bluuebunny/crossref_metadata_2025 huggingface dataset:
The longitudinal effects of seated isometric yoga on blood biomarkers, autonomic functions, and psychological parameters of patients with chronic fatigue syndrome: a pilot study
Authors: Oka Takakazu , Tanahashi Tokusei , Lkhagvasuren Battuvshin , Yamada Yu
Published: November 2019

Background

In a previous randomized controlled trial, we found that practicing seated isometric yoga regularly for 2 months improved the fatigue of patients with chronic fatigue syndrome (CFS) who are resistant to conventional therapy. The aim of this pilot study was to investigate the possible mechanisms behind this finding by comparing blood biomarkers, autonomic nervous function, and psychological indices before versus after an intervention period of seated isometric yoga practice.

Methods

Fifteen patients with CFS who did not show satisfactory improvements after at least 6 months of conventional therapy practiced seated isometric yoga (biweekly 20-min sessions with a yoga instructor and daily practice at home) for 2 months. The longitudinal effects of seated isometric yoga on fatigue, blood biomarkers, autonomic function, and psychological state were investigated by comparing the following parameters before and after the intervention period: Fatigue severity was assessed by the Chalder fatigue scale (FS) score. Levels of the blood biomarkers cortisol, DHEA-S, TNF-α, IL-6, prolactin, carnitine, TGF-β1, BDNF, MHPG, HVA, and α-MSH were measured. The autonomic nervous functions assessed were heart rate (HR) and HR variability. Psychological indices included the 20-item Toronto Alexithymia Scale (TAS-20) and the Hospital Anxiety and Depression Scale (HADS).

Results

Practicing seated isometric yoga for 2 months resulted in significant reductions in the Chalder FS (P = 0.002) and HADS-depression (P = 0.02) scores. No significant changes were observed in any other parameter evaluated. The change in Chalder FS score was not correlated with the change in HADS-depression score. However, this change was positively correlated with changes in the serum TNF-α levels (P = 0.048), the high frequency component of HR variability (P = 0.042), and TAS-20 scores (P = 0.001).

Conclusions

Regular practice of seated isometric yoga for 2 months reduced the fatigue and depressive symptom scores of patients with CFS without affecting any other parameters we investigated. This study failed to identify the markers responsible for the longitudinal fatigue-relieving effect of seated isometric yoga. However, considering that the reduced fatigue was associated with decreased serum TNF-α level and TAS-20 scores, fatigue improvement might be related to reduced inflammation and improved alexithymia in these patients.

Trial registration

University Hospital Medical Information Network (UMIN CTR)UMIN000009646. Registered Dec 27, 2012.
Novel nose poke-based temporal discrimination tasks with concurrent in vivo calcium imaging in freely moving mice
Authors: Marks William D. , Osanai Hisayuki , Yamamoto Jun , Ogawa Sachie K. , Kitamura Takashi
Published: November 2019

The hippocampus has been known to process temporal information as part of memory formation. While time cells have been observed in the hippocampus and medial entorhinal cortex, a number of the behavioral tasks used present potential confounds that may cause some contamination of time cell observations due to animal movement. Here, we report the development of a novel nose poke-based temporal discrimination task designed to be used with in vivo calcium imaging for the analysis of hippocampal time cells in freely moving mice. First, we developed a ten second held nose poke paradigm for use in mice to deliver a purer time metric for the analysis of time cell activity in hippocampus CA1. Second, we developed a temporal discrimination task that involves the association of held nose poke durations of differing lengths with differential spatial cues presented in arms on a linear I-maze. Four of five mice achieved successful temporal discrimination within three weeks. Calcium imaging has been successfully performed in each of these tasks, with time cell activity being detected in the 10s nose poke task, and calcium waves being observed in discrete components of the temporal discrimination task. The newly developed behavior tasks in mice serve as novel tools to accelerate the study of time cell activity and examine the integration of time and space in episodic memory formation.
Proteasomal cysteine deubiquitinase inhibitor b-AP15 suppresses migration and induces apoptosis in diffuse large B cell lymphoma
Authors: Jiang Liling , Sun Yuening , Wang Jinxiang , He Qingyan , Chen Xinmei , Lan Xiaoying , Chen Jinghong , Dou Q. Ping , Shi Xianping , Liu Jinbao
Published: November 2019

Background

The first line therapy for patients with diffuse large B cell (DLBCL) is R-CHOP. About half of DLBCL patients are either refractory to, or will relapse, after the treatment. Therefore, identifying novel drug targets and effective therapeutic agents is urgently needed for improving DLBCL patient survival. b-AP15, a selective small molecule inhibitor of proteasomal USP14 and UCHL5 deubiquitinases (DUBs), has shown selectivity and efficacy in several other types of cancer cells. This is the first study to report the effect of b-AP15 in DLBCL.

Methods

Cell lines of two DLBCL subtypes, Germinal Center B Cell/ GCB (SU-DHL-4, OCI-LY-1, OCI-LY-19) and Activated B Cell/ABC (SU-DHL-2), were used in the current study. Cell viability was measured by MTS assay, proliferation by trypan blue exclusion staining assay, cellular apoptosis by Annexin V-FITC/PI staining and mitochondrial outer membrane permeability assays, the activities of 20S proteasome peptidases by cleavage of specific fluorogenic substrates, and cell migration was detected by transwell assay in these GCB- and ABC-DLBCL cell lines. Mouse xenograft models of SU-DHL-4 and SU-DHL-2 cells were used to determine in vivo effects of b-AP15 in DLBCL tumors.

Results

b-AP15 inhibited proteasome DUB activities and activated cell death pathway, as evident by caspase activation and mitochondria apoptosis in GCB- and ABC- DLBCL cell lines. b-AP15 treatment suppressed migration of GCB- and ABC-DLBCL cells via inhibiting Wnt/β-catenin and TGFβ/Smad pathways. Additionally, b-AP15 significantly inhibited the growth of GCB- and ABC DLBCL in xenograft models.

Conclusions

These results indicate that b-AP15 inhibits cell migration and induces apoptosis in GCB- and ABC-DLBCL cells, and suggest that inhibition of 19S proteasomal DUB should be a novel strategy for DLBCL treatment.
STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873
Authors: Lin Linling , Xiao Jian , Shi Liang , Chen Wangwang , Ge Yugang , Jiang Mingkun , Li Zengliang , Fan Hao , Yang Li , Xu Zekuan
Published: November 2019

Background

Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC.

Methods

The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments.

Results

STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/β-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6.

Conclusions

STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/β-catenin signalling in GC.
The HOTAIR/miR-214/ST6GAL1 crosstalk modulates colorectal cancer procession through mediating sialylated c-Met via JAK2/STAT3 cascade
Authors: Liu Bing , Liu Qianqian , Pan Shimeng , Huang Yiran , Qi Yu , Li Shuangda , Xiao Yang , Jia Li
Published: November 2019

Background

The regulatory non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), emerge as pivotal markers during tumor progression. Abnormal sialylated glycoprotein often leads to the malignancy of colorectal cancer (CRC).

Methods

Differential levels of HOTAIR and ST6GAL1 are analyzed by qRT-PCR. Functionally, CRC cell proliferation, aggressiveness and apoptosis are measured through relevant experiments, including CCK8 assay, colony formation assay, transwell assay, western blot and flow cytometry. Dual-luciferase reporter gene assay and RIP assay confirm the direct interaction between HOTAIR and miR-214. The lung metastasis, liver metatstasis and xenografts nude mice models are established to show the in vivo effect of HOATIR.

Results

Here, differential levels of HOTAIR and ST6GAL1 are primarily observed in CRC samples and cells. Upregulated HOTAIR and ST6GAL1 are crucial predictors for poor CRC prognosis. Altered level of ST6GAL1 modulates CRC malignancy. Furthermore, ST6GAL1 and HOTAIR are confirmed as the direct targets of miR-214, and ST6GAL1 is regulated by HOTAIR via sponging miR-214. ST6GAL1 induces the elevated metabolic sialylation of c-Met, which is co-mediated by HOTAIR and miR-214. Sialylated c-Met affects the activity of JAK2/STAT3 pathway. The regulatory role of HOTAIR/miR-214/ST6GAL1 axis also impacts CRC procession. In addition, HOTAIR mediates lung metastasis, liver metastasis and tumorigenesis in vivo. ShHOTAIR and AMG-208 are combined to inhibit tumorigenesis for successful drug development.

Conclusion

The HOTAIR/miR-214/ST6GAL1 axis commands the CRC malignancy by modifying c-Met with sialylation and activating JAK2/STAT3 pathway. Our study presents novel insights into CRC progression and provided prospective therapeutic target for CRC.
A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation
Authors: Bertoni Michele , Telias Irene , Urner Martin , Long Michael , Del Sorbo Lorenzo , Fan Eddy , Sinderby Christer , Beck Jennifer , Liu Ling , Qiu Haibo , Wong Jenna , Slutsky Arthur S. , Ferguson Niall D. , Brochard Laurent J. , Goligher Ewan C.
Published: November 2019

Background

Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔPocc) could be used as a highly feasible non-invasive technique to screen for these conditions.

Methods

Respiratory muscle pressure (Pmus), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔPocc were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔPL,dyn and Pmus from ΔPocc was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China).

Results

Fifty-two daily recordings were collected in 16 patients. In this sample, Pmus and ΔPL were frequently excessively high: Pmus exceeded 10 cm H2O on 84% of study days and ΔPL,dyn exceeded 15 cm H2O on 53% of study days. ΔPocc measurements accurately detected Pmus > 10 cm H2O (AUROC 0.92, 95% CI 0.83–0.97) and ΔPL,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86–0.99). In the external validation cohort (n = 12), estimating Pmus and ΔPL,dyn from ΔPocc measurements detected excessively high Pmus and ΔPL,dyn with similar accuracy (AUROC ≥ 0.94).

Conclusions

Measuring ΔPocc enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.
DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits
Authors: Jiang Lin , Xue Chao , Dai Sheng , Chen Shangzhen , Chen Peikai , Sham Pak Chung , Wang Haijun , Li Miaoxin
Published: November 2019

The driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.
Metabolic engineering Escherichia coli for efficient production of icariside D2
Authors: Liu Xue , Li Lingling , Liu Jincong , Qiao Jianjun , Zhao Guang-Rong
Published: November 2019

Background

Icariside D2 is a plant-derived natural glycoside with pharmacological activities of inhibiting angiotensin-converting enzyme and killing leukemia cancer cells. Production of icariside D2 by plant extraction and chemical synthesis is inefficient and environmentally unfriendly. Microbial cell factory offers an attractive route for economical production of icariside D2 from renewable and sustainable bioresources.

Results

We metabolically constructed the biosynthetic pathway of icariside D2 in engineered Escherichia coli. We screened the uridine diphosphate glycosyltransferases (UGTs) and obtained an active RrUGT3 that regio-specifically glycosylated tyrosol at phenolic position to exclusively synthesize icariside D2. We put heterologous genes in E. coli cell for the de novo biosynthesis of icariside D2. By fine-tuning promoter and copy number as well as balancing gene expression pattern to decrease metabolic burden, the BMD10 monoculture was constructed. Parallelly, for balancing pathway strength, we established the BMT23–BMD12 coculture by distributing the icariside D2 biosynthetic genes to two E. coli strains BMT23 and BMD12, responsible for biosynthesis of tyrosol from preferential xylose and icariside D2 from glucose, respectively. Under the optimal conditions in fed-batch shake-flask fermentation, the BMD10 monoculture produced 3.80 g/L of icariside D2 using glucose as sole carbon source, and the BMT23–BMD12 coculture produced 2.92 g/L of icariside D2 using glucose–xylose mixture.

Conclusions

We for the first time reported the engineered E. coli for the de novo efficient production of icariside D2 with gram titer. It would be potent and sustainable approach for microbial production of icariside D2 from renewable carbon sources. E. coli–E. coli coculture approach is not limited to glycoside production, but could also be applied to other bioproducts.
Integrated strain- and process design enable production of 220 g L−1 itaconic acid with Ustilago maydis
Authors: Hosseinpour Tehrani Hamed , Becker Johanna , Bator Isabel , Saur Katharina , Meyer Svenja , Rodrigues Lóia Ana Catarina , Blank Lars M. , Wierckx Nick
Published: November 2019

Background

Itaconic acid is an unsaturated, dicarboxylic acid which finds a wide range of applications in the polymer industry and as a building block for fuels, solvents and pharmaceuticals. Currently,Aspergillus terreusis used for industrial production, with titers above 100 g L−1depending on the conditions. BesidesA. terreus,Ustilago maydisis also a promising itaconic acid production host due to its yeast-like morphology. Recent strain engineering efforts significantly increased the yield, titer and rate of production.

Results

In this study, itaconate production byU. maydiswas further increased by integrated strain- and process engineering. Next-generation itaconate hyper-producing strains were generated using CRISPR/Cas9 and FLP/FRT genome editing tools for gene deletion, promoter replacement, and overexpression of genes. The handling and morphology of this engineered strain were improved by deletion offuz7, which is part of a regulatory cascade that governs morphology and pathogenicity. These strain modifications enabled the development of an efficient fermentation process with in situ product crystallization with CaCO3. This integrated approach resulted in a maximum itaconate titer of 220 g L−1, with a total acid titer of 248 g L−1, which is a significant improvement compared to best published itaconate titers reached withU. maydisand withA. terreus.

Conclusion

In this study, itaconic acid production could be enhanced significantly by morphological- and metabolic engineering in combination with process development, yielding the highest titer reported with any microorganism.
First report of the influence of temperature on the bionomics and population dynamics of Aedes koreicus, a new invasive alien species in Europe
Authors: Marini Giovanni , Arnoldi Daniele , Baldacchino Frederic , Capelli Gioia , Guzzetta Giorgio , Merler Stefano , Montarsi Fabrizio , Rizzoli Annapaola , Rosà Roberto
Published: November 2019

Background

Aedes koreicus was detected in northern Italy for the first time in 2011, and it is now well established in several areas as a new invasive mosquito species. Data regarding the influence of temperature on mosquito survival and development are not available yet for this species.

Methods

We experimentally investigated the influence of different constant rearing temperatures (between 4 and 33 °C) on the survival rates and developmental times of different life stages of Ae. koreicus under laboratory conditions. The resulting data were subsequently used to inform a mathematical model reproducing the Ae. koreicus life-cycle calibrated to counts of adult females captured in the field in the autonomous province of Trento (northern Italy) between 2016 and 2018.

Results

We found that temperatures above 28 °C are not optimal for the survival of pupae and adults, whereas temperate conditions of 23–28 °C seem to be very favorable, explaining the recent success of Ae. koreicus at establishing into new specific areas. Our results indicate that Ae. koreicus is less adapted to local climatic conditions compared to Ae. albopictus, another invasive species which has been invading the area for the last three decades. Warmer seasons, which are more likely to occur in the future because of climate change, might extend the breeding time and therefore increase the abundance of Ae. koreicus in the study region.

Conclusions

Our findings provide, to our knowledge, the first evidence on how temperature influences the bionomics and dynamics of Ae. koreicus and highlight the need for further studies on the phenology of this species in temperate areas of Europe.
First detection of the kdr mutation (L1014F) in the plague vector Xenopsylla cheopis (Siphonaptera: Pulicidae)
Authors: Liu Nian , Feng Xiangyang , Li Mei , Qiu Xinghui
Published: November 2019

Background

The oriental rat flea, Xenopsylla cheopis, is the most efficient vector of the plague. Pyrethroid insecticides such as cypermethrin, cyhalothrin and deltamethrin have been often used to limit plague transmission via controlling the vector during outbreaks. However, this strategy is threatened by the development of insecticide resistance. Understanding the mechanisms underlying pyrethroid resistance is the prerequisite for successful flea control.

Methods

Partial DNA sequences of X. cheopis voltage gated sodium channel (VGSC) gene were amplified from a total of 111 individuals, collected from a natural plague epidemic foci in Baise City, Guangxi Zhuang Autonomous Region of China. These DNA fragments were sequenced. The frequency and distribution of kdr mutations were assessed in four X. cheopis populations. The origin of kdr mutations was investigated by phylogenetic and network analysis.

Results

The classical knockdown resistance (kdr) mutation (L1014F) was detected in four field populations at frequencies ranging between 0.021–0.241. The mutant homozygote was observed only in one of the four populations. Seven haplotypes were identified, with two of them carrying the resistance L1014F mutation. Phylogenetic tree and network analysis indicated that the L1014F allele was not singly originated. Based on polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) profiling, an easy-to-use and accurate molecular assay for screening individual fleas for the L1014F mutation was developed.

Conclusions

To our knowledge, this work represents the first report of the L1014F mutation in the plague vector X. cheopis. The incidence of the L1014F allele highlights the need of further studies on the phenotypic effect of this mutation in this plague vector. Early detection and monitoring of insecticide resistance is suggested in order to make effective control strategies in case of plague outbreaks in this region.
Liver fluke in Irish sheep: prevalence and associations with management practices and co-infection with rumen fluke
Authors: Munita Maria Pia , Rea Rosemary , Martinez-Ibeas Ana Maria , Byrne Noel , McGrath Guy , Munita-Corbalan Luis Enrique , Sekiya Mary , Mulcahy Grace , Sayers Ríona G.
Published: November 2019

Background

The present study aimed to identify the national prevalence of Fasciola hepatica in Irish sheep and to conduct a risk analysis assessment based on management and treatment practices in participating flocks. Also, co-infection with rumen fluke was quantified and its association with liver fluke and management practices was assessed.

Methods

A total of 305 sheep flocks were selected ensuring even national representation of the sheep population. Participating farms were asked to complete a survey questionnaire on farm management practices and submit faecal samples during the winter of 2014–2015. Pooled faecal samples were analysed for the presence of F. hepatica and co-infection with rumen fluke. Apparent and true prevalence were calculated, additionally, the rate of co-infection with rumen fluke was also obtained. Correlation and regression analyses were used for assessing associations between management practices, liver fluke infection and co-infection with rumen fluke.

Results

The national true prevalence of F. hepatica was 50.4% (n = 305). Regional prevalence varied from 41% in the east to 52% in the south. Co-infection with rumen fluke was observed in 40% of the studied population and correlated with increased F. hepatica egg counts (OR = 2.9; P ≤ 0.001). Predominant breeds were Suffolk, Texel and Horned Mountain breeds. Beef cattle were the most frequent type of other livestock present on farms and mixed species grazing was frequently reported (73%). More than half of the flocks reported a mid-to-late lambing period (March-April). Use of mountain land for grazing was of 32%. Flukicides were most commonly used twice over the autumn-winter period. Regression analyses highlighted significant association of F. hepatica status, with the presence of other livestock on farm, frequency of flukicides used during the winter and clinical presentation of liver fluke. A significant increase in eggs per gram of faeces was observed in Charollais sheep in comparison with all other breeds. Co-infection with F. hepatica and Calicophoron daubneyi was also significantly associated with the presence of other livestock on the farm, type of flukicide used and clinical fasciolosis.

Conclusions

The present study provides up-to-date information on the prevalence of F. hepatica in Irish sheep and adds insight to the epidemiology of the disease. These findings will be useful for designing new holistic control measures for F. hepatica infection.
Inhibition of spinal bone formation in AS: 10 years after comparing adalimumab to OASIS
Authors: van der Heijde Désirée , Landewé Robert
Published: November 2019

A decade has passed since the publication on the comparison of the effect of adalimumab with data from a historic cohort on the progression of structural damage in the spine of patients with ankylosing spondylitis (AS). No effect could be observed, and currently, there is still no definite proof that TNF inhibitors (TNFi) inhibit spinal structural damage. The findings of the publication are discussed within the context of the time at the publication and new developments.
Multilevel modelling of factors associated with caesarean section in Ethiopia: community based cross sectional study
Authors: Azene Abebaw Gedef , Aragaw Abiba Mihret , Birlie Mihretie Gedefaw
Published: November 2019

Objective

The aim of this study was to identify socio-demographic and health related factors associated with caesarean section in Ethiopia.

Results

A total of 256 mothers undergoing to CS among 7193 delivery. Average maternal age of a participant was 29.26 years and 80% of mothers having two and more children. A woman delivered in private institution was 30% (AOR = 1.29; 95% CI 1.25, 1.32) more likely undergoing CS as compared to home delivery. Factors associated with CS were higher education level (AOR = 1.09, 95% CI 1.07, 1.12), preceding birth interval (AOR = 1.01; 95% CI 1.00. 1.03), multiple pregnancy (AOR = 1.11; 95% CI 1.08, 1.15), multiple parity (AOR = 0.98; 95% CI 0.97, 0.99), large size the child (AOR = 1.01; 95% CI 1.001, 1.02), richest households (AOR = 0.98; 95% CI 0.97, 0.99), rural residence (AOR = 0.98 95% CI 0.96, 0.99) and Addis Ababa (AOR = 1.06; 95% CI 1.04,1.09). As a conclusion and recommendation, the prevalence of CS higher in private institutions and Addis Ababa, so professionals should apply CS alone medical indication.
Rapid diagnostics of orthopedic implant-associated infections using Unyvero ITI implant and tissue infection application is not optimal for Staphylococcus species identification
Authors: Aamot Hege Vangstein , Johnsen Bjørn Odd , Skråmm Inge
Published: November 2019

Objectives

This pilot study aimed to compare the commercial Unyvero ITI multiplex PCR application (U-ITI, Curetis GmbH) with conventional culturing concerning (a) detection of pathogens, (b) time to detection of pathogens and (c) time to and quality of antibiotic treatment recommendation in diagnostics of orthopedic implant-associated infections (OIAI).

Results

72 tissue biopsies from 15 consecutive patients with deep OIAI infections were analyzed with conventional culturing including phenotypic antibiotic susceptibility testing and the U-ITI. U-ITI showed lower sensitivity than conventional culturing concerning detection of pathogens (73% vs 93%). 4/15 patients would have been given false negative results by U-ITI, all of which were culture-positive for Staphylococcus species. Median time to detection of pathogens was 47 h and antibiotic resistance 89 h by conventional methods compared to 13.5 h with the U-ITI. The U-ITI did not detect antibiotic resistance, whereas conventional culturing showed resistance to antibiotics covered by the U-ITI panel in 2 patients. Time to detection of pathogens was improved, but the detection limit for staphylococci was unsatisfactory. Although the time to antibiotic treatment recommendation was significantly reduced, the U-ITI would have resulted in incorrect antibiotic recommendation in 2 patients. Our data do not support use of this assay in diagnostics.
Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study
Authors: Murata Tomokazu , Hiramatsu Yoichi , Yamada Fuminori , Seki Yoichi , Nagata Shinobu , Shibuya Takayuki , Yokoo Mizue , Noguchi Remi , Tanaka Mari , Oshiro Keiko , Matsuzawa Daisuke , Hirano Yoshiyuki , Shimizu Eiji
Published: November 2019

Objective

Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment.

Results

Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms.

Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320)
Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome
Authors: Frohlich Joel , Reiter Lawrence T. , Saravanapandian Vidya , DiStefano Charlotte , Huberty Scott , Hyde Carly , Chamberlain Stormy , Bearden Carrie E. , Golshani Peyman , Irimia Andrei , Olsen Richard W. , Hipp Joerg F. , Jeste Shafali S.
Published: November 2019

Following publication of the original article [1], we have been notified that the Ethics statement of the articles should be changed. The Ethics statement now reads:
Missed opportunities in large scale comparison of QSAR and conformal prediction methods and their applications in drug discovery
Authors: Krstajic Damjan
Published: November 2019

Recently Bosc et al. (J Cheminform 11(1): 4, 2019), published an article describing a case study that directly compares conformal predictions with traditional QSAR methods for large-scale predictions of target-ligand binding. We consider this study to be very important. Unfortunately, we have found several issues in the authors’ approach as well as in the presentation of their findings.
Optimal interference range for minimum Bayes risk in binomial and Poisson wireless networks
Authors: Ouyang Min , Shi Wenxiao , Zhang Ruidong , Liu Wei
Published: November 2019

Interference is the main performance-limiting factor in most wireless networks. Protocol interference model is extensively used in the design of wireless networks. However, the setting of interference range, a crucial part of the protocol interference model, is rather heuristic and remains an open problem. In this paper, we use the stochastic geometry and the direct approach to obtain the associated feasibility distributions. After that, we use the binary hypothesis testing to achieve the Bayes risk under binomial point process (BPP) and Poisson point process (PPP), respectively. According to the first derivative of the Bayes risk, we provide the equation to achieve the optimal interference range for minimum Bayes risk. We extend the method proposed by Wildman et al. to a more general situation. Furthermore, we show that for infinite PPP, those two methods converge to the same results. Several numerical results for wireless networks under BPP, finite PPP, and infinite PPP are given. Simulation results show that in the finite wireless network, the BPP method performs better than the PPP method.
Fixed point results in $M_{\nu }$-metric spaces with an application
Authors: Asim Mohammad , Uddin Izhar , Imdad Mohammad
Published: November 2019

In this paper, we introduce the concept of $M_{\nu}$

M
ν

-metric as a generalization of M-metric and ν-generalized metric and also prove an analogue of Banach contraction principle in an $M_{\nu}$

M
ν

-metric space. Also, we adopt an example to highlight the utility of our main result which extends and improves the corresponding relevant results of the existing literature. Finally, we use our main result to examine the existence and uniqueness of solution for a Fredholm integral equation.
Blow-up results for a quasilinear von Karman equation of memory type
Authors: Lee Mi Jin , Kang Jum-Ran
Published: November 2019

In this paper, we consider the blow-up result of solution for a quasilinear von Karman equation of memory type with nonpositive initial energy as well as positive initial energy. For nonincreasing function $g>0$
g
>
0
and nondecreasing function f, we prove a finite time blow-up result under suitable condition on the initial data.
Effect of bFGF and fibroblasts combined with hyaluronic acid-based hydrogels on soft tissue augmentation: an experimental study in rats
Authors: Lee Su Yeon , Park Yongdoo , Hwang Soon Jung
Published: November 2019

Background

Hyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane®).

Methods

The hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane® group (HGF), the hydrogel was replaced with Restylane® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR.

Results

The hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane® filler could not be observed, even though no inflammatory reactions were observed.

Conclusion

This study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.
Performance of Five Ultrasound Risk Stratification Systems in Selecting Thyroid Nodules for FNA
Authors: Castellana Marco , Castellana Carlo , Treglia Giorgio , Giorgino Francesco , Giovanella Luca , Russ Gilles , Trimboli Pierpaolo
Published: November 2019

Context

Ultrasound (US) risk stratification systems (RSSs) have been developed to reduce the number of unnecessary fine-needle aspiration procedures (FNA) in patients with thyroid nodules.

Objective

We conducted a systematic review and meta-analysis evaluating the ability of the 5 most common US RSSs for the appropriate selection of thyroid nodules for FNA.

Data sources

This systematic review and meta-analysis was registered on PROSPERO (CRD42019131771). PubMed, CENTRAL, Scopus, and Web of Science were searched until March 2019.

Study selection

Original articles reporting data on the performance of AACE/ACE/AME, ACR TI-RADS, ATA, EU-TIRADS, and K-TIRADS were included.

Data extraction

The number of nodules classified as true negative, true positive, false negative, and false positive was extracted. Summary operating points were estimated using a random-effects model. Interobserver agreement was also assessed.

Data synthesis

Twelve studies evaluating 18 750 thyroid nodules were included. Participants were adult outpatients with thyroid nodules submitted to either FNA or core-needle biopsy or surgery and with available US images. The final diagnosis for malignant nodules was generally based on histology, while cytology was used for benign nodules. Diagnostic odds ratio (DOR) ranged from 2.2 to 4.9. A head-to-head comparison showed a higher relative DOR for ACR-TIRADS versus ATA (P = .002) or K-TIRADS (P = .002), due to a higher relative likelihood ratio for positive results.

Conclusions

The present meta-analysis found a higher performance of ACR TI-RADS in selecting thyroid nodules for FNA. However, the comparison across the most common US RSSs was limited by the data available. Further studies are needed to confirm this finding.
Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD
Authors: Polyzos Stergios A , Perakakis Nikolaos , Boutari Chrysoula , Kountouras Jannis , Ghaly Wael , Anastasilakis Athanasios D , Karagiannis Asterios , Mantzoros Christos S
Published: November 2019

Aims

To investigate circulating levels and liver gene expression of 3 hormonal pathways associated with obesity, insulin resistance, and inflammation to identify leads towards potential diagnostic markers and therapeutic targets in patients with nonalcoholic fatty liver disease (NAFLD).

Methods

We compared circulating levels of (1) proglucagon-derived hormones (glucagon-like peptide [GLP]-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]), (2) follistatins-activins (follistatin-like [FSTL]3, activin B), (3) IGF axis (insulin-like growth factor [IGF]-1, total and intact IGF binding protein [IGFBP]-3 and IGFBP-4, and pregnancy-associated plasma protein [PAPP]-A) in 2 studies: (1) 18 individuals with early stage NAFLD versus 14 controls (study 1; early NAFLD study) and in (2) 31 individuals with biopsy proven NAFLD (15 with simple steatosis [SS] and 16 with nonalcoholic steatohepatitis [NASH]), vs 50 controls (24 lean and 26 obese) (study 2). Liver gene expression was assessed in 22 subjects (12 controls, 5 NASH, 5 NASH-related cirrhosis).

Results

Patients in early stages of NAFLD demonstrate higher fasting MPGF and lower incremental increase of glicentin during oral glucose tolerance test than controls. In more advanced stages, FSTL3 levels are higher in NASH than simple steatosis and, within NAFLD patients, in those with more severe lobular and portal inflammation. The IGF-1/intact IGFBP-3 ratio is lower in patients with liver fibrosis. Genes encoding follistatin, activin A, activin B, and the IGF-1 receptor are higher in NASH.

Conclusion

MPGF and glicentin may be involved in early stages of NAFLD, whereas FSTL3 and IGF-1/intact IGFBP3 in the progression to NASH and liver fibrosis respectively, suggesting potential as diagnostic markers or therapeutic targets.
Probability Forecasts and Their Combination: A Research Perspective
Authors: Winkler Robert L. , Grushka-Cockayne Yael , Lichtendahl Kenneth C. , Jose Victor Richmond R.
Published: November 2019

We explore some recent, and not so recent, developments concerning the use of probability forecasts and their combination in decision making. Despite these advances, challenges still exist. We expand on some important challenges influencing the “goodness” of combined probability forecasts such as miscalibration, dependence among forecasters, and selection of an appropriate evaluation measure while connecting the processes of aggregating and evaluating forecasts to decision making. Through three important applications from the domains of meteorology, economics, and political science, we illustrate state-of-the-art usage of probability forecasts: how they are combined, evaluated, and communicated to stakeholders. We expect to see greater use and aggregation of probability forecasts, especially given developments in statistical modeling, machine learning, and expert forecasting; the popularity of forecasting competitions; and the increased reporting of probabilities in the media. Our vision is that increased exposure to and improved visualizations of probability forecasts will enhance the public’s understanding of probabilities and how they can contribute to better decisions.
Setting Strategic Objectives for the Coalition for Epidemic Preparedness Innovations: An Exploratory Decision Analysis Process
Authors: Gouglas Dimitrios , Hoyt Kendall , Peacocke Elizabeth , Kaloudis Aristidis , Ottersen Trygve , Røttingen John-Arne
Published: November 2019

The authors demonstrate how decision analysis can support a rational and transparent approach to strategy formulation that considers and ranks the preferences of multiple stakeholders in an international coalition setting. They use value-focused thinking to identify and structure objectives and combine this with an explorative discrete-choice experiment to elicit preferences among objectives.
The Relationship between Transitive and Intransitive Verbs in English Language
Authors: Fiktorius Teddy
Published: November 2019

In the current research, the researcher employs descriptive method (library research) to elaborate on the relationship and differentiation between the English language transitive and intransitive verbs. The first parts explore the theoretical framework of the relationship and differentiation equipped with various sentences samples. The next part discusses the implications for English language teachers in coping with some grammatical confusion. Finally, some solutions as well as recommendations are proposed.
Rare health conditions 29: serpiginous choroiditis, haemolytic-uraemic syndrome, Kallman syndrome, Fabry disease
Authors: Barber Chris
Published: November 2019

The purpose of this series is to highlight a range of rare health conditions: those that affect no more and usually fewer than 1 person in every 2000. Many healthcare assistants and nurses will encounter some of these conditions, given the high number of them. This 29th article will briefly explore four of these rare conditions.
Defining Preliminary Research for Digital Game-Based Learning Evaluation: Best Practices
Authors: Pauline-Graf Denise , Mandel Susan Elaine
Published: November 2019

The surge of learners being immersed in computer game contexts for learning has instigated dialogue about the contextually appropriate collection of reliable and valid data to inform education-based decisions. The purpose of this article is to develop educational practitioners’ understanding of preliminary research work, and to inform educational researchers about design and reporting of preliminary research work, in the context of reported preliminary studies on Digital Game-Based Learning Interventions (DGBLIs). First a checklist of processes for the reporting of preliminary studies is provided. Second, a summary is offered of the characteristics of each type of preliminary study including the description, objectives, and methodology. Third, an example from peer-reviewed literature is identified of each type of preliminary study relevant to DGBLIs and conducted within the past five years. Evident from the examples selected, educational researchers and practitioners are best advised to recognize the characteristics of preliminary studies — pilot work, feasibility study, pilot study, pilot trial, and field test — to better inform DGBLIs before embarking on a full-scale study, and to meet the need of educational practitioners for concrete evidence about DGBLIs.
El potencial de las TIC para la interpretación y puesta en valor del patrimonio: la relación entre las TIC y la satisfacción de los visitantes a centros culturales
Authors: Quesada de la Rosa Ana
Published: November 2019

During the last years the impact of ICT into the cultural sector has exponentially grown up. New technologies offer innovative solutions to create new experiences for a non-stopping changing audience. Virtual Reality (VR) and Augmented Reality (AR) take the lead as two of the main ingredients on this recipe that we call ‘culture + technology’. The principal aim of this analysis has been to look over some of the study cases which analyze the impact of new technologies on cultural places’ visitors, aiming to glimpse part of their great potential. The results show that the use of new technologies, specially VR and AR, help to improve significantly user’s satisfaction by offering new learning experiences which makes easier for them to understand and connect with cultural heritage. In addition, the use of new technologies increases the intention of visit, as well as the return’s rate to a place they have already visited, key factors in every cultural management program.
Investigation of similarities and differences between Dance Tourism markets: the case of Patras, Greece
Authors: Zouni Georgia , Karlis Aggelos , Georgaki Ioanna
Published: November 2019

In every corner of the world, we observe that tourism destinations, having understood the importance of dance events, try to increase the presentation of such dance events, with the aim to attract and entertain tourists. Dance tourism constitutes a part of cultural tourism since, through that, opportunities for cultural experience are provided to tourists. The main aim of the present research is the investigation of the similarities and differences between Greek and Russian dance tourists towards dance tourism in a tourism destination (Patras, Greece), regarding: (a) the Demographic characteristics, (b) attitude towards dance tourism, and (c) attitude towards Patras as a dance tourism destination. Results show that younger individuals, mainly women, that are single, of high educational level, private-sector employees mainly, and of medium income are interested in dance tourism. Moreover, several interesting results found regarding attitude towards dance tourism, and attitude towards dance tourism destinations. The contribution of this study is twofold. For both For academia, this research might deepen the understanding of dance tourism travellers and its impact on destinations products formulation. For practitioners, this kind of approach might provide new and strategically important knowledge about attracting dance tourists.
Duarte Pacheco Pereira Descobridor do Brasil? Uma Outra Leitura do “Esmeraldo de Situ Orbis”
Authors: Dos Santos João Marinho
Published: November 2019

https://doi.org/10.14195/0870-4147_50_12
Santiago González Sánchez, La alta nobleza castellana a comienzos del siglo XV: consolidación de linajes y casas nobles, Madrid, Comité Español de Ciencias Históricas e Editorial Dykinson, 2018, 333 p., ISBN 978-84-9148-909-2
Authors: Feio Rodolfo Petronilho
Published: November 2019

https://doi.org/10.14195/0870-4147_50_20