bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-TrCP-mediated ubiquitination and degradation of Dlg5 regulates hepatocellular carcinoma cell proliferation
Authors: Wang Dongping , Zhang Qi , Li Fenfen , Wang Chan , Yang Changming , Yu Hong 
Published: November 2019

Abstract
Background
Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown.

Methods
The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and β-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by β-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice.

Results
Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or β-TrCP led to increased levels of Dlg5. β-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing β-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo.

Conclusion
Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by β-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.
Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies
Authors: Shirasu Naoto , Shibaguchi Hirotomo , Yamada Hiromi , Kuroki Masahide , Yasunaga Shin’ichiro 
Published: November 2019

Abstract
Background
Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting.

Methods
Cytotoxicity of AvIR-mediated PIT was evaluated by fluorescence imaging and cell viability assay. Phototoxic effect on tumorigenicity was assessed by tumorsphere-formation assay and Matrigel invasion assay. Cancer stem cell-like side-population (SP) cells were identified by flow cytometry.

Results
CHO cells stably expressing carcinoembryonic antigen or EpCAM were pre-labeled with each BioAb for the corresponding antigen, followed by AvIR administration. NIR light irradiation specifically killed the targeted cells, but not off-targets, demonstrating that the AvIR-mediated PIT does work as expected. CSC-like subpopulation of MCF-7 cells (CD24low/CD44high) and SP of HuH-7 cells (CD133+/EpCAM+) were effectively targeted and photokilled by AvIR-PIT with anti-CD44 BioAb or anti-CD133/anti-EpCAM BioAbs, respectively. As results, the neoplastic features of the cell lines were sufficiently suppressed. Cancer-associated fibroblast (CAF)-targeted AvIR-PIT by using anti-fibroblast activation protein BioAb showed an abolishment of CAF-enhanced clonogenicity of MCF-7 cells.

Conclusions
Collectively, our results demonstrate that AvIR-mediated PIT can greatly broaden the applicable range of target specificity, with feasibility of efficacious and integrative control of CSC and its microenvironment.
Assessment of eye fatigue caused by head-mounted displays using eye-tracking
Authors: Wang Yan , Zhai Guangtao , Chen Sichao , Min Xiongkuo , Gao Zhongpai , Song Xuefei 
Published: November 2019

Abstract
Background
Head-mounted displays (HMDs) and virtual reality (VR) have been frequently used in recent years, and a user’s experience and computation efficiency could be assessed by mounting eye-trackers. However, in addition to visually induced motion sickness (VIMS), eye fatigue has increasingly emerged during and after the viewing experience, highlighting the necessity of quantitatively assessment of the detrimental effects. As no measurement method for the eye fatigue caused by HMDs has been widely accepted, we detected parameters related to optometry test. We proposed a novel computational approach for estimation of eye fatigue by providing various verifiable models.

Results
We implemented three classifications and two regressions to investigate different feature sets, which led to present two valid assessment models for eye fatigue by employing blinking features and eye movement features with the ground truth of indicators for optometry test. Three graded results and one continuous result were provided by each model, respectively, which caused the whole result to be repeatable and comparable.

Conclusion
We showed differences between VIMS and eye fatigue, and we also presented a new scheme to assess eye fatigue of HMDs users by analysis of parameters of the eye tracker.
Following the legacy of professors Barbara Starfield and Leiyu Shi in Brazil as health policy: the National Health Survey (PNS), led by the Brazilian National Institute of Geography and Statistics (IBGE) and the Primary Care Assessment Tool (PCAT)
Authors: Harzheim Erno , Felipe Pinto Luiz , D’Avila Otavio Pereira , Hauser Lisiane 
Published: November 2019

AbstractWe present to the scientific community the pioneering of Brazilian National Institute of Geography and Statistics (IBGE, the Brazilian Census Bureau) in partnership with the Ministry of Health, the largest fieldwork ever conducted in a single country in the world, using the PCAT in a national household sample survey, visiting more than 100,000 households and 40% of the country’s municipalities. In Brazil, PCAT is being consolidated as an instrument to support public policy for the evaluation of primary health care. We believe that it represents a virtuous example of dialogue between scientific community and health management, following the legacy of Professors Barbara Starfield and Leiyu Shi.
Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort
Authors: Beck Iben Have , Timmermann Clara Amalie Gade , Nielsen Flemming , Schoeters Greet , Jøhnk Camilla , Kyhl Henriette Boye , Høst Arne , Jensen Tina Kold 
Published: November 2019

AbstractBackgroundAsthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children.MethodsWe studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex.ResultsAmong the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23).ConclusionOur findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.
FoxO3 regulates hepatic triglyceride metabolism via modulation of the expression of sterol regulatory-element binding protein 1c
Authors: Wang Liu , Zhu Xiaopeng , Sun Xiaoyang , Yang Xinyu , Chang Xinxia , Xia Mingfeng , Lu Yan , Xia Pu , Yan Hongmei , Bian Hua , Gao Xin 
Published: November 2019

Abstract
Background
Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism.

Methods
Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid.

Results
FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter.

Conclusions
FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation.
Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients
Authors: Han Jun , Lu Chaocheng , Meng Qingyang , Halim Alice , Yean Thong Jia , Wu Guohao 
Published: November 2019

AbstractBackgroundCancer cachexia is a clinical manifestation in various advanced cancers that characterized by muscle atrophy and fat loss as its main features; it is frequently associated with systemic inflammatory response. However, the differences in inflammatory response and lipid metabolism of different genders remain unclear. This study explores the difference between cachexic and non-cachexic patients in different genders and cancer types and focus on the plasma inflammation factors levels and lipid metabolism parameters in different genders.MethodsWe first analyzed the general characteristics in 311 cancer patients between cachexic and non-cachexic patients, with an emphasis on expression levels related to inflammatory factors and lipid metabolism parameters. We then further analyzed these characteristics in different genders and cancer types. Lastly, the correlations between plasma interleukin-6 (IL-6) and lipid metabolism parameters in cachexia patients of different genders were analyzed.ResultsAmong 311 patients, there were 74 cancer cachexia patients (50 males and 24 females) and 237non-cachexia patients (150 males and 87 females). Body mass index (BMI), TNM stage, plasma concentration of hemoglobin, platelet, lymphocyte count, total protein, albumin, prealbumin, total cholesterol, apolipoprotein E (ApoE), free fatty acid (FFA) and IL-6 were significantly different between cachexic and non-cachexic patients (allp < 0.05). In addition, these characteristics were different in different cancer types. When compared to male non-cachexic patients, male cachexic patients showed a significant increase in plasma levels of IL-6 and platelet, later TNM stage, with marked decrease in their plasma total protein, albumin, prealbumin, ApoE as well as their lymphocyte counts and hemoglobin levels (allp < 0.05). In comparison with female non-cachexic patients, female cachexic patients’ IL-6 levels and FFA were significantly elevated with noticeable decrease in their BMI, total cholesterol, ApoE and prealbumin, as well as later TNM stage (allp < 0.05). Correlation analysis revealed that IL-6 levels in female cachexic patients had a significant positive correlation with FFA expression, but this correlation not reflected in male patients.ConclusionThis study demonstrates the different metabolic characteristics of male and female cancer cachexia patients. Future study about cancer cachexia should pay attention to different genders and cancer types.
Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews
Authors: Rios Patricia , Cardoso Roberta , Morra Deanna , Nincic Vera , Goodarzi Zahra , Farah Bechara , Harricharan Sharada , Morin Charles M. , Leech Judith , Straus Sharon E. , Tricco Andrea C. 
Published: November 2019

Abstract
Background
This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with insomnia and identify where research or policy development is needed.

Methods
MEDLINE, Embase, PsycINFO, The Cochrane Library, and PubMed were searched from inception until June 14, 2017, along with relevant gray literature sites. Two reviewers independently screened titles/abstracts and full-text articles, and a single reviewer with an independent verifier completed charting, data abstraction, and quality appraisal.

Results
A total of 64 systematic reviews (35 with meta-analysis) were included after screening 5024 titles and abstracts and 525 full-text articles. Eight of the included reviews were rated as high quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool, and over half of the included articles (n = 40) were rated as low or critically low quality. Consistent evidence of effectiveness across multiple outcomes based on more than one high- or moderate quality review with meta-analysis was found for zolpidem, suvorexant, doxepin, melatonin, and cognitive behavioral therapy (CBT), and evidence of effectiveness across multiple outcomes based on one high-quality review with meta-analysis was found for temazepam, triazolam, zopiclone, trazodone, and behavioral interventions. These interventions were mostly evaluated in the short term (< 16 weeks), and there was very little harms data available for the pharmacological interventions making it difficult to evaluate their risk-benefit ratio.

Conclusions
Assuming non-pharmacological interventions are preferable from a safety perspective CBT can be considered an effective first-line therapy for adults with insomnia followed by other behavioral interventions. Short courses of pharmacological interventions can be supplements to CBT or behavioral therapy; however, no evidence regarding the appropriate duration of pharmacological therapy is available from these reviews.

Systematic review registration
PROSPERO CRD42017072527.
Assessing the accuracy of machine-assisted abstract screening with DistillerAI: a user study
Authors: Gartlehner Gerald , Wagner Gernot , Lux Linda , Affengruber Lisa , Dobrescu Andreea , Kaminski-Hartenthaler Angela , Viswanathan Meera 
Published: November 2019

AbstractBackgroundWeb applications that employ natural language processing technologies to support systematic reviewers during abstract screening have become more common. The goal of our project was to conduct a case study to explore a screening approach that temporarily replaces a human screener with a semi-automated screening tool.MethodsWe evaluated the accuracy of the approach using DistillerAI as a semi-automated screening tool. A published comparative effectiveness review served as the reference standard. Five teams of professional systematic reviewers screened the same 2472 abstracts in parallel. Each team trained DistillerAI with 300 randomly selected abstracts that the team screened dually. For all remaining abstracts, DistillerAI replaced one human screener and provided predictions about the relevance of records. A single reviewer also screened all remaining abstracts. A second human screener resolved conflicts between the single reviewer and DistillerAI. We compared the decisions of the machine-assisted approach, single-reviewer screening, and screening with DistillerAI alone against the reference standard.ResultsThe combined sensitivity of the machine-assisted screening approach across the five screening teams was 78% (95% confidence interval [CI], 66 to 90%), and the combined specificity was 95% (95% CI, 92 to 97%). By comparison, the sensitivity of single-reviewer screening was similar (78%; 95% CI, 66 to 89%); however, the sensitivity of DistillerAI alone was substantially worse (14%; 95% CI, 0 to 31%) than that of the machine-assisted screening approach. Specificities for single-reviewer screening and DistillerAI were 94% (95% CI, 91 to 97%) and 98% (95% CI, 97 to 100%), respectively. Machine-assisted screening and single-reviewer screening had similar areas under the curve (0.87 and 0.86, respectively); by contrast, the area under the curve for DistillerAI alone was just slightly better than chance (0.56). The interrater agreement between human screeners and DistillerAI with a prevalence-adjusted kappa was 0.85 (95% CI, 0.84 to 0.86%).ConclusionsThe accuracy of DistillerAI is not yet adequate to replace a human screener temporarily during abstract screening for systematic reviews. Rapid reviews, which do not require detecting the totality of the relevant evidence, may find semi-automation tools to have greater utility than traditional systematic reviews.
Migration routes and habitat use of a highly adaptable salmonid (sea trout, Salmo trutta) in a complex marine area
Authors: Kristensen Martin Lykke , Pedersen Martin Wæver , Thygesen Uffe Høgsbro , del Villar-Guerra Diego , Baktoft Henrik , Aarestrup Kim 
Published: November 2019

Abstract
Background
Understanding fish movements and migrations are paramount for management and conservation efforts. By applying Hidden Markov Models (HMMs) on records from electronic tags, migration routes of tagged fish can be reconstructed and new insights to the movement ecology of a species can be gained. We demonstrate the usability of HMMs on a widespread, iteroparous salmonid (sea trout, Salmo trutta) in a complex marine area with highly variable temperatures and salinities within small geographic distances. Understanding how the highly adaptable sea trout cope with these complex conditions could shed new light on factors driving the movement ecology of salmonids. Migration tracks of fish migrating at sea are reconstructed by applying an HMM on temperature and depth records from eight wild post-spawned sea trout from four Danish rivers.

Results
The fish migrated at sea for 47–142 days. Estimated positions of all fish were close to the coast (< 100 km) throughout the marine period, but migrations along coastlines up to 580 km away from the natal river occurred. Seven of eight individuals resided in or actively migrated into stratified or shallow marine areas that heat up fast during spring, while all eight individuals resided in deeper and more heterogeneous areas that heat up slow during summer. All fish entered the Skagerrak (located between Denmark and Norway) at some stage during summer. Migrations were directed into less saline areas during the first 15 days at sea for all individuals. Mean linear progression of the fish was 16 km day−1 (range 0–58 km day−1).

Conclusions
The results corroborate the expectation that sea trout are more coastally orientated than other salmonids, but also suggest that longer migrations occur in the seas surrounding Denmark compared to elsewhere. This could be a consequence of the fish seeking out habitats with optimal conditions (e.g. salinity, temperature, predation and foraging options) for growth in different parts of the year. The coinciding movement from shallow or stratified marine areas that heat up fast during spring to deeper, more well-mixed areas that heat up slow during summer suggested that some habitat selection had occurred. These results shed new light on factors influencing marine migrations in salmonids and demonstrate how HMMs can expand our knowledge on behaviour and movement ecology of marine fishes.
Cancer biomarkers for targeted therapy
Authors: Liu Delong 
Published: November 2019

AbstractTumor-associated antigens (TAA) or cancer biomarkers are major targets for cancer therapies. Antibody- based agents targeting the cancer biomarkers include monoclonal antibodies (MoAbs), radiolabeled MoAbs, bispecific T cell engagers, and antibody-drug conjugates. Antibodies targeting CD19, CD20, CD22, CD30, CD33, CD38, CD79B and SLAMF7 are in clinical applications for hematological malignancies. CD123, CLL-1, B cell maturation antigen, and CD138 are targets for cancer immunotherapeutic agents, including the chimeric antigen receptor - engineered T cells. Immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4 have led to the revolution of cancer immunotherapy. More ICIs targeting IDO, LAG3, TIM-3, TIGIT, SIGLECs, VISTA and CD47 are being explored. Small molecule inhibitors (SMIs) against tyrosine kinase oncoproteins such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, EGFR, ALK, HER2, VEGFR, FGFR, MEK, and MET have fundamentally changed the landscape of cancer therapy. SMIs against BCL-2, IDHs, BRAF, PI3 kinase, mTOR, PARP, and CDKs have become the mainstay in the treatment of a variety of cancer types. To reduce and avoid off-tumor toxicities, cancer-specific TAAs such as CD33 are being manufactured through systems biology approach. Search for novel biomarkers and new designs as well as delivery methods of targeted agents are fueling the next wave of advances in cancer therapy.