bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the closest health facility the one used in pregnancy care-seeking? A cross-sectional comparative analysis of self-reported and modelled geographical access to maternal care in Mozambique, India and Pakistan
Authors: Makacha Liberty , Makanga Prestige Tatenda , Dube Yolisa Prudence , Bone Jeffrey , Munguambe Khátia , Katageri Geetanjali , Sharma Sumedha , Vidler Marianne , Sevene Esperança , Ramadurg Umesh , Charantimath Umesh , Revankar Amit , von Dadelszen Peter 
Published: February 2020

Abstract
Background
Travel time to care is known to influence uptake of health services. Generally, pregnant women who take longer to transit to health facilities are the least likely to deliver in facilities. It is not clear if modelled access predicts fairly the vulnerability in women seeking maternal care across different spatial settings.

Objectives
This cross-sectional analysis aimed to (i) compare travel times to care as modelled in a GIS environment with self-reported travel times by women seeking maternal care in Community Level Interventions for Pre-eclampsia: Mozambique, India and Pakistan; and (ii) investigate the assumption that women would seek care at the closest health facility.

Methods
Women were interviewed to obtain estimated travel times to health facilities (R). Travel time to the closest facility was also modelled (P) (closest facility tool (ArcGIS)) and time to facility where care was sought estimated (A) (route network layer finder (ArcGIS)). Bland–Altman analysis compared spatial variation in differences between modelled and self-reported travel times. Variations between travel times to the nearest facility (P) with modelled travel times to the actual facilities accessed (A) were analysed. Log-transformed data comparison graphs for medians, with box plots superimposed distributions were used.

Results
Modelled geographical access (P) is generally lower than self-reported access (R), but there is a geography to this relationship. In India and Pakistan, potential access (P) compared fairly with self-reported travel times (R) [P (H0: Mean difference = 0)] < .001, limits of agreement: [− 273.81; 56.40] and [− 264.10; 94.25] respectively. In Mozambique, mean differences between the two measures of access were significantly different from 0 [P (H0: Mean difference = 0) = 0.31, limits of agreement: [− 187.26; 199.96]].

Conclusion
Modelling access successfully predict potential vulnerability in populations. Differences between modelled (P) and self-reported travel times (R) are partially a result of women not seeking care at their closest facilities. Modelling access should not be viewed through a geographically static lens. Modelling assumptions are likely modified by spatio-temporal and/or socio-cultural settings. Geographical stratification of access reveals disproportionate variations in differences emphasizing the varied nature of assumptions across spatial settings.
Trial registration ClinicalTrials.gov, NCT01911494. Registered 30 July 2013, https://clinicaltrials.gov/ct2/show/NCT01911494
A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma
Authors: Ma Hailong , Chang Hanyue , Yang Wenyi , Lu Yusheng , Hu Jingzhou , Jin Shufang 
Published: February 2020

Abstract
Background
Interferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown.

Methods
Differentially expressed lncRNAs were screened under IFNα stimulation using lncRNA sequencing. The role and mechanism of lncRNA in immunosuppression were investigated in HNSCC in vitro and in vivo.

Results
We identified a novel IFNα-induced upregulated lncRNA, lncMX1–215, in HNSCC. LncMX1–215 was primarily located in the cell nucleus. Ectopic expression of lncMX1–215 markedly inhibited expression of the IFNα-induced, immunosuppression-related molecules programmed cell death 1 ligand 1 (PD-L1) and galectin-9, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. Binding sites for H3K27 acetylation were found on PD-L1 and galectin-9 promoters. Mechanistically, we found that lncMX1–215 directly interacted with GCN5, a known H3K27 acetylase, to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1–215 and PD-L1 and galectin-9 expression were observed. Finally, overexpression of lncMX1–215 suppressed HNSCC proliferation and metastasis capacity in vitro and in vivo.

Conclusions
Our results suggest that lncMX1–215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC, thus providing novel insights into immune checkpoint blockade treatment.
The enigma of soluble LDLR: could inflammation be the key?
Authors: Mbikay Majambu , Mayne Janice , Chrétien Michel 
Published: February 2020

AbstractSoluble low-density lipoprotein receptor (sLDLR) is the circulating ectodomain of transmembrane LDLR. Its blood level strongly correlates with that of triglycerides (TG). This correlation has eluded satisfactory explanation. Hypertriglyceridemia and shedding of the ectodomain of many transmembrane receptors often accompany inflammatory states. The shedding mostly occurs through cleavage by a disintegrin-and-metalloproteinase-17 (ADAM-17), an enzyme activated by inflammation. It reduces the cellular uptake of TG-loaded lipoproteins, causing their accumulation in circulation; hence the correlation between plasma sLDLR and TG. Soluble LDLR could become a new surrogate marker of inflammation.
Short-term outcomes of laparoscopic intersphincteric resection with intraoperative radiotherapy using low-energy X-rays for primary locally advanced low rectal cancer: a single center experience
Authors: Xue Wangsheng , Wang Shuang , Zhao Zeyun , Li Yongbo , Shang An , Li Donglin , Yang Jianzheng , Wang Tiejun , Wang Min 
Published: February 2020

Abstract
Background
Even with the augmentative application of anal-preservation surgery in low rectal cancer, the role and indications of laparoscopic intersphincteric resection (Lap ISR) are still under debate, especially for T3 or node-positive (T3N0M0, T1–3N+M0) cancer, mainly due to the oncological safety and functional outcomes. INTRABEAM (Carl Zeiss, Germany) intraoperative radiotherapy (IORT) using low-energy X-rays features in accurate irradiation, less exposure, and reduced complications. Taking advantages of Lap ISR and INTRABEAM IORT, this innovative approach aims to increase the probability of the anal preservation with acceptable postoperative outcomes.

Materials and methods
From December 2015 to August 2019, we retrospectively analyzed the short-term outcomes of 12 patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1–3N+M0) primary locally advanced low rectal cancer. They all had received Lap ISR and INTRABEAM IORT with a dose of 16–18 Gy applied by an applicator through the anus (natural orifice). Then, with no pre- or postoperative radiotherapy given, the patients were suggested to receive 6–8 cycles of the XELOX chemotherapy regimen (oxaliplatin, 130 mg/m2 and capecitabine, 1000 mg/m2).

Results
All patients achieved R0 resection. The median radiation time was 27 min and 15 s, and the mean radiative dose was 17.3 Gy (range 16–18 Gy). The median follow-up time was 18.5 months (range 3–45 months). Two patients experienced local recurrence. Two male patients experienced anastomotic stenosis. Furthermore, one of them experienced perianal abscess and the other one experienced pulmonary metastasis after refusing to receive chemotherapy. One female patient with internal anal sphincter invasion experienced distant metastases to the liver and gluteus maximus muscle 35 months after IORT. No acute radiation injuries or symptoms were observed. Although they experienced a reduction in anal function, every patient was satisfied with the postoperative outcomes.

Conclusions
For patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1–3N+M0) primary locally advanced low rectal cancer, Lap ISR with INTRABEAM IORT may be a safe and feasible approach for anal preservation without compromising oncological outcomes.
Anal function and quality of life analysis after laparoscopic modified Parks for ultra-low rectal cancer patients
Authors: Ding Haibo , Li Jian , Chen Yuxiang , Yang Zhi , Peng Zha , Liao Xin 
Published: February 2020

Abstract
Background
To assess postoperative anal function and quality of life of ultra-low rectal cancer patients treated by laparoscopic modified Parks surgery.

Methods
From February 2017 to March 2019, 114 patients with ultra-low rectal cancer above T2 were treated respectively with ultra-low anterior resection (Dixon), modified coloanal anastomosis (modified Parks), and Miles according to the preoperative stage and anastomotic position. The postoperative anal function and Fecal Incontinence Quality of Life Scale (FIQL) of each patient were collected and synthetically analyzed.

Results
Compared with the Dixon group, the postoperative anal function and FIQL in the Parks group were poor at the early stage. However, from 6 to 12 months after surgery, the scores of anal function and FIQL in the Parks group were similar to those in the Dixon group (P > 0.05). Compared with the Miles group, the FIQL of the two groups were similar in the early postoperative stage. However, with the passage of time, from 3 to 9 months after surgery, the four domains of FIQL in the Parks group were higher than those in the Miles group successively (P < 0.05).

Conclusions
Laparoscopic modified Parks is a safe, effective, and economical anus-preserving surgery. Although its early anal function and FIQL were poor, it could gradually recover to the similar level as Dixon. Moreover, it can save the anus and obtain a better postoperative quality of life for some patients who previously could only undergo Miles.
Prognosis of limited-stage small cell lung cancer with comprehensive treatment including radical resection
Authors: Zhong Lili , Suo Jiaojiao , Wang Ya , Han Jialong , Zhou Huijie , Wei Hao , Zhu Jiang 
Published: February 2020

Abstract
Background
The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC.

Methods
We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference.

Results
The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group.

Conclusions
For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy.
Ranking of Iranian provinces based on healthcare infrastructures: before and after implementation of Health Transformation Plan
Authors: Shojaei Payam , bordbar Najmeh , Ghanbarzadegan Arash , Najibi Maryam , Bastani Peivand 
Published: February 2020

AbstractBackgroundHealth Transformation Plan (HTP) was occurred in 2014 to improve access and equity and reduce out of pocket payments in Iranian Health Care System. In this regard the aim of this study is evaluating and ranking the service provider’s infrastructures among the country provinces as an indicator of equity before and after implementation of the HTP.MethodsThis cross sectional study is conducted in 2017. The study population included 31 provinces of the country. Data related to 4 years from 2012 to 2016 were included from the data bases of Ministry of Health and Medical Education as well as the statistics yearbook of the country. The obtained results of multi-criteria decision-making methods were analyzed as well. SPSS18and Excel2013software were used for data analysis.ResultsBased on the VIKOR method, in 2012, Mazandaran, Tehran and Fars provinces and in 2013, the provinces of Tehran, Fars and Isfahan ranked from first to third respectively. Similarly after HTP, in 2015, the provinces of Tehran, Khorasan Razavi and Fars and in 2016 the provinces of Tehran, Fars and Khorasan Razavi have ranked from first to third respectively. Paramedic, dentist, pharmacist, medical institutions and hospital bed had a significant difference before and after the implementation of Health Transformation Plan, so that the number of these indicators increased after implementation of the HTP (Pvalue < 0.05).ConclusionsAccording to the results, there are many differences between the provinces and these disparities have not decreased significantly after HTP. Consequently, it is suggested to the health sector policy makers to make regional plans and allocate the budget of HTP, based on the status of the provinces. In addition, responding to these inequalities requires a transparent and systematic approach to provide the budget for allocating to the population, health needs, and the lack of development and geographical isolation of regions.
Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer
Authors: Wu Hua-Tao , Zhong Hui-Ting , Li Guan-Wu , Shen Jia-Xin , Ye Qian-Qian , Zhang Man-Li , Liu Jing 
Published: February 2020

AbstractZinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-β, β-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.
The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique
Authors: Bortolotto Chandra , Maglia Claudio , Ciuffreda Antonio , Coretti Manuela , Catania Roberta , Antonacci Filippo , Carnevale Sergio , Sarotto Ivana , Dore Roberto , Filippi Andrea Riccardo , Chiara Gabriele , Regge Daniele , Preda Lorenzo , Morbini Patrizia , Stella Giulia Maria 
Published: February 2020

Abstract
Background
Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN).

Methods
We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case.

Results
In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases,  > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case.

Conclusions
Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.
Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations
Authors: Dimitrijevic Carlsson Alexandra , Wahlund Kerstin , Kindgren Erik , Skogh Thomas , Starkhammar Johansson Carin , Alstergren Per 
Published: February 2020

Abstract
Background
The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA).

Methods
Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain–related disability, depression, stress, catastrophizing, pain locations and jaw function).

Results
JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity.

Conclusions
Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.
RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway
Authors: Hou Kun , Li Guichen , Zhao Jinchuan , Xu Baofeng , Zhang Yang , Yu Jinlu , Xu Kan 
Published: February 2020

AbstractBackgroundMesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats.MethodsWe established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays.ResultsThe dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis.ConclusionBMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.