bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma
Authors: Xu Wei , Zhou Wang , Cheng Mo , Wang Jing , Liu Zhian , He Shaohui , Luo Xiangji , Huang Wending , Chen Tianrui , Yan Wangjun , Xiao Jianru 
Published: January 2017

AbstractThe Wnt/β-catenin signaling is abnormally activated in the progression of hepatocellular carcinoma (HCC). BCL9 is an essential co-activator in the Wnt/β-catenin signaling. Importantly, BCL9 is absent from tumors originating from normal cellular counterparts and overexpressed in many cancers including HCC. But the mechanism for BCL9 overexpression remains unknown. Ample evidence indicates that hypoxia inducible factors (HIFs) play a role in the development of HCC. It was found in our study that BCL9 was overexpressed in both primary HCC and bone metastasis specimens; loss of BCL9 inhibited the proliferation, migration and angiogenesis of HCC; and that that hypoxia mechanically induced the expression of BCL9. BCL9 induction under the hypoxic condition was predominantly mediated by HIF-1α but not HIF2α. In vitro evidence from xenograft models indicated that BCL9 promoter/gene knockout inhibited HCC tumor growth and angiogenesis. Notably, we found that BCL9 and HIF-1α were coordinately regulated in human HCC specimen. The above findings suggest that hypoxia may promote the expression of BCL9 and associate with the development of HCC. Specific regulation of BCL9 expression by HIF-1α may prove to be an underlying crosstalk between Wnt/β-catenin signaling and hypoxia signaling pathways.
Alpha7 nicotinic acetylcholine receptor is required for amyloid pathology in brain endothelial cells induced by Glycoprotein 120, methamphetamine and nicotine
Authors: Liu Liqun , Yu Jingyi , Li Li , Zhang Bao , Liu Lingjuan , Wu Chun-Hua , Jong Ambrose , Mao Ding-An , Huang Sheng-He 
Published: January 2017

AbstractOne of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of α7 nAChR in up-regulation of Aβ induced by gp120, METH and NT. Aβ release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of α7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of Aβ, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and Aβ in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that α7 nAChR may play an important role in neuropathology caused by gp120, METH and NT, which are the major pathogenic factors contributing to the pathogenesis of HAND.
The Helicobacter cinaedi antigen CAIP participates in atherosclerotic inflammation by promoting the differentiation of macrophages in foam cells
Authors: D’Elios Mario Milco , Vallese Francesca , Capitani Nagaja , Benagiano Marisa , Bernardini Maria Lina , Rossi Mirko , Rossi Gian Paolo , Ferrari Mauro , Baldari Cosima Tatiana , Zanotti Giuseppe , de Bernard Marina , Codolo Gaia 
Published: January 2017

AbstractRecent studies have shown that certain specific microbial infections participate in atherosclerosis by inducing inflammation and immune reactions, but how the pathogens implicated in this pathology trigger the host responses remains unknown. In this study we show that Helicobacter cinaedi (Hc) is a human pathogen linked to atherosclerosis development since at least 27% of sera from atherosclerotic patients specifically recognize a protein of the Hc proteome, that we named Cinaedi Atherosclerosis Inflammatory Protein (CAIP) (n = 71). CAIP appears to be implicated in this pathology because atheromatous plaques isolated from atherosclerotic patients are enriched in CAIP-specific T cells (10%) which, in turn, we show to drive a Th1 inflammation, an immunopathological response typically associated to atherosclerosis. Recombinant CAIP promotes the differentiation and maintenance of the pro-inflammatory profile of human macrophages and triggers the formation of foam cells, which are a hallmark of atherosclerosis. This study identifies CAIP as a relevant factor in atherosclerosis inflammation linked to Hc infection and suggests that preventing and eradicating Hc infection could reduce the incidence of atherosclerosis.
Disease-modifying effect of intravenous immunoglobulin in an experimental model of epilepsy
Authors: Chen Min , Arumugam Thiruma V. , Leanage Gayeshika , Tieng Quang M. , Yadav Ashwin , Ullmann Jeremy F. P. , She David T. , Truong Vy , Ruitenberg Marc J. , Reutens David C. 
Published: January 2017

AbstractNovel therapies that prevent or modify the development of epilepsy following an initiating brain insult could significantly reduce the burden of this disease. In light of evidence that immune mechanisms play an important role in generating and maintaining the epileptic condition, we evaluated the effect of a well-established immunomodulatory treatment, intravenous immunoglobulin (IVIg), on the development of epilepsy in an experimental model of epileptogenesis. In separate experiments, IVIg was administered either before (pre-treatment) or after (post-treatment) the onset of pilocarpine status epilepticus (SE). Our results show that both pre- and post-treatment with IVIg attenuated acute inflammation in the SE model. Specifically, IVIg reduced local activation of glial cells, complement system activation, and blood-brain barrier damage (BBB), which are all thought to play important roles in the development of epilepsy. Importantly, post-treatment with IVIg was also found to reduce the frequency and duration of subsequent spontaneous recurrent seizures as detected by chronic video-electroencephalographic (video-EEG) recordings. This finding supports a novel application for IVIg, specifically its repurposing as a disease-modifying therapy in epilepsy.
Further evidence for microtubule-independent dimerization of TPPP/p25
Authors: Oláh J. , Szénási T. , Szunyogh S. , Szabó A. , Lehotzky A. , Ovádi J. 
Published: January 2017

AbstractTubulin Polymerization Promoting Protein (TPPP/p25) is a brain-specific disordered protein that modulates the dynamics and stability of the microtubule network by its assembly promoting, cross-linking and acetylation enhancing activities. In normal brain it is expressed primarily in differentiated oligodendrocytes; however, at pathological conditions it is enriched in inclusions of both neurons and oligodendrocytes characteristic for Parkinson’s disease and multiple system atrophy, respectively. The objective of this paper is to highlight a critical point of a recently published Skoufias’s paper in which the crucial role of the microtubules in TPPP/p25 dimerization leading to microtubule bundling was suggested. However, our previous and present data provide evidence for the microtubule-independent dimerization of TPPP/p25 and its stabilization by disulphide bridges. In addition, our bimolecular fluorescence complementation experiments revealed the dimerization ability of both the full length and the terminal-free (CORE) TPPP/p25 forms, however, while TPPP/p25 aligned along the bundled microtubule network, the associated CORE segments distributed mostly homogeneously within the cytosol. Now, we identified a molecular model from the possible ones suggested in the Skoufias’s paper that could be responsible for stabilization of the microtubule network in the course of the oligodendrocyte differentiation, consequently in the constitution of the myelin sheath.
Prediction of Local Quality of Protein Structure Models Considering Spatial Neighbors in Graphical Models
Authors: Shin Woong-Hee , Kang Xuejiao , Zhang Jian , Kihara Daisuke 
Published: January 2017

AbstractProtein tertiary structure prediction methods have matured in recent years. However, some proteins defy accurate prediction due to factors such as inadequate template structures. While existing model quality assessment methods predict global model quality relatively well, there is substantial room for improvement in local quality assessment, i.e. assessment of the error at each residue position in a model. Local quality is a very important information for practical applications of structure models such as interpreting/designing site-directed mutagenesis of proteins. We have developed a novel local quality assessment method for protein tertiary structure models. The method, named Graph-based Model Quality assessment method (GMQ), explicitly considers the predicted quality of spatially neighboring residues using a graph representation of a query protein structure model. GMQ uses conditional random field as its core of the algorithm, and performs a binary prediction of the quality of each residue in a model, indicating if a residue position is likely to be within an error cutoff or not. The accuracy of GMQ was improved by considering larger graphs to include quality information of more surrounding residues. Moreover, we found that using different edge weights in graphs reflecting different secondary structures further improves the accuracy. GMQ showed competitive performance on a benchmark for quality assessment of structure models from the Critical Assessment of Techniques for Protein Structure Prediction (CASP).
Global Legal History
Authors: Duve Thomas 
Published: January 2017

AbstractBecause of transformations in the world’s legal systems, there is a need for reflection about law and legal scholarship globally. There is a growing demand for global legal history; however, there is neither a consensus as to what this history is, nor what objectives this legal historiography pursues, or even how it relates to other disciplines. In addition, global legal history reflects the traditional multiplicity of methods, aims, and forms present in current juridical historiographies. This is why it is difficult to speak about a method of global legal history. This contribution—written from a Western, perspective—can only sketch out a general panorama and some particular methodological problems. It begins by considering meanings of “global legal history,” then sketches out some methodological approaches. The final remarks emphasize that not only the intellectual but also the institutional presuppositions for a global production of legal historical knowledge need to be established.
Enhanced Recovery Program and Length of Stay After Laparotomy on a Gynecologic Oncology Service
Authors: Dickson Elizabeth L. , Stockwell Erica , Geller Melissa A. , Vogel Rachel Isaksson , Mullany Sally A. , Ghebre Rahel , Witherhoff Boris J. N. , Downs Levi S. , Carson Linda F. , Teoh Deanna , Glasgow Michelle , Gerber Matt , Rivard Colleen , Erickson Britt K. , Hutchins Jacob , Argenta Peter A. 
Published: January 2017

OBJECTIVE:
To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service.

METHODS:
We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications.

RESULTS:
A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge.

CONCLUSION:
When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay.

CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.
Pregnancies After the Diagnosis of Mild Gestational Diabetes Mellitus and Risk of Cardiometabolic Disorders
Authors: Varner Michael W. , Rice Madeline Murguia , Landon Mark B. , Casey Brian M. , Reddy Uma M. , Wapner Ronald J. , Rouse Dwight J. , Tita Alan T. N. , Thorp John M. , Chien Edward K. , Saade George R. , Peaceman Alan M. , Blackwell Sean C. , Vandorsten J. Peter ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: January 2017

OBJECTIVE:
To assess the association of subsequent pregnancy with subsequent metabolic syndrome and type II diabetes mellitus after a pregnancy complicated by mild gestational diabetes mellitus (GDM).

METHODS:
We conducted a prospective observational follow-up study of women with mild GDM randomized from 2002 to 2007 to usual care or dietary intervention and glucose self-monitoring. Women were evaluated 5–10 years after the parent study. Participants were grouped according to the number of subsequent pregnancies (group A, none [reference]; group B, one; group C, two or greater). Serum triglycerides, glucose tolerance, high-density lipoprotein cholesterol, blood pressure, and waist circumference were assessed. Metabolic syndrome was diagnosed by American Heart Association and National Heart Lung and Blood Institute criteria. Multivariable regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs).

RESULTS:
Of 905 eligible women from the original trial, 483 agreed to participate, 426 of whom were included in this analysis. Groups A, B, and C consisted of 212, 143, and 71 women, respectively. Of women with subsequent pregnancies, 32% (69/214) had another pregnancy complicated with GDM. No difference between groups was observed for metabolic syndrome (group A, 34%; group B, 33%; group C, 30%). Subsequent pregnancies were associated with diabetes mellitus outside of pregnancy (group A, 5.2%; group B, 10.5%, RR 2.62, 95% CI 1.16–5.91; group C, 11.3%, RR 2.83, 95% CI 1.06–7.59), and if complicated with GDM (no subsequent GDM pregnancy, RR 1.99, 95% CI 0.82–4.84; subsequent GDM pregnancy, RR 3.75, 95% CI 1.60–8.82).

CONCLUSION:
In women with prior mild GDM, subsequent pregnancies did not increase the frequency of metabolic syndrome, but subsequent pregnancies with GDM increased the risk of diabetes mellitus outside of pregnancy.
Explaining How Cognitive Behavioral Approaches Work for Low Back Pain
Authors: Fordham Beth , Ji Chen , Hansen Zara , Lall Ranjit , Lamb Sarah E. 
Published: January 2017

Study Design.
This is secondary research examining the longitudinal mediation effect within a structural equation model.

Objective.
To identify possible mechanisms that mediate the effects of a cognitive behavioral approach upon disability and pain in low back pain patients.

Summary of Background Data.
Cognitive behavioral interventions (CBIs) can improve pain and disability in low back pain (LBP) but the mechanisms of action are unclear. We used data from a large randomized controlled trial to investigate mediators of the treatment effect of CBI.

Methods.
Pain self-efficacy, fear avoidance, and physical and mental functioning were selected as candidate mediators based on the theoretical rationale of the intervention. The primary treatment outcomes were the Roland Morris Questionnaire (RMDQ) and the modified Von Korff scale (MVK pain and disability) at 12 months. We used structural equation models to estimate the contribution of mediators. All models were tested for goodness-of-fit using χ

2
, Root Mean Square Error of Approximation, Adjusted Goodness of Fit Index, and Bentler Comparative Fit Index.

Results.
We included 701 adults with LBP. The average RMDQ score at baseline for those on the intervention arm was 8.8 (Standard Deviation 5.0). The intervention was effective in reducing disability and pain at 12 months. Change in mental functioning was not a significant mediator. Changes to pain self-efficacy, fear avoidance, and physical functioning were causal mediators of the treatment effect at 12 months (RMDQ b= –0.149, P < 0.001; MVK-pain b = –0.181, P < 0.001 and MVK-disability b = –0.180, P < 0.001). Overall, the SEM model exceeded the threshold for acceptable goodness-of-fit.

Conclusion.
Fear avoidance and self-efficacy were important causal mediators of the cognitive behavioral treatment effect. Self-assessed change in physical function was a causal mediator but mental functioning was not. This suggests people need to experience meaningful change in physical function and beliefs but not in mental functioning associated with LBP, to achieve a treatment benefit.

Level of Evidence: 2
Prior Use of Calcium Channel Blockers Is Associated With Decreased Mortality in Critically Ill Patients With Sepsis: A Prospective Observational Study
Authors: Wiewel Maryse A. , van Vught Lonneke A. , Scicluna Brendon P. , Hoogendijk Arie J. , Frencken Jos F. , Zwinderman Aeilko H. , Horn Janneke , Cremer Olaf L. , Bonten Marc J. , Schultz Marcus J. , van der Poll Tom 
Published: January 2017

Objectives:
Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.

Design:
A prospective observational study.

Setting:
The ICUs of two tertiary care hospitals in the Netherlands.

Patients:
In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.

Interventions:
None.

Measurements and Main Results:
Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31–0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.

Conclusions:
Prior calcium channel blocker use is associated with reduced mortality in patients following ICU admission with sepsis.
The Evaluation of Corneal Fragility After UVA/Riboflavin Crosslinking
Authors: Li Zhiwei , Wang Yumeng , Xu Yanyun , Jhanji Vishal , Zhang Chunxiao , Mu Guoying 
Published: January 2017

Purpose:
To evaluate the fragility of cornea after UVA/riboflavin crosslinking (CXL).

Methods:
Sixty New Zealand rabbits received UVA/riboflavin crosslinking treatment (wavelength 365 nm, irradiance 3.0 mW/cm2, and total dose 5.4 J/cm2) on right eyes. Animals were sacrificed before and immediately after treatment (day 0), day 1, 3, 7, and 28 after treatment. A 4×10 mm corneal strip for biomechanical evaluation was harvested after sacrifice. The corneal fragility was evaluated by measurement of elongation rate, whereby the elongation rate equals elongation length/baseline length.

Results:
The Youngs modulus and maximal stress were 1.41±0.51 MPa and 5.56±1.84 MPa before CXL, and increased to 2.31±0.68 MPa (P=0.008) and 9.25±2.74 MPa (P=0.04), respectively, on day 0, then maintained a stable level within a 28 days follow-up. The elongation rate was 62.04±9.34% before CXL and decreased to 48.95%±8.24% (P=0.02) on day 0, then maintained a stable level within a 28 days follow-up.

Conclusions:
This study showed an increase in the corneal fragility after UVA/riboflavin crosslinking along with an increase in the corneal stiffness. A long-term follow-up should be taken to evaluate the potential deleterious effect of the increasing corneal fragility after UVA/riboflavin crosslinking.
Middle-Ear Sound Transmission Under Normal, Damaged, Repaired, and Reconstructed Conditions
Authors: Dong Wei , Tian Ying , Gao Xin , Jung Timothy T. K. 
Published: January 2017

Hypothesis:
We hypothesize that current clinical treatment strategies for the disarticulated or eroded incus have the effect of combining the incus and stapes of the human middle ear (ME) into one rigid structure, which, while capable of adequately transmitting lower-frequency sounds, fails for higher frequencies.

Background:
ME damage causes conductive hearing loss (CHL) and while great progress has been made in repairing or reconstructing damaged MEs, the outcomes are often far from ideal.

Methods:
Temporal bones (TBs) from human cadavers, a laser Doppler vibrometer (LDV), and a fiber-optic based micro-pressure sensor were used to characterize ME transmission under various ME conditions: normal; with a disarticulated incus; repaired using medical glue; or reconstructed using a partial ossicular replacement prosthesis (PORP).

Results:
Repairing the disarticulated incus using medical glue, or replacing the incus using a commercial PORP, provided similar restoration of ME function including almost perfect function at frequencies below 4 kHz, but with more than a 20-dB loss at higher frequencies. Associated phase responses under these conditions sometimes varied and seemed dependent on the degree of coupling of the PORP to the remaining ME structure. A new ME-prosthesis design may be required to allow the stapes to move in three-dimensional (3-D) space to correct this deficiency at higher frequencies.

Conclusions:
Fixation of the incus to the stapes or ossicular reconstruction using a PORP limited the efficiency of sound transmission at high frequencies.