bluuebunny/crossref_metadata_2025 huggingface dataset:
Graft failure of IgA nephropathy in renal allografts following living donor transplantation: predictive factor analysis of 102 biopsies
Authors: Zhang Jin , Chen Guo-dong , Qiu Jiang , Liu Guo-chang , Chen Li-zhong , Fu Kai , Wu Zi-xuan
Published: November 2019

Background To investigate predictive factors related to graft failure of IgA nephropathy(IgAN) in renal allografts following living donor transplantation. Methods We identified a series of 102 biopsies diagnosed as IgAN in renal allografts following living donor transplantation from July 2004 to January 2017 at our center, and assess the predict value of the Lee's classification and the 2009 Oxford classification in IgAN in renal allografts, clinical, ultrasonic and pathological characteristics at biopsy and the outcomes were retrospectively analyzed. Results The 5-year graft cumulative survival rate after transplantation was 91.4%. The 4-year graft cumulative survival rate after biopsy diagnosis of IgAN in renal allografts was 59.6%. The mean time ± SD to disease was 4.7 ± 3.5 years. The color doppler ultrasound and blood flow imagine showed the echo enhancement, the reduced blood flow distribution, the reduced peak systolic velocity of main renal artery, and the increased resistance index of arcuate renal artery were valuable in evaluating the graft dysfunction. The Cox multivariate analysis revealed that the 24-h urinary protein level (HR 1.6 for 1-g increase, 95%CI 1.2-2.0), estimated glomerular filtration rate (eGFR) (HR 1.0 for 1-mL/min/1.73m^2 decline, 95%CI 1.0-1.1), and mesangial C1q deposition (HR 3.0, 95%CI 1.2-7.4) at biopsy were independent predictive factors of graft failure of IgAN in renal allografts. Conclusions IgAN in renal allografts occurred frequently within 5 years after transplantation. The risk of graft failure should be taken seriously in patients who exhibit heavy proteinuria and/or a declined eGFR as the initial symptoms; a high lesion grade (grade IV-V of Lee’s classification) and/or mesangial C1q deposition may also indicated a poor outcome.
Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma
Authors: Chen Wenli , Cheng Xing , Wang Xiaobo , Hu Wenjie , Wang Jinshan , Liao Chuangxin
Published: November 2019

Background: Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. Methods: In this study, we examined CAV-1 expression levels and vasculogenic mimicry in human glioma cell lines and in 94 human gliomas with different grades and presented cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, Western blotting, CCK-8 assays, tubule formation assays. Results: Cav-1 expression and VM formation were positively correlated with each other and both are closely associated with glioma development and progression as evidenced by the presence of cystic tumor, the shortened survival time and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Conclusion: Collectively, our study identifies Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.
Cerebrovascular events in hemodialysis patients; a retrospective observational study
Authors: Ozelsancak Ruya , Micozkadioglu Hasan , Torun Dilek , Tekkarismaz Nihan
Published: November 2019

Background: This study reports findings in subjects who underwent brain imaging for any reason, and examined factors influencing cerebrovascular events (CVEs) in hemodialysis (HD) patients.
Methods: We reviewed the files of patients on HD between January 2015 and January 2018. A total of 432 patients who underwent HD for at least 5 months by the January 2015 and who were older than 18 years were included in the study; 264 had been examined by cerebral computed tomography or magnetic resonance imaging examination within the 3 years. Cerebrovascular pathology was detected in 139 of 264 patients.
Results: Of the 139 patients, 65 (24.62 %) had ischemic lesions, 25 (9.47%) had hemorrhagic lesions, and 49 (18.56%) had cerebral small vessel disease (CSVD). We compared recorded data and later clinical findings between patients with and those without CVEs. The cause of end-stage renal disease was diabetes in 58.5% of patients with ischemic lesions, 52% in those with hemorrhagic lesions, and 55% in those with CSVD (P < 0.05). Patients with cerebrovascular ischemia were older (P = 0.0001) and had lower serum creatinine (sCr) (P = 0.0001) and higher serum C-reactive protein (CRP) (P = 0.002) levels than normal subjects. Hemorrhagic patients were older (P = 0.003) and had lower sCr (P = 0.003) and serum predialysis potassium (P = 0.003) and parathyroid hormone (PTH) (P = 0.004) levels than normal subjects. Patients with CSVD were older (P < 0.0001) and had lower sCr (P < 0.0001), phosphorus (P < 0.007), and PTH (P < 0.013) and higher CRP (P < 0.002) levels than normal subjects.
Conclusions: HD patients with CVEs are older and typically have diabetes mellitus and lower sCr levels.
Differential Diagnosis of Pancreatic Serous Cystadenomas and Mucinous Cystadenomas: Utility of Textural Features in Combination with Morphological Characteristics
Authors: Yang Jing , Guo Xinli , Zhang Hao , Zhang Weiwei , Song Jinen , Xu Hui , Ma Xuelei
Published: November 2019

Background Texture analysis of medical images has been reported to be a reliable method for differential diagnosis of neoplasms. This study was to investigate the performance of textural features and the combined performance of textural features and morphological characteristics in the differential diagnosis of pancreatic serous and mucinous cystadenomas. Methods. We retrospectively reviewed 59 patients with pancreatic serous cystadenoma and 32 patients with pancreatic mucinous cystadenoma at our hospital. A three-dimensional region of interest (ROI) around the margin of the lesion was drawn manually in the CT images of each patient, and textural parameters were retrieved from the ROI. Textural features were extracted using the LifeX software. The least absolute shrinkage and selection operator (LASSO) method was applied to select the textural features. The differential diagnostic capabilities of morphological features, textural features, and their combination were evaluated using receiver operating characteristic (ROC) analysis, and the area under the receiver operating characteristic curve (AUC) was used as the main indicator. Diagnostic accuracy based on the AUC values is defined as follows: 0.9–1.0, excellent; 0.8–0.9, good; 0.7–0.8, moderate; 0.6–0.7, fair; 0.5–0.6, poor. Results. In the differential diagnosis of pancreatic serous and mucinous cystadenomas, the combination of morphological characteristics and textural features (AUC 0.893, 95% CI 0.816-0.970) is better than morphological characteristics (AUC 0.783, 95% CI 0.665-0.900) or textural features (AUC 0.777, 95% CI 0.673-0.880) alone. Conclusions. In conclusion, our preliminary results highlighted the potential of CT texture analysis in discriminating pancreatic serous cystadenoma from mucinous cystadenoma. Furthermore, the combination of morphological characteristics and textural features can significantly improve the diagnostic performance, which may provide a reliable method to select patients with indication for surgical intervention in consideration of the different treatment principles of the two diseases.
Recovery of Paired T Cell Receptors from Single-cell Seq-Well Libraries
Authors: Tu Ang A. , Gierahn Todd M. , Monian Brinda , Morgan Duncan M. , Mehta Naveen K. , Ruiter Bert , Shreffler Wayne G. , Shalek Alex K. , Love J. Christopher
Published: November 2019

High-throughput 3’ single-cell RNA-Sequencing (scRNA-Seq) allows for cost-effective, detailed characterization of thousands of individual immune cells from healthy and diseased tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including the variable sequences of T cell receptors (TCRs) that confer antigen specificity in T cells. Here, we present an enrichment strategy that enables simultaneous analysis of TCR variable sequences and corresponding full transcriptomes from 3’ barcoded scRNA-Seq samples. This approach is compatible with common 3’ scRNA-Seq methods, and adaptable to processed samples post hoc. We applied the technique to resolve clonotype-to-phenotype relationships among antigen-activated T cells from immunized mice and from patients with food allergy. We observed diverse but preferential cellular phenotypes manifest among subsets of expanded clonotypes, including functional Th2 states associated with food allergy. These results demonstrate the utility of our method when studying complex diseases in which clonotype-driven immune responses are critical to understanding the underlying biology.
Short-term Results Of Sclerotherapy With 3% Polidocanol Foam For Symptomatic Second- And Third-degree Haemorrhoidal Disease
Authors: Lobascio Pierluigi , Laforgia Rita , Novelli Eugenio Novelli , Perrone Fabrizio , Salvo Maria Di , Pezzolla Angela , Trompetto Mario , Gallo Gaetano
Published: November 2019

Background . Haemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most common proctological diseases. Sclerotherapy (ST) with 3% polidocanol foam induces an inflammatory reaction with sclerosis of the submucosal tissue and consequent suspension of the haemorrhoidal tissue. The aim of this study was to evaluate the short-term effectiveness and safety of ST with 3% polidocanol foam for the treatment of symptomatic second- and third-degree HD. Methods . A total of 66 patients with symptomatic second- and third-degree HD underwent a single ST session between March 2017 and July 2018. A visual analogue scale score was used to assess post-operative pain and patient satisfaction. The symptoms severity and anal continence were investigated through the Hemorrhoid Severity Score (HSS) and Vaizey score, respectively, at baseline, at 4 weeks and after 1 year. Results . Fifty-seven out of 66 patients were male (86.3%), and the mean age was 52 (29-75; SD ± 12) years. The mean operative time was 4.5 (2-6; SD ± 1.23) minutes. No intraoperative complications and no drug-related side effects occurred. The overall success rate was 78.8% (52/66 patients) after a single ST session and 86% after two ST sessions (57/66 patients). The mean treatment effect, obtained comparing preoperative and T5 symptom scores in each patient, showed a mean change of 7.88 (p<0.001). All patients resumed their normal daily activities the day after the procedures. Conclusions . ST with 3% polidocanol foam is a safe, cost-effective and repeatable conservative treatment.
Risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease
Authors: Yu Xindi , Chen Maolin , Liu Xu , Chen Yiwei , Hao Zedong , Zhang Haibo , Wang Wei
Published: November 2019

Background: The aim of our study was to analyze the risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease (CHD). Methods: We performed a retrospective cohort study, and children with CHD who underwent open-heart surgeries at Shanghai Children’s Medical Center from January 1, 2012 to December 31, 2018 were included. The baseline characteristics of these patients of different ages, including neonates (0-1 months old), infants (1-12 months old) and children (1-10 years old), were analyzed, and the association of risk factors with postoperative nosocomial infection were assessed. Results: A total of 11651 subjects were included in the study. The overall nosocomial infection rate was 10.8%. Nosocomial infection rates in neonates, infants, and children with congenital heart disease were 32.9%, 15.4%, and 5.2%, respectively. Multivariate logistic regression analysis found age (OR 0798, 95%CI: 0.769-0.829; P<0.001), STS risk grade (OR 1.267, 95%CI: 1.159-1.385; P<0.001), body mass index (BMI) <5th percentile (OR 1.295, 95%CI: 1.023-1.639; P=0.032), BMI ＞95th percentile (OR 0.792, 95%CI: 0.647-0.969; P=0.023), cardiopulmonary bypass (CPB) time (OR 1.008, 95%CI: 1.003-1.012; P<0.001) and aortic clamping time （OR 1.009, 1.002-1.015; P = 0.008）were significantly associated with nosocomial infection in CHD infants. After adjusted for confounding factors, we found STS risk grade (OR 1.38, 95%CI: 1.167-1.633; P<0.001), BMI<5th percentile (OR 1.934, 95%CI: 1.377-2.715; P<0.001), CPB time (OR 1.018, 95%CI: 1.015-1.022; P<0.001), lymphocyte/WBC ratio﹤cut off value (OR 3.818, 95%CI: 1.529-9.533; P=0.004) and AST＞cut off value (OR 1.546, 95%CI: 1.119-2.136; P=0.008) were significantly associated with nosocomial infection in CHD children. Conclusion: Our study suggested STS risk grade, BMI, CPB duration, low lymphocyte/WBC or high neutrophil/WBC ratio were independently associated with nosocomial infection in CHD infant and children after cardiac surgery.
The geography of evolutionary divergence in the highly endemic avifauna from the Sierra Madre del Sur, Mexico
Authors: Rocha-Méndez Alberto , SÁNCHEZ-GONZÁLEZ LUIS A. , GONZÁLEZ CLEMENTINA , NAVARRO-SIGÜENZA ADOLFO G.
Published: November 2019

Background Mesoamerica is a remarkable region with a high geological and ecological complexity. Within northern Mesoamerica, the biotic province of the Sierra Madre del Sur (SMS) in southwestern Mexico harbors exceptionally high avian endemism and diversity. Herein, we searched for spatially and temporally concordant phylogeographic patterns, in four bird genera from three distinct avian orders co-distributed across Mesoamerica and investigated their causes through hypothesis testing regarding historical processes. Selected species include endemic and differentiated populations across the montane forests of Mesoamerica, and particularly within the SMS. Results We gathered mitochondrial DNA sequences for at least one locus from 177 individuals across all species. We assessed genetic structure, demographic history, and defined a framework for the coalescent simulations used in biogeographic hypothesis testing temporal and spatial co-variance. Our analyses suggested shared phylogeographic breaks in areas corresponding to the SMS populations, and between the main montane systems in Mesoamerica, with the Central Valley of Oaxaca and the Nicaragua Depression being the most frequently shared breaks among analyzed taxa. Nevertheless, dating analyses and divergence patterns observed were consistent with the hypothesis of broad vicariance across Mesoamerica derived from mechanisms operating at distinct times across taxa in the SMS. Conclusions Our study provides a framework for understanding the evolutionary origins and historical factors enhancing speciation in well-defined regions within Mesoamerica, indicating that the evolutionary history of extant biota inhabiting montane forests is complex and often idiosyncratic.
Predictive factors for the presence of invasive components in patients diagnosed with ductal carcinoma in situ based on preoperative biopsy
Authors: Lee Kwan Ho , Han Jeong Woo , Kim Eun Young , Yun Ji Sup , Park Yong Lai , Park Chan Heun
Published: November 2019

Background In patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively.Methods Patients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens.Results Of the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR=0.26, C.I.=0.07-0.93, p=0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR=2.39, C.I.=1.05-5.42, p=0.038 in univariate analysis, HR=2.86, C.I.=1.14-7.14, p=0.025 in multivariate analysis).Conclusions Mass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.
Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT
Authors: Zhang Zhimin , Wang Ge , Jin Feng , Zheng Jijun , Xiao He , Lei Lin , Luo Jia , chen chuan
Published: November 2019

Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT.
Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG) , who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. We used the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively.

Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 9 down-regulated miRNAs, 1 up-regulated and 6 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After significantly down-regulated miRNAs from EG versus CG were removed, only 9 different miRNAs were significantly reduced. In the serum samples of 48 NPC patients, there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT. We calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=004）.
Conclusions: For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs such as miRNA-29a, miRNA-125b and miRNA-26b etc, play an important role in predicting prognosis factors for PFS and OS, which will contribute to the strategic direction of future research.
Regulatory Roles of Differentially Expressed MicroRNAs in Metabolic Processes in Negative Lens-Induced Myopia Guinea Pigs
Authors: Guo Dadong , Ding Meihua , Song Xiaoli , Sun Yuanyuan , Li Guoping , Li Zonghong , Wei Huixia , Wu Jianfeng , Jiang Wenjun , Bi Hongsheng
Published: November 2019

Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expressions, influencing the development of diseases. In order to investigate the alterations of microRNAs profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expressions of differentially expressed microRNAs. We successfully established a negative NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. In summary, we found the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.
Prevalence of and Characteristics Associated with In-Hospital Mortality in a Ugandan Neurology Ward
Authors: Diaz Monica Maria , Hu Xin , Fenton Brenda T , Kimuli Ivan , Lee Allison , Lindsey Hayley , Bigelow Jeffrey K , Maiser Samuel , Altalib Hamada H. , Sico Jason J
Published: November 2019

Background ― While the burden of neurologic illness in developing countries is increasing, less is known about mortality among patients admitted to sub-Saharan African hospitals with neurologic disease. We sought to characterize the rate and patient-level predictors of in-hospital mortality in a Ugandan Neurology ward.
Methods ― Data was prospectively collected on 335 patients admitted to the Neurology ward of Mulago Hospital, Kampala, Uganda. Kaplan-Meier survival curves and multivariate COX proportional hazard modeling were used to assess survival.
Results ―Within our sample (n=307), 35.8% received no diagnosis at time of hospital admission. Stroke (27.3%), head trauma (19.6%), and malaria (16.0%) were the most common diagnoses. Among the 56 (18.5%) patients who died during the index hospitalization, the most common diagnosis at admission and at death was stroke. Adjusted regression analysis showed that patients without a diagnosis at time of death (HR=7.01 [2.42-20.35], p<.001) and those with diagnoses of infections (HR=5.21 [2.16-12.58], p=<.001), stroke (HR=2.69 [1.20-6.04], p=.017), or head trauma (HR=3.39, [1.27-9.07], p=0.15) had worse survival.
Conclusions ― In-hospital mortality affected nearly 20% of the cohort, with worse survival among those without a diagnosis and with infections, stroke, head trauma. Future work should identify reasons for increased mortality among these high-risk groups and implement targeted interventions.
MicroRNA-183-5p acts as a potential diagnostic biomarker for atherosclerosis and regulates the growth of vascular smooth muscle cell
Authors: Sun Bin , Shan Zhengkun , Sun Guoyu , Wang Xiaolong
Published: November 2019

Background Atherosclerosis (AS) is a multifactorial chronic disease, and vascular smooth muscle cells (VSMCs) plays an important role in the pathology of AS. MicroRNAs regulate multiple cellular biological processes. This study aimed to investigate the clinical value of miR-183-5p in AS patients, and further explored the effects of miR-183-5p on the proliferation and migration of VSMCs. Methods qRT-PCR was used to test the level of miR-183-5p. The diagnostic value of miR-183-5p for AS patients was assessed by a receiver operating characteristic (ROC) analysis. Cell proliferation and migration were determined via CCK-8 and Transwell assay. Results MiR-183-5p was highly expressed in AS patients compared with the healthy group. Serum miR-183-5p expression was positively associated with CIMT and CRP in AS patients. The ROC analysis suggested that miR-183-5p had quality to be used as a biomarker with high specificity and sensitivity for AS detection. Overexpression of miR-183-5p promoted the proliferation and migration of VSMCs. Downregulation of miR-183-5p attenuated ox-LDL stimulated VSMCs proliferation and migration. Conclusion MiR-183-5p is highly expressed in AS patients, and downregulation of miR-183-5p attenuated ox-LDL stimulated VSMCs proliferation and migration. MiR-183-5p may be a key molecular for the diagnosis and treatment of AS in the future.
Cost-effectiveness of insulin degludec versus insulin glargine U100 in adults with type 1 and type 2 diabetes mellitus in Bulgaria
Authors: Russel-Szymczyk Monika , Valov Vasil , Savova Alexandra , Manova Manoela
Published: November 2019

Background This study investigates the cost-effectiveness of insulin degludec (degludec) versus biosimilar insulin glargine U100 (glargine U100) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in Bulgaria.Methods A simple, short-term model was used to compare the treatment costs and outcomes associated with hypoglycaemic events with degludec versus glargine U100 in patients with T1DM and T2DM from the perspective of the Bulgarian National Health Insurance Fund. Cost-effectiveness was analysed over a 1-year time horizon using data from clinical trials. The outcome measure was the incremental cost-effectiveness ratio (ICER).Results Degludec was highly cost-effective versus glargine U100 in people with T1DM and T2DM in Bulgaria. The ICERs were estimated to be 4,493.68 BGN/quality-adjusted life year (QALY) in T1DM, 399.11 BGN/QALY in T2DM on basal oral therapy (T2DM BOT ) and 7,365.22 BGN/QALY in T2DM on basal bolus therapy (T2DM B/B ), which all fall below the cost-effectiveness threshold of 39,619 BGN in Bulgaria. Insulin costs were higher with degludec in all three patient groups, however these were partially offset by savings from a reduction in hypoglycaemic events with degludec versus glargine U100. Sensitivity analysis demonstrated that the results were robust and largely insensitive to variations in input parameters. At a willingness-to-pay threshold of 39,619 BGN/QALY, the probability of degludec being cost-effective versus glargine U100 was 60.0% in T1DM, 99.4% in T2DM BOT and 91.3% in T2DM B/B .Conclusion Degludec is a cost-effective alternative to biosimilar glargine U100 for patients with T1DM and T2DM in Bulgaria. Degludec could be of particular benefit to those patients suffering recurrent hypoglycaemia and those who require additional flexibility in the dosing of insulin.
Elevated levels of serum urokinase plasminogen activator predict poor prognosis in hepatocellular carcinoma after resection
Authors: Tsai Ming-Chao , Yen Yi-Hao , Chang Kuo-Chin , Hung Chao-Hung , Chen Chien-Hung , Lin Ming-Tsung , Hu Tsung-Hui
Published: November 2019

Background Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease that is involved in the invasiveness and progression of cancer. There is good evidence that uPA expression is a clinically relevant biomarker in some solid tumors, but its role in hepatocellulcar carcinoma (HCC) is uncertain. We evaluated the prognostic value of serum uPA before surgery in HCC patients receiving curative resection.Methods Serum uPA levels were determined by enzyme-linked immunosorbent assay in 282 HCC patients who received complete liver resections at Kaohsiung Chang Gung Memorial Hospital. Overall survival (OS) curves were constructed using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional -hazards regression model was used to identify independent prognostic factors. The median follow-up time was 52 months.Results Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS ( p = 0.002). Patients with liver cirrhosis, hypoalbuminemia, and thrombocytopenia were significantly more likely to present with elevated uPA levels. Multivariate Cox regression analyses indicated that high pretreatment serum uPA [hazard ratio (HR), 1.848, p = 0.006], vascular invasion (HR, 2.940, p <0.001), and pathology stage III/IV (HR, 3.517, p <0.001) were independent prognostic factors for OS. In further stratified analyses, the combination of serum uPA and AFP had more capacity to predict OS.Conclusions We conclude that uPA is a clinically relevant biomarker in HCC patients receiving curative resection, with higher expression of uPA being associated with higher mortality. This also highlights the potential utility of uPA as a therapeutic target for improved treatment strategies.
IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival
Authors: Nawas Afshan F. , Kanchwala Mohammed , Thomas-Jardin Shayna E. , Dahl Haley , Daescu Kelly , Bautista Monica , Anunobi Vanessa , Wong Ally , Meade Rachel Katherine , Mistry Ragini , Ghatwai Nisha , Bayerl Felix , Xing Chao , Delk Nikki
Published: November 2019

Background Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.Methods We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set.Results We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9 ) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired hormone receptor independence and treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.
Acute suppurative thyroiditis with thyroid abscess in adults: clinical presentation, treatment and outcomes
Authors: Falhammar Henrik , Wallin Göran , Calissendorff Jan
Published: November 2019

Background: Abscess in the thyroid gland is a rare but severe infectious disease. The condition can have anatomic or iatrogenic underlying causes. If untreated it could be fatal. Pathogens vary considerably. Treatment is intravenous antibiotics, drainage, and sometimes surgery. Methods: The electronic medical records of all adult patients with acute thyroiditis 2003–2017 treated at the Karolinska University Hospital (catchment area 2 million) in Sweden were systematically reviewed. Results: Five patients were found in the catchment area. One patient from another region but known to us was also included. Thus, six patients (aged 28-73 years) were included in the study. Median length of hospital stay was 7.5 days (4-79 days). All were treated with antibiotics (intravenous n=5, oral n=1). Total antibiotic treatment duration was 13.5 days (10-41 days). Blood cultures were positive in three (streptococcus pneumonia, streptococci sanguineous, pepto streptococci), deep tissue culture in three (escherichia coli, candida, hemophilic influenza) and no positive culture at all in two. Drainage was used in three patients. All patients recovered without recurrences. Surgery was performed twice in the acute phase in one. There was no recurrence during 7 years (3-12) of follow-up, but one patient died after three years (severe heart failure and pneumonia). Conclusion: Thyroid abscess in adults is extremely rare nowadays in the developed world. With prompt antibiotic therapy, drainage and in some cases thyroidectomy the prognosis seems favourable.
Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients
Authors: Kishimoto Takumi , Fujimoto Nobukazu , Ebara Takeshi , Omori Toyonori , Oguri Tetsuya , Niimi Akio , Yokoyama Takako , Kato Munehiro , Usami Ikuji , Nishio Masayuki , Yoshikawa Kosho , Tokuyama Takeshi , Tamura Mouka , Yokoyama Yoshifumi , Tsuboi Ken , Matsuo Yoichi , Xu Jiegou , Takahashi Satoru , Abdelgied Mohamed , Alexander William T. , Alexander David B , Tsuda Hiroyuki
Published: November 2019

Background: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. Methods: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. Results: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM patients. Conclusions: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.
Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction
Authors: Huang Xiaocong , Chen Lei , Cai Yujing , Wei Jinfeng , Lin Lina , Sun Jie , Peng Xuemei , Wang Sheng
Published: November 2019

Purpose This study was designed to examine whether severe aortic regurgitation (AR) will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction.Methods A total of 32 patients were divided into two groups: the AR group (n=16) and the control group (n=16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 minutes after intravenous injection of 0.15mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography.Results The time to maximal neuromuscular block was prolonged from 2.07(0.08) minutes to 4.03(0.14) minutes, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P<0.01) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K 12 = 0.19(0.02) and K 21 = 0.11(0.01) in the AR group vs. K 12= 0.26(0.01) and K 21 = 0.19(0.01) in the control group, P<0.01) compared to the control group.Conclusion Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings from this study may provide useful guidance for safe administration of cisatracurium and reasonable prediction of PD responses during anaesthetic induction among patients with severe AR.
Serum Amyloid A Protein as a Potential Biomarker in predicting acute onset and association with in-hospital death in acute aortic dissection
Authors: He Yuchen , Ma Changcheng , Xing Jia , Wang Shiyue , Chao Ji , Han Yanshuo , Zhang Jian
Published: November 2019

Background: Acute aortic dissection (AAD) is a life-threatening disorder in vascular surgery with a high early mortality. Serum amyloid A (SAA) is a kind of acute-phase protein with a rapid diagnostic value in other diseases. However, the researches on the performance of SAA for the diagnosis of AAD is still lacking. This retrospective study aimed to evaluate the SAA levels and further explore its potential diagnostic role in AAD patients.
Methods: SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) in 63 controls and 87 AAD patients. Laboratory examinations were also performed. And relative clinical information was collected from participants included in this study.
Results: SAA levels were significantly higher in AAD patients than those in healthy controls. SAA levels were independently associated with the risk of AAD. There was a positive significant correlation between SAA and C reactive protein (R=0.442, and P=0.001). Based on receiver-operating characteristic (ROC) analysis, the area under the curve (AUC) of SAA for the diagnosis of AAD were 0.942 with optimal cut-off points of 0.427mg/L. For in-hospital mortality, the AUC of SAA were 0.732 with optimal cut-off points of 0.500mg/L. According to logistic regression analysis, higher SAA levels represent a higher risk of in-hospital mortality (OR=1.25; 95%CI: 1.07-1.47; P=0.005).
Conclusion: Our findings demonstrated that SAA levels were significantly enhanced in AAD. SAA was closely correlated with inflammatory parameters and coagulation-related parameters in AAD. Furthermore, SAA could be a potential bio-marker for identifying AAD in the early diagnosis. Finally, SAA >5.0 mg/L are independently related to AAD in-hospital mortality.
Assessment of Educational Needs and Design of a Preceptor Development Program for Health Professional Education Programs in Qatar – ‘The Practice Educators’ Academy’
Authors: Mukhalalati Banan , Awaisu A , Elshami S , Paravattil B , Zolezzi M , Abu-Hijleh M , Moslih-Almoslih A , Carr A , Bawadi H , Romanowski M , Almahasneh R , Bacha R
Published: November 2019

Background: Experiential learning is the backbone of many healthcare professional education programs; however, the quality of learning is profoundly dependent on the skills, experiences, and proficiency of the clinical preceptors who largely contribute to this experience. This study was conducted at the Qatar University Health Cluster, which comprises of the Colleges of Pharmacy, Medicine, and Health Sciences, with a primary objective of identifying the educational and teaching needs of preceptors in order to design and validate an educational professional development program. Methods: This study adopted a mixed methods approach and was conducted in three stages: 1) assessment of preceptor educational needs; 2) design of ‘The Practice Educators’ Academy’ program; 3) validation and refinement of the designed program. The needs’ assessment was conducted at all three colleges through a validated survey and focus groups with preceptors, students, and clinical faculty members. The sample included 209 survey respondents and 11 focus group sessions.Results: Results yielded five key themes and a variety of individual preferences, which were used to design a five-module face-to-face two-day interactive workshop. For validation of the designed program, the syllabus was shared with purposively selected scholars and experts in the area of health professions education, and their feedback was collected and critically examined. Further refinement of the program was performed based on this feedback resulting in a representative and validated program ready for piloting. Conclusion: A preceptor development program on experiential teaching and learning skills was successfully designed and validated, with the needs of the clinical preceptors at its core.
Needs assessment for a curriculum for difficult conversations in a neurology residency training program in China
Authors: Zhou Lixin , Wu Bo , Wu Liyong , Cheng Xin , Hu Bo , Yao Ming , Zhu Yicheng , Peng Bin , Cui Liying , Ni Jun
Published: November 2019

Background Communication skill is a core competency in neurology residency training. Specific training in this area at the residency level is often lacking, especially regarding difficult conversations. The aim of this study is to evaluate the current state in which neurology programs in China teach residents about difficult conversations and determine whether there is a perceived need for a formalized educational curriculum in this field.Method An anonymous, 27-question, cross-sectional online survey addressing difficult conversations for neurological residents were distributed to five grade-A, class-3 hospitals selected from the affiliated teaching hospitals of medical schools qualified to provide neurology residency training in China.Results A total of 182 residents responded to the survey, and the response rate was 67.16% (182/271). Of the participants, 84.6% were female and the average age was 26.8 years. The majority of respondent residents (n=168; 92.31%) reported being exposed to at least one difficult conversation in their medical careers. Only 43 (23.63%) participants reported having previously received formal communication skills training. In comparison with residents without previous training, those with previous training indicated significantly more confidence(P=0.003)and were under lower pressure(P=0.037) in managing difficult conversations. Only 97 (53.3%) residents indicated interest in receiving formal training. Time, lack of enthusiasm, lack of educational materials and faculty expertise were commonly cited barriers to formalized training.Conclusion This survey provides a contemporary assessment of the current status of education on the topic of difficult conversations in neurology residency training. Our results suggest that there is an unmet need to further develop and implement educational activities by teaching residents to lead difficult conversations. Targeted communication curriculum in difficult conversation should be further developed and implemented for the neurological residents in China.
Experience of Nurse Educators on the Implementation of the Competency-Based Curriculum for Nursing and Midwifery Programmes in Tanzania: A mixed method study.
Authors: Mmari Vumilia Bettuel , Lilian Mselle Teddy , Stephen Kibusi Mathew , Osaki Kalafunja Mlang'a
Published: November 2019

Background: In Tanzania, the competency based curriculum was introduced in 2008. Despite the government efforts to ensure its effective implementation, there has been a public concern on graduate nurse's and midwives' competencies in providing quality nursing care in the country. This concern has influenced people to question the process of the implementation of competency based curriculum for nursing and midwifery programmes. This study describes experience of the nurse educators in implementing the competency based curriculum for nursing and midwifery programmes in Tanzania.Methods: Convergent parallel mixed method approach was used to explore the experience of nurse educators implementing competency based curriculum. To enhance the validity of the findings, 240 nurse educators, out of 264, answered a questionnaire while the remaining 24 were interviewed. Further, a retrospective observation was done to triangulate the information obtained from the questionnaire and interviews. Results: The study found out that nurse educators struggle implementing the competency based curriculum and 92% of the participants could not clearly explain the concept of the approach itself. 234 of them used lecture discussion (97%) while simulation was used by 128 (53%). Challenges associated with employing participatory teaching and learning methods reported by most participants included time constraints (61; 25%), some method require special skills to teach(33; 13% and tutors needed training on the competency based curriculum to implement it (13; 5%).Conclusion: The results conclude that an understanding of the competency based curriculum is limited among educators. Furthermore, they revealed challenges in employing the participatory teaching and learning methods, hence, underscoring the need to put in place a sustainable strategy for continuous personal development and mentorship. Keywords: Competency based curriculum, implementation fidelity, nurse educators' experience, nursing and midwifery training programmes.
Evidence of high bednet usage from a list randomization experiment in rural Gambia
Authors: Brew Joe , Pinder Margaret , Dalessandro Umberto , Lindsay Steven W , Jones Carloine , Sicuri Elisa
Published: November 2019

Background Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly and where there is potential for social desirability bias, i.e. where the respondent may give an answer that they think the recorder wants to hear. Sleeping under a long-lasting insecticidal net (LLIN) is an important intervention for malaria prevention, yet it is difficult to gauge the extent to which coverage (how many nets are in the community) differs from usage (how many people sleep under a net). We employed a novel method, list randomization, which partially obscures respondents' answers to sensitive questions, as a mean to provide an accurate estimate of LLIN usage in The Gambia.Methods We surveyed 196 residents from 196 households recruited into a randomised controlled trial assessing the effect of a housing intervention on malaria. In the current experiment, 98 of the 196 study participants were randomly assigned to the control group and received a four-question list about non-sensitive behaviours; the other participants in the intervention group, received the same list, with the addition of one question on a sensitive behaviour; whether or not they had used a bednet the previous night. Participants were read the list of questions and then said how many of the statements were true. We estimated bednet usage by calculating the difference in means between the total number of affirmative items between the two groups, and quantified uncertainty using a t-test.Results The mean number of affirmative responses in the control group was 2.60 of four statements (95% confidence interval, 95% CI, = 2.50-2.70), compared with 3.68 (95% CI = 3.59-3.78) in the intervention group. Such difference (1.08; 95% CI = 94.9-100%) suggests approximately 100% bednet usage.Conclusions Our findings suggest complete universal bednet usage in the study area. Further validation of the list randomization method in areas with lower net coverage is required.