bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative evaluation of the effect of different growth media on in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients&nbsp;
Authors: Sörensen Michael , Khakimov Bakhodur , Nurjadi Dennis , Boutin Sébastien , Yi Buqing , Dalpke Alexander H. , Eigenbrod Tatjana 
Published: November 2020

Abstract
Long-term treatment with azithromycin is a therapeutic option in Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa. It was recently shown that azithromycin has direct antimicrobial activity when P. aeruginosa isolates are tested in Roswell Park Memorial Institute medium supplemented with fetal calf serum (RPMI 1640/FCS) by broth microdilution. We now investigated whether (i) azithromycin might also be active against multidrug resistant (MDR) P. aeruginosa isolated from CF patients and (ii) how in vitro sensitivity assays perform in synthetic cystic fibrosis sputum medium (SCFM), a medium that mimics the particular CF airway environment. In 17 (59%) out of 29 MDR P. aeruginosa CF isolates MICs for azithromycin ranged between 0.25 and 8 µg/ml and 12 isolates (41%) showed a MIC ≥512 µg/ml when measured in RPMI/FCS. In contrast, MICs were ≥256 µg/ml for all P. aeruginosa MDR isolates when tested in either SCFM or in conventional cation-adjusted Mueller Hinton Broth. High MIC values observed in CF adapted medium SCFM for both PAO1 and MDR P. aeruginosa CF isolates, as opposed to findings in RPMI, argue against routine azithromycin MIC testing of CF isolates.
Plasmodium falciparum Multidrug Resistance Gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region
Authors: Adamu Auwal , Jada Mahmoud Suleiman , Haruna Hauwa Mohammed Sani , Yakubu Bassa Obed , Ibrahim Mohammed Auwal , Balogun Emmanuel Oluwadare , Sakura Takaya , Inaoka Daniel Ken , Kita Kiyoshi , Hirayama Kenji , Culleton Richard , Shuaibu Mohammed Nasir 
Published: November 2020

Abstract
Background The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria.Methods Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analysed using Pearson Chi-square and Fisher's exact (FE) tests.Results The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, 𝜒² = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, 𝜒² = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.10, P = 0.00), followed by NYD with a prevalence of 49.00% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states.Conclusion The present study suggests that strains of P. falciparum with reduced sensitivity to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.
Clinical profiles of subclinical disease among pulmonary tuberculosis patients: a prospective cohort study in South Korea
Authors: Min Jinsoo , Chung Chaeuk , Jung Sung Soo , Park Hye Kyeong , Lee Sung-Soon , Lee Ki Man 
Published: November 2020

Abstract
Background: Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. We aimed to describe the clinical and laboratory findings of subclinical disease among pulmonary TB patients and compared treatment outcomes for subclinical and active diseases.Methods: In this prospective cohort study, we enrolled adult patients aged ≥19 years with pulmonary TB between 2016 and 2018. Subclinical TB was defined as radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented a two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active diseases using multivariable binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort.Results: Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariable analysis showed that age <65 years was the only variable significantly associated with subclinical disease. Subclinical disease had a significantly lower proportion of acid-fast bacilli smear and culture positivity and multiple lobe involvement compared to active disease. The white blood cell counts, platelet counts, and C-reactive protein levels were significantly higher among patients with active disease than among those with subclinical disease. Among 319 patients with treatment success in the drug-susceptible cohort, six (1.9%) recurrent cases were identified, and all were active disease. Patients with subclinical disease had a higher proportion of favourable outcomes; however, its odds ratio was insignificant.Conclusions: Nearly one-fifth of tuberculosis cases were subclinical in South Korea. Despite its milder clinical presentation and lower level of inflammatory markers, the treatment outcomes of subclinical TB were not significantly different from that of active disease.
Usability evaluation of an integrated electronic medication management system implemented in an Oncology setting using the Unified Theory of the Acceptance and Use of Technology.
Authors: Dabliz Racha , Poon Simon K. , Ritchie Angus , Burke Rosemary , Penm Jonathan 
Published: November 2020

Abstract
Background: Medication management processes in an Oncology setting are complex and difficult to examine in isolation from interrelated processes and contextual factors. This qualitative study aims to evaluate the usability of an Electronic Medication Management System (EMMS) implemented in a specialised oncology unit using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework.Methods: The study was conducted in a 12-bed outpatient Oncology unit of a major teaching hospital six months following implementation of a commercial EMMS. In-depth semi-structured interviews were conducted with doctors, nurses and pharmacists using the system to assess usability. The UTAUT framework was used to analyse the results, which facilitated evaluation of interrelated aspects and provided a structured summary of user experience and usability factors.Results: Direct cross-comparison between user groups illustrated that doctors and pharmacists were generally satisfied with the facilitating conditions (hardware and training), but had divergent perceptions of performance (automation, standardised protocols and communication and documented) and effort (mental and temporal demand). In counterpoint, nurses were generally satisfied across all constructs. Prior experience using an alternative EMMS influenced performance and effort expectancy and was related to early dissatisfaction with the implemented system. Furthermore, whilst not originally designed for the healthcare setting, the flexibility of the UTAUT allowed for translation to the hospital environment.Conclusion: Nurses demonstrated overall satisfaction with the EMMS, whilst doctors and pharmacists perceived some usability problems, particularly related to restricted automaticity and system complexity, which hindered user uptake and EMMS success. The study demonstrates the feasibility and utility of the UTAUT framework to evaluate usability of an EMMS for multiple user groups in the Oncology setting.
Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer and Choroidal Metastases: Long-Term Outcome and Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Bouchez Clémentine , Pluvy Johan , Soussi Ghassen , Nguenang Marina , Brosseau Solenn , Tourne Morgan , Collin Mégane , Théou-Anton Nathalie , Guyard Alice , Ammar Jamila , Khalil Antoine , Zalcman Gérard , Gounant Valérie 
Published: November 2020

Abstract
Background: Choroidal metastases are the most common eye metastatic site. The prevalence of choroidal metastases in NSCLC patients has been reported to vary from 0.2% to 7% in historical series. Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). This study sought to describe the prevalence of choroidal metastases among patients with EGFR-mutated NSCLC and their characteristics, and to estimate their impact on prognosis.Methods: We conducted a single-center retrospective study including all consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018. The EGFR-mutant NSCLC patients were identified via the Department of Genetics’ files. Patients who exhibited choroidal metastases were compared to patients without choroidal metastases. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups. The study was approved by the IRB as CEPRO number #2020-010.Results: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time.Median follow-up was 42.2 mo (95%CI [37.2 - 47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1 - 51.4]) versus 27.9 mo (95%CI [16.9 - 38.9]) in the non-choroidal metastasis group (p=0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6% and 0%, respectively, versus 55.8% and 26.3% in the non-choroidal metastasis subset.Conclusions: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.
Effect of PTH and corticotomy on implant movement under mechanical force
Authors: Kim Jiyeon , Kim Heon-Young , Kim Won-Ho , Kim Jin-Woo , Kim Minji 
Published: November 2020

Abstract
Background Osseointegrated implants are considered as clinically non-movable. Parathyroid hormone (PTH) is known to play a significant role in the regulation of bone remodeling and in intermittent, low doses, result in osteoanabolic effects. This study aimed to investigate the effects of PTH and corticotomy, both under traction force, on osseointegrated implants.MethodsFour implants—two in each hemimandible—were placed in each of the three study mongrels. Each mongrels were designated as control, normal dose PTH (PTH-1), and high dose PTH (PTH-2) groups, with each groups further subdivided into non-surgery implant and surgery implant. After osseointegration, mechanical force with NiTi closed coil springs (500g) was applied around each implants. Corticotomy was performed around one of four implants in each mongrels. Parathyroid hormone was administered locally on a weekly basis for 20 weeks. Clinical movement of the implants were evaluated with the superimposed 3D- scanned data, bone- microarchitectural and histologic examinations. ResultsSuperimposition analysis showed continuous movement of the non-surgery implant of PTH-1 group. Movement was further justified with lowest bone implant contact (adjusted BIC; 44.77%) in histomorphometric analysis. Upregulation of bone remodeling around the implant was observed in the normal dose PTH group. In the surgery implants, the remarkably higher adjusted BIC compared to the non-surgery implants indicated increased bone formation around the implant surface. ConclusionThe results indicate that the catabolic and anabolic balance of osseointegrated implants in terms of bone remodeling can be shifted via various interventions including pharmacological, surgical and mechanical force. Clinical RelevanceUpregulated bone remodeling by PTH and corticotomy under continuous mechanical force showed the possible implications for the movement of osseointegrated dental implant.
Comparisons of Simulation Results between Passive and Active FSI Models for Left Ventricle in Hypertrophic Obstructive Cardiomyopathy
Authors: Huang Xueying , Deng Long , Zuo Heng , Yang Chun , Song Yunhu , Lesperance Mary , Tang Dalin 
Published: November 2020

Abstract
Background. Patient-specific active Fluid-Structure Interactions (FSI) model is a useful approach to non-invasively investigate the hemodynamics in the heart. However, it takes a lot of effort to obtain the proper external force boundary conditions for active models, which heavily restrained the time-sensitive clinical applications of active computational models. Methods. The simulation results of 12 passive FSI models based on 6 patients’ pre-operative and post-operative CT images were compared with corresponding active models to investigate the differences in hemodynamics and cardiac mechanics between these models. Results. It was found that there was no significant difference in shear stress and pressure difference on mitral valve leaflet (MVL) between passive and active models, but a significant difference was found in wall stress on the inner boundary of left ventricle (Endocardium). It was also found that flow shear stress and pressure difference on the MVL were significantly decreased after successful surgery in both active and passive models.Conclusion. Our results suggested that the passive models may provide good approximated hemodynamic results at 5% RR interval, which is crucial for analyzing the initiation of systolic anterior motion (SAM). Comparing to active models, the passive models decrease the complexity of the modeling construction and the difficulty of convergence significantly. Therefore, with proper boundary conditions and sufficient clinical data, the passive computational model may be a good substitution model for the active model to perform hemodynamic analysis for left ventricle to investigate the mechanisms of the initiation of SAM.
HDAC2 inhibits EMT-mediated cancer metastasis by downregulating the long noncoding RNA H19 in colorectal cancer
Authors: Hu Xue-ting , Xing Wei , Zhao Rong-sen , Tan Yan , Wu Xiao-feng , Ao Luo-quan , Li Zhan , Yao Meng-wei , Yuan Mu , Guo Wei , Li Shang-ze , Yu Jian , Ao Xiang , xu xiang 
Published: November 2020

Abstract
Background: Emerging evidence suggests that epithelial mesenchymal transition (EMT) and epigenetic mechanisms promote metastasis. Histone deacetylases (HDACs) and noncoding RNAs (ncRNAs) are important epigenetic regulators. Here, we elucidated a novel role of histone deacetylase 2 (HDAC2) in regulating EMT and CRC metastasis via ncRNA.Methods: The expression of HDACs in CRC was analyzed using the public databases and matched primary and metastatic tissues, and CRC cells with different metastatic potentials (DLD1, HCT116, SW480 and SW620). Microarray analysis was used to identify differential genes in parental and HDAC2 knockout CRC cells. EMT and histone modifications were determined using western blot and immunofluorescence. Migration ability was assessed by transwell assay, and metastasis was assessed in vivo using a tail vain injection. Gene expression and regulation was assessed by RT-PCR, chromatin immunoprecipitation and reporter assays. Protein interaction was assessed by immunoprecipitation. Specific siRNAs targeting H19, SP1 and MMP14 were used to validate their role in HDAC2 loss induced EMT and metastasis.Results: Reduced HDAC2 expression was associated with poor prognosis in CRC patients and found in CRC metastasis. HDAC2 deletion or knockdown induced EMT and metastasis by upregulating the long noncoding RNA H19 (LncRNA H19). HDAC2 inhibited LncRNA H19 expression by histone H3K27 deacetylation in its promoter via binding with SP1. LncRNA H19 functioned as a miR-22-3P sponge to increase the expression of MMP14. HDAC2 loss strongly promoted CRC lung metastasis, which was suppressed LncRNA H19 knockdown. Conclusion: Our study supports HDAC2 as a CRC metastasis suppressor through the inhibition of EMT and the expression of H19 and MMP14.
Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma&nbsp;
Authors: Yuan Qiuyun , Yang Wanchun , Zhang Shuxin , Li Tengfei , Zuo Mingrong , Zhou Xingwang , Li Junhong , Li Mao , Xia Xiaoqiang , Chen Mina , Liu Yanhui 
Published: November 2020

Abstract
Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.
Analysis of IL-1β, CXCL8, and TNF-α levels in the crevicular fluid of patients with periodontitis or healthy implants
Authors: Aleksandrowicz Paweł , Brzezińska-Błaszczyk Ewa , Kozłowska Elżbieta , Żelechowska Paulina , Borgonovo Andrea Enrico , AGIER JUSTYNA 
Published: November 2020

Abstract
Background: Our study aimed to assess the level of IL-1β, CXCL8, and TNF-α in peri-implant sulcular fluid (PISF) collected from patients with no clinical symptoms of mucositis or peri-implantitis and compare them with cytokine concentration in gingival crevicular fluid (GCF) acquired from patients with healthy periodontium and those with varying severity of periodontitis.Methods: A total of 189 subjects were included in the study, and GCF/PISF samples were checked for IL-1β, CXCL8, and TNF-α levels using an ELISA test.Results: The IL-1β level in PISF in patients with implants was significantly lower than in GCF in patients with mild, moderate, or severe periodontitis. The CXCL8 level in PISF was considerably lower than in patients with moderate periodontitis. The TNF-α level in PISF in patients with implants was markedly higher compared to subjects with healthy periodontium or patients with mild periodontitis.Conclusion: Analysis of cytokine levels may help describe the pathogenesis and early diagnosis of peri-implantitis and prevision in high-risk patients.
Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer
Authors: Hussung Saskia , Akhoundova Dilara , Hipp Julian , Follo Marie , Klar Rhena , Philipp Ulrike , Scherer Florian , von Bubnoff Nikolas , Duyster Justus , Börries Melanie , Wittel Uwe , Fritsch Ralph 
Published: November 2020

Abstract
Background: Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19-9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters. Methods: Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19-9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020.Results: Out of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19-9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19-9 levels outperformed either individual marker. cfKRASmut outperformed CA 19-9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS. Conclusions: Integrated analysis of cfKRASmut and CA 19-9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker`s specific potential.