Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term response to first-line bevacizumab-based therapy in patients with metastatic breast cancer: results of the observational “LORENA” study

Background Randomized controlled trials of the first-line combination of bevacizumab and chemotherapy in patients with metastatic breast cancer (MBC) have shown improvements in tumor response and progression-free survival (PFS). Objective The aim of this ambispective, observational study (LORENA) was to describe the clinical characteristics of long-term responders to bevacizumab-based therapy. Patients and methods This study consisted of a retrospective and a prospective phase. During the retrospective phase, patients with HER2-negative MBC who were treated with bevacizumab-based first-line therapy were included. During the prospective phase, patients with PFS of ≥12 months were treated according to routine clinical practice procedures. Overall survival (OS) and PFS were estimated using the Kaplan–Meier method. Univariate and multivariate analyses of prognostic factors were performed. Results In total, 148 women were included (median age: 50 years; range: 29–81 years). The mean duration of exposure to bevacizumab was 18 months. The majority of patients experienced objective response (complete: 23%; partial: 57%). Median PFS was 22.7 months and median OS was 58.2 months. In multivariate analyses, patients receiving maintenance hormonal therapy (MHT) had longer PFS (P=0.002; hazard ratio [HR] =1.8) and OS (P=0.009; HR=2.0), while patients not previously treated with taxanes had longer OS (P<0.0001; HR =3.3). No unexpected adverse events were observed. Conclusion The results of this study suggest, that among long-term responders, first-line bevacizumab-based therapy is more effective in patients who had not been previously treated with taxanes, and that MHT provides additional therapeutic benefits by extending PFS and OS.
Polymorphisms of the Multidrug Pump ABCG2: A Systematic Review of Their Effect on Protein Expression, Function, and Drug Pharmacokinetics

The widespread expression and polyspecificity of the multidrug ABCG2 efflux transporter make it an important determinant of the pharmacokinetics of a variety of substrate drugs. Null ABCG2 expression has been linked to the Junior blood group. Polymorphisms affecting the expression or function of ABCG2 may have clinically important roles in drug disposition and efficacy. The most well-studied single nucleotide polymorphism (SNP), Q141K (421C>A), is shown to decrease ABCG2 expression and activity, resulting in increased total drug exposure and decreased resistance to various substrates. The effect of Q141K can be rationalized by inspection of the ABCG2 structure, and the effects of this SNP on protein processing may make it a target for pharmacological intervention. The V12M SNP (34G>A) appears to improve outcomes in cancer patients treated with tyrosine kinase inhibitors, but the reasons for this are yet to be established, and this residue’s role in the mechanism of the protein is unexplored by current biochemical and structural approaches. Research into the less-common polymorphisms is confined to in vitro studies, with several polymorphisms shown to decrease resistance to anticancer agents such as SN-38 and mitoxantrone. In this review, we present a systematic analysis of the effects of ABCG2 polymorphisms on ABCG2 function and drug pharmacokinetics. Where possible, we use recent structural advances to present a molecular interpretation of the effects of SNPs and indicate where we need further in vitro experiments to fully resolve how SNPs impact ABCG2 function.
The PROCLIPI international registry of early‐stage mycosis fungoides identifies substantial diagnostic delay in most patients

Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging.
Interactive Development of Cyber Physical Systems Using UETPN Model

This paper presents a novel approach to synthesise hybrid controllers. A two-phase multi-objective evolutive algorithm was used to generate Unified Enhanced Timed Petri Net (UETPN) models. These models combine capabilities of timed Petri-nets, fuzzy logic systems and simple arithmetic operators. They can handle both event-like and continuous inputs (and outputs). The first phase of the algorithm uses Koza style genetic programming combined with multi-objective methods such as NSGA-II and SPEA2 to obtain an initial model. The second phase improves the initial model with recombining the fuzzy rules with genetic algorithm GA. In order to generate UETPN models (with GP), an intermediate language was designed, called UETPN Lisp. Four example are presented to exemplify the potential of the orooosed framework.
Increased risk of incident nasopharyngeal carcinoma with exposure to air pollution

Background Nasopharyngeal carcinoma (NPC) is a race-specific malignancy. The nasal cavity is the main entry point for air pollutants or poisonous gases into the human body. However, the risk of NPC in populations exposed to air pollution remains unknown. Methods We combined data from the Taiwan Air Quality Monitoring Database (TAQMD) and the Longitudinal Health Insurance Database (LHID) to assess the risk of NPC in a population exposed to air pollution. Results Multivariate analysis revealed positive trends for the association between the risk of NPC and exposure to air pollution. After adjusting for potential covariates, the risk of developing NPC increased with the increase in nitrogen dioxide (NO2) and fine particulate matter (PM2.5) exposure concentrations from 1.39 to 2.28 and 2.01 to 1.97, respectively, compared to the risks at the lowest concentration levels. Conclusions We identified a significant risk of NPC in a population exposed to air pollution. However, this study had several limitations. Moreover, additional experimental and clinical studies on the associations between environmental factors and NPC risk are warranted.
Microwave Ablation in Intermediate Hepatocellular Carcinoma in Cirrhosis: An Italian Multicenter Prospective Study

Abstract Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone. Methods: This multicenter study included 215 cirrhotics (age range: 67–84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3–8 cm) [group A], 70 had 2 nodules (Ø 3–6 cm) [group B] and 36 had 3–5 nodules (Ø 1.5–6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS). Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5–3.5 cm nodules. In nodules >3.5–5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5–8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival. Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome.
STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells

Production of TGF-β by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-β generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-β generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell–inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-β propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-β–dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-β requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-β production by T cells, our results support a two-step model, composed of STAT6 and furin.
Association between medication adherence and illness perceptions in atrial fibrillation patients treated with direct oral anticoagulants: An observational cross-sectional pilot study

Objective The aim of this study was to examine the association between medication adherence and illness perceptions, and to explore the factors associated with poor medication adherence in atrial fibrillation (AF) patients receiving direct oral anticoagulants (DOACs) in a real-world clinical setting. Methods An observational cross-sectional pilot study was conducted at a single Japanese university hospital. One hundred and twenty-nine patients who were diagnosed with AF and who were taking DOACs were recruited from outpatients between January 4th and April 25th, 2017. We evaluated medication adherence to DOACs using the Morisky Medication Adherence Scale-8 (MMAS-8) and illness perceptions using the Brief Illness Perception Questionnaire (BIPQ). The patients’ characteristics and clinical data were collected from electronic medical records. Results Ninety-nine (76.7%) patients (male, n = 74; mean age, 71.4±9.8 years) participated in this study. According to the MMAS-8, 21 (21.2%) of the patients were classified into the poor adherence group (MMAS-8 score of <6), and 78 (78.8%) were classified into the good adherence group (MMAS-8 score of 6–8). A multivariate logistic regression analysis revealed that age (per year, odds ratio [OR] 0.912, 95% confidence interval [CI] 0.853–0.965, p = 0.001), a history of warfarin use (OR 0.181, 95% CI 0.033–0.764, p = 0.019), duration of DOAC exposure (per 100 days, OR 1.245, 95% CI 1.084–1.460, p = 0.001), and the BIPQ emotional response score (per 1 point, OR 1.235, 95% CI 1.015–1.527, p = 0.035) were significantly associated with poor medication adherence in AF patients receiving DOACs. Conclusion Poor medication adherence to DOACs was strongly associated with a stronger emotional response (i.e. stronger feelings of anger, anxiety, and depression), as well as younger age, the absence of a history of warfarin treatment, and longer DOAC exposure. Further evaluation of the factors associated with medication adherence in AF patients and the development and execution of strategies for improving poor adherence are warranted in the real-world clinical setting.
Surrogate endpoints shortening the therapeutic evaluation duration for different subgroups of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A retrospective analysis of 830 patients stratified by the 8th edition of the UICC/AJCC staging system and plasma Epstein-B

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to <5-year in stages I-II patients. The year of surrogate endpoints could be ahead in stages II-IVA with high EBV DNA.
Türkiye’de Tütün Kontrolü Politikalar Kapsamında İletişim Faaliyetleri ve Tütün Kontrolü Haberleri

Tutun kontrolu kavrami; tutun kullanmaya baslamayi onleme, tutun kullananlarin birakmasini saglama ve tutun dumanindan pasif etkilenimin onlenmesi olarak uc asamada mudahale surecini icermektedir. Turkiye’de tutun kontrolune yonelik mevzuat calismalari ilk olarak 1996 yilinda ilk tutun kontrolu yasasi ile uygulamaya baslanmis olup, kapsami 2008 yilinda genisletilmistir. Ozellikle 2008 yilinda cikarilan yasa ile tum kapali ortamlarda tutun kullaniminin yasaklanmis ve toplumun tutun dumanindan pasif etkilenmesini onlemeye yonelik bircok calisma yurutulmustur. Bu calisma 2007, 2008 ve 2009 yillarinda Turkiye’de yazili basinda tutun kontrolu konusunda yazilmis haber ve kose yazilarinin yillara ve gazetelere gore dagilimini ve tutun kontrolune bakislarini (destekleyen ve elestiren) ele almistir. Arastirma kapsaminda 4 ulusal gazetede toplam 1999 haber ve yazi incelenmistir. Kampanyanin basladigi ve devam ettigi 2008 ve 2009 yilinda tum gazetelerde haber sayisi belirgin olarak artmistir. Yillar itibariyle tum turler icerisinde en cok haber turunde yazilara rastlanmistir (%76,5). Haberlerin yaklasik % 90’ni destekleyen yani mevcut tutun kontrolu politikalarini onaylayan cercevelerden verilmistir. Analiz tutun kontrolu cabalarinin onemli bir parcasi olarak toplumun bilgilendirilmesi ve saglik iletisimi faaliyetlerinin onemini ortaya koymaktadir
Evidence of embryonic regulation of maternally derived yolk corticosterone

ABSTRACT In recent years, the potential for maternal stress effects to adaptively alter offspring phenotype has received considerable attention. This research has identified offspring traits that are labile in response to maternal stress; however, an understanding of the mechanisms underlying these effects is lagging and is crucial to appreciating the significance of this maternal effect. In the present study, we sought to better understand maternal stress effects by examining the potential for embryonic regulation of corticosterone exposure, determining the phenotypic consequences of elevated corticosterone during development, and characterizing the levels of maternally transferred corticosterone in unmanipulated eggs using Trachemys scripta. By dosing eggs with tritiated corticosterone and tracking the steroid throughout development, we found that most corticosterone is metabolized, and less than 1% of the corticosterone dose reaches the embryo as free corticosterone. We also found that exogenous dosing of corticosterone, in concentrations sufficient to overwhelm embryonic metabolism, reduces embryonic survival and negatively impacts hatchling traits important to fitness. Our results demonstrate that concentrations of maternal corticosterone in the yolks of unmanipulated eggs are low and are significantly lower than the doses of corticosterone required to elicit phenotypic effects in hatchlings. Taken together, these results provide evidence that both the embryo and the female may minimize corticosterone accumulation in the embryo to avoid reductions in embryonic survival and negative impacts on offspring phenotype and fitness. Summary: Embryos are capable of metabolizing maternally derived yolk corticosterone to minimize exposure during development and to avoid deleterious effects on phenotype and survival.
Deep Hashing for Semi-supervised Content Based Image Retrieval

Content-based image retrieval is an approach used to query images based on their semantics. Semantic based retrieval has its application in all fields including medicine, space, computing etc. Semantically generated binary hash codes can improve content-based image retrieval. These semantic labels / binary hash codes can be generated from unlabeled data using convolutional autoencoders. Proposed approach uses semi-supervised deep hashing with semantic learning and binary code generation by minimizing the objective function. Convolutional autoencoders are basis to extract semantic features due to its property of image generation from low level semantic representations. These representations of images are more effective than simple feature extraction and can preserve better semantic information. Proposed activation and loss functions helped to minimize classification error and produce better hash codes. Most widely used datasets have been used for verification of this approach that outperforms the existing methods.
Molecular Characterization of HBV DNA Integration in Patients with Hepatitis and Hepatocellular Carcinoma

Infection by chronic hepatitis B virus (HBV) is one of the major causes of liver cirrhosis and primary hepatocellular carcinoma (HCC). Viral DNA integration into the host cell genome is a key mechanism of hepatocarcinogenesis. However, the molecular characterization and the potential clinical implications of HBV DNA integration into patients suffering from different hepatitis and HCC remain unclear. In this study, we analyzed HBV integrations in patients with hepatitis B and HCC using HBV probe-based capturing and next-generation sequencing. The results revealed that the sizes of the HBV integrations ranged from 28 bp to 3215 bp, including the full-length HBV DNA sequence. The integration breakpoints were preferentially distributed in the viral enhancer, X protein, and core protein regions of the HBV genome. The number of HBV integrations followed an increasing trend from hepatitis to HCC, which was positively correlated with the HBV virus load in patients with hepatitis. The number of HBV integrations in the HBeAg positive chronic hepatitis B group was significantly greater than that in the other hepatitis B groups (P < 0.05). However, the relative abundance of HBV integrations was significantly higher in HCC tissues than in the adjacent liver tissues. Interestingly, 61.6% (8/13) of HBV-human DNA integration fragments could be detected at the RNA level. Our results also showed that HBV integration-targeted genes (ITGs) were significantly enriched in many cancer-related pathways, such as MAPK, extracellular matrix (ECM)-receptor interaction, and the hedgehog signaling pathway. Individuals with HBV integrations exhibited shorter disease-free survival (DFS) and overall survival (OS) than those without HBV integrations in some ITGs including LINC00293 (long intergenic non-protein coding RNA 293; DFS P = 0.008, OS P = 0.009), FSHB (follicle stimulating hormone beta subunit; DFS P = 0.05, OS P = 0.186), and LPHN3 (latrophilin-3; DFS P = 0.493, OS P = 0.033). This study determined the underlying mechanism of HBV DNA integration in liver diseases and laid the foundation for future studies on the pathogenesis of liver cancer.
Can lichen sclerosus be diagnosed by preputial appearance or symptoms?

Introduction Lichen sclerosus (LS), or balanitis xerotica obliterans, is a chronic, inflammatory disease accompanied by cicatrizing skin conditions resulting in pathologic phimosis. LS can be detected clinically by the whitish appearance of the glans or the foreskin, thickened, nonretractable foreskin, dysuria, and spraying. However, diagnosis is confirmed histopathologically. Purpose The aim of this study was to investigate whether LS can be diagnosed on the basis of clinical manifestation and symptoms. Patients and methods A retrospective analysis was performed, which included boys referred to our institutions for phimosis evaluation between May 2001 and December 2016. Pediatric urologists clinically diagnosed LS preoperatively. Boys with voiding problems, recurrent balanoposthitis, or who were unresponsive to topical steroid treatment underwent surgical treatment. Patients who underwent religious circumcisions were not included. Results Three-hundred twenty boys diagnosed with phimosis were identified, and 71 (22%) boys underwent surgery. Fifty-eight boys underwent complete or partial circumcision, and 13 boys underwent a dorsal slit or preputioplasty. Thirty foreskin samples were sent for histopathologic examination. Histopathologic evaluation showed evidence of LS in 13 of 30 (43%) circumcised boys, chronic inflammation in ten (33%), no abnormality in four (13%), dysplasia in two (7%), and acute inflammation in one (3%). In the 22 boys who were clinically diagnosed with LS, 13 patients had histopathologic evidence of LS (59%). Visually, eleven cases had whitish foreskins and 21 cases had thickened nonretractable foreskins, of which there were seven (64%) (P>0.05) and 12 (57%) (P<0.01) cases, respectively. These cases were histopathologically diagnosed with LS. Both whitish and thickened, nonretractable foreskin was observed in eight patients, of which seven (88%) (P<0.01) were also histologically diagnosed with LS. There was no correlation between histopathologic diagnosis and preoperative symptoms such as dysuria, ballooning, spraying, or penile pain (P>0.2). Conclusion It is difficult to reliably distinguish whether a patient has histopathological LS by clinical findings alone.
Blocking FGFR4 exerts distinct anti‐tumorigenic effects in esophageal squamous cell carcinoma

The FGFR family can be activated by FGFs and plays important roles in regulating cell growth, differentiation, migration, and angiogenesis. Recent studies have suggested that FGFR4 could regulate several processes, including tumor progression. Esophageal squamous cell carcinoma (ESCC) is a malignancy with high global occurrence. However, the molecule mechanism and the potential roles of FGFR4 in ESCC remain unknown.
The effects of aqueous and ethanolic leaf extracts of Vernonia amygdalina on some vital organs in adult Wistar rats

The aim of this study was to comparatively determine the effects of aqueous and ethanolic extracts of Vernonia amygdalina (Asteraceae) leaves, adopting histological procedures on the liver, stomach and kidney in adult wistar rats.There were four groups of animals: A, B, C and D. Groups A, B and C served as the treated animals while group D served as the control animals. Each of the groups was further subdivided into two i.e A1 & A2; B1 & B2; C1 & C2 and D1 & D2. Animals in groups A1, B1 and C1 were administered orally with aqueous extract of V. amygdalina 100, 200 and 300 mg/kg respectively while animals in groups A2, B2 and C2 were administered orally with ethanolic extract of V. amygdalina 100, 200 and 300 mg/kg respectively. The control groups, D1 and D2, received equal volume of normal saline. There were no significant derangement in the cytoarchitecture of the stomach, liver and kidney. Rather, the cytoarchitecture of the animals treated with both the ethanolic and aqueous extracts (300mg/kg) of V. amygdalina were better organized when compared with the control. It was therefore concluded that both ethanolic and aqueous leaf extracts of V. amygdalina are non-toxic and may possess cytoprotective potential.