Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrode Afterload: A Valuable Technique in a Case of Short Electrode Insertion

Introduction. The location of the electrode inside the cochlea is important for speech performance. However, many variables, including array length, insertion depth, and individual anatomy, may affect the intracochlear position of the electrode. Insertion deeper than 20 mm and revision surgery are critical situations in which residual hearing and electrode integrity may be at risk. This case report challenges this hypothesis and raises the following question: is it possible to achieve a better speech understanding with an electrode afterload without compromising residual hearing? Case Report. A 73-year-old female patient showed up for evaluation of hearing loss. The patient was operated four times in an external hospital due to cholesteatoma formation in the right ear. Related to a poor aided speech understanding, a CI-surgery was performed. 5 months after the surgery, the subject returned with poor speech understanding. A revision surgery was performed, where the first white marker of the electrode was seen in the round window (20 mm). The electrode was inserted 4 mm deeper into the cochlea. After six and twelve months, the results of the Freiburger monosyllabic speech test improved till 25% and 45%, respectively. Discussion. Hearing preservation is possible with a revisional deeper insertion from 20 mm to 24 mm. In this case, a partial obliteration of an open cavity made the electrode surgically easily accessible. This allowed the deeper insertion during the revision surgery. In a regular surgical field with a posterior tympanotomy, the revision surgery is more challenging and brings the electrode into the risk of an iatrogenic destruction. Conclusion. This case of an electrode afterload after having inserted the electrode initially to mm, demonstrates that hearing can be preserved and speech perception can improve after performing this maneuver.
Carbapenem-Resistant Enterobacter hormaechei ST1103 with IMP-26 Carbapenemase and ESBL Gene blaSHV-178

Purpose To investigate the occurrence and genetic characteristics of the blaIMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51. Methods Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes. Results The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding blaIMP-26 which surrounding genetic context was intI1-blaIMP-26-ltrA-qacE∆1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6ʹ)-IIc, blaSHV-178, blaDHA-1, blaTEM-1, blaIMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19. Conclusion In our study, we identified a conjugative IncHI2/2A plasmid carrying blaIMP-26 and blaSHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.
First Study of Antimicrobial Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Against Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infection in Tehran, Iran

Purpose Pseudomonas aeruginosa causes complicated and/or nosocomial UTI. These infections are usually associated with severe and multi-drug resistant P. aeruginosa isolates. As there is no study about the activity of novel antibiotics ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) against P. aeruginosa isolates in Iran, we aimed to evaluate for the first time the efficacy of these agents against P. aeruginosa isolated from patients with UTI in Iran. Then, the genetic diversity of the resistant isolates was assayed. Methods In this study, a total of 200 P. aeruginosa isolates were collected from patients with UTI in Tehran, Iran. Disk diffusion and Minimum Inhibitory Concentration (MIC) methods were applied to determine the resistance of the isolates to CZA, C/T, and the other antibiotics. Extended-spectrum β-lactamases (ESBLs) and Metallo Beta Lactamase (MBL) production were assayed by Combination disk diffusion test (CDDT). Polymerase chain reaction (PCR) was carried out to detect the resistance genes, including beta-lactamases and carbapenemases genes. Finally, genomic analysis of the isolates was performed using the Pulse field gel electrophoresis (PFGE). Results Among the isolates, 16 (8%) were resistant to CZA and C/T that MIC confirmed it. The resistant isolates showed high resistance to the other classes of antibiotics. Among the resistant isolates, 31.2% and 75% were ESBL and MBL producers, respectively. The prevalence of blaOXA10, blaVIM, blaOXA48, blaOXA2, and blaCTX-M was 100%, 50%, 31.2%, 25%, and 12.5%. Furthermore, two isolates (12.5%) harbored blaPER and blaNDM genes. The resistant isolates were grouped into 14 distinct pulsotypes and two shared pulsotypes were found. Conclusion Ceftazidime-avibactam and ceftolozane-tazobactam showed high activity against the P. aeruginosa isolated from patients with UTI in Iran. The low rate of resistance to the antibiotics is also alarming and should be considered to avoid further spreading of the antibiotic resistance among the P. aeruginosa and the other bacteria.
Norepinephrine Induces Lung Microvascular Endothelial Cell Death by NADPH Oxidase-Dependent Activation of Caspase-3

Norepinephrine (NE) is the naturally occurring adrenergic agonist that is released in response to hypotension, and it is routinely administered in clinical settings to treat moderate to severe hypotension that may occur during general anesthesia and shock states. Although NE has incontestable beneficial effects on blood pressure maintenance during hypotensive conditions, deleterious effects of NE on endothelial cell function may occur. In particular, the role of reactive oxygen species (ROS) and NADPH oxidase (Nox) on the deleterious effects of NE on endothelial cell function have not been fully elucidated. Therefore, we investigated the effects of NE on ROS production in rat lung microvascular endothelial cells (RLMEC) and its contribution to cell death. RLMEC were treated with NE (5 ng/mL) for 24 hours and ROS production was assessed by CellROX and DCFDA fluorescence. Nox activity was assessed by NADPH-stimulated ROS production in isolated membranes and phosphorylation of p47phox; cell death was assessed by flow cytometry and DNA fragmentation. Caspase activation was assessed by fluorescent microscopy. Nox1, Nox2, and Nox4 mRNA expression was assessed by real-time PCR. NE increased ROS production, Nox activity, p47phox phosphorylation, Nox2 and Nox4 mRNA content, caspase-3 activation, and RLMEC death. Phentolamine, an α1-adrenoreceptor antagonist, inhibited NE-induced ROS production and Nox activity and partly inhibited cell death while β-blockade had no effect. Apocynin and PEGSOD inhibited NE-induced caspase-3 activation and cell death while direct inhibition of caspase-3 abrogated NE-induced cell death. PEG-CAT inhibited NE-induced cell death but not caspase-3 activation. Collectively, these results indicate that NE induces RLMEC death via activation of Nox by α-adrenergic signaling and caspase-3-dependent pathways. NE has deleterious effects on RLMECs that may be important to its long-term therapeutic use.
Possible role of EphA4 and VEGFR2 interactions in neural stem and progenitor cell differentiation

Neural stem and progenitor cells (NSPCs) are important pluripotent stem cells, which have potential applications for cell replacement therapy. Ephrin receptors (Ephs) and angiogenic growth factor receptors have a major impact on the proliferation and differentiation of NSPCs. Potential interactions between EphA4 and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2, and their roles in NSPC differentiation in vitro remain unknown. In the present study, mouse embryonic NSPCs were treated with ephrin-A1 or VEGF165 alone as well as with combination treatment (ephrin-A1 + VEGF165). Immunoprecipitation and immunoblot assays demonstrated that wild-type EphA4, but not the EphA4 kinase-dead mutant, interacted with VEGFR2 when overexpressed in 293T cells. This interaction was inhibited by dominant-negative EphA4. The percentage of β-tubulin III (Tuj1)+, but not glial fibrillary acid protein (GFAP)+ cells, was increased in the ephrin-A1 + VEGF165 combination group as compared to the VEGF165 alone group in mouse embryonic NSPCs. VEGF165-induced neuronal differentiation was potentiated by ephrin-A1 in NSPCs in vitro and ephrin-A1- or VEGF165-stimulated EphA4 and VEGFR2 interactions may mediate the signaling pathway.
Antifungal Activity of ZnO Nanoparticles and Nystatin and Downregulation of SAP1-3 Genes Expression in Fluconazole-Resistant Candida albicans Isolates from Vulvovaginal Candidiasis

Purpose Antifungal resistance and virulence properties of Candida albicans (C. albicans) are growing health problems worldwide. The present study aims to investigate the effect of Zinc Oxide (ZnO) nanoparticles and Nystatin on SAP1-3 genes expression in C. albicans isolates of females with Vulvovaginal Candidiasis (VVC) isolated from Sayad Shirazi Obstetrics and Gynecology Hospital in Northeastern Iran during 2017–2018. Patients and Methods In this descriptive-analytic study, vaginal samples were collected from 280 VVC women. 196 (70%) of C. albicans isolates were identified by phenotypic and ITS genotypic methods. Susceptibility to Fluconazole C. albicans isolates was determined by the disk diffusion method. Detection of ERG11 gene was done by RT-PCR technique. Results It was revealed that PCR amplified the ERG11 gene in all of the Fluconazole-resistant isolates. Real-time PCR was used to survey the effects of 3±1. 7µg/mL concentrations of ZnO nanoparticles and Nystatin on expression of SAP1-3 genes before and after treatment. 186 (95%) susceptible C. albicans and 10 (5%) Fluconazole-resistant C. albicans isolates from VVC were exposed to sub-minimum inhibitory concentrations (Sub-MIC) of ZnO-np (range=0.02–12 μg/mL). Sub-MIC concentration was used for each strain, which reduced the expression of SAP1-3 genes to 1.8 MIC in the vaginal swabs. The observed reduction in gene expression was significant for both ZnO nanoparticles and Nystatin (P=0.01 and P=0.07, respectively). Conclusion ZnO as antifungal agent can well reduce the growth and gene expression of SAP1-3 in the pathogenesis of VVC.
Species distribution and susceptibility profiles of Candida species isolated from vulvovaginal candidiasis, emergence of C. lusitaniae

Background and Purpose: The aim of the current study was to investigate the epidemiology of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC), as well as the antifungal susceptibility patterns of Candida species isolates. Materials and Methods: A cross-sectional study was carried out on 260 women suspected of VVC from February 2017 to January 2018. In order to identify Candida species isolated from the genital tracts, the isolates were subjected to polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using enzymes Msp I and sequencing. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guidelines (M27-A3). Results: Out of 250 subjects, 75 (28.8%) patients were affected by VVC, out of whom 15 (20%) cases had RVVC. Among the Candida species, C. albicans was the most common species (42/95; 44.21%), followed by C. lusitaniae (18/95; 18.95%), C. parapsilosis (13/95; 13.69%), C. glabrata (8/95; 8.42%), C. kefyr (6/95; 6.31%), C. famata (5/95; 5.26%), C. africana (2/95; 2.11%), and C. orthopsilosis (1/95; 1.05%), respectively. Multiple Candida species were observed in 28% (21/75) of the patients. Nystatin showed the narrowest range of minimum inhibitory concentration (MIC) (0.25-16 μg/ml) against all Candida strains, whereas fluconazole (0.063-64 μg/ml) demonstrated the widest MIC range. In the current study, C. lusitaniae, as the second most common causative agent of VVC, was susceptible to all antifungal agents. Furthermore, 61.1% of C. lusitaniae isolates were inhibited at a concentration of ≤ 2 μg/ml, while 38.9% (n=7) of them exhibited fluconazole MICs above the epidemiologic cutoff values (ECV). Candida species showed the highest overall resistance against fluconazole (61.3%), followed by itraconazole (45.2%) and caspofungin (23.7%). All of C. albicans strains were resistant to itraconazole with a MIC value of ≥ 1 μg/ml; in addition, 87.5% of them were resistant to fluconazole. Moreover, 100% and 87.5% of C. glabrata strains were resistant to caspofungin and fluconazole, respectively. Conclusion: As the findings revealed, the majority of VVC cases were caused by non-albicans Candida species which were often more resistant to antifungal agents. Candida lusitaniae generally had fluconazole MICs above the ECV. Given the propensity of C. lusitaniae to develop resistance under drug pressure, antifungals should be administered with caution. The emergence of these species justify the epidemiological surveillance surveys to watch out the distribution of yeast species.
Subcellular Performance of Nanoparticles in Cancer Therapy

Abstract With the advent of nanotechnology, various modes of traditional treatment strategies have been transformed extensively owing to the advantageous morphological, physiochemical, and functional attributes of nano-sized materials, which are of particular interest in diverse biomedical applications, such as diagnostics, sensing, imaging, and drug delivery. Despite their success in delivering therapeutic agents, several traditional nanocarriers often end up with deprived selectivity and undesired therapeutic outcome, which significantly limit their clinical applicability. Further advancements in terms of improved selectivity to exhibit desired therapeutic outcome toward ablating cancer cells have been predominantly made focusing on the precise entry of nanoparticles into tumor cells via targeting ligands, and subsequent delivery of therapeutic cargo in response to specific biological or external stimuli. However, there is enough room intracellularly, where diverse small-sized nanomaterials can accumulate and significantly exert potentially specific mechanisms of antitumor effects toward activation of precise cancer cell death pathways that can be explored. In this review, we aim to summarize the intracellular pathways of nanoparticles, highlighting the principles and state of their destructive effects in the subcellular structures as well as the current limitations of conventional therapeutic approaches. Next, we give an overview of subcellular performances and the fate of internalized nanoparticles under various organelle circumstances, particularly endosome or lysosome, mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus, by comprehensively emphasizing the unique mechanisms with a series of interesting reports. Moreover, intracellular transformation of the internalized nanoparticles, prominent outcome and potential affluence of these interdependent subcellular components in cancer therapy are emphasized. Finally, we conclude with perspectives with a focus on the contemporary challenges in their clinical applicability.
Inhibition of cyclinB1 Suppressed the Proliferation, Invasion, and Epithelial Mesenchymal Transition of Hepatocellular Carcinoma Cells and Enhanced the Sensitivity to TRAIL-Induced Apoptosis

Background CyclinB1 is highly expressed in various tumor tissues and plays an important role in tumor progression. However, its role in hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of this study was to explore the role of cyclinB1 in the development and progression of HCC. Methods The expression of cyclinB1 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database, and detected in HCC tissues and HCC cell lines through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. CyclinB1-short hairpin RNA (Sh-cyclinB1) was transfected into HCC cells to knockdown cyclinB1, and the effect of cyclinB1 knockdown on HCC was examined via the MTT assay, colony formation assay, wound healing assay, scratch assay, cell cycle analysis in vitro, and xenograft model in nude mice. In addition, the role of cyclinB1 on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis was measured using flow cytometry and Western blotting. Results The GEPIA database analysis showed that cyclinB1 was highly expressed in HCC tissues. The results of qRT-PCR and Western blotting proved that the expression of cyclinB1 was significantly increased in HCC tissues and cell lines. The data of the MTT assay, colony formation assay, and cell cycle analysis indicated that cyclinB1 knockdown inhibited the proliferation of HCC cells. In addition, cell migration, invasion, and epithelial mesenchymal transition were also impaired by cyclinB1 knockdown. Furthermore, the xenograft model in nude mice demonstrated that inhibition of cyclinB1 suppressed tumor growth and metastasis in vivo. Finally, the results of flow cytometry and Western blotting indicated that inhibition of cyclinB1 enhanced the sensitivity of HCC cells to TRAIL-induced apoptosis. Conclusion Overall, these data provide reasonable evidence that cyclinB1 may serve as a proto-oncogene during the progression of HCC.
Human insulin modulates α-synuclein aggregation via DAF-2/DAF-16 signalling pathway by antagonising DAF-2 receptor in C. elegans model of Parkinson’s disease

Insulin-signalling is an important pathway in multiple cellular functions and organismal ageing across the taxa. A strong association of insulin-signalling with Parkinson’s disease (PD) has been proposed but the exact nature of molecular events and genetic associations are yet to be understood. We employed transgenic C. elegans strain harboring human α-synuclein::YFP transgene, towards studying the aggregation pattern of α-synuclein, a PD-associated endpoint, under human insulin (Huminsulin®) treatment and DAF-16/DAF-2 knockdown conditions, independently and in combination. The aggregation was increased when DAF-16 was knocked-down independently or alongwith a co-treatment of Human insulin (HumINS) and decreased when DAF-2 was knocked-down independently or alongwith a co-treatment of HumINS; whereas HumINS treatment per se, reduced the aggregation. Our results depicted that HumINS decreases α-synuclein aggregation via DAF-2/DAF-16 pathway by acting as an antagonist for DAF-2 receptor. Knockdown of reported DAF-2 agonist (INS-6) and antagonists (INS-17 and INS-18) also resulted in a similar effect on α-synuclein aggregation. Further by utilizing bioinformatics tools, we compared the differences between the binding sites of probable agonists and antagonists on DAF-2 including HumINS. Our results suggest that HumINS treatment and DAF-16 expression play a protective role against α-synuclein aggregation and its associated effects.
Coping Assessment Tools in the Family Caregivers of Patients with Breast Cancer: A Systematic Review

Background Breast cancer is a problem that affects not only the individual’s health and quality of life, but also the functionality of the family system. Caregivers experience stress when their patients cannot cope with the symptoms of their disease. The stress experienced by caregivers gives rise to psychological and physical symptoms in them. This study seeks to present a complete set of tools for assessing coping in the spouses or caregivers of women with breast cancer and evaluate the various instruments developed within these lines of inquiry. Methods A search was carried out in PubMed, Scopus, Web of Science, CINAHL, PsycINFO, Medline, ProQuest, Scopus and Google Scholar and also in the reference lists of the key articles retrieved for any coping assessment instrument targeting family caregivers’ needs that had acceptable psychometric properties and was published until September 2019. The instruments used to assess coping in the spouses and caregivers of women with breast cancer were thus identified and their properties were described. Results Overall, 88 adaptation assessment tools related to family caregivers of patients with breast cancer were identified in 28 related articles. The tools examine different dimensions of adaptation such as satisfaction, stress, burden and needs of spouses and caregivers of patients with breast cancer. Conclusion Assessing family caregivers’ coping is essential for providing them with the appropriate sources of support. Although several instruments have been used to assess coping in the spouses and caregivers of women with breast cancer, the properties of these instruments have to be examined before they can be more widely implemented.
Dental Pulp Stem Cells: Advances to Applications

Abstract Dental pulp stem cells (DPSCs) have a high capacity for differentiation and the ability to regenerate a dentin/pulp-like complex. Numerous studies have provided evidence of DPSCs’ differentiation capacity, such as in neurogenesis, adipogenesis, osteogenesis, chondrogenesis, angiogenesis, and dentinogenesis. The molecular mechanisms and functions of DPSCs’ differentiation process are affected by growth factors and scaffolds. For example, growth factors such as basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and bone morphogenic proteins (BMPs) influence DPSC fate, including in differentiation, cell proliferation, and wound healing. In addition, several types of scaffolds, such as collagen, hydrogel, decellularized bioscaffold, and nanofibrous spongy microspheres, have been used to characterize DPSC cellular attachment, migration, proliferation, differentiation, and functions. An appropriate combination of growth factors and scaffolds can enhance the differentiation capacity of DPSCs, in terms of optimizing not only dental-related expression but also dental pulp morphology. For a cell-based clinical approach, focus has been placed on the tissue engineering triad [cells/bioactive molecules (growth factors)/scaffolds] to characterize DPSCs. It is clear that a deep understanding of the mechanisms of stem cells, including their aging, self-renewal, microenvironmental homeostasis, and differentiation correlated with cell activity, the energy for which is provided from mitochondria, should provide new approaches for DPSC research and therapeutics. Mitochondrial functions and dynamics are related to the direction of stem cell differentiation, including glycolysis, oxidative phosphorylation, mitochondrial metabolism, mitochondrial transcription factor A (TFAM), mitochondrial elongation, and mitochondrial fusion and fission proteins. This review summarizes the effects of major growth factors and scaffolds for regenerating dentin/pulp-like complexes, as well as elucidating mitochondrial properties of DPSCs for the development of advanced applications research.