bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA PVT1 up-regulation is a poor prognosticator and serves as a therapeutic target in esophageal adenocarcinoma
Authors: Xu Yan , Li Yuan , Jin Jiankang , Han Guangchun , Sun Chengcao , Pizzi Melissa Pool , Huo Longfei , Scott Ailing , Wang Ying , Ma Lang , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Vellano Christopher , Yang Liuqing , Lin Chunru , Kim Youngsoo , MacLeod A. Robert , Wang Linghua , Wang Zhenning , Song Shumei , Ajani Jaffer A. 
Published: October 2019

Abstract
Background
PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC.

Methods
PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo.

Results
PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1+ cells. Mechanistically, we discovered mutual regulation of PVT1 and YAP1 in EAC cells. Inhibition of PVT1 by PVT1 ASOs suppressed YAP1 expression through increased phosphor-LATS1and phosphor-YAP1 while knockout of YAP1 in EAC cells significantly suppressed PVT1 levels indicating a positive regulation of PVT1 by YAP1. Most importantly, we found that targeting both PVT1 and YAP1 using their specific ASOs led to better antitumor activity in vitro and in vivo.

Conclusions
Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.
Potential excess of vaginal examinations during the management of labor: frequency and associated factors in 13 Peruvian hospitals
Authors: Zafra-Tanaka Jessica Hanae , Montesinos-Segura Renee , Flores-Gonzales Pamela D. , Taype-Rondan Alvaro 
Published: October 2019

AbstractBackgroundA high number of vaginal examinations (VEs) may lead to a higher risk of infections, as well as discomfort/dissatisfaction with intrapartum care.ObjectiveTo determine the frequency of potential excess of vaginal examinations (PEVE) during the management of labor and identify its associated factors, in Peruvian hospitals.MethodsSecondary analysis of the data collected in theDisrespEct and abuse during ChIlDbirth in pEru (DECIDE)study, held between April and May 2016. In this study, women hospitalized in Peruvian hospitals right after giving birth were surveyed by trained personnel. PEVE, the main outcome, was considered as five or more vaginal examinations (VEs) performed during the management of labor. Poisson regression models with robust variance were performed to calculate crude and adjusted prevalence ratios (cPR and aPR) as well as their 95% confidence intervals (95% CI).ResultsOne thousand four hundred twenty registries of 13 hospitals from 8 Peruvian cities were evaluated. The number of women studied at each hospital ranged between 100 and 129. The median age was 26 years (interquartile rank: 22–31). The median number of VEs was 3 (interquartile rank: 2–5). The proportion of women who underwent PEVE was 33.9%, this ranged from 0.9 to 69.9% at the studied hospitals. The frequency of PEVE was higher in women who attended > 2 obstetric psychoprophylaxis sessions, compared to those who attended ≤ 2 sessions (aPR: 1.78 95% CI: 1.01–3.12); and among women who gave birth between 18:00 h and 23:59 h, compared to those who did it between 7:00 and 17:59 h (aPR: 1.28 95% CI: 1.04–1.57).ConclusionAround one in three women underwent a PEVE, although this frequency varied widely across the evaluated hospitals. Women with more psychoprophylaxis sessions, and who gave birth between 18:00 h and 23:59 h, had a higher PEVE frequency. Future studies should assess in depth the causes and consequences of this high frequency.
Elevated expression of mcl-1 inhibits apoptosis and predicts poor prognosis in patients with surgically resected non-small cell lung cancer
Authors: Wen Qiuyuan , Zhan Yuting , Zheng Hongmei , Zang Hongjing , Luo Jiadi , Zhang Yuting , Wang Weiyuan , Feng Juan , Lu Junmi , Chen Lingjiao , Fan Songqing 
Published: October 2019

Abstract

Background
Mcl-1, an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-PARP) can serve as a marker of cell apoptosis. Previously we reported that treatment of Mnk inhibitor CGP57380 resulted in decreased Mcl-1 expression while increased c-PARP expression in non-small cell lung cancer (NSCLC) cells. In this study, we aimed to investigate association between Mcl-1 expression and clinicopathological features of NSCLC, and their correlation between Mcl-1 and both proliferation index (PI) and apoptotic index (AI) in NSCLC patients.

Methods
Tissue microarrays (TMA) including 350 cases of surgically resected NSCLC were utilize and stained with Mcl-1, Ki-67 and c-PARP antibodies, PI and AI were then evaluated, respectively.

Results
Higher Mcl-1 expression and PI were observed in NSCLC compared with non-cancerous lung tissues (non-CLT), while AI was significantly lower in lung adenocarcinoma (ADC) compared with non-CLT. Additionally, Mcl-1 expression in lung ADC was evidently higher than that of in lung squamous cell carcinoma (SCC). The elevated Mcl-1 expression was associated with PI, and inversely related to AI in NSCLC. NSCLC patients with elevated Mcl-1 expression and high PI, or with high Mcl-1 expression and low AI had remarkably shorter overall survival time than these patients with low Mcl-1 expression.

Conclusions
Elevated expression of Mcl-1 might be inversely proportional to disease progression of NSCLC patients by promoting cell proliferation and inhibiting apoptosis, and Mcl-1 might serve as novel biomarker of poor prognosis for NSCLC patients.
Validation of revision data for total hip and knee replacements undertaken at a high volume orthopaedic centre against data held on the National Joint Registry
Authors: Afzal Irrum , Radha Sarkhell , Smoljanović Tomislav , Stafford Giles H. , Twyman Roy , Field Richard E. 
Published: October 2019

Abstract

Background
With over 2.35 million records, the National Joint Registry (NJR) is the largest arthroplasty registry in the world. It provides a powerful tool to monitor implant survivorship and influence different surgical strategies. To date, little work has been undertaken to investigate the validity of the ‘Reason for Revision’ recorded in Consultant Outcome Reports on the NJR.

Methods
The NJR was queried to identify all revisions on the THR performed at a single centre over an 11-year period. Review and validation of ‘Reason for Revision’ for each case was undertaken using radiological imaging studies, pathology, histology, microbiology and electronic medical records.

Results
Of the 22,046 primary total hip replacements (THR) and total knee replacements (TKR) undertaken by 23 surgeons at our hospital, over an 11-year period, 1.35% (297) were subsequently reported to the NJR as revised. Discrepancies in reporting to the NJR were identified for 41 cases (25.63%) for THR and 28 (20.40%) cases for TKR. Revision for infection was under-reported for both THR and TKR by 1.88% and 3.65% respectively. Reporting of adverse soft tissue reaction to particulate debris for THR was unreported by 11%. Progressive arthritis following a TKR was unreported by 6.56%. All the cases reported as ‘other’ (8.75% for THRs and 3.65% for TKRs) were reclassified to the most appropriate ‘reason for revision’ category. The ‘reason for revision’ data is recorded to the NJR with findings at the time of surgery. It is some days before microbiology and histology reports become available and source data is not always updated.

Conclusion
If an average of 23% wrong data entry at a highly organised institution is replicated throughout the UK, a formal process to validate primary and revision data submitted to the NJR should be considered. Local scrutiny, review and validation of revision data are all vital to optimise the value of the NJR. Accurate data recorded to the NJR is imperative to provide safe and effective improvements in orthopaedic surgery.
Emodin promotes fibroblast apoptosis and prevents epidural fibrosis through PERK pathway in rats
Authors: Xiong Guirun , Chen Hui , Wan Qi , Dai Jihang , Sun Yu , Wang Jingcheng , Li Xiaolei 
Published: October 2019

Abstract

Background
Laminectomy is usually classed as a common orthopedic surgery, but postoperative epidural fibrosis often leads to less-than-desirable clinical outcomes. As demonstrated by prior studies, emodin (EMO) exerts an anti-fibrotic effect. Here, we carried out investigation into the inhibitory effect created by EMO application on epidural fibrosis after laminectomy in rats.

Methods
The paper conducts a series of experiment. In vitro, we observed the effect of EMO on fibroblasts by Cell Counting Kit-8 (CCK-8) assay. Apoptosis of fibroblasts induced by EMO was detected by western blot, TUNEL assay, and flow cytometry. The results revealed that EMO was capable of inducing fibroblast apoptosis, and the proteins of PERK pathway also changed accordingly. In vivo, the effect of EMO on epidural fibrosis in 12 male Sprague-Dawley rats was observed by histological staining.

Results
CCK-8 assay indicated that EMO was effective in reducing fibroblast viability in a time- and a dose-dependent manner. TUNEL assay and flow cytometry analysis have demonstrated that the apoptotic rate of fibroblasts increased as the EMO concentration rose. Western blot analysis proved that EMO promoted the relative expression of p-perk and p-eIF2α and that the expression of its downstream proteins CHOP and GRP78 was also enhanced. The expression of apoptotic protein Bax and cleaved PARP was upregulated, whereas the expression of anti-apoptotic protein Bcl-2 was downregulated. In addition, histological and immunohistochemical analysis demonstrated that EMO functioned to inhibit epidural fibrosis and increase GRP78 expression in fibrous tissue by promoting apoptosis of fibroblasts.

Conclusions
EMO could have inhibitory effect on epidural fibrosis in a concentration-dependent manner. The potential mechanism might be through PERK signaling pathway to promote fibroblast apoptosis. It has a possibility to be taken as a novel method for the treatment of epidural fibrosis.
“With every passing day I feel like a candle, melting little by little.” experiences of long-term displacement amongst Syrian refugees in Shatila, Lebanon
Authors: Syam Hanadi , Venables Emilie , Sousse Bernard , Severy Nathalie , Saavedra Luz , Kazour Francois 
Published: October 2019

Abstract

Background
Long term displacement and exposure to challenging living conditions can influence family dynamics; gender roles; violence at home and in the community and mental well-being. This qualitative study explores these issues as perceived by Syrian refugees who have been living in Shatila, a Palestinian camp in South Beirut, Lebanon, for at least 2 years.

Methods
Twenty eight in-depth interviews with men and women were conducted between February and June 2018. Women were recipients of mental health services, and men were recruited from the local community. Interviews were conducted in Arabic, translated, transcribed, coded and analysed using thematic content analysis.

Results
Our results show patterns of harsh living conditions similar to those described earlier in the course of the Syrian refugee crisis. Lack of infrastructure, overcrowding, cramped rooms and violence were all reported. Participants also described a lack of social support, discrimination and harassment within the host community, as well as limited social support networks within their own Syrian refugee community. Family dynamics were affected by the increased responsibilities on men, women and children; with additional economic and employment demands on men, women assuming the roles of ‘mother and father’ and children having to work and contribute to the household. Participants discussed several types of violence, including parental violence against children and violence in the community. Violence against women was also reported. Reported mental health issues included depression, anxiety, sadness, frustration, hopelessness, self-neglect and a loss of sense of self and self-worth. Some participants expressed a wish to die.

Conclusions
This study describes experiences of changing gender roles, family dynamics, violence and mental health after long-term displacement in in Shatila camp, South Beirut as perceived by Syrian refugees. A lack of safety and security coupled with economic hardship rendered refugees even more susceptible to exploitation and harassment. Parental violence was the most commonly reported type of domestic violence.
Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells
Authors: Li Fujun , Miao Lixia , Xue Teng , Qin Hao , Mondal Santanu , Thompson Paul R. , Coonrod Scott A. , Liu Xiaoqiu , Zhang Xuesen 
Published: October 2019

Abstract

Background
Tamoxifen resistance presents a huge clinical challenge for breast cancer patients. An understanding of the mechanisms of tamoxifen resistance can guide development of efficient therapies to prevent drug resistance.

Methods
We first tested whether peptidylarginine deiminase 2 (PAD2) may be involved in tamoxifen-resistance in breast cancer cells. The effect of depleting or inhibiting PAD2 in tamoxifen-resistant MCF-7 (MCF7/TamR) cells was evaluated both in vitro and in vivo. We then investigated the potential of Cl-amidine, a PAD inhibitor, to be used in combination with tamoxifen or docetaxel, and further explored the mechanism of the synergistic and effective drug regimen of PADs inhibitor and docetaxel on tamoxifen-resistant breast cancer cells.

Results
We report that PAD2 is dramatically upregulated in tamoxifen-resistant breast cancer. Depletion of PAD2 in MCF7/TamR cells facilitated the sensitivity of MCF7/TamR cells to tamoxifen. Moreover, miRNA-125b-5p negatively regulated PAD2 expression in MCF7/TamR cells, therefore overexpression of miR-125b-5p also increased the cell sensitivity to tamoxifen. Furthermore, inhibiting PAD2 with Cl-amidine not only partially restored the sensitivity of MCF7/TamR cells to tamoxifen, but also more efficiently enhanced the efficacy of docetaxel on MCF7/TamR cells with lower doses of Cl-amidine and docetaxel both in vivo and in vivo. We then showed that combination treatment with Cl-amidine and docetaxel enhanced p53 nuclear accumulation, which synergistically induced cell cycle arrest and apoptosis. Meanwhile, p53 activation in the combination treatment also accelerated autophagy processes by synergistically decreasing the activation of Akt/mTOR signaling, thus enhancing the inhibition of proliferation.

Conclusion
Our results suggest that PAD2 functions as an important new biomarker for tamoxifen-resistant breast cancers and that inhibiting PAD2 combined with docetaxel may offer a new approach to treatment of tamoxifen-resistant breast cancers.
Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients
Authors: Peters Brandilyn A. , Wilson Melissa , Moran Una , Pavlick Anna , Izsak Allison , Wechter Todd , Weber Jeffrey S. , Osman Iman , Ahn Jiyoung 
Published: October 2019

AbstractBackgroundRecent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.MethodsIn melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.ResultsHigher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance ofBacteroides ovatus,Bacteroides dorei,Bacteroides massiliensis,Ruminococcus gnavus, andBlautia productawere related to shorter PFS, andFaecalibacterium prausnitzii,Coprococcus eutactus,Prevotella stercorea,Streptococcus sanguinis,Streptococcus anginosus, andLachnospiraceae bacterium 3 1 46FAAto longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways ofl-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis.ConclusionsThis work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.
DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer
Authors: Awada Z. , Nasr R. , Akika R. , Cahais V. , Cuenin C. , Zhivagui M. , Herceg Z. , Ghantous A. , Zgheib N. K. 
Published: October 2019

AbstractBackgroundBisphenol A (BPA), an estrogen-like endocrine disruptor used in plastics, has been associated with development and promotion of breast cancer, so plastic manufacturers shifted towards less-studied analogs, BPF and BPS. Studying the associated DNA methylome-wide mechanisms of these derivatives is timely, particularly in comparison with BPA.MethodsWe assessed proliferation, cell cycle, and migration of breast cancer cells (estrogen receptor (ER)-positive: MCF-7 and ER-negative: MDA-MB-231) treated with BPF and BPS ± estrogen receptor inhibitor (ERI) in comparison to BPA ± ERI. RNA expression and activity of DNA (de)methylation enzymes andLINE-1methylation were quantified. DNA methylome-wide analysis was evaluated in bisphenol-exposed cells and compared to clinical breast cancer data.ResultsThe three bisphenols caused ER-dependent increased proliferation and migration of MCF-7 but not MDA-MB-231 cells, with BPS being 10 times less potent than BPA and BPF. Although they have similar chemical structures, the three bisphenols induced differential DNA methylation alterations at several genomic clusters of or single CpG sites, with the majority of these being ER-dependent. At equipotent doses, BPA had the strongest effect on the methylome, followed by BPS then BPF. No pathways were enriched for BPF while BPA- and BPS-induced methylome alterations were enriched in focal adhesion, cGMP-PKG, and cancer pathways, which were also dysregulated in methylome-wide alterations comparing ER-positive breast cancer samples to adjacent normal tissues.ConclusionsThe three bisphenols have important epigenetic effects in breast cell lines, with those of BPA and BPS overlapping with cancer-related pathways in clinical breast cancer models. Hence, further investigation of their safety is warranted.
Oscillation of third-order neutral differential equations with damping and distributed delay
Authors: Wei Meihua , Jiang Cuimei , Li Tongxing 
Published: October 2019

Abstract
The present paper focuses on the oscillation of the third-order nonlinear neutral differential equations with damping and distributed delay. The oscillation of the third-order damped equations is often discussed by reducing the equations to the second-order ones. However, by applying the Riccati transformation and the integral averaging technique, we give an analytical method for the estimation of Riccati dynamic inequality to establish several oscillation criteria for the discussed equation, which show that any solution either oscillates or converges to zero. The results make significant improvement and extend the earlier works such as (Zhang et al. in Appl. Math. Lett. 25:1514–1519 2012). Finally, some examples are given to demonstrate the effectiveness of the obtained oscillation results.
A comparative finite analysis of the mechanical behavior of ProTaper NEXT and WaveOne rotary files
Authors: Omar Nada , Ismail Amira Galal , Galal Manar , Zaazou Mohamed H. , Mohamed Mohamed Abdullah 
Published: October 2019

Abstract
Finite element analysis was used to evaluate the stress distribution, estimate the residual stresses, bending, and amount of displacement of two nickel-titanium instruments manufactured by the same M-wire technology but with different cross-section.

Materials and methods
Two brands of Ni-Ti instruments ProTaper NEXT (Dentsply Maillefer), and WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) were scanned with stereomicroscope to produce a two-dimensional model for each file using computer-aided design programs (CAD) (SolidWorks software package), which then was converted into stereolithographic extension to be readable by programming software (MATLAB software) to produce three-dimensional models. The mathematical analysis of files was performed on SolidWorks software package. The mechanical behavior of the two files was analyzed numerically in a SolidWorks package to simulate and measure torsion, bending, and file displacement. Application of a shear moment (torsion) 2.5 N/mm moment of force was applied to the shaft in a clockwise direction, while the last 4 mm of the tip was rigidly constrained to evaluate the stress distribution on each file. As for Cantilever bending, a concentrated load of 1 N at the tip of the file with its shaft rigidly held in place was applied for the finite element models. The vertical displacement was measured and the von Mises stress distribution was evaluated.

Results
The WaveOne file showed higher torsional stresses accumulation than those accumulated in the ProTaper NEXT. While the ProTaper NEXT showed more bending and file displacement than those showed by WaveOne file.

Conclusions
The two files rotary models highlighted the different mechanical properties of the files although they share the same manufactured technology M-wire. The ProTaper NEXT showed less torsional stress accumulation and more bending properties.