Miracle-dz/UniFAR-FTUs huggingface dataset:
Downregulation of CDH16 in Papillary Thyroid Cancer and Its Potential Molecular Mechanism Analysed by qRT-PCR, TCGA and in silico Analysis

Objective Thyroid cancer has the highest prevalence among the cancer types that affect the endocrine system; however, its molecular mechanisms are not yet determined. Cadherin-16 (CDH16) plays an important role in the tumorigenesis of human cancers, but its influence on papillary thyroid cancer (PTC) is poorly investigated. This study aimed to explore the role of CDH16 in PTC. Methods We performed quantitative real-time polymerase chain reaction to investigate CDH16 expression in PTC. The clinical significance of CDH16 expression in PTC was then evaluated using The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis was also conducted to determine the potential molecular mechanisms of CDH16. Results CDH16 was remarkably downregulated in PTC tumors compared with that in corresponding normal thyroid tissues in the local and TCGA cohorts. This downregulation was associated with unfavorable clinicopathological features, including histological type, high tumor stage, aggressive lymph node metastasis (LNM), and advanced clinical stage. In addition, logistic analyses revealed that the reduced expression of CDH16 can aggravate the risk of LNM in PTC. Bioinformatics analysis indicated that the co-expressed CDH16 genes mainly participated in signaling the cancer-related pathways. Conclusion CDH16 is involved in PTC progression and acts as an LNM-related gene in PTC.
Type C Personality and Depression Among Newly Diagnosed Breast Cancer Patients: The Mediating Role of Sense of Coherence

Purpose This study aims to explore the mediating role of sense of coherence in the relationship of type C personality and depression among newly diagnosed breast cancer patients. Methods A descriptive and correlational survey was conducted in 600 breast cancer patients aged ≥18 years from September 2018 to March 2019 in Zhengzhou, China. The demographic questionnaire, Cancer Behavior Scale, Sense of Coherence Scale and Hamilton Depression Scale were included in this study. Data analysis was performed by correlation analysis, multiple linear regression analysis, and structural equation modeling. Results The valid questionnaires were 575 (effective response rate: 95.8%). The score of sense of coherence was negatively correlated with type C personality and depression (r = −0.41, P < 0.01; r = −0.58, P < 0.01); the score of type C personality and depression were positively correlated (r = 0.51, P < 0.01). The results of multiple linear regression analysis revealed that the effect of type C personality on depression was partly mediated by sense of coherence, which was confirmed by structural equation modeling. The mediation effect accounts for 45.2% (0.269/0.594) of the total effect. Conclusion The results of this study revealed that sense of coherence as a partial mediating role is essential for reducing the influence of type C personality on depression. Early and targeted psychological interventions on sense of coherence are needed to alleviate the symptom of depression in newly diagnosed breast cancer patients.
Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence

Abstract Levonadifloxacin and its prodrug alalevonadifloxacin are novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone, formulated for intravenous and oral administration, respectively. Various in vitro and in vivo studies have established their antimicrobial spectrum against clinically significant Gram-positive, Gram-negative, atypical, and anaerobic pathogens. The potent activity of levonadifloxacin against MRSA, quinolone-resistant Staphylococcus aureus, and hetero-vancomycin-intermediate strains is an outcome of its well-differentiated mechanism of action involving preferential targeting to DNA gyrase. Potent anti-staphylococcal activity of levonadifloxacin was also observed in clinically relevant experimental conditions such as acidic pH, the intracellular environment, and biofilms, suggesting that the drug is bestowed with enabling features for the treatment of difficult-to-treat MRSA infections. Levonadifloxacin also retains clinically relevant activity against resistant respiratory pathogens such as macrolide- and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis and, in conjunction with clinically established best-in-class human epithelial lung fluid concentration, has promising potential in the management of recalcitrant respiratory infections. Attractive features, such as resistance to NorA efflux, divergent mechanism of action in S. aureus, cidality against high-inoculum cultures, and low mutant prevention concentration, are likely to confer favorable resistance-suppression features to both agents. In vivo studies have shown promising efficacy in models of acute bacterial skin and skin structure infection, respiratory infections, pyelonephritis, and peritonitis at human-equivalent mouse doses. Both formulations were well tolerated in multiple phase I studies and overall showed a dose-dependent exposure. In particular, oral alalevonadifloxacin showed excellent bioavailability (~90%), almost mirroring the pharmacokinetic profile of intravenous levonadifloxacin, indicating the prodrug’s seamless absorption and efficient cleavage to release the active parent drug. Hepatic impairment studies showed that clinical doses of levonadifloxacin/alalevonadifloxacin are not required to be adjusted for various degrees of hepatic impairment. With the successful completion of phase II and phase III studies for both levonadifloxacin and alalevonadifloxacin, they represent clinically attractive therapeutic options for the treatment of infections caused by multi-drug-resistant Gram-positive organisms. Herein, we review the current evidence on therapeutically appealing attributes of levonadifloxacin and alalevonadifloxacin, which are based on a range of non-clinical in vitro and in vivo investigations and clinical studies.
Tibial Plateau Leveling Osteotomy for Cranial Cruciate Ligament Rupture in Canines: Patient Selection and Reported Outcomes

Abstract Cranial cruciate ligament (CCL) rupture is one of the most common causes of pelvic limb lameness in dogs. In a CCL deficient stifle, joint lameness develops from cranial tibial translation in relation to the distal femoral condyles. The tibial plateau leveling osteotomy (TPLO) is a well-described surgical procedure that neutralizes tibiofemoral shear force by altering the tibial plateau via a proximal tibial osteotomy, and subsequently restores normal limb function. Current literature for the TPLO was reviewed and used to describe the optimal patient selection and to report clinical outcome with the TPLO in comparison to other surgical options for CCL rupture. The clinical outcomes reported to date, particularly those utilizing objective outcome data, support the TPLO as being able to consistently return dogs to normal limb function with a low risk for long-term morbidity. The TPLO procedure was found to be widely applicable to dogs ranging from small breed to large and giant breed, and does not appear to have some of the limitations that exist with alternative surgical options. This review concludes that the TPLO is an excellent treatment option for any dog with CCL rupture due to the excellent long-term outcome and high rate of owner satisfaction previously reported. Despite these conclusions, it is important to remember that treatment selection for CCL rupture remains dependent on multiple considerations including patient factors, surgeon experience, and costs.
Characterization of Antibiotic-Susceptibility Patterns, Virulence Factor Profiles and Clonal Relatedness in Proteus mirabilis Isolates from Patients with Urinary Tract Infection in Iran

Purpose Proteus mirabilis is one of the most important agents of urinary tract infection (UTI). As there are limited data abou the pathogenicity P. mirabilis isolated from Iran, we investigated the virulence characteristics and antibiotic resistance in the isolates. Finally, the genotypic patterns were evaluated by Pulse field gel electrophoresis (PFGE). Methods A total of 110 isolates of P. mirabilis causing UTIs were isolated from patients in Tehran, Iran. The virulence characteristics and antimicrobial susceptibility were assayed using phenotypic methods. Extended-spectrum β-lactamases (ESBLs) production was assayed by the combination disk diffusion test (CDDT). Presence of virulence genes and antimicrobial-resistant genes was detected by Polymerase chain reaction (PCR). Finally, thirty-three isolates were selected for PFGE. Results All isolates showed the ability of biofilm and hemolysin formation. Antibiotic resistance ranged from 59.1% about cotrimoxazole to 2.7% about amoxicillin-clavulanic acid. Sixteen (14.5%) of the isolates were classified as multi-drug resistant (MDR). All isolates amplified mrpH, mrpA, pmfA, ureG and hpmA genes. Furthermore, the prevalence of zapA, fliC, ptaA, and ucaA genes was 98.2%, 98.2%, 95.5%, and 95.5%, respectively. The prevalence of plasmid-mediated quinolone resistance (PMQR) genes was 4.5% and 0.9% for aac(6ʹ)-Ib-cr and qnrA, respectively. Twenty-eight pulsotypes were detected among the 33 isolates by PFGE that pulsotypes 1, 2 and 4 with two isolates and pulsotype 3 with three isolates were the most prevalent ones. Conclusion It was found that the P. mirabilis isolates had high frequency of virulence factors. In addition, antibiotic resistance to some antibiotics and also production of ESBLs is alarming and shows the need for hygienic procedures to prevent the dissemination of antibiotic resistance. Although PFGE showed genetic diversity among the isolates, finding of several pulsotypes among the isolates should be considered an alarm to prevent these infections in hospital environments.
Prognostic Significance of FKBP14 in Gastric Cancer

Introduction Although our understanding on gastric cancer biology is better than a decade ago, its practical effect on screening and diagnosis remains limited. Moreover, there are no markers that can be accurately used in the clinic to diagnose early-stage gastric cancer or monitor the patient’s response to therapy. Herein, we investigate whether FKBP14 is involved in the progression of gastric cancer. Methods The AGS cell line was chosen for over-expression analysis, whereas the SGC-7901 cell line was selected for knock-down analysis. AGS cells were transfected with an FKBP14 overexpression plasmid (AGS-PLV.O-FLAG). The expression pattern of FKBP14 in both cell lines was determined by Western blot and RT-PCR. Cell proliferation was assessed using Cell Counting Kit-8, whereas apoptosis was performed using flow cytometry. The expression of FKBP14 in 70 Chinese patients with gastric cancer was also investigated using tissue microarrays and compared with gastric cancer patients from The Cancer Genome Atlas. Results FKBP14 was highly expressed in SGC7901 and had a relatively low expression in AGS cells. Upregulation of FKBP14 in AGS cells promoted migration and invasion and inhibits apoptosis. Knock-down of FKBP14 resulted in a suppression in migration and invasion and promoted apoptosis in the SGC-7901 cell line. Effectively, gastric cancer patients had a higher expression of FKBP14, with a lower survival rate (P = 0.028). Patients with a high expression of FKBP14 were significantly correlated with lymph node metastasis (P =0.016), and an advanced histologic grade (P =0.021). Conclusion FKBP14 is often up-regulated in gastric cancer. Patients with a high expression of FKBP14 are usually associated with worse overall survival. FKBP14 is an oncogene in gastric cancer, and is a potential biomarker for GC diagnosis, invasion, and prognosis.
EUS-guided gallbladder drainage: a learning curve modified by technical progress

Abstract Introduction Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an efficacious and safe option for patients who cannot undergo cholecystectomy. It is a technically challenging procedure, requiring skills in EUS, and ERCP. The aim of this study was to define the learning curve for EUS-GBD. Patients and methods Consecutive patients undergoing EUS-GBD by a single operator were included from a prospective registry over 5 years. Demographics, procedure information, post-procedure follow-up data, and information on adverse events were collected. Non-linear regression and CUSUM analyses were conducted for the learning curve. Clinical success was defined as resolution of cholecystitis post-procedure. Results Forty-eight patients were included (58 % male, mean age 76 years). Twenty patients (42 %) had malignant cholecystitis. Most patients had lumen-apposing metal stents (LAMS) (15 mm, n = 29, 60 %; 10 mm, n = 8, 7 %). The remaining patients had FCSEMS (n = 9, 19 %) or plastic stents alone (n = 2, 4 %). Clinical success was achieved in 36 (86 %) of patients. Of the remaining 12, 7 were lost to follow-up and 5 had persistent cholecystitis. 9 patients (19 %) had adverse events including bleeding (n = 4), liver abscesses (n = 2), and hypotension. Two patients passed away post-procedure. Median procedure time was 41 minutes (range 16 – 121 min), with the 41-minute time occurring during the 19th procedure. Procedure durations further reduced, with the last 10 procedures being 20 minutes or under (nonlinear regression p value P < 0.0001). Conclusion Endoscopists experienced in EUS-GBD are expected to achieve a reduction in procedure time over successive cases, with efficiency reached at 41 minutes and a learning rate of 19 cases. Continued improvement is demonstrated with additional experience
Role of Olaparib as Maintenance Treatment for Ovarian Cancer: The Evidence to Date

Abstract PARP inhibitors have shown significant promise in the treatment of ovarian cancer. Olaparib is a PARP inhibitor that has been approved for maintenance for BRCA-mutated ovarian cancer in the recurrent and front-line setting as well as for treatment of BRCA-mutated ovarian cancer in patients who have received multiple prior lines of chemotherapy. In this review, we focus on the use of olaparib in the maintenance setting including the evidence to date, ongoing research, and future directions.
Comparative Results Between “Epi-Off” Conventional and Accelerated Corneal Collagen Crosslinking for Progressive Keratoconus in Pediatric Patients

Purpose The aim of our study was to evaluate the efficacy and safety of epi-off conventional and accelerated corneal collagen cross-linking in the treatment of progressive keratoconus in pediatric patients up to 4 years after treatment. Patients and methods Conventional (standard) CXL epi-off technique was performed in 37 eyes (S-CXL group) and accelerated CXL in 27 eyes (A-CXL group). Refraction, keratometry, cylindrical equivalent, spherical equivalent, slit lamp examination, pachymetry, corneal tomography, anterior segment ocular coherence tomography and visual acuity were performed up to 4 years. Results In the S-CXL group: the flat K values decreased from 47.41±3.39 D to 45.36±3.62 D at 4 years (p=0.004); steep K decreased from 51.98±4.11 to 50.21±4.81 D at 4 years (p=0.0078); mean K decreased with 1.99 D at 4 years (p=0.009). In the A-CXL group: the flat K values decreased from 46.97±4.17 D to 44.97±4.24 D at 4 years (p=0.048); steep K decreased from 50.55±4.10 D to 48.75±4.17 D at 4 years (p=0.0287); mean K decreased from 48.79±3.86 D to 46.86±4.11 D at 4 years (p=0.0356). The preoperative mean UCVA in the S-CXL group was 0.8 ±0.23 logMar and improved during the follow-up reaching 0.65 ±0.24 logMar at 4 years (p=0.072). The baseline mean UCVA in A-CXL group was 0.77±0.25 logMar and increased during the follow-up to 0.63 ±0.25 logMar at 4 years (p=0.0039). A similar improvement of BCVA was observed during the follow-up. Conclusion Epi-off conventional and accelerated CXL are efficient procedures for progressive keratoconus in pediatric patients. Accelerated and conventional CXL were comparable at all time points and both represent viable options for the therapy of KC in these patients.
Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T cell-mediated anti-tumor responses

The synthetic oligonucleotide SD-101 is a potent and specific agonist for toll-like receptor 9. Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade. To build upon this strategy, we studied the enhancement of SD-101 activities by combination with low-dose cyclophosphamide, a well-characterized agent with potentially complementary activities. In multiple mouse tumor models, we demonstrate substantial anti-tumor activity of the combination, compared to each single agent. Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors. Mechanistic studies encompassing global gene expression changes and characterization of immune cell infiltrates show the rapid, sequential induction of innate and adaptive responses and identify discrete contributions of SD-101 and cyclophosphamide. Importantly, these changes were prominent in tumors not injected directly with SD-101. Combination treatment resulted in creation of a permissive environment for a systemic anti-tumor immune response, including a reduction of intratumoral regulatory T cells (Tregs) and an increase in “M1” versus “M2” tumor-associated macrophage (TAM) phenotypes. Additionally, we observed increased immunogenic cell death as well as antigen processing in response to combination treatment.
Prenatal Exposure to Lead and Chromium is Associated with IL-13 Levels in Umbilical Cord Blood and Severity of Atopic Dermatitis: COCOA Study

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.
HIIT is not superior to MICT in altering blood lipids: a systematic review and meta-analysis

Objective To compare the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on adult lipid profiles; to identify training or participant characteristics that may determine exercise-induced change in total cholesterol (TC), triglycerides (TRG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Design Systematic review and meta-analysis. Data sources English language searches of several databases were conducted from inception until September 2019. Eligibility criteria for excluding studies Inclusion: (1) published randomised controlled human trials with group population n≥5; (2) intervention duration ≥4 weeks; (3) comparing HIIT with MICT; and (4) reporting pre–post intervention lipid measurements. Exclusion: subjects with chronic disease, <18 years, pregnant/lactating, in elite athletic training; and studies with a dietary or pharmaceutical intervention component. Results Twenty-nine data sets (mmol/L) of 823 participants were pooled and analysed. Neither HIIT nor MICT was better in decreasing TC (0.10 (−0.06 to 0.19), p=0.12, I2=0%), TRG (−0.05 (−0.11 to 0.01), p=0.10, I2=0%), LDL-C (0.05 (−0.06 to 0.17), p=0.37, I2=0%), or TC/HDL-C (−0.03 (−0.36 to 0.29), p=0.85, I2=0%). HIIT significantly raised HDL-C (0.07 (0.04 to 0.11), p<0.0001, I2=0%) compared with MICT. Conclusion Neither HIIT nor MICT is superior for altering TC, TRG, or LDL-C, or TC-HDL-C ratio. Compared with MICT, HIIT appeared to significantly improve HDL-C. Clinicians may prescribe either protocol to encourage participation in exercise and reduce cardiovascular risk. To raise HDL-C, HIIT may result in a larger effect size compared with MICT. PROSPERO registration number CRD42019136722.
LncRNA SNHG5 Promotes Proliferation of Glioma by Regulating miR-205-5p/ZEB2 Axis

Background Glioma is a common primary brain tumor with extremely poor prognosis outcomes. Increasing evidences have proved the relation between lncRNAs and glioma onset and progression. LncRNA SNHG5 involves in the biological activities of tumor cells, such as proliferation, migration and metastasis. Nevertheless, it is still necessary to explain the molecular mechanism and biofunction of SNHG5 in glioma. Materials and methods Quantitative real-time PCR (qRT-PCR) was performed to analyze expressions of SNHG5, miR-205-5p and ZEB2 in tumor tissues and cell lines. The cell counting kit-8 (CCK-8) assay, plate and soft agar colony formation assays were performed to evaluate cell proliferation ability. RNA immunoprecipitation assay and dual-luciferase reporter assay were used to confirm the interaction among SNHG5, miR-205-5p and ZEB2. The protein level of ZEB2 was measured by Western blot. Results Based on our findings, compared with normal tissues, the elevated expression of SNHG5 and decreased expression of miR-205-5p were observed in glioma tissues. The downregulation of SNHG5 exerted an obvious inhibitory effect on glioma cells in terms of their proliferation. With regard to the underlying mechanism, SNHG5 presented a direct inhibitory influence on miR-205-5p which targeted to the 3′-UTR region of zinc finger E-box binding homeobox 2 (ZEB2) mRNA. As a competing endogenous RNA (ceRNA), SNHG5 sponged miR-205-5p, regulating the expression of ZEB2 thereby. Conclusion These discoveries indicate that SNHG5 promotes proliferation of glioma by regulating miR-205-5p/ZEB2 axis.