bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation
Authors: Brito Cheila , Azevedo Ana , Esteves Susana , Marques Ana Rita , Martins Carmo , Costa Ilda , Mafra Manuela , Bravo Marques José M. , Roque Lúcia , Pojo Marta 
Published: October 2019

Abstract

Background
Significant advances in the molecular profiling of gliomas, led the 2016 World Health Organization (WHO) Classification to include, for the first-time, molecular biomarkers in glioma diagnosis: IDH mutations and 1p/19q codeletion. Here, we evaluated the effect of this new classification in the stratification of gliomas previously diagnosed according to 2007 WHO classification. Then, we also analyzed the impact of TERT promoter mutations, PTEN deletion, EGFR amplification and MGMT promoter methylation in diagnosis, prognosis and response to therapy in glioma molecular subgroup.

Methods
A cohort of 444 adult gliomas was analyzed and reclassified according to the 2016 WHO. Mutational analysis of IDH1 and TERT promoter mutations was performed by Sanger sequencing. Statistical analysis was done using SPSS Statistics 21.0.

Results
The reclassification of this cohort using 2016 WHO criteria led to a decrease of the number of oligodendrogliomas (from 82 to 49) and an increase of astrocytomas (from 49 to 98), while glioblastomas (GBM) remained the same (n = 256). GBM was the most common diagnosis (57.7%), of which 55.2% were IDH-wildtype. 1p/19q codeleted gliomas were the subgroup associated with longer median overall survival (198 months), while GBM IDH-wildtype had the worst outcome (10 months). Interestingly, PTEN deletion had poor prognostic value in astrocytomas IDH-wildtype (p = 0.015), while in GBM IDH-wildtype was associated with better overall survival (p = 0.042) as well as MGMT promoter methylation (p = 0.009). EGFR amplification and TERT mutations had no impact in prognosis. Notably, EGFR amplification predicted a better response to radiotherapy (p = 0.011) and MGMT methylation to chemo-radiotherapy (p = 0.003).

Conclusion
In this study we observed that the 2016 WHO classification improved the accuracy of diagnosis and prognosis of diffuse gliomas, although the available biomarkers are not enough. Therefore, we suggest MGMT promoter methylation should be added to glioma classification. Moreover, we found two genetic/clinical correlations that must be evaluated to understand their impact in the clinical setting: i) how is PTEN deletion a favorable prognostic factor in GBM IDH wildtype and an unfavorable prognostic factor in astrocytoma IDH wildtype and ii) how EGFR amplification is an independent and strong factor of response to radiotherapy.
A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model
Authors: Sudeep Heggar V. , Venkatakrishna Karempudi , Amrutharaj Ballal , Anitha  , Shyamprasad Kodimule 
Published: October 2019

Abstract

Background
Benign prostatic hyperplasia (BPH) is a pathological condition affecting older men. BPH complications often lead to deterioration in the quality of life. Serenoa repens (Saw Palmetto) is used for treating lower urinary tract infections in traditional medicine.

Methods
This study was performed to compare the efficacy of β-sitosterol enriched saw palmetto oil (VISPO) and conventional saw palmetto oil (SPO) extracted using supercritical fluid extraction, in alleviating the BPH complications using testosterone-induced BPH model rats. The animals received testosterone (5 mg/kg s.c.) with or without SPO and VISPO (200 and 400 mg/kg b.w.) or Finasteride (1 mg/kg b.w.) p.o. for 28 days. At the end of the experiment, overnight fasted animals were euthanized, blood samples collected for serum analysis of testosterone. Prostate tissue histomorphology was examined by hematoxylin and eosin (H&E) staining. Western blot analysis was performed using prostate tissue homogenates.

Results
VISPO exhibited superior efficacy compared to SPO as evident from the significant decrease in prostate weight to body weight ratio, serum testosterone level and increase in growth inhibition of prostate tissue compared to BPH group (p < 0.001). Histological examination of prostate tissue samples showed that VISPO treatment was comparatively better than SPO in improving the hyperplastic patterns. Further, VISPO significantly regulated the expression of inflammatory and apoptotic marker proteins in BPH rats.

Conclusion
Our data provide experimental evidence that β-sitosterol enriched saw palmetto oil could be higher efficacious in treating the BPH complications compared to the conventional saw palmetto oil preparations.
“As we have gathered with a common problem, so we seek a solution”: exploring the dynamics of a community dialogue process to encourage community participation in family planning/contraceptive programmes
Authors: Crankshaw Tamaryn L. , Kriel Yolandie , Milford Cecilia , Cordero Joanna Paula , Mosery Nzwakie , Steyn Petrus S. , Smit Jennifer 
Published: October 2019

Abstract

Background
Community dialogues have been widely used as a method for community engagement and participation to cover a broad range of areas. However, there has been limited documentation and evaluation of the process, particularly as a method towards achieving family planning and contraception (FP/C) programme goals. As part of the development of an intervention package aimed at increasing community and health care provider (HCP) participation in the provision of FP/C, feasibility testing of the intervention approach (a community dialogue between communities and health facilities) was carried out. Our findings offer a systematic description and evaluation of the community dialogue process, with key recommendations towards future implementation.

Methods
The dialogue was evaluated in three ways: 1) through participant observation during the community dialogue, 2) via a standardised feasibility testing tick-list for all observers of the dialogue, and 3) through three focus group discussions (FGDs) consisting of different groups of stakeholders who participated in the community dialogue. In total, 28 community members, HCPs, and key stakeholders attended the community dialogue (22 females, 6 males). Twenty-seven of the community dialogue participants participated in one of 3 FGDs held after the dialogue. Six evaluators assessed feasibility of the dialogue process.

Results
There was good attendance, representation and participation amongst community and provider sectors based on the participant observations using the standardized feasibility check-list. The community dialogue process received positive feedback in the FGDs and was demonstrated to be feasible and acceptable. Key factors contributing to the success of the community dialogue included a skilled facilitator, good representation of participants, establishing ground rules, good timekeeping, and using a Theory of Change to facilitate goal identification and dialogue. Issues to consider are the underlying power differentials related to age, profession and gender which caused initial feelings of anxiety amongst some participants.

Conclusions
Our formative findings offer a systematic description and evaluation of a community dialogue process with key recommendations that may be considered when constituting similar community dialogues in the future.
Effects of insect diets on the gastrointestinal tract health and growth performance of Siberian sturgeon (Acipenser baerii Brandt, 1869)
Authors: Józefiak Agata , Nogales-Mérida Silvia , Rawski Mateusz , Kierończyk Bartosz , Mazurkiewicz Jan 
Published: October 2019

Abstract

Background
Insects in the fish diet are a natural source of protein, fat, and other nutrients. These meals are considered an ecological replacement for fishmeal to improve growth parameters. The application of insect meals to fish diets has been studied, especially in continental fish. Data regarding the effects of insect meals on the gut health of Siberian sturgeon are not available. This study investigated the effects of full-fat Hermetia illucens (HI) and Tenebrio molitor (TM) meals on the gut health of juvenile Siberian sturgeon. Growth performance, gastrointestinal tract (GIT) histomorphology and the microbiome composition of juvenile Siberian sturgeon were analyzed.

Results
The inclusion of insect meals did not affect the growth performance or the survival rate. In the gastrointestinal tract histomorphology, a reduction in the mucosa thickness with the HI treatment was observed. In contrast, fish fed the TM diet had an increase in the thickness of the muscular layer. There were no observed significant differences in villus height among treatments. The analysis of the selected microbiota populations in the Siberian sturgeon gastrointestinal tract showed that insect addition affected the composition of the microbiome. The greatest effect on bacterial populations (Clostridium leptum subgroup, Enterobacteriaceae, Clostridium coccoides – Eubacterium rectale cluster, Aeromonas spp., Bacillus spp., Carnobacterium spp., Enterococcus spp. and Lactobacillus group) was observed with the HI diet (P < 0.05). The TM-based diet increased counts in the following bacterial groups: Clostridium coccoides – Eubacterium rectale cluster, Bacillus spp., Carnobacterium spp., and Enterococcus spp. In contrast, the TM diet decreased the total number of bacteria. The TM diet did not significantly affect the Clostridium leptum subgroup, Enterobacteriaceae, Aeromonas spp. or the Lactobacillus group.

Conclusions
Fish meal replacement by the inclusion of 15% of full-fat Hermetia illucens and Tenebrio molitor (15%) meals did not affect the growth performance, survival rate or villus height of juvenile Siberian sturgeon. The present study suggests that an H. illucens-based diet positively affects the gut microbiota composition and intestinal morphology of juvenile Siberian sturgeon without negative changes in the villus height.
The effectiveness of marine based fatty acid compound (PCSO-524) and firocoxib in the treatment of canine osteoarthritis
Authors: Vijarnsorn Monchanok , Kwananocha Irin , Kashemsant Narudee , Jarudecha Thitichai , Lekcharoensuk Chalermpol , Beale Brian , Peirone Bruno , Lascelles B. Duncan X. 
Published: October 2019

AbstractBackgroundNSAIDs are accepted as the most predictably efficacious medical treatment of the clinical signs of osteoarthritis (OA). The marine-based fatty-acid compound PCSO-524 has been proposed as an adjunctive treatment for canine OA, however benefits of this agent is still controversial. The purpose of this study was to evaluate and compare the effectiveness of PCSO-524 combined with the NSAID firocoxib using force plate gait analysis, orthopedic assessment score (OAS) and canine brief pain inventory score (CBPI) in dogs with OA.A prospective, randomized, double-blinded study was conducted. Seventy-nine dogs that had hip and/or stifle OA were assigned randomly into three treatment groups: firocoxib, PCSO-524 and combination of firocoxib and PCSO-524, orally for 4 weeks. Peak vertical force (PVF, expressed as a percentage of bodyweight), OAS, CBPI, serum prostaglandin E2concentration, hematology and blood chemistry values were evaluated before treatment (Day0), as well as at the second (Day14) and fourth week (Day28) during treatment.ResultsWithin group analysis revealed significant increases in PVF over the 4-week treatment period for firocoxib, PCSO-524 and the combination (p < 0.05). Mean increases in PVF were 3.25 ± 4.13, 2.01 ± 3.86, 4.11 ± 4.69%BW (mean ± SD) respectively. The OAS showed non-significant change in all treatment groups. There were significant decreases in CBPI pain severity score (PSS) and CBPI pain interference scores (PIS) within some groups over time, however no significant differences were found between the groups. Significantly decreased serum PGE2concentration (p < 0.05) was found in the combination group. Significant increases in BUN and creatinine (p < 0.05) compared to pre-treatment values were found in the firocoxib and combination groups but not in the PCSO-524 group at day28, but all values in all dogs remained within the normal ranges.ConclusionsThe results of this study suggested combination of both PCSO-524 and firocoxib is more effective in alleviation of inflammation and improvement of weight bearing ability when compared to the uses of either PCSO-524 or firocoxib alone. Further clinical studies are needed to confirm this, and to determine if there is any benefit of PCSO-524 over placebo.
pH and redox dual-responsive nanoparticles based on disulfide-containing poly(β-amino ester) for combining chemotherapy and COX-2 inhibitor to overcome drug resistance in breast cancer
Authors: Zhang Sipei , Guo Nan , Wan Guoyun , Zhang Tao , Li Chunyu , Wang Yongfei , Wang Yinsong , Liu Yuanyuan 
Published: October 2019

Abstract

Background
Multidrug resistance (MDR) generally leads to breast cancer treatment failure. The most common mechanism of MDR is the overexpression of ATP-binding cassette (ABC) efflux transporters such as P-glycoprotein (P-gp) that reduce the intracellular accumulation of various chemotherapeutic agents. Celecoxib (CXB), a selective COX-2 inhibitor, can dramatically enhance the cytotoxicity of doxorubicin (DOX) in breast cancer cells overexpressing P-gp. Thus it can be seen that the combination of DOX and CXB maybe obtain synergistic effects against breast cancer by overcoming drug resistance.

Results
In this study, we designed a pH and redox dual-responsive nanocarrier system to combine synergistic effects of DOX and CXB against drug resistant breast cancer. This nanocarrier system denoted as HPPDC nanoparticles showed good in vitro stability and significantly accelerated drug releases under the acidic and redox conditions. In drug-resistant human breast cancer MCF-7/ADR cells, HPPDC nanoparticles significantly enhanced the cellular uptake of DOX through the endocytosis mediated by CD44/HA specific binding and the down-regulated P-gp expression induced by COX-2 inhibition, and thus notably increased the cytotoxicity and apoptosis-inducing activity of DOX. In MCF-7/ADR tumor-bearing nude mice, HPPDC nanoparticles showed excellent tumor-targeting ability, remarkably enhanced tumor chemosensitivity and reduced COX-2 and P-gp expressions in tumor tissues.

Conclusion
All results demonstrated that HPPDC nanoparticles can efficiently overcome drug resistance in breast cancer both in vitro and in vivo by combining chemotherapy and COX-2 inhibitor. In a summary, HPPDC nanoparticles show a great potential for combination treatment of drug resistant breast cancer.
DNA methylation exploration for ARDS: a multi-omics and multi-microarray interrelated analysis
Authors: Zhang Shi , Wu Zongsheng , Xie Jianfeng , Yang Yi , Wang Lei , Qiu Haibo 
Published: October 2019

AbstractBackgroundDespite advances in clinical management, there are currently no novel therapeutic targets for acute respiratory distress syndrome (ARDS). DNA methylation, as a reversible process involved in the development and progression of many diseases, would be used as potential therapeutic targets to improve the treatment strategies of ARDS. However, the meaningful DNA methylation sites associated with ARDS still remain largely unknown. We sought to determine the difference in DNA methylation between ARDS patients and healthy participants, and simultaneously, the feasible DNA methylation markers for potential therapeutic targets were also explored.MethodsMicroarray data of human blood samples for ARDS and healthy participants up to June 2019 was searched in GEO database. The difference analyses between ARDS and healthy population were performed through limma R package, and furthermore, interrelated analyses of DNA methylation and transcript were accomplished by VennDiagram R package. Perl and sva R package were used to merge microarray data and decrease heterogeneities among different studies. The biological function of screened methylation sites and their regulating genes were annotated according to UniProt database and Pubmed database. GO term and KEGG pathway enrichment analyses were conducted using DAVID 6.8 and KOBAS 3.0. The meaningful DNA methylation markers to distinguish ARDS from healthy controls were explored through ROC (receiver operating characteristic curves) analyses.ResultsFive datasets in GEO databases (one DNA methylation dataset, three mRNA datasets, and one mRNA dataset of healthy people) were enrolled in present analyses finally, and the series were GSE32707, GSE66890, GSE10474, GSE61672, and GSE67530. These databases included 99 patients with ARDS (within 48 h of onset) and 136 healthy participants. Difference analyses indicated 44,439 DNA methylation alterations and 29 difference mRNAs between ARDS and healthy controls. 40 methylation variations regulated transcription of 16 genes was explored via interrelated analysis. According to the functional annotations, 30 DNA methylation sites were related to the imbalance of inflammation or immunity, endothelial function, epithelial function and/or coagulation function. cg03341377, cg24310395, cg07830557 and cg08418670, with AUC up to 0.99, might be the meaningful characteristics with the highest performance to distinguish ARDS from healthy controls.Conclusions44,439 DNA methylation alterations and 29 difference mRNAs exist between ARDS and healthy controls. 30 DNA methylation sites may regulate transcription of 10 genes, which take part in pathogenesis of ARDS. These findings could be intervention targets, with validation experiments to be warranted to assess these further.
Advantages of using 3D virtual reality based training in persons with Parkinson’s disease: a parallel study
Authors: Cikajlo Imre , Peterlin Potisk Karmen 
Published: October 2019

Abstract

Background
Parkinson’s disease (PD) is a slowly progressive neurodegenerative disease. There are mixed reports on success of physiotherapy in patients with PD. Our objective was to investigate the functional improvements, motivation aspects and clinical effectiveness when using immersive 3D virtual reality versus non-immersive 2D exergaming.

Methods
We designed a randomized parallel study with 97 patients, but only 20 eligible participants were randomized in 2 groups; the one using 3D Oculus Rift CV1 and the other using a laptop. Both groups participated in the 10-session 3 weeks training with a pick and place task in the virtual world requiring precise hand movement to manipulate the virtual cubes. The kinematics of the hand was traced with Leap motion controller, motivation effect was assessed with modified Intrinsic Motivation Inventory and clinical effectiveness was evaluated with Box & Blocks Test (BBT) and shortened Unified Parkinson’s disease rating scale (UPDRS) before and after the training. Mack-Skilling non-parametrical statistical test was used to identify statistically significant differences (p < 0.05) and Cohen’s U3 test to find the effect sizes.

Results
Participants in the 3D group demonstrated statistically significant and substantially better performance in average time of manipulation (group x time, p = 0.009), number of successfully placed cubes (group x time, p = 0.028), average tremor (group x time, p = 0.002) and UPDRS for upper limb (U3 = 0.35). The LCD and 3D groups substantially improved their BBT score with training (U3 = 0.7, U3 = 0.6, respectively). However, there were no statistically significant differences in clinical tests between the groups (group x time, p = 0.2189, p = 0.2850, respectively). In addition the LCD group significantly decreased the pressure/tension (U3 = 0.3), the 3D did not show changes (U3 = 0.5) and the differences between the groups were statistically different (p = 0.037). The 3D group demonstrated important increase in effort (U3 = 0.75) and perceived competences (U3 = 0.9).

Conclusions
The outcomes of the study demonstrated that the immersive 3D technology may bring increased interests/enjoyment score resulting in faster and more efficient functional performance. But the 2D technology demonstrated lower pressure/tension score providing similar clinical progress. A study with much larger sample size may also confirm the clinical effectiveness of the approaches.

Trial registration
The small scale randomized pilot study has been registered at ClinicalTrials.gov Identifier: NCT03515746, 4 May 2018
A novel wearable device to deliver unconstrained, unpredictable slip perturbations during gait
Authors: Rasmussen Corbin M. , Hunt Nathaniel H. 
Published: October 2019

Abstract

Background
Task-specific perturbation training is a widely studied means of fall prevention, utilizing techniques that induce slips or slip-like perturbations during gait. Though effective, these methods only simulate narrow ranges within the larger space of possible slipping conditions encountered in daily life. Here we describe and test a novel, wearable apparatus designed to address these limitations and simulate a diverse range of slipping disturbances.

Methods
The device consists of wireless triggering and detachable outsole components that provide adequate friction with the floor when secured to the wearer’s foot, but suddenly create a low-friction surface underfoot upon release. “Benchtop” tests were carried out to quantify device triggering characteristics (i.e. cutting temperature, release delay) and the resulting friction reduction. The device was also tested on six healthy young adults (3 female, age 23 ± 2.4 years), who walked with and without the device to observe how gait kinematics and spatiotemporal parameters were influenced, then performed 12 walking trials ending with a slip delivered by the device. Each participant also completed a survey to obtain opinions on device safety, device comfort, slip realism, and slip difficulty. A linear mixed effects analysis was employed to compare subject spatiotemporal parameters with and without the apparatus, as well as correlation coefficients and root mean square errors (RMSE) to assess the impact of the device on lower limb gait kinematics. Slip onset phases, distances, directions, velocities, and recovery step locations were also calculated.

Results
This device rapidly diminishes available friction from static coefficients of 0.48 to 0.07, albeit after a substantial delay (0.482 ± 0.181 s) between signal reception and outsole release. Strong correlations (R > 0.93) and small RMSE between gait kinematics with and without the device indicate minimal effects on natural gait patterns, however some spatiotemporal parameters were significantly impacted. A diverse range of slip perturbations and recovery steps were successfully elicited by the device.

Conclusions
Our results highlight the efficacy and utility of a wearable slipping device to deliver diverse slip conditions. Such an apparatus enables the study of unconstrained slips administered across the gait cycle, as well as during different locomotor behaviors like turning, negotiating slopes, and level changes.