bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: A synthetic dsRNA, as a TLR3 pathwaysynergist, combined with sorafenib suppresses HCC in vitro and in vivo
Authors: Xu Yu-Yin , Chen Li , Wang Gui-Lan , Zhou Jia-Ming , Zhang Yi-Xin , Wei Yin-Ze , Zhu Yuan-Yuan , Qin Jing 
Published: November 2013

Abstract
Background
Recent studies have demonstrated that synthetic dsRNAs may produce therapeutic effects in a target-independent manner through stimulation of the toll-like receptor-3 (TLR3)/interferon pathway; as a result, angiogenesis and proliferation of tumor cells are inhibited. Thus, this pathway may become a potential target of dsRNA in tumor suppression. In this study, we evaluated the role of synthetic dsRNA as a TLR3 synergist and by combining with sorafenib in anti-hepatocellular carcinoma (HCC) in vitro and in vivo.

Methods
Four dsRNAs were designed and synthesized. One of them that was capable of activating TLR3 most effectively in human HCC cell line (HepG2.2.15) was selected as a TLR3 synergist (called BM-06). Subsequently, the expression of proteins relating to TLR3 signaling pathway, such as NF-κB, caspase 8 survivin, bcl-2 and PCNA affected by BM-06, sorafenib alone or in combination, was compared. The migration, proliferation and apoptosis of HepG2.2.15 cells were evaluated in presence of BM-06, sorafenib alone or in combination of both. The similar treatments were also applied in an SD rat primary HCC model.

Results
qRT-PCR data showed that the expression of TLR3 and NF-κB in HepG2.2.15 cells was enhanced. BM-06 was selected as a TLR3 synergist capable of activating the TLR3/interferon pathway most effective among 4 synthetic dsRNAs. The migration and proliferation were significantly inhibited in treated HepG2.2.15 cells with BM-06 or Sorafenib alone as compared with PBS-sham control (P < 0.01). However, the role of combination BM-06 with Sorafenib was the most prominent. Tumor cell apoptotic rate was increased by BM-06 or combination when compared to PBS or poly(I:C) (P < 0.05). Similarly, in orthotopic HCC SD rats, the effect of the combination was superior to either agent alone on the inhibition of tumor growth and induction of HCC cell apoptosis (P < 0.05).

Conclusions
dsRNA alone was capable of inhibiting the proliferation of HepG2.2.15 cells and tumor growth of orthotopic HCC SD rats, but the effect of combination of dsRNA with sorafenib was more prominent. These findings implicate the potential role of combined use of a dsRNA, a TLR3 synergist, and sorafenib in inhibition of HCC.
An evidential reasoning based model for diagnosis of lymph node metastasis in gastric cancer
Authors: Zhou Zhi-Guo , Liu Fang , Jiao Li-Cheng , Wang Zhi-Long , Zhang Xiao-Peng , Wang Xiao-Dong , Luo Xiao-Zhuo 
Published: November 2013

AbstractBackgroundLymph node metastasis (LNM) in gastric cancer is a very important prognostic factor affecting long-term survival. Currently, several common imaging techniques are used to evaluate the lymph node status. However, they are incapable of achieving both high sensitivity and specificity simultaneously. In order to deal with this complex issue, a new evidential reasoning (ER) based model is proposed to support diagnosis of LNM in gastric cancer.MethodsThere are 175 consecutive patients who went through multidetector computed tomography (MDCT) consecutively before the surgery. Eight indicators, which are serosal invasion, tumor classification, tumor enhancement pattern, tumor thickness, number of lymph nodes, maximum lymph node size, lymph node station and lymph node enhancement are utilized to evaluate the tumor and lymph node through CT images. All of the above indicators reflect the biological behavior of gastric cancer. An ER based model is constructed by taking the above indicators as input index. The output index determines whether LNM occurs for the patients, which is decided by the surgery and histopathology. A technique called k-fold cross-validation is used for training and testing the new model. The diagnostic capability of LNM is evaluated by receiver operating characteristic (ROC) curves. A Radiologist classifies LNM by adopting lymph node size for comparison.Results134 out of 175 cases are cases of LNM, and the remains are not. Eight indicators have statistically significant difference between the positive and negative groups. The sensitivity, specificity and AUC of the ER based model are 88.41%, 77.57% and 0.813, respectively. However, for the radiologist evaluating LNM by maximum lymph node size, the corresponding values are only 63.4%, 75.6% and 0.757. Therefore, the proposed model can obtain better performance than the radiologist. Besides, the proposed model also outperforms other machine learning methods.ConclusionsAccording to the biological behavior information of gastric cancer, the ER based model can diagnose LNM effectively and preoperatively.
Efficient BST2 antagonism by Vpu is critical for early HIV-1 dissemination in humanized mice
Authors: Dave Vibhuti P , Hajjar Fadi , Dieng Mame Massar , Haddad Élie , Cohen Éric A 
Published: November 2013

Abstract

Background
Vpu is a multifunctional accessory protein that enhances the release of HIV-1 by counteracting the entrapment of nascent virions on infected cell surface mediated by BST2/Tetherin. Vpu-mediated BST2 antagonism involves physical association with BST2 and subsequent mislocalization of the restriction factor to intracellular compartments followed by SCF(β-TrCP) E3 ligase-dependent lysosomal degradation. Apart from BST2 antagonism, Vpu also induces down regulation of several immune molecules, including CD4 and SLAMF6/NTB-A, to evade host immune responses and promote viral dissemination. However, it should be noted that the multiple functions of Vpu have been studied in cell-based assays, and thus it remains unclear how Vpu influences the dynamic of HIV-1 infection in in vivo conditions.

Results
Using a humanized mouse model of acute infection as well as CCR5-tropic HIV-1 that lack Vpu or encode WT Vpu or Vpu with mutations in the β-TrCP binding domain, we provide evidence that Vpu-mediated BST2 antagonism plays a crucial role in establishing early plasma viremia and viral dissemination. Interestingly, we also find that efficient HIV-1 release and dissemination are directly related to functional strength of Vpu in antagonizing BST2. Thus, reduced antagonism of BST2 due to β-TrCP binding domain mutations results in decreased plasma viremia and frequency of infected T cells, highlighting the importance of Vpu-mediated β-TrCP-dependent BST-2 degradation for optimal initial viral propagation.

Conclusions
Overall, our findings suggest that BST2 antagonism by Vpu is critical for efficient early viral expansion and dissemination during acute infection and as such is likely to confer HIV-1 increased transmission fitness.
“Spin” in wound care research: the reporting and interpretation of randomized controlled trials with statistically non-significant primary outcome results or unspecified primary outcomes
Authors: Lockyer Suzanne , Hodgson Rob , Dumville Jo C , Cullum Nicky 
Published: November 2013

Abstract

Background
Spin in the reporting of randomized controlled trials, where authors report research in a way that potentially misrepresents results and mislead readers, has been demonstrated in the broader medical literature. We investigated spin in wound care trials with (a) no statistically significant result for the primary outcome and (b) no clearly specified primary outcome.

Methods
We searched the Cochrane Wounds Group Specialised Register of Trials for randomized controlled trials (RCTs). Eligible studies were: Parallel-group RCTs of interventions for foot, leg or pressure ulcers published in 2004 to 2009 (inclusive) with either a clearly identified primary outcome for which there was a statistically non-significant result (Cohort A) or studies that had no clear primary outcome (Cohort B).
We extracted general study details. For both Cohorts A and B we then assessed for the presence of spin. For Cohort A we used a pre-defined process to assess reports for spin. For Cohort B we aimed to assess spin by recording the number of positive treatment effect claims made. We also compared the number of statistically significant and non-significant results reported in the main text and the abstract looking specifically for spin in the form of selective outcome reporting.

Results
Of the 71 eligible studies, 28 were eligible for Cohort A; of these, 71% (20/28) contained spin. Cohort B contained 43 studies; of these, 86% (37/43) had abstracts that claimed a favorable treatment claim. Whilst 74% (32/43) of main text results in Cohort B included at least one statistically non-significant result, this was not reflected in the abstract where only 28% contained (12/43) at least one statistically non-significant result.

Conclusions
Spin is a frequent phenomenon in reports of RCTs of wound treatments. Studies without statistically significant results for the primary outcome used spin in 71% of cases. Furthermore, 33% (43/132) of reports of wound RCTs did not specify a primary outcome and there was evidence of spin and selective outcome reporting in the abstracts of these. Readers should be wary of only reading the abstracts of reports of RCTs of wound treatments since they are frequently misleading regarding treatment effects.
Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro
Authors: Schlaich Fabian , Brons Stephan , Haberer Thomas , Debus Jürgen , Combs Stephanie E , Weber Klaus Josef 
Published: November 2013

Abstract

Background
Characterization of combination effects of chemotherapy drugs with carbon ions in comparison to photons in vitro.

Methods
The human colon adenocarcinoma cell line WiDr was tested for combinations with camptothecin, cisplatin, gemcitabine and paclitaxel. In addition three other human tumour cell lines (A549: lung, LN-229: glioblastoma, PANC-1: pancreas) were tested for the combination with camptothecin. Cells were irradiated with photon doses of 2, 4, 6 and 8 Gy or carbon ion doses of 0.5, 1, 2 and 3 Gy. Cell survival was assessed using the clonogenic growth assay. Treatment dependent changes in cell cycle distribution (up to 12 hours post-treatment) were measured by FACS analysis after propidium-iodide staining. Apoptosis was monitored for up to 36 hours post-treatment by Nicoletti-assay (with qualitative verification using DAPI staining).

Results
All cell lines exhibited the well-known increase of killing efficacy per unit dose of carbon ion exposure, with relative biological efficiencies at 10% survival (RBE10) ranging from 2.3 to 3.7 for the different cell lines. In combination with chemotherapy additive toxicity was the prevailing effect. Only in combination with gemcitabine or cisplatin (WiDr) or camptothecin (all cell lines) the photon sensitivity was slightly enhanced, whereas purely independent toxicities were found with the carbon ion irradiation, in all cases. Radiation-induced cell cycle changes displayed the generally observed dose-dependent G2-arrest with little effect on S-phase fraction for all cell lines for photons and for carbon ions. Only paclitaxel showed a significant induction of apoptosis in WiDr cell line but independent of the used radiation quality.

Conclusions
Combined effects of different chemotherapeutics with photons or with carbon ions do neither display qualitative nor substantial quantitative differences. Small radiosensitizing effects, when observed with photons are decreased with carbon ions. The data support the idea that a radiochemotherapy with common drugs and carbon ion irradiation might be as feasible as respective photon-based protocols. The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments.
Hypernatremia in patients with severe traumatic brain injury: a systematic review
Authors: Kolmodin Leif , Sekhon Mypinder S , Henderson William R , Turgeon Alexis F , Griesdale Donald EG 
Published: November 2013

Abstract

Background
Hypernatremia is common following traumatic brain injury (TBI) and occurs from a variety of mechanisms, including hyperosmotic fluids, limitation of free water, or diabetes insipidus. The purpose of this systematic review was to assess the relationship between hypernatremia and mortality in patients with TBI.

Methods
We searched the following databases up to November 2012: MEDLINE, EMBASE, and CENTRAL. Using a combination of MeSH and text terms, we developed search filters for the concepts of hypernatremia and TBI and included studies that met the following criteria: (1) compared hypernatremia to normonatremia, (2) adult patients with TBI, (3) presented adjusted outcomes for mortality or complications.

Results
Bibliographic and conference search yielded 1,152 citations and 11 abstracts, respectively. Sixty-five articles were selected for full-text review with 5 being included in our study. All were retrospective cohort studies totaling 5,594 (range 100–4,296) patients. There was marked between-study heterogeneity. The incidence of hypernatremia ranged between 16% and 40%. Use of hyperosmolar therapy was presented in three studies (range 14-85% of patients). Hypernatremia was associated with increased mortality across all four studies that presented this outcome. Only one study considered diabetes insipidus (DI) in their analysis where hypernatremia was associated with increased mortality in patients who did not receive DDAVP.

Conclusions
Although hypernatremia was associated with increased mortality in the included studies, there was marked between-study heterogeneity. DI was a potential confounder in several studies. Considering these limitations, the clinical significance of hypernatremia in TBI is difficult to establish at this stage.
Natural weathering studies of oil palm trunk lumber (OPTL) green polymer composites enhanced with oil palm shell (OPS) nanoparticles
Authors: Islam Md Nazrul , Dungani Rudi , Abdul Khalil HPS , Alwani M Siti , Nadirah WO Wan , Fizree H Mohammad 
Published: November 2013

AbstractIn this study, a green composite was produced from Oil Palm Trunk Lumber (OPTL) by impregnating oil palm shell (OPS) nanoparticles with formaldehyde resin. The changes of physical, mechanical and morphological properties of the OPS nanoparticles impregnated OPTL as a result of natural weathering was investigated. The OPS fibres were ground with a ball-mill for producing nanoparticles before being mixed with the phenol formaldehyde (PF) resin at a concentration of 1, 3, 5 and 10% w/w basis and impregnated into the OPTL by vacuum-pressure method. The treated OPTL samples were exposed to natural weathering for the period of 6 and 12 months in West Java, Indonesia according to ASTM D1435-99 standard. Physical and mechanical tests were done for analyzing the changes in phenol formaldehyde-nanoparticles impregnated (PF-NPI) OPTL. FT-IR and SEM studies were done to analyze the morphological changes. The results showed that both exposure time of weathering and concentration of PF-NPI had significant impact on physical and mechanical properties of OPTL. The longer exposure of samples to weathering condition reduced the wave numbers during FT-IR test. However, all these physical, mechanical and morphological changes were significant when compared with the untreated samples or only PF impregnated samples. Thus, it can be concluded that PF-NP impregnation into OPTL improved the resistance against natural weathering and would pave the ground for improved products from OPTL for outdoor conditions.
Proteomic profiling and functional characterization of early and late shoulder osteoarthritis
Authors: Wanner John Paul , Subbaiah Roopashree , Skomorovska-Prokvolit Yelenna , Shishani Yousef , Boilard Eric , Mohan Sujatha , Gillespie Robert , Miyagi Masaru , Gobezie Reuben 
Published: November 2013

Abstract
Introduction
The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the 'whole joint’, the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable 'snapshot’ of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF.

Methods
A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines.

Results
Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA.

Conclusions
The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a 'chronic wound’ that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction.
Trends in physician diagnosed gout and gout therapies in the US: results from the national ambulatory health care surveys 1993 to 2009
Authors: Krishnan Eswar , Chen Linjun 
Published: November 2013

Abstract
Introduction
Gouty arthritis (gout) is primarily cared for in ambulatory care settings. Although the prevalence of gout in the US is thought to be increasing, there have been few data on this as well as temporal changes in gout medication use.

Methods
We analyzed annual visit and drug utilization data from national sample surveys of physician practices and hospital outpatient clinics in the US from 1993 to 2009. Gout diagnosis was recorded by individual physicians.

Result
The frequency of visits for gout increased three-fold from 1993 through 2009; most of the increases were observed from 2003 onwards. The increase was only partly explained by changes in age and gender composition of the surveys over time. A concomitant increase in prescriptions for allopurinol and colchicine and decrease in prescriptions for anti-inflammatories was observed. Aspirin use, a putative risk factor for gout and gout flares, increased substantially over this period. Probenecid use was negligible. Frequency of systemic steroid use has not changed over time.

Conclusions
The number of ambulatory visits for gout has increased almost three-fold in the first decade of the millennium coinciding with increases in physician and patient awareness. This increase was primarily due to visits among the elderly. Uricosuric use remained negligible whereas the uses of allopurinol and colchicine have increased rapidly. Use of traditional non-steroidals has declined, possibly due to safety concerns whereas glucocorticoid use remains unchanged.
Cellular mosaicism for X-linked polymorphisms and IRAK1 expression presents a distinct phenotype and improves survival following sepsis
Authors: Chandra Rachna , Federici Stephanie , Németh Zoltán H , Csóka Balázs , Thomas James A , Donnelly Robert , Spolarics Zoltán 
Published: November 2013

ABSTRACTChrX cellular mosaicism for X-linked genetic polymorphisms in females versus the single ChrX representation in males denotes a genetic difference, which may contribute to gender bias in the inflammatory response. This hypothesis was tested in female F1 offspring of consomic mice (BL6J-ChrXA/J/NaJ) that were homokaryotic or mosaic for the active BL6 and AJ ChrXs or for IRAK1 deficiency linked to the BL6 ChrX. Sepsis was initiated by CLP. IRAK1-deficient and IRAK1-mosaic mice showed similar protection from sepsis-induced mortality and reduced IL-6 and IL-10 release compared with WT. BM cellularity and blood B cell counts were increased in naive IRAK1-mosaic mice compared with WT-mosaic or IRAK1-deficient animals. Sepsis-induced BM cell depletion was greater in IRAK1-mosaic mice compared with WT-mosaic or IRAK1-deficient subjects, whereas splenic B and T cell depletion was less in IRAK1-mosaic and IRAK1-deficient than WT-mosaic mice. Skewing toward AJ or BL6-ChrX-expressing cells was assessed by testing allele-specific expression of strain-variant Xkrx and BTK genes. In naive IRAK1-mosaic mice, BM and blood cells with the active BL6-ChrX, were greater than cells expressing the AJ-ChrX (cell ratio 2.5 in IRAK1-mosaic; 1.5 in WT-mosaic mice). Sepsis decreased cell ratios more in IRAK1-mosaic than in WT-mosaic mice. The study reveals functional variability in cellular mosaicism for IRAK1 expression and natural X-linked polymorphisms during sepsis. Mosaicism for IRAK1 expression is accompanied by skewing toward deficient immune cell populations, producing a phenotype that is preconditioned for improved sepsis outcome similar to that observed in IRAK1 deficiency.
Should the Affordable Care Act's Preventive Services Coverage Provision Be Used to Widely Disseminate Whole Genome Sequencing to Americans?
Authors: Payne Perry W. 
Published: November 2013

Abstract
I argue that the provision of the Patient Protection and Affordable Care Act (ACA) of 2010, which eliminates cost sharing for preventive services, should be utilized as a pathway for reimbursing whole genome sequencing (WGS) and making it widely available to most Americans. This act provides multiple routes for determining which preventive services receive this designation. Three of these routes should be considered as pathways for reimbursing WGS, including approval by the United States Preventive Services Task Force, inclusion in the guidelines of the American Academy of Pediatrics Bright Futures Project, and classification as a preventive service for women by the Institute of Medicine. There are valid arguments against the expansion of this technology, including inadequate national and state laws prohibiting genetic discrimination, informed consent limitations, and potentially expensive genome interpretations. These concerns should not inhibit the wide dissemination of this technology, as current efforts by the NIH and industry to expand the use of genome sequencing demonstrate. The ACA should be used as a tool to prevent disparities in access to genome information in the United States and avoid the development of a two-tiered health system based on those with and without genome sequence data.