Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Omics and Statistical Learning Integration for the Discovery and Validation of Novel Diagnostic Signatures in Colorectal Cancer

The advancement of bioinformatics and machine learning has facilitated the discovery and validation of omics-based biomarkers. This study employed a novel approach combining multi-platform transcriptomics and cutting-edge algorithms to introduce novel signatures for accurate diagnosis of colorectal cancer (CRC). Different random forests (RF)-based feature selection methods including the area under the curve (AUC)-RF, Boruta, and Vita were used and the diagnostic performance of the proposed biosignatures was benchmarked using RF, logistic regression, naïve Bayes, and k-nearest neighbors models. All models showed satisfactory performance in which RF appeared to be the best. For instance, regarding the RF model, the following were observed: mean accuracy 0.998 (standard deviation (SD) < 0.003), mean specificity 0.999 (SD < 0.003), and mean sensitivity 0.998 (SD < 0.004). Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Some biomarkers were found to be enriched in epithelial cell signaling in Helicobacter pylori infection and inflammatory processes. The overexpression of TGFBI and S100A2 was associated with poor disease-free survival while the down-regulation of NR5A2, SLC4A4, and CD177 was linked to worse overall survival of the patients. In conclusion, novel transcriptome signatures to improve the diagnostic accuracy in CRC are introduced for further validations in various clinical settings.
Casting a Spotlight on the Right Ventricle in Systemic Sclerosis

Pulmonary arterial hypertension (PAH) and other pulmonary issues such as interstitial fibrosis have emerged as the leading causes of mortality in systemic sclerosis (SSc). 1 Whereas scleroderma renal crisis was once the leading cause of mortality among SSc patients, PAH now accounts for 26% of SSc-related mortalities.1 This is in part because, among those with World Health Organization (WHO) Group I PAH, the subset of systemic sclerosis-associated PAH (SSc-PAH) experiences disproportionately worse morbidity, mortality, and response to pulmonary vasodilator therapy. Recent studies have revealed that the key factor in this discrepancy is likely inadequate compensation of the right ventricle (RV) in SSc-PAH. RV compensation is paramount in PAH, and failure of RV adaptation leads to inadequate coupling between RV contractility and the increased pulmonary arterial afterload of PAH. Our group and others have shown that SSc-PAH patients demonstrate decreased RV contractile function, both at rest2 and with exercise stress,3 when compared to those with idiopathic PAH. Furthermore, we recently showed that this in vivo RV contractile dysfunction closely correlates with underlying defects in RV sarcomere contractility, directly measured from RV myocytes isolated from human SSc-PAH patients. This article is protected by copyright. All rights reserved.
Clinical Features and Prognostic Factors in Elderly Ewing Sarcoma Patients

BACKGROUND Elderly patients with Ewing sarcoma have a very poor prognosis, and treatment remains a challenge. However, the outcomes and potential prognostic factors of elderly Ewing sarcoma patients are rarely documented. Therefore, we investigated the prognosis of this special cohort and determine independent prognostic factors. MATERIAL AND METHODS A cohort of Ewing sarcoma patients aged over 40 years from 1973 to 2015 was identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and a Cox proportional hazard regression model were used for the prognostic analysis. RESULTS A total of 162 patients were included with a mean age of 53 years. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates of the entire group were 43.7% and 47.9%, respectively. The sex, location, tumor size, and radiation treatment had no effect on survival outcomes on univariate analysis. Tumor stage, surgery, and chemotherapy were significant indicators of both OS and CSS on multivariable analysis. CONCLUSIONS Surgery in combination with chemotherapy had a significant survival benefit in elderly Ewing sarcoma patients and should be recommended.
Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model

Resistance to endocrine therapy remains a clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer. We investigated if adding a traditional Asian herbal mixture consisting of 12 herbs, called Jaeumkanghwa-tang (JEKHT), to tamoxifen (TAM) therapy might prevent resistance and recurrence in the ER+ breast cancer model of 7,12-dimethylbenz[a]anthracene (DMBA)-exposed Sprague–Dawley rats. Rats were divided into four groups treated as follows: 15 mg/kg TAM administered via diet as TAM citrate (TAM only); 500 mg/kg JEKHT administered via drinking water (JEKHT only group); TAM + JEKHT and no treatment control group. The study was replicated using two different batches of JEKHT. In both studies, a significantly higher proportion of ER+ mammary tumors responded to TAM if animals also were treated with JEKHT (experiment 1: 47% vs 65%, P = 0.015; experiment 2: 43% vs 77%, P < 0.001). The risk of local recurrence also was reduced (31% vs 12%, P = 0.002). JEKHT alone was mostly ineffective. In addition, JEKHT prevented the development of premalignant endometrial lesions in TAM-treated rats (20% in TAM only vs 0% in TAM + JEKHT). Co-treatment of antiestrogen-resistant LCC9 human breast cancer cells with 1.6 mg/mL JEKHT reversed their TAM resistance in dose–response studies in vitro. Several traditional herbal medicine preparations can exhibit anti-inflammatory properties and may increase anti-tumor immune activities in the tumor microenvironment. In the tumors of rats treated with both JEKHT and TAM, expression of Il-6 (P = 0.03), Foxp3/T regulatory cell (Treg) marker (P = 0.033) and Tgfβ1 that activates Tregs (P < 0.001) were significantly downregulated compared with TAM only group. These findings indicate that JEKHT may prevent TAM-induced evasion of tumor immune responses.
Actinidia arguta (Hardy Kiwi) Root Extract Exerts Anti-cancer Effects via Mcl-1-Mediated Apoptosis in Cholangiocarcinoma

Abstract Cholangiocarcinoma (CCA) is a highly aggressive and chemoresistant liver malignancy. Thus, identification of strategies to overcome insensitivity to apoptosis and growth inhibition is a growing focus of research in this malignancy. This study evaluated the potential anti-cancer effects of an ethanol extract from the Actinidia arguta (Hardy Kiwi) root (RAE) on CCA. Our data demonstrated that RAE decreased cell viability and induced apoptosis by activation of Caspase 3, Caspase 8, and Poly (ADP-ribose) polymerase (PARP) in two CCA cell lines. RAE induced a decrease in Mcl-1 in cultured CCA cells and in xenograft CCA tumors. Administration of RAE every other day led to significant growth inhibition in tumor burden xenograft CCA mice. Western blotting analysis of paired human CCA and normal adjacent tissues from the same patient revealed that CCA tissues exhibited significantly higher Mcl-1 expression than normal tissues. Taken together, our findings demonstrated the anti-cancer effects of RAE on CCA both in vitro and in vivo. These data suggest that RAE may be a promising anti-CCA agent and could be beneficial in the treatment of CCA through the targeting of Mcl-1.
Platelet transfusions and mortality in necrotizing enterocolitis

Prior studies have suggested an association between platelet transfusions (PTXs) and worse outcomes among infants with necrotizing enterocolitis (NEC), potentially mediated by proinflammatory factors released by platelets. However, the effects of storage on platelet proinflammatory factor release and the confounding role of illness severity on NEC outcomes have not been determined.
Circulating androgen levels before and after oophorectomy in premenopausal and postmenopausal women

Abstract Objective: This study aimed to determine the effect of oophorectomy on baseline serum levels of androgens and estrogens in premenopausal and postmenopausal women. Methods: Fourteen premenopausal and 10 postmenopausal women underwent total hysterectomy and bilateral oophorectomy for benign disease of the uterus. Serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol-17β-glucuronide (3α-diol G), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by highly specific immunoassays prior to surgery and 2 weeks afterward. Free T and free E2 were calculated. Differences were determined between preoperative (preop) and postoperative (postop) samples, and between premenopausal and postmenopausal women. Results: In premenopausal women, postop levels of total and free T, DHT, and total and free E2 decreased significantly from preop. Postop levels of DHEAS, A, 3α-diol G, and SHBG were decreased, but not significantly different from preop. In postmenopausal women, postop levels of total and free T and total and free E2 decreased significantly from preop, but there was little change in the other compounds. Significant differences in the mean change from baseline between premenopausal and postmenopausal women were observed only for E1 and total and free E2. Conclusion: The significant decrease in serum T in postmenopausal women following oophorectomy adds to the evidence that the postmenopausal ovary continues to produce T.
Multi-step genomic dissection of a suspected intra-hospital Helicobacter cinaedi outbreak

Helicobacter cinaedi is an emerging pathogen causing bacteraemia and cellulitis. Nosocomial transmission of this microbe has been described, but detailed molecular-epidemiological analyses have not been performed. Here, we describe the results of a multi-step genome-wide phylogenetic analysis of a suspected intra-hospital outbreak of H. cinaedi that occurred in a hospital in Japan. The outbreak was recognized by the infectious control team (ICT) of the hospital as a sudden increase in H. cinaedi bacteraemia. ICT defined this outbreak case based on 16S rRNA sequence data and epidemiological information, but were unable to determine the source and route of the infections. We therefore re-investigated this case using whole-genome sequencing (WGS). We first performed a species-wide analysis using publicly available genome sequences to understand the level of genomic diversity of this under-studied species. The clusters identified were then separately analysed using the genome sequence of a representative strain in each cluster as a reference. These analyses provided a high-level phylogenetic resolution of each cluster, identified a confident set of outbreak isolates, and discriminated them from other closely related but distinct clones, which were locally circulating and invaded the hospital during the same period. By considering the epidemiological data, possible strain transmission chains were inferred, which highlighted the role of asymptomatic carriers or environmental contamination. The emergence of a subclone with increased resistance to fluoroquinolones in the outbreak was also recognized. Our results demonstrate the impact of the use of a closely related genome as a reference to maximize the power of WGS.
White Matter Connectome Edge Density in Children with Autism Spectrum Disorders: Potential Imaging Biomarkers Using Machine-Learning Models

Prior neuroimaging studies have reported white matter network underconnectivity as a potential mechanism for autism spectrum disorder (ASD). In this study, we examined the structural connectome of children with ASD using edge density imaging (EDI), and then applied machine-learning algorithms to identify children with ASD based on tract-based connectivity metrics. Boys aged 8-12 years were included: 14 with ASD and 33 typically developing children. The edge density (ED) maps were computed from probabilistic streamline tractography applied to high angular resolution diffusion imaging. Tract-based spatial statistics was used for voxel-wise comparison and coregistration of ED maps in addition to conventional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Tract-based average DTI/connectome metrics were calculated and used as input for different machine-learning models: naïve Bayes, random forest, support vector machines (SVMs), and neural networks. For these models, cross-validation was performed with stratified random sampling ( × 1,000 permutations). The average accuracy among validation samples was calculated. In voxel-wise analysis, the body and splenium of corpus callosum, bilateral superior and posterior corona radiata, and left superior longitudinal fasciculus showed significantly lower ED in children with ASD; whereas, we could not find significant difference in FA, MD, and RD maps between the two study groups. Overall, machine-learning models using tract-based ED metrics had better performance in identification of children with ASD compared with those using FA, MD, and RD. The EDI-based random forest models had greater average accuracy (75.3%), specificity (97.0%), and positive predictive value (81.5%), whereas EDI-based polynomial SVM had greater sensitivity (51.4%) and negative predictive values (77.7%). In conclusion, we found reduced density of connectome edges in the posterior white matter tracts of children with ASD, and demonstrated the feasibility of connectome-based machine-learning algorithms in identification of children with ASD.
Sentinel lymph node mapping of the canine anal sac using lymphoscintigraphy: A pilot study.

Sentinel lymph node mapping and biopsy are important parts of oncologic staging in human medicine. Sentinel lymph node mapping enables identification of the first lymph node to receive lymphatic drainage while avoiding unnecessary lymph node dissection. Anal sac adenocarcinoma is the most common malignant neoplasm of the canine perineal area. For dogs with anal sac adenocarcinoma, lympadenectomy and metastasis to the iliosacral lymphocentrum are negative prognostics indicators. The objectives of this prospective, two by two, crossover pilot study were to establish the feasibility of lymphoscintigraphy using Technetium-99 sulfur colloid of the canine anal sac of healthy dogs, compare two injection techniques, and the time for identification of sentinel lymph nodes using each technique. We hypothesized that both intramural and perimural injections of the canine anal sac would identify similar sentinel lymph node drainage. The sentinel lymph node was identified in all dogs using either technique. Intramural injection of the canine anal sac showed radiopharmaceutical uptake faster than perimural injection technique (P = 0.040). There was concordance between intramual and perimural techniques for the sentinel lymph node identified in 50% of cases. A sacral lymph node was identified as sentinel in three of eight dogs (37.5%). Lymphoscintigraphy of the canine anal sac is safe and feasible in normal dogs; however, the method of injection technique seems to have a significant effect on the sentinel lymph node identified.
The Association of Whole Grain Intake and Fasting Insulin in a Biracial Cohort of Young Adults: The CARDIA Study.

Background Whole grain consumption may influence insulin through beneficial effects on satiety and body weight, intestinal absorption, or the action of specific nutrients or constituents. Design and Methods We examined the associations of whole grain intake, assessed by a diet history interview at baseline (year 0) and year 7, with body mass index (BMI), waist-hip ratio (WHR), and fasting insulin in 3,627 Black and White adults in the Coronary Artery Risk Development in Young Adults Study (CARDIA). We estimated year 0 and year 7 cross-sectional associations accounting for correlation between years using repeated measures regression. Results After adjustment for age, education, energy intake, CARDIA field center, physical activity, alcohol consumption, and cigarette smoking, whole grain consumption was unrelated to WHR and inversely related to body mass index only in Whites at year 7. Whole grain consumption was inversely related to fasting insulin in Whites at year 0 and Black men and Whites at year 7. Mean differences for year 7 fasting insulin between the least vs. most frequent categories of whole grain consumption (0-2 vs. > 9 times/week) were 2.2, 1.0 and 1.0 μU/mL in Black men, white men, and white women, respectively (p < 0.05). The inverse association of whole grain intake and fasting insulin remained significant (p < 0.05) after adjustment for body mass index. Potentially mediating nutrients explaining part of the relationship between whole grain intake and fasting insulin were dietary magnesium and fiber. Conclusions The independent inverse relationship between whole grain consumption and fasting insulin levels may have important public health implications in light of the low consumption of whole grains and the increasing prevalence of obesity and diabetes in the US.
Risk of peripheral artery disease in human immunodeficiency virus infected individuals.

According to the report from the World Health Organization (WHO), 1.8 million individuals become HIV infected every year (1). Several studies have demonstrated higher incidence, prevalence and progression of subclinical atherosclerosis in HIV infected individuals as compared to general population despite optimal control of traditional risk factors (2,3).
A Plant-Based Meal Increases Gastrointestinal Hormones and Satiety More Than an Energy- and Macronutrient-Matched Processed-Meat Meal in T2D, Obese, and Healthy Men: A Three-Group Randomized Crossover Study

Gastrointestinal hormones are involved in regulation of glucose metabolism and satiety. We tested the acute effect of meal composition on these hormones in three population groups. A randomized crossover design was used to examine the effects of two energy- and macronutrient-matched meals: a processed-meat and cheese (M-meal) and a vegan meal with tofu (V-meal) on gastrointestinal hormones, and satiety in men with type 2 diabetes (T2D, n = 20), obese men (O, n = 20), and healthy men (H, n = 20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 min. Visual analogue scale was used to assess satiety. We used repeated-measures Analysis of variance (ANOVA) for statistical analysis. Postprandial secretion of GLP-1 increased after the V-meal in T2D (by 30.5%; 95%CI 21.2 to 40.7%; p < 0.001) and H (by 15.8%; 95%CI 8.6 to 23.5%; p = 0.01). Postprandial plasma concentrations of amylin increased in in all groups after the V-meal: by 15.7% in T2D (95%CI 11.8 to 19.6%; p < 0.001); by 11.5% in O (95%CI 7.8 to 15.3%; p = 0.03); and by 13.8% in H (95%CI 8.4 to 19.5%; p < 0.001). An increase in postprandial values of PYY after the V-meal was significant only in H (by 18.9%; 95%CI 7.5 to 31.3%; p = 0.03). Satiety was greater in all participants after the V-meal: by 9% in T2D (95%CI 4.4 to 13.6%; p = 0.004); by 18.7% in O (95%CI 12.8 to 24.6%; p < 0.001); and by 25% in H (95%CI 18.2 to 31.7%; p < 0.001). Our results indicate there is an increase in gut hormones and satiety, following consumption of a single plant-based meal with tofu when compared with an energy- and macronutrient-matched processed-meat meat and cheese meal, in healthy, obese and diabetic men.
MARKALI ÜRÜN İLE İLGİLİ TÜKETİCİ DÜŞÜNCELERİNİN BELİRLENMESİ ÜZERİNE BİR ARAŞTIRMA

Pazarlama dunyasindaki yogun rekabet ortaminda tuketiciler, ayni urun grubuna ait pek cok farkli marka arasinda surekli olarak tercih yapmak durumunda kalmaktadirlar. Bu noktada marka degeri, marka cagrisimi, marka sadakati gibi kavramlar bu tercihleri dogrudan etkilemektedir. Markali urunun tuketicide yaptigi cagrisim, tuketici temelli marka degeri anlayisinin da dogmasina yol acmistir. Buna gore tuketiciler, markali urun kavramina oznel tepkiler vermekte, satin alma davranislarini da bu tepkiler dogrultusunda duzenlemektedirler. Tuketicilerin verdigi tepkilerin oznel olmasi, isletmelerin tuketici davranislari konusunda daha hassas olmalarina yol acmis, uzun vadede de tuketici temelli marka degeri anlayisinin isletmeler tarafindan benimsenmesi sonucunu dogurmustur. Her musteri farkli bir sosyo-ekonomik yapiya, farkli bir kulture, farkli bir egitim ve gelir duzeyine sahip oldugu icin, her tuketicinin markali urun olgusuna verdigi tepkiler farkli olabilmektedir. Yapilan calismada, markali urunlerle ilgili tuketici dusuncelerini ortaya koyabilmek icin Edirne Ilinde 500 kisiye anket yapilmistir. Elde edilen veriye, SPSS 20 istatistiki paket programi kullanilarak frekans dagilimi, acimlayici faktor analizi, guvenilirlik analizi, dogrulayici faktor analizi yapilmistir. Acimlayici Faktor analizi sonucu 5 alt boyut (Guvenilir ve Dayanikli, Kalite-Fiyat iliskisi, Reklam ve Musteri Memnuniyeti, Prestij, Marka Bagimliligi) belirlenmistir. Acimlayici faktor analizi ile belirlenen faktorlerin, faktor yapilarinin uygunlugunu ortaya koymak amaciyla dogrulayici faktor analizi yapilmistir. Daha sonra, Markali Urun ile ilgili Tuketici Dusunceleri Olceginin alt boyutlarina hangi testin yapilip yapilmayacagini belirlemek icin Kolmogorov Smirnov testi yapilmistir. Dagilimin normal olmadigina karar verilerek Kruskal Wallis ve Mann-Whitney U testleri uygulanmistir. Test sonuclarinda, Markali Urun ile ilgili Tuketici Dusunceleri Olceginin alt boyutlarindan; Guvenilir ve Dayanikli olmasi (F1), Kalite- Fiyat iliskisi (F2), Reklam ve Musteri Memnuniyeti(F3), Prestij(F4), Marka Bagimliligi(F5) faktorlerinin cinsiyete gore farklilik gosterdigi, Kalite- Fiyat iliskisi (F2), , Prestij(F4), Marka Bagimliligi(F5) faktorlerinin yasa gore, Guvenilir ve Dayanikli olmasi (F1), Reklam ve Musteri Memnuniyeti(F3), Marka Bagimliligi(F5) faktorlerinin egitim ve meslege gore, Marka Bagimliligi(F5) faktorunun medeni duruma gore, Guvenilir ve Dayanikli olmasi (F1), Kalite- Fiyat iliskisi (F2), Reklam ve Musteri Memnuniyeti(F3), Prestij(F4)faktorlerinin gelire gore farklilik gosterdigi tespit edilmistir.
Hypertension Assessment Using Photoplethysmography: A Risk Stratification Approach

Hypertension is a common chronic cardiovascular disease (CVD). Early screening and diagnosis of hypertension plays a major role in its prevention and in the control of CVDs. Our study discusses the early screening of hypertension while using the morphological features of photoplethysmography (PPG). Numerous morphological features of PPG and its derivative waves were defined and extracted. Six types of feature selection methods were chosen to screen and evaluate these PPG morphological features. The optimal features were comprehensively analyzed in relation to the physiological processes of the cardiovascular circulatory system. Particularly, the intrinsic relation and physiological significance between the formation process of systolic blood pressure (SBP) and PPG morphology features were analyzed in depth. A variety of linear and nonlinear classification models were established for the comparison trials. The F1 scores for the normotension versus prehypertension, normotension and prehypertension versus hypertension, and normotension versus hypertension trials were 72.97%, 81.82%, and 92.31%, respectively. In summary, this study established a PPG characteristic analysis model and established the intrinsic relationship between SBP and PPG characteristics. Finally, the risk stratification of hypertension at different stages was examined and compared based on the optimal feature subset.