Miracle-dz/UniFAR-FTUs huggingface dataset:
Low PTEN expression and overexpression of phosphorylated AktSer473 and AktThr308 are associated with poor overall survival in upper tract urothelial carcinoma

The PI3K/Akt signaling pathway serves an essential role in various cellular processes, including cell growth, survival, cell motility, angiogenesis and cell metabolism. Loss of PTEN expression and hyperactivation of Akt can result in tumorigenesis. Previous studies observed expression of the Akt protein and absence of the PTEN protein in bladder cancer and non-small cell lung carcinoma tissues. The aim of the present study was to evaluate the expression status and prognostic value of PTEN and the PI3K/Akt signaling pathway in Taiwanese patients with upper tract urothelial carcinoma (UTUC). Archival formalin-fixed, paraffin-embedded (FFPE) tissues from 65 UTUC cases were stained via immunohistochemistry for PTEN, phosphorylated (p)Akt serine (Ser)473 and pAkt threonine (Thr)308. The expression levels of each protein were significantly correlated with clinicopathological parameters. PTEN, pAktSer473 and pAktThr308 protein expression levels were higher in adjacent normal tissues compared with those in tumor tissues. Cytoplasmic PTEN protein expression levels were lower in high-stage tumors compared with those in low-stage tumors, and nuclear and cytoplasmic pAktThr308 protein expression levels were higher in high-grade tumors compared with those in low-grade tumors. Univariate analysis showed that high pathological tumor stage (pT2-4) [P=0.01; hazard ratio (HR)=3.40; 95% confidence interval (CI), 1.34–8.60], metastatic status (P=0.003; HR=3.55, 95% CI, 1.55–8.11), low cytoplasmic PTEN protein expression levels (P=0.016; HR=3.14; 95% CI, 1.24–7.95) and high cytoplasmic pAktSer473 protein expression levels (P=0.019, HR=2.71, 95% CI, 1.18–6.21) were predictive of poor overall survival. However, only metastatic status (P=0.031; HR=2.73; 95% CI, 1.10–6.78), low cytoplasmic PTEN protein expression levels (P=0.017; HR=3.29; 95% CI, 1.24–8.73) and high cytoplasmic pAktSer473 protein expression levels (P=0.027; HR=2.64; 95% CI, 1.12–6.23) remained significant in the multivariate analysis. Kaplan-Meier survival analysis showed that high T stage, metastasis, low expression levels of cytoplasmic PTEN protein and high expression levels of cytoplasmic pAktSer473 protein were significantly associated with poor survival (P=0.006, 0.001, 0.011 and 0.014, respectively). Co-expression of PTENlow/pAktSer473/high and pAktThr308/high phenotypes was associated with a less favorable overall survival (P=0.001). Overall, the present findings demonstrated that low expression levels of PTEN and high expression levels of pAktSer473 and pAktThr308 were predictors for poor overall survival in patients with UTUC.
Combined Administration of Bisphosphonates, Chemotherapeutic Agents, and/or Targeted Drugs Increases the Risk for Stage 3 Medication-Related Osteonecrosis of the Jaw: A 4-Year Retrospective Study

Objectives Patients with stage 3 medication-related osteonecrosis of the jaw (MRONJ) suffer from severe complications. Chemotherapeutic agents and targeted drugs are considered to be associated with the development of MRONJ. However, little is known regarding the association of those agents with stage 3 MRONJ. The purpose of this study is to analyze the comprehensive medication history of patients with advanced-stage MRONJ (stage 2 and stage 3) and evaluate the possible risk factors for stage 3 MRONJ. Patients and Methods. Sixty patients with advanced-stage MRONJ were involved in this retrospective study. Patients with developmental maxillofacial anomalies, previous radiation in the head and neck areas, and jaw bone tumors were excluded from the study. All patients were divided into two groups by their MRONJ stage (stage 2 or stage 3). Demographic and clinical characteristics, comprehensive medication data (bisphosphonates, chemotherapeutic agents, targeted drugs, and immunosuppressive agents), and results of serological biomarkers were recorded and compared between two groups. Univariate and multivariate logistic regressions were performed by SPSS 25.0 for evaluating risk factors of stage 3 MRONJ. Results Our results indicate that chemotherapy (adjusted OR = 3.43; 95% CI: 1.03 to 11.38), targeted drugs (adjusted OR = 3.69; 95% CI: 1.06 to 12.80), and maxillary lesions (adjusted OR = 4.26; 95% CI: 1.19 to 15.23) increase the risk of stage 3 MRONJ. Conclusion The outcome of this study justifies that chemotherapeutic agents and targeted drugs are probably risk factors for stage 3 MRONJ. In addition, the osteonecrosis in maxilla is more easily to develop into stage 3 MRONJ. Intense clinical observation is recommended in MRONJ patients with maxillary osteonecrosis and in those who concurrently administered bisphosphonates, chemotherapeutic agents, and/or targeted drugs. This trial is registered with ChiCTR2000032428.
Impact of Histological and Molecular Parameters on Prognosis of Oral Squamous Cell Carcinoma: Analysis of 290 Cases

Background Nodal metastasis is a critical factor in predicting the prognosis of oral squamous cell carcinoma (OSCC). When patients present with a clinically positive neck, the treatment of choice is radical neck dissection. However, management of a clinically negative neck is still a subject of significant controversy. Aim This study was carried out in order to propose a model to predict regional lymph node metastasis of OSCC using histological parameters such as tumour stage, tumour size, pattern of invasion (POI), differentiation of tumour, and host immune response, together with the expression levels of six biomarkers (periostin, HIF-1α, MMP-9, β-catenin, VEGF-C, and EGFR), and, furthermore, to compare the impact of all these parameters on recurrence and 3 yr and 5 yr survival rates. Materials and Method. Histological materials collected from the archives were used to evaluate histological parameters and immunohistochemical profiles. Standard methods were used for immunohistochemistry and for evaluation of results. Data related to recurrence and survival (3 and 5 years) was also recorded. Clinical data was collected from patients' records. Results Male to female ratio was 3 : 1. The commonest site of OSCC was the buccal mucosa, and majority of them were T3 or T4 tumours presented at stage 4. 62.5% of the tumours were well differentiated. Three-year and 5-year survival rates were significantly associated with lymph node metastasis and recurrence. POI was significantly correlated with tumour size, stage, 3-year survival, EGFR, HIF-1α, periostin, and MMP-9 (p < 0.05). Expression of EGFR showed a direct association with metastasis (p < 0.05). Conclusion POI, level of differentiation, and expression of EGFR are independent prognostic markers for lymph node metastasis. Therefore, these parameters may help in treatment planning of a clinically negative neck.
Preference and Experience of Colonic Examination for Participants Presenting to Hospitals with a Positive Fecal Immunochemical Test Result

Purpose Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination. Patients and Methods Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience. Results The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups. Conclusion Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more “comfortable” examination. Clinicians should therefore be aware of patients’ potential preference for noninvasive colorectal examinations.
CA125, CEA, CA19-9, and Heteroploid Cells in Ascites Fluid May Help Diagnose Peritoneal Carcinomatosis in Patients with Gastrointestinal and Ovarian Malignancies

Background This study explored the value of ascites and serum CA125, CEA, and CA19-9 levels and ascites DNA ploidy analysis for the diagnosis of peritoneal carcinomatosis (PC) in patients with gastrointestinal and ovarian malignancies, which can cause ascites and may disseminate peritoneally. Methods We measured ascites and serum levels of CA125, CEA, CA19-9 and performed an ascites DNA ploidy analysis in 58 patients with PC and 44 patients without PC. Results We found that a high expression level of CA125 in ascites fluid was associated with the occurrence of PC in patients with gastrointestinal and ovarian malignancies (P<0.001), and that high CEA and CA19- 9 levels in ascites fluid were associated with PC in patients with gastrointestinal malignancies (P=0.001, P=0.002). But, these tumor marker expression levels in ascites fluid were not significantly associated with the PC stage (P>0.05). We found similar serum levels of CA125, CEA, and CA19-9 between patients with gastrointestinal and ovarian malignancies and PC and those without PC (P>0.05). We found that the presence of three or more cells with heteroploid in the ascites samples was significantly associated with PC in gastrointestinal and ovarian malignancies (P<0.001). In addition, the best ROC curves and highest AUCs were achieved by combining the CA125 level and heteroploid cell analysis results (AUC for gastrointestinal and ovarian malignancies, 0.815, AUC for gastrointestinal malignancies, 0.873). Moreover, the combined ascites CA125 level and result of heteroploid cell analysis provided the best diagnostic sensitivity and specificity for PC (75.9% and 79.5%, respectively, in gastrointestinal and ovarian malignancies; 85.0% and 86.7%, respectively, in gastrointestinal malignancies). Conclusion Ascites levels of CA125, CEA, CA19-9, and heteroploid cells can be considered valuable markers for the diagnosis of PC in patients with gastrointestinal and ovarian cancer.
The Changing Face of Cystic Fibrosis and Its Implications for Screening

Early diagnosis, multidisciplinary care, and optimized and preventive treatments have changed the face of cystic fibrosis. Life expectancy has been expanded in the last decades. Formerly a pediatric disease, cystic fibrosis has reached adulthood. Mutation-specific treatments will expand treatment options and give hope for further improvement of quality of life and life expectancy. Newborn screening for CF fits perfectly into these care structures and offers the possibility of preventive treatment even before symptoms occur. Especially in countries without screening, newborn screening will fulfill that promise only with increased awareness and new care structures.
Postoperative New-Onset Atrial Fibrillation following Noncardiac Operations: Prevalence, Complication, and Long-Term MACE

Background Postoperative new-onset atrial fibrillation (POAF) is a common complication following cardiothoracic surgery, but little is known regarding its occurrence and outcome following noncardiothoracic surgery. This study was intended to examine the incidence of POAF in noncardiothoracic surgeries performed under general anesthesia and its effects on the length of hospitalization stay, short-term and long-term morbidity, and mortality. Methodology. We conducted a retrospective observational descriptive study. The study population consists of patients hospitalized in surgical wards from January 2014 to December 2017. Surgery was defined as noncardiac or thoracic procedure conducted under general anesthesia. Results A total of 24,125 general anesthesia operations were performed at 7 surgical wards. About two-fifth of the operations (40%) were operated electively, and the rest underwent emergency surgery. The mean age was 63.78 ± 11.50, and more than half (56.9%) of the participants were female. The prevalence of POAF was 2.69 per 1000 adult patients (95% CI: 2.11–3.43) and vary significantly among wards. The highest prevalence was observed after hip fixation and laparotomy surgeries (54.9 and 26.7 per 1000 patients, respectively). The median length of hospitalization was significantly higher in POAF patients (21.0 vs. 4.8 days, p < 0.001). Patients who developed POAF had significantly higher mortality rates, both inhospital (200 vs. 7.56 deaths per 1000, p=0.001) and 1 year (261.5 vs. 33.3 per 1000, p=0.001, respectively). There was no significant association between outcome and treatment modalities such as rate or rhythm control and anticoagulant use. Conclusion New-onset AF following noncardiac surgery is rare, yet poses significant clinical implications, both immediate and long-term. POAF is associated with a longer length of hospitalization and a significantly higher mortality rate, both in short- and long-term.
Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N1,N12-diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.
In-Hospital Complications and Readmission in Patients with Hemophilia Undergoing Hip or Knee Arthroplasty

Background: Individuals with hemophilia undergoing hip or knee arthroplasty are at risk for complications such as bleeding and infection. However, data on hospital length of stay (LOS) and readmission rates compared with nonhemophilic controls are lacking. This study compared the complication rates, LOS, and unplanned 30-day readmission rates between patients with hemophilia and nonhemophilic controls. Methods: This retrospective cohort study used the Pennsylvania Health Care Cost Containment Council (PHC4) database from 2007 to 2015 to compare outcomes in patients with hemophilia and nonhemophilic controls undergoing partial and total hip arthroplasty, knee arthroplasty, and revision knee arthroplasty. Results: A total of 118 patients with hemophilia and 3,811 controls were identified. Compared with controls, patients with hemophilia had a higher risk of bleeding complications after hip procedures (38.7% versus 16.1%, p = 0.003), a higher risk of surgical site infection after knee procedures (8.1% versus 1.1%, p < 0.001), longer median LOS after hip (6 versus 3 days, p < 0.001) and knee (5 versus 3 days, p < 0.001) procedures, and higher rates of unplanned 30-day readmission after hip (22.6% versus 4.1%, p < 0.001) and knee (10.3% versus 4.5%, p = 0.018) procedures. The most common reason for unplanned 30-day readmission in patients with hemophilia was bleeding or the patient’s underlying coagulopathy (25.1%). Conclusions: Patients with hemophilia undergoing hip or knee arthroplasty had a higher incidence of postoperative bleeding (hip procedures) and surgical site infections (knee procedures), longer LOS, and higher rates of unplanned 30-day readmission compared with nonhemophilic controls. Key limitations of our study include the potential for inaccurate coding, the relatively small number of patients in the hemophilia cohort, and the uneven distribution of procedure type in the hemophilia and control cohorts. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Factors Associated with Exercise-Induced Desaturation in Patients with Chronic Obstructive Pulmonary Disease

Purpose The 6-min walk test (6MWT) is a useful tool to assess the physiologic function in patients with chronic obstructive pulmonary disease (COPD). The recent study showed that patients with COPD with oxygen desaturation during the 6MWT had an increased risk of exacerbation and death compared with those without oxygen desaturation. This study aimed to explore the potential risk factors for exercise-induced desaturation (EID) in patients with COPD. Patients and Methods Adult patients with COPD were enrolled from the Chang Gung Research Database between January 2013 and January 2017. Age, sex, body mass index, underlying diseases, medications, and results of the pulmonary function tests and 6MWT were retrospectively collected and analyzed. Results Among 1768 patients with COPD, 932 (52.7%) had oxygen desaturation, and the other 836 (47.3%) had no desaturation during the 6MWT. The patients with EID had a shorter 6-min walk distance than those without desaturation (352.08±120.29 vs 426.56±112.56, p<0.0001). In the multivariate logistic regression analysis, older age, female sex, lower forced expiratory volume in 1 s, and comorbidity with atrial fibrillation (AF) were associated with oxygen desaturation during the 6MWT. Patients with EID had higher exacerbation frequency than those without desaturation in the 1-year follow-up period (0.59±1.50 vs 0.34±1.26, p<0.0001). Patients with COPD with AF also had a higher rate of exacerbation requiring emergency department visit or hospitalization in the 1-year follow-up. Conclusion This study demonstrates that older age, low FEV1, and female sex are risk factors for EID. Desaturation during 6MWT is related to frequent acute exacerbation of COPD in the 1-year follow-up.
Penicillin Impact on Survivorship, Development, and Adult Longevity of Drosophila melanogaster (Diptera: Drosophilidae)

Abstract Survivorship, developmental period, and adult longevity of the fruit fly, Drosophila melanogaster Meigen (Diptera: Drosophilidae), exposed to penicillin G, a beta-lactam antibiotic, was determined in laboratory testing. In the study, neonate larvae were placed and reared on dietary antibiotics at concentrations of 100, 200, 400, or 800 mg/L. All penicillin concentrations significantly decreased survivorship in an inverse relationship with third instars, pupae, and adults. Larvae fed on control diets of 0 mg/L of penicillin had a survival level of 91.00 ± 3.27% to third instar and pupation, and 89.00 ± 4.09% to adult emergence. Feeding on a diet containing the highest concentration of penicillin (800 mg/L) significantly decreased survivorship to third instar to 11.00 ± 2.59% (χ2 = 128.051; df = 1; P = 0.0001) and to pupation (χ2 = 131.233; df = 1; P = 0.0001) and adult emergence to approximately 10.00 ± 1.00% (χ2 = 124.832; df = 1; P = 0.0001). The highest concentration of dietary penicillin (800 mg/L) also significantly prolonged developmental time from neonate to third instars by 1.5 d (F = 17.229; df = 4; P = 0.0001) and from neonate to adult emergence by 3 d (F = 2.004; df = 4; P = 0.032). Compared to the control group, adult longevity was significantly reduced by the antibiotic in a dose-related manner. The use of this antibiotic in insect artificial rearing enables an extensive search of possible insecticidal action of penicillin with high dietary levels for agricultural purposes.
BALLI: Bartlett-Adjusted Likelihood-based LInear Model Approach for Identifying Differentially Expressed Gene with RNA-seq Data

Motivation Transcriptomic profiles can improve our understanding of the phenotypic molecular basis of biological research, and many statistical methods have been proposed to identify differentially expressed genes under two or more conditions with RNA-seq data. However, statistical analyses with RNA-seq data often suffer from small sample sizes, and global variance estimates of RNA expression levels have been utilized as prior distributions for gene-specific variance estimates, making it difficult to generalize the methods to more complicated settings. We herein proposed a Bartlett-Adjusted Likelihood based LInear mixed model approach (BALLI) to analyze more complicated RNA-seq data. The proposed method estimates the technical and biological variances with a linear mixed effect model, with and without adjusting small sample bias using Bartlett’s corrections. Results We conducted extensive simulations to compare the performance of BALLI with those of existing approaches (edgeR, DESeq2, and voom). Results from the simulation studies showed that BALLI correctly controlled the type-1 error rates at the various nominal significance levels, and produced better statistical power and precision estimates than those of other competing methods in various scenarios. Furthermore, BALLI was robust to variation of library size. It was also successfully applied to Holstein milk yield data, illustrating its practical value. Availability and Implementation BALLI is implemented as R package and freely available at http://healthstat.snu.ac.kr/software/balli/. Contact won1@snu.ac.kr Supplementary Information Supplementary data are available at Bioinformatics online
Effect of supplementation of Oregano (Origanum onites) Dried Leaves on the Intestinal Properties in Japanese Quails

1Department of Animal Nutrition, University of Veterinary and Animal Sciences, Lahore (CVAS, Jhang), Pakistan 2Department of Animal Nutrition, Afyon Kocatepe University, Afyonkarahisar 03200, Turkey 3Department of Pathology, Afyon Kocatepe University, Afyonkarahisar 03200, Turkey 4Department of Medical Services and Techniques, Bingol University, Bingol 12000, Turkey Article Information Received 02 November 2017 Revised 30 Decemb r 2017 Accepted 10 January 2018 Available online 28 May 2018