Miracle-dz/UniFAR-FTUs huggingface dataset:
Increase in antibiotic resistant Helicobacter pylori in a University Hospital in Japan

Background Eradication effectively prevents Helicobacter pylori-associated diseases; however, H. pylori antibiotic resistance has increased throughout Japan and worldwide. This study aimed to assess rates of resistance to antibiotics; amoxicillin, clarithromycin and metronidazole in a University Hospital in Japan. Materials and methods H. pylori (208 strains) were isolated from patients at the Okayama University Hospital in Japan. The minimum inhibitory concentrations (MIC) were determined using the mean values of the E-test to determine the antimicrobial susceptibilities of the strains. Sequencing and gene analysis were performed to analyze resistance genes to clarithromycin and amoxicillin. Results Rates of amoxicillin, clarithromycin, and metronidazole resistance were 13%, 48%, and 49%, respectively. Genetic analysis indicated that the A2143G point mutation in 23S rDNA is closely associated with the MIC of clarithromycin. The MIC in amoxicillin-resistant strains increased with an increase in the number of PBP1A amino acids mutations. Conclusion Genetic analysis for resistant strains is not clinically effective in cases of amoxicillin resistance. Numerous bacteria with already high antibiotic resistance rates have been isolated in large hospitals such as a University Hospital. For effective eradication therapy, MIC measurement should be considered via several methods.
The contribution of ABCG2 G34A and C421A polymorphisms to multiple myeloma susceptibility

Background Breast cancer resistance protein BCRP, belonging to superfamily G of the adenosine triphosphate-binding cassette (ABC) transporters, is an efflux pump and plays a critical role in protecting cells against xenobiotics and toxic compounds including (pro)carcinogens. BCRP is expressed in many tissues, including hematopoietic stem cells. Genetic variants such as single nucleotide polymorphisms (SNPs) can change the gene expression and/or reduce their products’ activity which may affect an individual’s susceptibility to xenobiotics and the development of carcinoma. These changes may affect the exposure of blood cells to toxic compounds, which increases the risk of multiple myeloma. The aim of this study was to determine polymorphisms at positions G34A and C421A of the ABCG2 gene in multiple myeloma in the Polish population for the first time. Materials and methods Material for the study included DNA isolated from nucleus of cells of peripheral blood of patients diagnosed with multiple myeloma (investigated group N=181) and from healthy people (control group N=97). Research into the polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism technique. Results The present study showed a statistically significant association between SNP C421A of the ABCG2 gene and the risk of developing multiple myeloma (P=0.0218). No statistically significant relationship was found for the other parameters analyzed, such as age, gender, or type of secreted immunoglobulin. Conclusion Preliminary studies indicate that SNP C421A may become a potential predictor for the development of multiple myeloma.
Hypoxic non-small-cell lung cancer cell-derived exosomal miR-21 promotes resistance of normoxic cell to cisplatin

Purpose To explore the effects of hypoxic non-small-cell lung cancer (NSCLC)-derived exosomes on NSCLC resistance to cisplatin. Materials and methods Exosomes were isolated by differential centrifugation and characterized by transmission electron microscope and Western blotting. Quantitative real-time PCR was used to measure miR-21 levels. MTT assays and colony formation assays were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance. Results Hypoxic NSCLC cell-derived exosomes facilitate normoxic cell resistance to cisplatin. In addition, hypoxia enhanced the miR-21 expression in NSCLC cells and cell-derived exosomes. Interestingly, changes in miR-21 levels in the hypoxia-induced exosomes affected the sensitivity of recipient cells to cisplatin. Mechanically, exosomal miR-21 promoted cisplatin resistance by downregulating phosphatase and tensin homolog (PTEN). The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN. Moreover, high miR-21 expression was associated with shorter median survival period in patients undergoing pharmacotherapy, but no association was observed in patients who were not under pharmacotherapy. Conclusion Exosomal miR-21 derived from hypoxic NSCLC cells may promote cisplatin resistance, which indicates that exosomal miR-21 might be a potential biomarker and therapeutic target to address NSCLC chemoresistance.
Photocatalytic antibacterial application of zinc oxide nanoparticles and self-assembled networks under dual UV irradiation for enhanced disinfection

Background Zinc oxide (ZnO) nanoparticles and their networks have been developed for use in various applications such as gas sensors and semiconductors. Aim In this study, their antibacterial activity against Escherichia coli under dual ultraviolet (UV) irradiation for disinfection was investigated. Materials and methods ZnO nanoparticles were synthesized and immobilized onto silicon (Si) wafers by self-assembly. The physicochemical properties and antibacterial activity of ZnO nanoparticles and their networks were evaluated. Gene ontology was analyzed and toxicity levels were also monitored. Results Synthesized ZnO nanoparticles were spherical nanocrystals (<100 nm; Zn, 47%; O, 53%) that formed macro–mesoporous three-dimensional nanostructures on Si wafers in a concentration-dependent manner. ZnO nanoparticles and their networks on Si wafers had an excellent antibacterial activity against E. coli under dual UV irradiation (>3log CFU/mL). Specifically, arrayed ZnO nanoparticle networks showed superior activity compared with free synthesized ZnO nanoparticles. Oxidative stress-responsive proteins in E. coli were identified and categorized, which indicated antibacterial activity. Synthesized ZnO nanoparticles were less cytotoxic in HaCaT with an IC50 of 6.632 mg/mL, but phototoxic in Balb/c 3T3. Conclusion The results suggested that ZnO nanoparticles and their networks can be promising photocatalytic antibiotics for use in next-generation disinfection systems. Their application could also be extended to industrial and clinical use as effective and safe photocatalytic antibiotics.
Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion through inhibiting the PI3K/AKT signaling pathway in gastric cancer cells

Introduction Poor prognosis of gastric cancer (GC) has partly been a result of late diagnosis due to nonspecific symptoms in the early stages. The overall survival rate of patients with GC is quite low. Here, we presented the functional role and potential mechanism of long noncoding RNA STXBP5-AS1 in GC. Materials and methods CCK-8, scratch wound healing and Transwell assays were conducted to analyze proliferation, migration, and invasion of SGC7901 and MKN45 cells. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to investigate the relationship between STXBP5-AS1 and STXBP5. Finally, the correlation between STXBP5-AS1 and phosphorylated AKT1 (p-AKT1) was explored to reveal the potential mechanism of STXBP5-AS1 in GC. Western blot assays were performed to analyze phosphorylated AKT1 (p-AKT1) and AKT levels. Results Our results suggested that STXBP5-AS1 suppressed proliferation, migration, and invasion, and the upregulation of STXBP5-AS1 significantly repressed STXBP5 expression, and knockdown of STXBP5-AS1 promoted STXBP5 expression. In addition, the p-AKT1 level decreased when STXBP5-AS1 was overexpressed and the p-AKT1 level increased with STXBP5-AS1 knockdown in SGC7901 and MKN45 cells. Conclusion In summary, our results indicate that STXBP5-AS1 inhibits cell proliferation, migration, and invasion through PI3K/AKT in GC.
Improving the Training Process of Anesthesiology Residents Through the Mentorship-Based Approach

Background Although mentoring has been accepted as an effective and nourishing component in medical learning, known mentoring programs for the residents are lacking in most countries. Objectives To evaluate the mentoring program for anesthesiology residents at Shahid Beheshti University, an examination was designed to explore the styles of mentoring programs, as well as the aims and outcome followed by such programs. Methods In October 2016, Anesthesiology Department of Shahid Beheshti University of Medical Sciences enrolled all the nine educational wards in “mentorship program”. Twelve members of the faculty were chosen to be mentor. This program contained: (a) Creating online groups for reporting, feedbacks, and problem-solving, (b) integrating each chapter of textbooks for studying program each month, (c) establishing formative and summative assessments (i.e., PMP, OSCE, multiple choice exams), (d) role-playing for stress management of level 4 residents. Our main objective was to provide the residents with the provision of mentors. The goals of our programs were: Arrange a safe environment to encourage and foster reflection, promote self-care and wellness, guide special development, provide a resource for residents pursuing control, enrich team constructing and problem-solving skills, and promotion in career counseling of anesthesia residents at Shahid Beheshti University of Medical Sciences enrolled in this program from 2014 to 2017. We retrospectively compared 2 periods before (2014 - 2015) and after (2016 - 2017) of monthly examination and educational conference. Results In the academic stage from 2014 - 2015, the overall first-time license rate for the IBA written QE was 7 of 14 (50%) and in the period of 2016 - 2017, the general rate was 11 of 14 (78%) and in the period of 2017 - 2018, it was 12 of 14 (85%). For each extra year experiencing the program, the odds ratio for passing IBA written QE was 1.7 (P < 0.05). The median Iranian Board of Anesthesiology In-Training Examination (IBAITE) percentile was considerably greater in period 2 than period 1 (P < 0.05). Also, there was a significant correlation between IBAITE score and first-time passing rates for the IBA written QE (0.55, P < 0.05). Conclusions The results of this study demonstrated the clinical mentorship program as an effective method in improving theoretical, clinical, and professional achievement of anesthesiology residents. Programmed mentorship could significantly improve the educational goal achievements for anesthesiology residents. Mentoring programs are needed to be more used; however, need to be assessed and evaluated, especially regarding the professional aspects of education. Medical schools could subsequently be assessed regarding the number and quality of their running mentorship programs as a quality improvement tool.
Identification of potentially inappropriate medications with risk of major adverse cardiac and cerebrovascular events among elderly patients in ambulatory setting and long-term care facilities

Purpose Cardiovascular diseases (CVDs) are extremely common among the elderly, but information on the use of potentially inappropriate medications (PIMs) with cardiovascular risk is scarce. We aimed to determine the prevalence of PIMs with risk of cardiac and cerebrovascular adverse events (CCVAEs), including major adverse cardiac and cerebrovascular events (MACCE). Patients and methods A cross-sectional study was performed using a convenience sample from four long-term care facilities and one community pharmacy in Portugal. Patients were included if they were aged 65 or older and presented at least one type of medication in their medical and pharmacotherapeutic records from 2015 until December 2017. The main outcome was defined as the presence of PIMs with risk of MACCE and was assessed by applying a PIM-MACCE list that was developed from a previous study. All medications included in this list were assessed for their availability in Portugal. Results A total of 680 patients were included. Of those, 428 (63%) were female with a mean age of 78.4±8.1 years. Four-hundred and four (59.4%) patients were taking medications associated with CCVAEs risk (mean =1.7±1.0 drugs/patient), including 264 patients (38.8%) who used drugs with MACCE risk (mean =1.4±0.8 drugs/patient). Fifty percent of patients with a previous history of CVD (n=521) were taking PIMs with risk of CCVAEs, including 30.0% with risk of MACCE. Conclusion Our findings show that 50% of patients with previous history of CVD were taking drugs with risk of CCAVEs and 30% with risk of MACCE. More tailored tools for the management of drug therapy in elderly patients with CVD are of major importance in clinical practice.
Prognostic implications and oncogenic roles of MYBL2 protein expression in esophageal squamous-cell carcinoma

Background The MYBL2 gene, a highly conserved member of the Myb transcription-factor family, has been implicated in the genesis and progression of many types of tumors. Methods We analyzed the expression of MYBL2 and Ki67 in tissue samples of esophageal squamous-cell carcinoma (ESCC) patients by immunohistochemistry. We further analyzed the effect of MYBL2 on cell proliferation and DNA replication using a CCK8 assay, 5-ethynyl-2′-deoxyuridine–retention assay, flow-cytometry analysis, real-time quantitative PCR, Western blot, and a xenograft model of ESCC cells in nude mice. Results MYBL2 expression was significantly higher in ESCC tissue when compared to the adjacent normal tissue (P=0.007). MYBL2 was found to be positively correlated with Ki67 (γ=0.286, P=0.003). Furthermore, Kaplan–Meier curves indicated that MYBL2 expression in ESCC tissue was associated with poor patient outcome (P<0.001), with MYBL2-positive patients who exhibited high Ki67 expression in ESCC tissue showing the worst prognosis for overall survival (P=0.003). Our in vitro results showed that downregulation of MYBL2 in ESCC cell lines inhibited cell proliferation and DNA replication (P<0.05 for both). We also found that loss of MYBL2 caused a reduction in levels of cell cycle-related G2/M proteins CDK1 and cyclin B1 in ESCC cells. In contrast, overexpression of MYBL2 caused an increase in these proteins. In vivo, we found that in nude mice that received cells knocked down for MYBL2, tumor growth was inhibited in comparison to the group that received control cells (P<0.05). Conclusion MYBL2 overexpression induces tumor proliferation in ESCC cells by regulating cell-cycle at the S and G2/M phase. Therefore, MYBL2 may serve as a novel prognostic biomarker in ESCC patients.
In vitro activity and pharmacodynamic/pharmacokinetic parameters of clarithromycin and azithromycin: why they matter in the treatment of respiratory tract infections

Clarithromycin and azithromycin are second-generation macrolides established and widely used for treating a range of upper and lower respiratory tract infections. Extensive clinical trials data indicate that these drugs are highly effective in these applications and broadly comparable in their clinical and microbiological effectiveness. However, consideration of pharmacokinetic, metabolic, and tissue-penetration data, including the significant antibacterial activity of the metabolite 14-hydroxy-clarithromycin, plus the findings of pharmacodynamic modeling, provide evidence that the long half-life and lower potency of azithromycin predispose this agent to select for resistant isolates. Comparison of the “mutant-prevention concentrations” of clarithromycin and azithromycin, and examination of large-scale epidemiological data from Canada, also support the view that these drugs differ materially in their propensity to promote resistance among bacterial strains implicated in common respiratory infections, and that clarithromycin may offer important advantages over azithromycin that should be considered when choosing a macrolide to treat these conditions.
Orbital Radiotherapy Plus Concomitant Steroids in Moderate-to-Severe Graves’ Ophthalmopathy: Good Results After Long-Term Follow-Up

Background Orbital radiotherapy (RT) is an effective and consolidate treatment for steroid-refractory Graves’ ophthalmopathy (GO); however, long term effects are not well known. Objectives The aim of this study was to evaluate the long term efficacy and toxicity of orbital RT plus concomitant systemic steroids in a population of patients with moderate-to-severe GO or with eyesight threatening symptoms refractory to steroids. Methods Forty patients with moderate-to-severe GO or with eyesight threatening symptoms not responsive/resistant to steroids were treated with orbital RT at the dose of 20 Gy in 10 fractions plus concomitant steroids. Clinical activity score (CAS) and symptoms status were evaluated to determine response to the treatment. Results We reported overall improvement of symptoms, in particular, a regression at 1-year of diplopia in 32.5% eye movement impairment in 42.5%, eyesight in 27.5% and a 2 point reduction in CAS. After a median time of 56 months 21.9% of the patients underwent orbital decompression for relapse of GO, 4.8% received surgical correction of strabismus, and 2.4% received eyelid lipectomy. Acute toxicity was mild; grade 1 - 2 keratitis occurred in 19.5% of the patients and grade 3 keratitis was observed in 2.4% of the patients. Cataract occurred in 7.4% of the patients after a median time of 24-month-follow-up. No secondary malignancies were reported. Conclusions Our results reported the long-term efficacy and the good tolerance of orbital RT. The combination of RT plus steroids in this setting may avoid or delay performing the surgery in some cases.
Meeting Between Rumi and Shams in Notch Signaling; Implications for Pain Management: A Narrative Review

The meeting between Rumi and Shams, in the 13th century, was a turning point in the life of Rumi leading to a revolutionary effect in his thoughts, ideas, and poems. This was an ever-inspiring meeting with many results throughout the centuries. This meeting has created some footprints in cellular and molecular medicine: The discovery of two distinct genes in Drosophila, i.e. Rumi and Shams and their role in controlling Notch signaling, which has a critical role in cell biology. This nomination and the interactions between the two genes has led us to a number of novel studies during the last years. This article reviews the interactions between Rumi and Shams and their effects on Notch signaling in order to find potential novel drugs for pain control through drug development studies in the future.
Comparison of Intravenous Dexmedetomidine-Propofol Versus Ketofol for Sedation During Awake Fiberoptic Intubation: A Prospective, Randomized Study

Background Management of difficult airway due to laryngeal mass is a major challenge to the anesthesiologists, and awake fiberoptic intubation (AFOI) would be the technique of choice. Objectives The current study aimed at comparing the effects of administration of dexmedetomidine-propofol or ketofol for sedation during AFOI in terms of intubation conditions, hemodynamic stability, and patients and anesthesiologist’s satisfaction. Methods Eighty adult patients, 18 - 60 years old, ASA (the American Society of Anesthesiologists) physical status I-III, with difficult airway due to laryngeal mass and planned for AFOI were enrolled. Sedation was randomly given to the patients according to their assigned group by either dexmedetomidine-propofol (group D; n = 40) or ketofol (group K; n = 40). Outcome variables included time to reach Ramsay sedation scale (RSS) ≥ 3, intubation time, number of patients in need of rescue propofol, patient’s discomfort score, tolerance to endoscopy and intubation, hemodynamic parameters, patients and anesthesiologist’s satisfaction, and occurrence of side effects. Results Time to reach RSS ≥ 3 and intubation time were significantly shorter, and fewer patients required rescue propofol in the K group as compared to the D group (P = 0.000*, and 0.035*, respectively). Higher discomfort score and better tolerance to endoscopy and intubation were noticed in group K than group D, but with no statistical significance (P = 0.132, 0.137, and 0.211, respectively). Patients in group D had significantly lower mean arterial pressure (MAP) and heart rate (HR) after the loading dose till five minutes after intubation (P = 0.000*). There was no significant difference in patients’ satisfaction between the two groups (P = 0.687), while anesthesiologist’s satisfaction was higher in group K compared with that of group D (P = 0.013*). Cough score as well as incidence of unfavorable respiratory outcomes were not significantly different between the two groups (P = 0.611, 0.348, respectively). Conclusions Ketofol and dexmedetomidine-propofol combination were suitable and satisfactory for AFOI. However, ketofol was more advantageous in offering faster onset of sedation, shorter intubation time, stable hemodynamic profile, as well as higher anesthesiologist’s satisfaction when compared to dexmedetomidine-propofol.
Cortiva Versus AlloDerm Ready-to-use in Prepectoral and Submuscular Breast Reconstruction: Prospective Randomized Clinical Trial Study Design and Early Findings

Background: Several acellular dermal matrices (ADMs) can be used to provide soft-tissue support for post- and prepectoral prosthetic breast reconstructions. Yet, several recent meta-analysis suggest that due to a lack of rigorous evaluation in the setting of head-to-head prospective randomized control trials, few reliable conclusions regarding performance outcomes can be drawn. We compare Cortiva 1 mm to AlloDerm RTU in the setting of submuscular reconstruction in one study, and prepectoral in the second. Moreover, we present the findings from the interim analysis in our submuscular study. Methods: Using a single-blinded prospective randomized control trial design, we compare outcomes in 180 patients undergoing submuscular breast reconstruction with 16 × 8 cm ADM support (either Cortiva 1 mm or AlloDerm RTU). A parallel study evaluates 16 × 20 cm sheets of these ADMs in 180 patients undergoing prepectoral reconstructions. Time to drain removal, complications, fill volumes, patient-reported outcomes, and narcotic consumption are prospectively evaluated. Results: Interim analysis of 59 breasts in the submuscular study arm (Cortiva n = 31; AlloDerm n = 28) revealed no statistically significant differences with respect to outcome. At the time of interim analysis, the AlloDerm RTU group contained a higher proportion of never-smokers (P = 0.009), while patients implanted with Cortiva 1 mm received a larger tissue expander (P = 0.02). Conclusion: We present a protocol for a robust randomized control trial to evaluate outcomes in both submuscular and prepectoral prosthetic breast reconstruction assisted by 2 distinct types of ADM. Our interim analysis reveals no evidence of inferiority of outcomes in a comparison of AlloDerm to Cortiva.