bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the EQ-5D-3 L and EQ-5D-5 L: studying measurement and scores in Indonesian type 2 diabetes mellitus patients
Authors: Arifin Bustanul , Purba Fredrick Dermawan , Herman Hendra , Adam John M. F. , Atthobari Jarir , Schuiling-Veninga Catharina C. M. , Krabbe Paul F. M. , Postma Maarten J. 
Published: February 2020

Abstract
Background
The EuroQoL five-dimensional instrument (EQ-5D) is the favoured preference-based instrument to measure health-related quality of life (HRQoL) in several countries. Two versions of the EQ-5D are available: the 3-level version (EQ-5D-3 L) and the 5-level version (EQ-5D-5 L). This study aims to compare specific measurement properties and scoring of the EQ-5D-3 L (3 L) and EQ-5D-5 L (5 L) in Indonesian type 2 diabetes mellitus (T2DM) outpatients.

Methods
A survey was conducted in a hospital and two primary healthcare centres on Sulawesi Island. Participants were asked to complete the two versions of the EQ-5D instruments. The 3 L and 5 L were compared in terms of distribution and ceiling, discriminative power and test-retest reliability. To determine the consistency of the participants’ answers, we checked the redistribution pattern, i.e., the consistency of a participant’s scores in both versions.

Results
A total of 198 T2DM outpatients (mean age 59.90 ± 11.06) completed the 3 L and 5 L surveys. A total of 46 health states for 3 L and 90 health states for 5 L were reported. The ‘11121’ health state was reported most often: 17% in the 3 L and 13% in the 5 L. The results suggested a lower ceiling effect for 5 L (11%) than for 3 L (15%). Regarding redistribution, only 6.1% of responses were found to be inconsistent in this study. The 5 L had higher discriminative power than the 3 L version. Reliability as reflected by the index score was 0.64 for 3 L and 0.74 for 5 L. Pain/discomfort was the dimension mostly affected, whereas the self-care dimension was the least affected.

Conclusions
This study suggests that the 5 L-version of the EQ-5D instrument performs better than the 3 L-version in T2DM outpatients in Indonesia, regarding measurement and scoring properties. As such, our study supports the use of the 5 L as the preferred health-related quality of life measurement tool.
We did not do a trial but this study was approved by the Medical Ethics Committee of Universitas Gadjah Mada Yogyakarta, Indonesia (document number KE/FK/1188/EC, 12 November 2014, amended 16 March 2015).
Extracellular vesicles originating from glioblastoma cells increase metalloproteinase release by astrocytes: the role of CD147 (EMMPRIN) and ionizing radiation
Authors: Colangelo Nicholas W. , Azzam Edouard I. 
Published: February 2020

Abstract
Background
Glioblastoma multiforme is an aggressive primary brain tumor that is characterized by local invasive growth and resistance to therapy. The role of the microenvironment in glioblastoma invasiveness remains unclear. While carcinomas release CD147, a protein that signals for increased matrix metalloproteinase (MMP) release by fibroblasts, glioblastoma does not have a significant fibroblast component. We hypothesized that astrocytes release MMPs in response to CD147 contained in glioblastoma-derived extracellular vesicles (EVs) and that ionizing radiation, part of the standard treatment for glioblastoma, enhances this release.

Methods
Astrocytes were incubated with EVs released by irradiated or non-irradiated human glioblastoma cells wild-type, knockdown, or knockout for CD147. Levels of CD147 in glioblastoma EVs and MMPs secreted by astrocytes were quantified. Levels of proteins in the mitogen activated protein kinase (MAPK) pathway, which can be regulated by CD147, were measured in astrocytes incubated with EVs from glioblastoma cells wild-type or knockdown for CD147. Immunofluorescence was performed on the glioblastoma cells to identify changes in CD147 localization in response to irradiation, and to confirm uptake of the EVs by astrocytes.

Results
Immunoblotting and mass spectrometry analyses showed that CD147 levels in EVs were transiently increased when the EVs were from glioblastoma cells that were irradiated with γ rays. Specifically, the highly-glycosylated 45 kDa form of CD147 was preferentially present in the EVs relative to the cells themselves. Immunofluorescence demonstrated that astrocytes incorporate glioblastoma EVs and subsequently increase their secretion of active MMP9. The increase was greater if the EVs were from irradiated glioblastoma cells. Testing MAPK pathway activation, which also regulates MMP expression, showed that JNK signaling, but not ERK1/2 or p38, was increased in astrocytes incubated with EVs from irradiated compared to non-irradiated glioblastoma cells. Knockout of CD147 in glioblastoma cells blocked the increased JNK signaling and the rise in secreted active MMP9 levels.

Conclusions
The results support a tumor microenvironment-mediated role of CD147 in glioblastoma invasiveness, and reveal a prominent role for ionizing radiation in enhancing the effect. They provide an improved understanding of glioblastoma intercellular signaling in the context of radiotherapy, and identify pathways that can be targeted to reduce tumor invasiveness.

Graphical abstract
Rectification of radiotherapy-induced cognitive impairments in aged mice by reconstituted Sca-1+ stem cells from young donors
Authors: Wlodarek Lukasz , Cao Feng , Alibhai Faisal J. , Fekete Adam , Noyan Nima , Tobin Stephanie W. , Marvasti Tina B. , Wu Jun , Li Shu-Hong , Weisel Richard D. , Wang Lu-Yang , Jia Zhengping , Li Ren-Ke 
Published: February 2020

Abstract
Background
Radiotherapy is widely used and effective for treating brain tumours, but inevitably impairs cognition as it arrests cellular processes important for learning and memory. This is particularly evident in the aged brain with limited regenerative capacity, where radiation produces irreparable neuronal damage and activation of neighbouring microglia. The latter is responsible for increased neuronal death and contributes to cognitive decline after treatment. To date, there are few effective means to prevent cognitive deficits after radiotherapy.

Methods
Here we implanted hematopoietic stem cells (HSCs) from young or old (2- or 18-month-old, respectively) donor mice expressing green fluorescent protein (GFP) into old recipients and assessed cognitive abilities 3 months post-reconstitution.

Results
Regardless of donor age, GFP+ cells homed to the brain of old recipients and expressed the macrophage/microglial marker, Iba1. However, only young cells attenuated deficits in novel object recognition and spatial memory and learning in old mice post-irradiation. Mechanistically, old recipients that received young HSCs, but not old, displayed significantly greater dendritic spine density and long-term potentiation (LTP) in CA1 neurons of the hippocampus. Lastly, we found that GFP+/Iba1+ cells from young and old donors were differentially polarized to an anti- and pro-inflammatory phenotype and produced neuroprotective factors and reactive nitrogen species in vivo, respectively.

Conclusion
Our results suggest aged peripherally derived microglia-like cells may exacerbate cognitive impairments after radiotherapy, whereas young microglia-like cells are polarized to a reparative phenotype in the irradiated brain, particularly in neural circuits associated with rewards, learning, and memory. These findings present a proof-of-principle for effectively reinstating central cognitive function of irradiated brains with peripheral stem cells from young donor bone marrow.
MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming
Authors: Liu Yang , Lu Li-Li , Wen Duo , Liu Dong-Li , Dong Li-Li , Gao Dong-Mei , Bian Xin-Yu , Zhou Jian , Fan Jia , Wu Wei-Zhong 
Published: February 2020

Abstract
Background
MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated.

Methods
We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip.

Results
Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/β-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3miR-612-OE and HCCLM3hadha-KD cells were decreased nearly by 40% and 60% of their counterparts (p < 0.05). The levels of acetyl CoA were significantly decreased, about 1/3 (p > 0.05) or 1/2 (p < 0.05) of their controls, in exogenous miR-612 or hadha-shRNA transfected HCCLM3 cell lines. Besides, overexpression of hadha cell lines had a high expression level of total cholesterol, especially 27-hydroxycholesterol (p < 0.005). SREBP2 protein expression level as well as its downstream targets, HMGCS1, HMGCR, MVD, SQLE were all deregulated by HADHA. Meanwhile, the ATP levels were reduced to 1/2 and 1/4 in HCCLM3miR-612-OE (p < 0.05) and HCCLM3hadha-KD (p < 0.01) respectively. Moreover, patients with low miR-612 levels and high HADHA levels had a poor prognosis with shorter overall survival.

Conclusion
miR-612 can suppress the formation of invadopodia, EMT, and HCC metastasis and by HADHA-mediated lipid programming, which may provide a new insight of miR-612 on tumor metastasis and progression.
Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting
Authors: Yu Chaosheng , Chen Fang , Wang Xiaoqi , Cai Zhimou , Yang Mengxue , Zhong Qingwen , Feng Jialian , Li Junzheng , Shen Congxiang , Wen Zhong 
Published: February 2020

Abstract
Background
Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial–mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression.

Methods
Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133+ cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133+ CSCs.

Results
We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133+ cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133+ CSCs.

Conclusions
Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200b-regulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.
Comparison of adverse events between video and direct laryngoscopes for tracheal intubations in emergency department and ICU patients–a systematic review and meta-analysis
Authors: Jiang Jia , Kang Na , Li Bo , Wu An-Shi , Xue Fu-Shan 
Published: February 2020

AbstractObjectiveThis systematic review and meta-analysis was designed to determine whether video laryngoscope (VL) compared with direct laryngoscope (DL) could reduce the occurrence of adverse events associated with tracheal intubation in the emergency and ICU patients.MethodsThe current issue of Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (from database inception to October 30, 2018) were searched. The RCTs, quasi-RCTs, observational studies comparing VL and DL for tracheal intubation in emergency or ICU patients and reporting the rates of adverse events were included. The primary outcome was the rate of esophageal intubation (EI). Review Manager 5.3 software was used to perform the pooled analysis and assess the risk of bias for each eligible RCT. The ACROBAT-NRSi Cochrane Risk of Bias Tool was applied to assess the risk of bias for each eligible observational study.ResultsTwenty-three studies (13,117 patients) were included in the review for data extraction. Pooled analysis showed a lower rate of EI by using VL (relative risk [RR], 0.24;P < 0.01; high-quality evidence for RCTs and very low-quality evidence for observational studies). Subgroup analyses based on the type of studies, whether a cardiopulmonary resuscitation study, or operators’ expertise showed a similar lower rate of EI by using VL compared with DL in all subgroups (P < 0.01) except for experienced operators (RR, 0.44;P = 0.09). There were no significant differences between devices for other adverse events (P > 0.05), except for a lower incidence of hypoxemia when intubation was performed with VL by inexperienced operators (P = 0.03).ConclusionsBased on the results of this analysis, we conclude that compared with DL, VL can reduce the risk of EI during tracheal intubation in the emergency and ICU patients, but does not provide significant benefits on other adverse events associated with tracheal intubation.
Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa-exposed BALB/c mice upon clearance of infection
Authors: Chunda Valerine C. , Ritter Manuel , Bate Ayukenchengamba , Gandjui Narcisse V. T. , Esum Mathias E. , Fombad Fanny F. , Njouendou Abdel J. , Ndongmo Patrick W. C. , Taylor Mark J. , Hoerauf Achim , Layland Laura E. , Turner Joseph D. , Wanji Samuel 
Published: February 2020

Abstract
Background
Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis.

Methods
Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc−/− mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days post-infection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology.

Results
In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and immunoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns.

Conclusions
This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and immunoglobulins secretion patterns which might contribute to immunity and protection against reinfection.
Epidemiology of blood flukes (Digenea: Spirorchiidae) in sea turtles from Tyrrhenian and Adriatic Seas, off Italy
Authors: Santoro Mario , Marchiori Erica , Cassini Rudi , Drigo Michele , Iaccarino Doriana , Di Nocera Fabio , Degli Uberti Barbara , De Luca Giovanna , D’Amore Marianna , Centelleghe Cinzia , Pietrobelli Mario , Marcer Federica 
Published: February 2020

Abstract
Background
The Spirorchiidae is a family of blood flukes parasitizing turtles. Spirorchiids may cause a wide range of inflammatory reactions in the vascular system of their host being frequently implicated with stranding and death of sea turtles worldwide. Recent studies revealed the presence of two spirorchiid species in the Mediterranean basin. Our study presents comparative epidemiological data of spirorchiid infections in loggerhead turtles (Caretta caretta) stranded during an eight-year period from Adriatic and Tyrrhenian Seas, and the first report of Neospirorchis Neogen-11 in a green turtle (Chelonia mydas).

Methods
We screened a total of 319 carcasses of loggerhead turtles stranded from January 2011 to December 2018 along the Tyrrhenian coast (n = 111) and the north-western Adriatic coast (n = 208) of Italy using traditional (copromicroscopy and histopathology) and molecular assays. Three green turtles from the Tyrrhenian coast were also included in the study.

Results
A total of 56 (17.5%) loggerhead turtles and one green turtle (33.3%) were found to be infected with spirorchiid flukes. Amplification, sequencing of the ITS2 region of the ribosomal RNA gene cluster and BLAST analysis confirmed the presence of Hapalotrema mistroides and Neospirorchis Neogen-11 in 51 (16.0%) and 24 (7.5%) loggerhead turtles, respectively, and Neospirorchis Neogen-11 in an infected green turtle. Differences in prevalence of infection between the two sampling areas were found.

Conclusions
The risk of spirorchiid infection in the Tyrrhenian Sea is lower than in the Adriatic Sea and in general the risk of infection in the Mediterranean is lower than in other geographical locations. Differences in the prevalence of infection between the two sampling areas were related to the differences of regional habitats supporting different abundance of spirorchiid intermediate hosts. A systematic monitoring to evaluate the progress of the infection is recommended, as well as studies on the occurrence and distribution of spirorchiid species from other Mediterranean areas.
Imaging methods used in the assessment of environmental disease networks: a brief review for clinicians
Authors: Cedillo-Pozos Aime , Ternovoy Sergey K. , Roldan-Valadez Ernesto 
Published: February 2020

AbstractBackgroundAcross the globe, diseases secondary to environmental exposures have been described, and it was also found that existing diseases have been modified by exposure to environmental chemicals or an environmental factor that has been found in their pathogenesis. The Institute of Medicine has shared a permanent concern related to the nations environmental health capacity since 1988.Main bodyContemporary imaging methods in the last 15 years started reporting alterations in different human systems such as the central nervous system, cardiovascular system and pulmonary system among others; evidence suggests the existence of a human environmental disease network. The primary anatomic regions, affected by environmental diseases, recently assessed with imaging methods include Brain (lead exposure, cerebral stroke, pesticide neurotoxicity), uses MRI, DTI, carotid ultrasonography and MRS; Lungs (smoke inhalation, organophosphates poisoning) are mainly assessed with radiography; Gastrointestinal system (chronic inflammatory bowel disease), recent studies have reported the use of aortic ultrasound; Heart (myocardial infarction), its link to environmental diseased has been proved with carotid ultrasound; and Arteries (artery hypertension), the impairment of aortic mechanical properties has been revealed with the use of aortic and brachial ultrasound.ConclusionsEnvironmental epidemiology has revealed that several organs and systems in the human body are targets of air pollutants. Current imaging methods that can assess the deleterious effects of pollutants includes a whole spectrum: radiography, US, CT and MRI. Future studies will help to reveal additional links among environmental disease networks.
The effect of the MR pulse sequence on the regional corpus callosum morphometry
Authors: Alhazmi Fahad H. , Abdulaal Osama M. , Qurashi Abdulaziz A. , Aloufi Khalid M. , Sluming Vanessa 
Published: February 2020

Abstract
Background and purposes
Brain morphometry is an important assessment technique to assess certain morphological brain features of various brain regions, which can be quantified in vivo by using high-resolution structural magnetic resonance (MR) imaging. This study aims to investigate the effect of different types of pulse sequence on regional corpus callosum (CC) morphometry analysis.

Materials and methods
Twenty-one healthy volunteers were scanned twice on the same 3T MRI scanner (Magnetom Trio, Siemens, Erlangen, Germany) equipped with an 8-channel head coil. Two different MR pulse sequences were applied to acquire high-resolution 3D T1-weighted images: magnetization-prepared rapid gradient-echo (MP-RAGE) and modified driven equilibrium Fourier transform (MDEFT) pulse sequence. Image quality measurements such as SNR, contrast-to-noise ratio, and relative contrast were calculated for each pulse sequence images independently. The values of corpus callosum volume were calculated based on the vertex of reconstructed surfaces. The paired dependent t test was applied to compare the means of two matched groups.

Results
Three sub-regional CC, namely anterior, mid-anterior, and posterior, resulted in an estimated volume difference between MDEFT and MP-RAGE pulse sequences. Central and mid-posterior sub-regional CC volume resulted in not significant difference between the two named pulse sequences.

Conclusion
The findings of this study demonstrate that combining data from different pulse sequences in a multisite study could make some variations in the results.