bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ischemic stroke in Morocco: a systematic review
Authors: Kharbach Ahmed , Obtel Majdouline , Lahlou Laila , Aasfara Jehanne , Mekaoui Nour , Razine Rachid 
Published: December 2019

AbstractBackgroundThe aim of this systematic review is to determine the epidemiological and etiological profiles, the influential factors of the prehospital delay, thrombolysis management, the acute and 3-month mortality rate and the genetic aspect of ischemic stroke in Morocco.MethodsThe present work is a systematic review that was conducted according to the recommendations of the “Preferred reporting items for systematic reviews and meta-analysis”. We used Pubmed, Sciencedirect, Scopus, Clinicalkey, and Google scholar databases for the raking of the gray literature during the time frame 2009 and 2018. The protocol of the review was registered in the PROSPERO register (CRD42018115206).These studies were analyzed based on: Age, sex ratio, risk factors, etiological profile according to Trial of ORG classification 10,172 in Acute Stroke Treatment, prehospital delay average and its influential factors, thrombolyzed patients’ proportion, acute and 3-month mortality and the genetic factors of ischemic stroke in Morocco.ResultsTwenty-nine (n = 29) studies were selected. The average age ranged from 49 ± 15.2 to 67.3 ± 9.9 years old. Moreover, we reported male predominance within all ages in 13 studies. High blood pressure, diabetes, smoking and heart disease were the four identified main risk factors by the prementioned studies. Atherosclerosis and cardioembolic were the main described etiologies of cerebral ischemia, and the average prehospital time ranged from 26 to 61.9 h. The proportion of thrombolysed patients ranged from 1.8% to 2.9%, the mortality rate varied in the acute phase from 3 to 13%, and the 3-month mortality ranged from 4.3 to 32.5%. It is also important to highlight that most of these studies, which were conducted in hospital environment, have a reduced sample size and no confidence interval.ConclusionsIschemic stroke is affecting more likely the young population with male predominance. Moreover, the long prehospital delay and the low proportion of thrombolysed patients are alarming. This indicates the need to investigate in depth the key factors influencing the access to care for Moroccan patients in order to improve the management of this neurologic deficit in Morocco.
Top research priorities for preterm birth: results of a prioritisation partnership between people affected by preterm birth and healthcare professionals
Authors: Oliver Sandy , Uhm Seilin , Duley Lelia , Crowe Sally , David Anna L. , James Catherine P. , Chivers Zoe , Gyte Gill , Gale Chris , Turner Mark , Chambers Bev , Dowling Irene , McNeill Jenny , Alderdice Fiona , Shennan Andrew , Deshpande Sanjeev 
Published: December 2019

Abstract
Background
We report a process to identify and prioritise research questions in preterm birth that are most important to people affected by preterm birth and healthcare practitioners in the United Kingdom and Republic of Ireland.

Methods
Using consensus development methods established by the James Lind Alliance, unanswered research questions were identified using an online survey, a paper survey distributed in NHS preterm birth clinics and neonatal units, and through searching published systematic reviews and guidelines. Prioritisation of these questions was by online voting, with paper copies at the same NHS clinics and units, followed by a decision-making workshop of people affected by preterm birth and healthcare professionals.

Results
Overall 26 organisations participated. Three hundred and eighty six people responded to the survey, and 636 systematic reviews and 12 clinical guidelines were inspected for research recommendations. From this, a list of 122 uncertainties about the effects of treatment was collated: 70 from the survey, 28 from systematic reviews, and 24 from guidelines. After removing 18 duplicates, the 104 remaining questions went to a public online vote on the top 10. Five hundred and seven people voted; 231 (45%) people affected by preterm birth, 216 (43%) health professionals, and 55 (11%) affected by preterm birth who were also a health professional. Although the top priority was the same for all types of voter, there was variation in how other questions were ranked.
Following review by the Steering Group, the top 30 questions were then taken to the prioritisation workshop. A list of top 15 questions was agreed, but with some clear differences in priorities between people affected by preterm birth and healthcare professionals.

Conclusions
These research questions prioritised by a partnership process between service users and healthcare professionals should inform the decisions of those who plan to fund research. Priorities of people affected by preterm birth were sometimes different from those of healthcare professionals, and future priority setting partnerships should consider reporting these separately, as well as in total.
Can introvoxel incoherent motion MRI be used to differentiate patients with placenta accreta spectrum disorders?
Authors: Lu Tao , Pu Hong , Li Kui-de , Mei Jie , Huang Meng-wei , Wang Shao-yu 
Published: December 2019

Abstract
Background
The incidence of PAS disorders increased rapidly in recent years, and introvoxel incoherent motion (IVIM) MRI has been applied in the assessment of placenta. The study aims to investigate whether the parameters from IVIM can be used to differentiate patients with PAS disorders complicating placenta previa and secondly to differentiate different categories of PAS disorders.

Methods
The study participants were comprised of 99 patients with placenta previa, including 16 patients with placenta accreta, 51 patients with increta, 8 patients with percreta and 24 patients without PAS disorders between 28 + 0 and 39 + 6 weeks. IVIM MRI was performed on a 1.5 T scanner. Perfusion fraction (f), pseudodiffusion coefficient (D*) and diffusion coefficient (D) were calculated.

Results
Women with PAS disorders had a higher perfusion fraction (p = 0.019) than women without the disease. Multiple comparisons showed perfusion fraction in patients without PAS disorders was significantly lower than in patients with placenta accreta and percreta(P = 0.018 and 0.033 respectively), but was not lower than in patients with increta(p = 1).

Conclusion
Patients with placenta accreta and percreta differed in placental perfusion fraction from women with increta and without PAS disorders.
Clinical interventions that influence vaginal birth after cesarean delivery rates: Systematic Review & Meta-Analysis
Authors: Wingert Aireen , Hartling Lisa , Sebastianski Meghan , Johnson Cydney , Featherstone Robin , Vandermeer Ben , Wilson R. Douglas 
Published: December 2019

Abstract
Background
To systematically review the literature on clinical interventions that influence vaginal birth after cesarean (VBAC) rates.

Methods
We searched Ovid Medline, Ovid Embase, Wiley Cochrane Library, CINAHL via EBSCOhost; and Ovid PsycINFO. Additional studies were identified by searching for clinical trial records, conference proceedings and dissertations. Limits were applied for language (English and French) and year of publication (1985 to present). Two reviewers independently screened comparative studies (randomized or non-randomized controlled trials, and observational designs) according to a priori eligibility criteria: women with prior cesarean sections; any clinical intervention or exposure intended to increase the VBAC rate; any comparator; and, outcomes reporting VBAC, uterine rupture and uterine dehiscence rates. One reviewer extracted data and a second reviewer verified for accuracy. Meta-analysis was conducted using Mantel-Haenszel (random effects model) relative risks (VBAC rate) and risk differences (uterine rupture and dehiscence). Two reviewers independently conducted methodological quality assessments using the Mixed Methods Appraisal Tool (MMAT).

Results
Twenty-nine studies (six trials and 23 cohorts) examined different clinical interventions affecting rates of vaginal deliveries among women with a prior cesarean delivery (CD). Methodological quality was good overall for the trials; however, concerns among the cohort studies regarding selection bias, comparability of groups and outcome measurement resulted in higher risk of bias. Interventions for labor induction, with or without cervical ripening, included pharmacologic (oxytocin, prostaglandins, misoprostol, mifepristone, epidural analgesia), non-pharmacologic (membrane sweep, amniotomy, balloon devices), and combined (pharmacologic and non-pharmacologic). Single studies with small sample sizes and event rates contributed to most comparisons, with no clear differences between groups on rates of VBAC, uterine rupture and uterine dehiscence.

Conclusions
This systematic review evaluated clinical interventions directed at increasing the rate of vaginal delivery among women with a prior CD and found low to very low certainty in the body of evidence for cervical ripening and/or labor induction techniques. There is insufficient high-quality evidence to inform optimal clinical interventions among women attempting a trial of labor after a prior CD.
Occurrence of paratesticular ganglioneuroma 18 years after concurrent adrenal ganglioneuroma and papillary thyroid carcinoma – a case report
Authors: Fang Chu-Wen , Wang Jyh-Seng , Wu Tony T. , Lin Jen-Tai 
Published: December 2019

Abstract
Background
Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare.

Case presentation
Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later.

Conclusions
We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.
Elucidating the expression and function of Numbl during cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM)
Authors: Huang Yuejiao , Huang Xianting , Cheng Chun , Xu Xiaohong , Liu Hong , Yang Xiaojing , Yao Li , Ding Zongmei , Tang Jie , He Song , Wang Yuchan 
Published: December 2019

AbstractBackgroundCell adhesion-mediated drug resistance (CAM-DR) is a major clinical problem that prevents successful treatment of multiple myeloma (MM). In particular, the expression levels of integrin β1 and its sub-cellular distribution (internalization and trafficking) are strongly associated with CAM-DR development.MethodsDevelopment of an adhesion model of established MM cell lines and detection of Numbl and Integrinβ1 expression by Western Blot analysis. The interaction between Numbl and Integrinβ1 was assessed by a co-immunoprecipitation (CO-IP) method. Calcein AM assay was performed to investigate the levels of cell adhesion. Finally, the extent of CAM-DR in myeloma cells was measured using cell viability assay and flow cytometry analysis.ResultsOur preliminary date suggest that Numbl is differentially expressed in a cell adhesion model of MM cell lines. In addition to binding to the phosphotyrosine-binding (PTB) domain, the carboxyl terminal of Numbl can also interact with integrin β1 to regulate the cell cycle by activating the pro-survival PI3K/AKT signaling pathway. This study intends to verify and elucidate the interaction between Numbl and integrin β1 and its functional outcome on CAM-DR. We have designed and developed a CAM-DR model using MM cells coated with either fibronectin or bone marrow stromal cells. We assessed whether Numbl influences cell-cycle progression and whether it, in turn, contributes to activation of PI3K/AKT signal pathway through the adjustment of its carboxyl end. Finally, we showed that the interaction of Numbl with integrin β1 promotes the formation of CAM-DR in MM cells.ConclusionsOur findings elucidated the specific molecular mechanisms of CAM-DR induction and confirmed that Numbl is crucial for the development of CAM-DR in MM cells.
TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin
Authors: Jiang Yanan , Zhang Jing , Zhao Jimin , Li Zhenzhen , Chen Hanyong , Qiao Yan , Chen Xinhuan , Liu Kangdong , Dong Ziming 
Published: December 2019

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear.MethodsTissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings.ResultsThe enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin.ConclusionThe findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.
Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study
Authors: Glaser Rebecca L. , York Anne E. , Dimitrakakis Constantine 
Published: December 2019

AbstractBackgroundTestosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole.MethodsThe 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis (N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of ‘person-time of observation’ for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data.ResultsAs of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y (p < 0.001) and historical controls.ConclusionLong term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.
Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study
Authors: Lu Ying , Chen Dagui , Liang Jinhui , Gao Jianquan , Luo Zhanxiong , Wang Rensheng , Liu Wenqi , Huang Changjie , Ning Xuejian , Liu Meilian , Huang Haixin 
Published: December 2019

Abstract
Background
Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy.

Methods
This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015–2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy.

Results
A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033).

Conclusion
For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation.

Trial registration
The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.
Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer
Authors: Suh Hoon Young , Choi Hongyoon , Paeng Jin Chul , Cheon Gi Jeong , Chung June-Key , Kang Keon Wook 
Published: December 2019

Abstract
Background
The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC).

Methods
We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival.

Results
In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC.

Conclusions
As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.

Trial registration
Not applicable.
Downregulated SPINK4 is associated with poor survival in colorectal cancer
Authors: Wang Xiaojie , Yu Qian , Ghareeb Waleed M. , Zhang Yiyi , Lu Xingrong , Huang Ying , Huang Shenghui , Sun Yanwu , Lin Jiayi , Liu Jin , Chi Pan 
Published: December 2019

AbstractBackgroundSPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown.MethodsWe retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center.ResultsSPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort.ConclusionsWe concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.