against tan spot, Stagonospora nodorum blotch (SNB), and Fusarium Head Blight (FHB).

Results

A diverse response was observed in 121 LCs for all three diseases. The majority of LCs were moderately susceptible to susceptible to tan spot Ptr race 1 (84%) and FHB (96%) whereas a large number of LCs were resistant or moderately resistant against tan spot Ptr race 5 (95%) and SNB (54%). Thirteen LCs were identified in this study could be a valuable source for multiple resistance to tan spot Ptr races 1 and 5, and SNB, and another five LCs could be a potential source for FHB resistance. GWAS analysis was carried out using disease phenotyping score and 8807 SNPs data of 118 LCs, which identified 30 significant marker-trait associations (MTAs) with -log10 (p-value) > 3.0. Ten, five, and five genomic regions were found to be associated with resistance to tan spot Ptr race 1, race 5, and SNB, respectively in this study. In addition toTsn1, several novel genomic regionsQ.Ts1.sdsu-4BSandQ.Ts1.sdsu-5BS(tan spot Ptr race 1) andQ.Ts5.sdsu-1BL,Q.Ts5.sdsu-2DL,Q.Ts5.sdsu-3AL, andQ.Ts5.sdsu-6BL(tan spot Ptr race 5) were also identified. Our results indicate that these putative genomic regions contain several genes that play an important role in plant defense mechanisms.

Conclusion

Our results suggest the existence of valuable resistant alleles against leaf spot diseases in Watkins LCs. The single-nucleotide polymorphism (SNP) markers linked to the quantitative trait loci (QTLs) for tan spot and SNB resistance along with LCs harboring multiple disease resistance could be useful for future wheat breeding.
Did the ban on serving raw beef liver in restaurants decrease Enterohemorrhagic Escherichia coli infection in Japan?: an interrupted time-series analysis
Authors: Iwata Kentaro , Goto Michihiko
Published: November 2019

Background

Enterohemorrhagic Escherichia coli (EHEC) is an important pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). After an EHEC outbreak involving uncooked beef, serving raw beef liver dishes at restaurants was completely banned starting on July 1, 2012 in Japan. However, its long-term associations with the incidence rates of EHEC infections have never been assessed by formal interrupted time-series analysis (ITSA).

Methods

A retrospective cohort study to assess the impact of banning raw beef liver provision at restaurants was conducted. The weekly incidence of asymptomatic and symptomatic EHEC infections, the incidence of HUS, and deaths were extracted from the national reportable diseases database from January 2008 to December 2017. ITSA was conducted to evaluate the impact of banning raw beef liver from July 2012. To account for a potential simultaneous external effect, the additional regulation on raw beef red meat handling (implemented in May 2011) and the seasonality were also incorporated into the model.

Results

There were 32,179 asymptomatic and 21,250 symptomatic EHEC infections (including 717 HUS cases and 26 deaths) reported during the study period. During the pre-intervention period (before week 27, 2012), there were 0.45 asymptomatic EHEC infections per million-persons per week. The mean post-intervention asymptomatic EHEC infections were 0.51 per million-persons per week. ITSA revealed no baseline trend or change in the intercept and trend (0.002 infections per million-persons per week, 95% Confidence interval − 0.03-0.04, p = 0.93, 1.22, CI -1.96-4.39, p = 0.45, and − 0.006, CI -0.003-0.02, p = 0.68, respectively). For symptomatic EHEC infections, there were 0.30 cases per million per week during the pre-intervention period, and it became 0.33 cases per million per week after the intervention. Time series modeling again did not show a significant baseline trend or changes in the intercept and trend (0.0005, CI -0.02-0.02, p = 0.96, 0.69, CI -1.75-3.12, p = 0.58, and − 0.003, CI -0.02-0.01, p = 0.76, respectively).

Conclusion

We did not find a statistically significant reduction in the overall incidence rates of both asymptomatic and symptomatic EHEC infections in Japan after implementing measures, including a ban on serving raw beef liver dishes in the restaurant industry.
Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection
Authors: Gao Jian , Ren Wenjun , Xiao Chunhong , Wang Lie , Huang Qiaojia , Zhang Zaizhong , Dang Yuan , Weng Pengcheng , Wang Hui , Fang Xuehong , Zhuang Minxian , Lin Liying , Chen Shaoquan
Published: November 2019

Background

The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA).

Methods

We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies.

Results

Multivariable analysis showed that patients with the CT + TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p = 0.004) and death (HR 1.429, p = 0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT + TT genotype (20, 27 months) than in patients with the CC genotype (36, 43 months, p = 0.001, p < 0.001). Patients with the CT + TT genotype who were male or ≥ 60 years, or who had a tumor ≥5 cm or a moderately differentiated tumor were at significantly higher risk of recurrence and death. SLC39A6 was overexpressed in tissues from GA patients and in GA cell lines, and SLC39A6 knockdown in GA cell lines inhibited their proliferation, migration and invasion.

Conclusion

SLC39A6 rs1050631 correlates with post-resection prognosis of GA patients and SLC39A6 may participate in GA onset or progression.
CircAGFG1 promotes cervical cancer progression via miR-370-3p/RAF1 signaling
Authors: Wu Fengqin , Zhou Jingjing
Published: November 2019

Background

In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells.

Methods

High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities.

Results

The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1.

Conclusion

The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.
A reactive oxygen species scoring system predicts cisplatin sensitivity and prognosis in ovarian cancer patients
Authors: Sun Chaoyang , Guo Ensong , Zhou Bo , Shan Wanying , Huang Jia , Weng Danhui , Wu Peng , Wang Changyu , Wang Shixuan , Zhang Wei , Gao Qinglei , Xu Xiaoyan , Wang Beibei , Hu Junbo , Ma Ding , Chen Gang
Published: November 2019

Background

To reveal roles of reactive oxygen species (ROS) status in chemotherapy resistance and to develop a ROS scoring system for prognosis prediction in ovarian cancer.

Methods

We tested the sensitizing effects of ROS elevating drugs to cisplatin (cDDP) in ovarian cancer both in vitro and in vivo. A ROS scoring system was developed using The Cancer Genome Atlas (TCGA) database of ovarian cancer. The associations between ROS scores and overall survival (OS) were analyzed in TCGA, Tothill dataset, and our in-house dataset (TJ dataset).

Results

ROS-inducing drugs increased cisplatin-induced ovarian cancer cell injury in vitro and in vivo. ROS scoring system was established using 25 ROS-related genes. Patients were divided into low (scores 0–12) and high (scores 13–25) score groups. Improved patient survival was associated with higher scores (TCGA dataset hazard ratio (HR) = 0.43, P < 0.001; Tothill dataset HR = 0.65, P = 0.022; TJ dataset HR = 0.40, P = 0.003). The score was also significantly associated with OS in multiple datasets (TCGA dataset r2 = 0.574, P = 0.032; Thothill dataset r2 = 0.266, P = 0.049; TJ dataset r2 = 0.632, P = 0.001) and with cisplatin sensitivity in ovarian cancer cell lines (r2 = 0.799, P = 0.016) when used as a continuous variable. The scoring system showed better prognostic performance than other clinical factors by receiver operating characteristic (ROC) curves (TCGA dataset area under the curve (AUC) = 0.71 v.s. 0.65, Tothill dataset AUC = 0.73 v.s. 0.67, TJ dataset AUC = 0.74 v.s. 0.66).

Conclusions

ROS status is associated with chemotherapy resistance. ROS score system might be a prognostic biomarker in predicting the survival benefit from ovarian cancer patients.
Making the business case for an addiction medicine consult service: a qualitative analysis
Authors: Priest Kelsey C. , McCarty Dennis
Published: November 2019

Background

As the drug poisoning crisis worsens in North America and opioid use disorder (OUD)-related hospital admissions increase, policymakers and hospital administrators are beginning to recognize the important role of hospitals in the OUD care continuum. This study explores and describes how U.S. addiction medicine physicians created and presented business propositions to hospital administrators to support the development of addiction medicine consult (AMC) services.

Methods

Fifteen qualitative interviews were completed with board-certified or board-eligible addiction medicine physicians from 14 U.S. hospitals. The interviews occurred as part of a broader mixed methods study exploring hospital service delivery for patients admitted with OUD. Using a directed content analysis, the transcribed interviews were coded, analyzed, and final themes consolidated.

Results

Semi-structured interviews completed with addiction medicine physicians from established (n = 9) and developing (n = 5) AMC services at 14 U.S. hospitals explored how clinical champions persuaded hospital administrators to support AMC service development. Four elements were foundational to making the “business case”: 1) describing the prevalence of substance use disorder (SUD) or OUD in the hospital; 2) identifying the negative financial impacts of not treating SUDs during hospitalization; 3) highlighting the ongoing care quality and treatment gap for hospitalized patients with SUDs; and 4) noting the success of other institutional AMC services. Study findings informed the creation of tools to support AMC service development: 1) an AMC service business case template, and 2) an AMC service design and operations resource list.

Conclusions

OUD-related hospital admissions are unlikely to abate. Hospital administrators should consider innovative care delivery mechanisms to improve care for persons with OUD. AMC services may be a promising delivery mechanism to achieve this aim. For clinical and administrative champions, understanding how to communicate the potential effectiveness of this intervention to hospital leaders is an essential first step to AMC service creation.
Establishment of a model for equine small intestinal disease: effects of extracorporeal blood perfusion of equine ileum on metabolic variables and histological morphology – an experimental ex vivo study
Authors: Unterköfler Maria S. , McGorum Bruce C. , Milne Elspeth M. , Licka Theresia F.
Published: November 2019

Background

In horses a number of small intestinal diseases is potentially life threatening. Among them are Equine Grass Sickness (EGS), which is characterised by enteric neurodegeneration of unknown aetiology, as well as reperfusion injury of ischaemic intestine (I/R), and post-operative ileus (POI), common after colic surgery. The perfusion of isolated organs is successfully used to minimize animal testing for the study of pathophysiology in other scenarios. However, extracorporeal perfusion of equine ileum sourced from horses slaughtered for meat production has not yet been described. Therefore the present study evaluated the potential of such a model for the investigation of small intestinal diseases in an ex vivo and cost-efficient system avoiding experiments in live animals.

Result

Nine ileum specimens were sourced from horses aged 1–10 years after routine slaughter at a commercial abattoir. Ileum perfusion with oxygenated autologous blood and plasma was successfully performed for 4 h in a warm isotonic bath (37.0–37.5 °C). Ileum specimens had good motility and overall pink to red mucosa throughout the experiment; blood parameters indicated good tissue vitality: 82 ± 34 mmHg mean arterial partial pressure of oxygen (pO2) compared to 50 ± 17 mmHg mean venous pO2,48 ± 10 mmHg mean arterial partial pressure of carbon dioxide (pCO2) compared to 66 ± 7 mmHg venous pCO2and 9.8 ± 2.8 mmol/L mean arterial lactate compared to 11.6 ± 2.7 mmol/L venous lactate. There was a mild increase in ileum mass reaching 105 ± 7.5% of the pre-perfusion mass after 4 hours. Histology of haematoxylin and eosin stained biopsy samples taken at the end of perfusion showed on average 99% (±1%) histologically normal neurons in the submucosal plexus and 76.1% (±23.9%) histologically normal neurons in the myenteric plexus and were not significantly different to control biopsies.

Conclusion

Extracorporeal, normothermic perfusion of equine ileum over 4 h using autologous oxygenated blood/plasma perfusate showed potential as experimental model to test whether haematogenous or intestinal exposure to neurotoxins suspected in the pathogenesis of EGS can induce neuronal damage typical for EGS. Also, this model may allow investigations into the effect of pharmaceuticals on I/R injury, as well as into the pathogenesis of equine POI.
ATM controls DNA repair and mitochondria transfer between neighboring cells
Authors: Jin Sha , Cordes Nils
Published: November 2019

Intercellular communication is essential for multicellular tissue vitality and homeostasis. We show that healthy cells message protective signals through direct cell–cell connections to adjacent DNA–damaged cells in a microtubule–dependent manner. In DNA–damaged cells, mitochondria restoration is facilitated by fusion with undamaged mitochondria from healthy cells and their DNA damage repair is optimized in presence of healthy cells. Both, mitochondria transfer and intercellular signaling for an enhanced DNA damage response are critically regulated by the activity of the DNA repair protein ataxia telangiectasia mutated (ATM). These healthy–to–damaged prosurvival processes sustain normal tissue integrity and may be exploitable for overcoming resistance to therapy in diseases such as cancer.
Pathological pain processing in mouse models of multiple sclerosis and spinal cord injury: contribution of plasma membrane calcium ATPase 2 (PMCA2)
Authors: Mirabelli Ersilia , Ni Li , Li Lun , Acioglu Cigdem , Heary Robert F. , Elkabes Stella
Published: November 2019

Background

Neuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2+/−mice is paralleled by increased sensitivity to evoked nociceptive pain. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI.

Methods

EAE was induced in female and male C57Bl/6N mice via inoculation with myelin oligodendrocyte glycoprotein fragment 35–55 (MOG35–55) emulsified in Complete Freund’s Adjuvant (CFA). CFA-inoculated mice were used as controls. A severe SC contusion injury was induced at thoracic (T8) level in female C57Bl/6N mice. Pain was evaluated by the Hargreaves and von Frey filament tests. PMCA2 levels in the lumbar DH were analyzed by Western blotting. The effectors that decrease PMCA2 expression were identified in SC neuronal cultures.

Results

Increased pain in EAE and SCI was paralleled by a significant decrease in PMCA2 levels in the DH. In contrast, PMCA2 levels remained unaltered in the DH of mice with EAE that manifested motor deficits but not increased pain. Interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6 expression were robustly increased in the DH of mice with EAE manifesting pain, whereas these cytokines showed a modest increase or no change in mice with EAE in the absence of pain. Only IL-1β decreased PMCA2 levels in pure SC neuronal cultures through direct actions.

Conclusions

PMCA2 is a contributor to neuropathic pain mechanisms in the DH. A decrease in PMCA2 in DH neurons is paralleled by increased pain sensitivity, most likely through perturbations in calcium signaling. Interleukin-1β is one of the effectors that downregulates PMCA2 by acting directly on neurons.
Reduction of dose to duodenum with a refined delineation method of Para-aortic region in patients with locally advanced cervical Cancer receiving prophylactic extended-field radiotherapy
Authors: Yang Bo , Liu Xiaoliang , Hu Ke , Qiu Jie , Zhang Fuquan , Hou Xiaorong , Yan Junfang , Meng Qingyu , Wang Weiping , Yu Lang , Wang Yijun
Published: November 2019

Background

To compare irradiation dose to the second and third portions of duodenum (Duo2 and Duo3) with a new refined and old delineation method of para-aortic region for patients with locally advanced cervical cancer (LACC) receiving prophylactic extended-field radiotherapy (EFRT).

Methods

Twenty consecutive patients with LACC were treated with prophylactic EFRT from January 2016 to January 2017 at our institute. Two delineation methods of para-aortic region were designed for each patient, the old delineation method ensured a full coverage of aortic and inferior vena cava, while the right paracaval region above L3 was omitted from CTV in the new delineation method. Patients received a dose of 50.4Gy in 28 fractions for PCTV and a dose of 60.2Gy in 28 fractions for PGTV with volumetric-modulated arc therapy (VMRT). The dose delivered to Duo2 and Duo3 with these two delineation methods were compared.

Results

All treatment plans achieved excellent target volume coverage with 95% of PCTV receiving 50.4Gy and 95% of PGTV receiving 60.2Gy. There was no difference between delineation methods in low dose level (V5, V10, V15, V20, V25) for Duo2 and Duo3. The V30, V35, V40, V45, V50, Dmax, Dmean and D2cc for Duo2 with the new and old delineation methods were 55.76% vs 80.54% (P = 0.009), 34.72% vs 70.91% (P < 0.001), 18.69% vs 55.46% (P < 0.001), 8.20% vs 41.49% (P < 0.001), 1.86% vs 21.60% (P < 0.001), 49.58Gy vs 52.91Gy (P = 0.002), 30.38Gy vs 39.22Gy (P = 0.001) and 37.90Gy vs 48.64Gy (P < 0.001) respectively. For Duo3, the new delineation method achieved significant advantages in V30, V35, V40, V45, V50 and Dmean over the old one (96.82% vs 99.25%, P = 0.021; 89.65% vs 97.21%, P = 0.001; 79.50% vs 93.18%, P < 0.001; 65.63% vs 82.93%, P < 0.001; 43.39% vs 65.60%, P < 0.001; 46.09Gy vs 49.24Gy, P < 0.001), no deference was observed regarding D2cc and Dmax with these two delineation methods.

Conclusion

With the new delineation method of para-aortic area in prophylactic EFRT, significant reduction of irradiation dose to the second and third portions of duodenum in high dose area was obtained. This may further lower the incidence of duodenal toxicity when performing prophylactic EFRT for patients with LACC.
Reducing complexity: explaining inborn errors of metabolism and their treatment to children and adolescents
Authors: Zeltner Nina A. , Welsink-Karssies Mendy M. , Landolt Markus A. , Bosshard-Bullinger Dominique , Keller Fabia , Bosch Annet M. , Groenendijk Marike , Grünert Sarah C. , Karall Daniela , Rettenbacher Beatrix , Scholl-Bürgi Sabine , Baumgartner Matthias R. , Huemer Martina
Published: November 2019

Background

Inborn errors of metabolism (IEM) are a group of rare, heterogeneous and complex genetic conditions. Clinically, IEM often affect the central nervous system and other organs. Some carry the risk of progression and / or potentially life-threatening crises. Many patients have to adhere to lifelong dietary or drug treatment.

The complexity of IEM makes it difficult for patients and caregivers to understand their pathophysiology, inheritance and therapy rationale. Especially patients reaching adolescence may have only limited knowledge of their condition since medical care has often entirely been handled by their parents. Knowledge about disease and treatment, however, constitute pillars of self-responsible disease management. Not many standardized patient education materials on IEM are available and their comprehensibility has not been systematically investigated.

Methods

We developed and tested patient education materials for school-aged children and adolescents with IEM. Informative texts and illustrations in paper form and as videos were developed by an international network of metabolic care professionals together with a graphic artist and experts for easy-to-read language. The materials were presented in standardized single or group training sessions to 111 individuals; first, to 74 healthy children and adolescents (recruited via public schools) and consecutively to 37 paediatric patients with IEM (phenylketonuria, galactosemia, urea cycle defects, lysosomal storage disorders) from six metabolic centres. Knowledge-gain was assessed by pre- and post-testing.

Results

Knowledge-gain was significant in healthy children and adolescents as well as in patients (p < .001, r =. -77 /. -70). Effect sizes were large in both groups (r = -.77 / -.70). This result was independent from family language and teacher-rated concentration or cognitive capacity in healthy children.

Conclusion

The newly developed patient education materials are a powerful tool to improve disease- and treatment-related knowledge. They facilitate communication between the medical team and children and adolescents with IEM and their caregivers.
C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy
Authors: Garam Nóra , Prohászka Zoltán , Szilágyi Ágnes , Aigner Christof , Schmidt Alice , Gaggl Martina , Sunder-Plassmann Gere , Bajcsi Dóra , Brunner Jürgen , Dumfarth Alexandra , Cejka Daniel , Flaschberger Stefan , Flögelova Hana , Haris Ágnes , Hartmann Ágnes , Heilos Andreas , Mueller Thomas , Rusai Krisztina , Arbeiter Klaus , Hofer Johannes , Jakab Dániel , Sinkó Mária , Szigeti Erika , Bereczki Csaba , Janko Viktor , Kelen Kata , Reusz György S. , Szabó Attila J. , Klenk Nóra , Kóbor Krisztina , Kojc Nika , Knechtelsdorfer Maarten , Laganovic Mario , Lungu Adrian Catalin , Meglic Anamarija , Rus Rina , Kersnik-Levart Tanja , Macioniene Ernesta , Miglinas Marius , Pawłowska Anna , Stompór Tomasz , Podracka Ludmila , Rudnicki Michael , Mayer Gert , Romana Rysava  , Reiterova Jana , Saraga Marijan , Tomáš Seeman  , Zieg Jakub , Sládková Eva , Szabó Tamás , Capitanescu Andrei , Stancu Simona , Tisljar Miroslav , Galesic Kresimir , Tislér András , Vainumäe Inga , Windpessl Martin , Zaoral Tomas , Zlatanova Galia , Csuka Dorottya
Published: November 2019

Background

Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors.

Results

One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF.

Conclusions

In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.
Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson’s disease
Authors: Huebecker Mylene , Moloney Elizabeth B. , van der Spoel Aarnoud C. , Priestman David A. , Isacson Ole , Hallett Penelope J. , Platt Frances M.
Published: November 2019

Background

Haploinsufficiency in the Gaucher disease GBA gene, which encodes the lysosomal glucocerebrosidase GBA, and ageing represent major risk factors for developing Parkinson’s disease (PD). Recently, more than fifty other lysosomal storage disorder gene variants have been identified in PD, implicating lysosomal dysfunction more broadly as a key risk factor for PD. Despite the evidence of multiple lysosomal genetic risks, it remains unclear how sphingolipid hydrolase activities, other than GBA, are altered with ageing or in PD. Moreover, it is not fully known if levels of glycosphingolipid substrates for these enzymes change in vulnerable brain regions of PD. Finally, little is known about the levels of complex gangliosides in substantia nigra which may play a significant role in ageing and PD.

Methods

To study sphingolipid hydrolase activities and glycosphingolipid expression in ageing and in PD, two independent cohorts of human substantia nigra tissues were obtained. Fluorescent 4-methylumbelliferone assays were used to determine multiple enzyme activities. The lysosomal GBA and non-lysosomal GBA2 activities were distinguished using the inhibitor NB-DGJ. Sensitive and quantitative normal-phase HPLC was performed to study glycosphingolipid levels. In addition, glycosphingolipid levels in cerebrospinal fluid and serum were analysed as possible biomarkers for PD.

Results

The present study demonstrates, in two independent cohorts of human post-mortem substantia nigra, that sporadic PD is associated with deficiencies in multiple lysosomal hydrolases (e.g. α-galactosidase and β-hexosaminidase), in addition to reduced GBA and GBA2 activities and concomitant glycosphingolipid substrate accumulation. Furthermore, the data show significant reductions in levels of complex gangliosides (e.g. GM1a) in substantia nigra, CSF and serum in ageing, PD, and REM sleep behaviour disorder, which is a strong predictor of PD.

Conclusions

These findings conclusively demonstrate reductions in GBA activity in the parkinsonian midbrain, and for the first time, reductions in the activity of several other sphingolipid hydrolases. Furthermore, significant reductions were seen in complex gangliosides in PD and ageing. The diminished activities of these lysosomal hydrolases, the glycosphingolipid substrate accumulation, and the reduced levels of complex gangliosides are likely major contributors to the primary development of the pathology seen in PD and related disorders with age.
Ovarian endometrioma – a possible finding in adolescent girls and young women: a mini-review
Authors: Gałczyński Krzysztof , Jóźwik Maciej , Lewkowicz Dorota , Semczuk-Sikora Anna , Semczuk Andrzej
Published: November 2019

Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17–44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.
Imported cutaneous leishmaniasis: molecular investigation unveils Leishmania major in Bangladesh
Authors: Khan Md Anik Ashfaq , Chowdhury Rajashree , Nath Rupen , Hansen Sören , Nath Progga , Maruf Shomik , Abd El Wahed Ahmed , Mondal Dinesh
Published: November 2019

Background

The main clinical forms of leishmaniasis in Bangladesh are visceral leishmaniasis and post-kala-azar dermal leishmaniasis, which are caused by Leishmania donovani. Imported cutaneous leishmaniasis (CL) is emerging globally due mainly to increased human mobility. In recent years, several imported CL cases have also been reported in Bangladesh. Sporadic atypical cases of CL can be challenging for diagnosis and clinical management, while occurrence of infection on a frequent basis can be alarming. We report of a case of a Bangladeshi temporary-migrant worker who, upon return, presented development of skin lesions that are characteristic of CL.

Methods

A serum sample was collected and tested with an rK39 immunochromatographic test. Nucleic acid from skin biopsy derived culture sample was extracted and screened with a real-time PCR assay which targets the conserved REPL repeat region of L. donovani complex. The internal transcribed spacer 2 region of the ribosomal RNA gene cluster was amplified and sequenced.

Results

The suspect had a history of travel in both CL and VL endemic areas and had a positive rK39 test result. Based on clinical presentation, travel history and demonstration of the parasite in the skin biopsy, CL was diagnosed and the patient underwent a combination therapy with Miltefosine and liposomal amphotericin B. While typical endemic species were not detected, we identified Leishmania major, a species that, to our knowledge, has never been reported in Bangladesh.

Conclusions

Proper monitoring and reporting of imported cases should be given careful consideration for both clinical and epidemiological reasons. Molecular tests should be performed in diagnosis to avoid dilemma, and identification of causative species should be prioritized.
Two-weight norm inequalities for fractional integral operators with $A_{\lambda,\infty}$ weights
Authors: Pan Junren , Sun Wenchang
Published: November 2019

In this paper, we introduce a new class of weights, the$A_{\lambda, \infty}$Aλ,∞weights, which contains the classical$A_{\infty}$A∞weights. We prove a mixed$A_{p,q}$Ap,q–$A_{\lambda,\infty}$Aλ,∞type estimate for fractional integral operators.
Globally convergent method for designing twice spline contractual function
Authors: Zhu Zhichuan , Yao Yonghong , Postolache Mihai
Published: November 2019

To design a quadratic spline contractual function in the case of discretely unknown nodes, a modified constraint shifting homotopy algorithm for solving principal–agent problems is constructed in the paper. Then the existence of globally convergent solution to KKT systems for the principal–agent problem with spline contractual function is proved under a much weaker condition. The proposed algorithm only requires that any initial point is in the shifted feasible set but not necessarily in the original feasible set.