Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer

Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.
Selection of Stent Type in Patients With Atrial Fibrillation Presenting With Acute Myocardial Infarction: An Analysis From the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry—Get With the Guidelines

Background Patients receiving oral anticoagulation in addition to dual‐antiplatelet therapy are known to be at high risk for bleeding events; thus, the selection of a drug‐eluting stent (DES) versus a bare metal stent (BMS) can have important implications for patients with atrial fibrillation (AF) presenting with acute myocardial infarction (MI). Methods and Results From the National Cardiovascular Data Registry ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry—Get With the Guidelines, we identified 14 427 AF patients presenting with acute MI undergoing percutaneous coronary intervention from 2008 to 2014. Temporal trends and hospital variation in DES use were examined, as were patterns of use by stroke risk (CHA2DS2‐VASc) and bleeding risk ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation). Among patients with linked Medicare data (n=2844), multivariable Cox regression modeling was used to compare risks for a composite outcome (all‐cause mortality, readmission for stroke, or MI), readmission for stroke, revascularization, and major bleeding at 1 year. A DES was used in 8414 (58.9%) MI patients with AF, increasing from 47.1% in 2008 to 67.9% in 2014, with wide variation among hospitals. DES placement was more common than BMS placement among patients at high stroke risk (CHA2DS2‐VASc ≥2) and high bleeding risk (ATRIA ≥4). Although aspirin and a P2Y12 inhibitor were prescribed for >95% of all patients regardless of stent type at discharge, warfarin was prescribed less frequently among patients receiving a DES than a BMS (31% versus 39%, P<0.001). The composite outcome was similar between patients with a DES or BMS at 1 year (22% versus 26%; adjusted hazard ratio: 0.88; 95% confidence interval [CI], 0.76–1.03). Conclusions Use of DESs among MI patients with AF has increased over time, but substantial hospital‐level variation was observed. Patients with AF meeting indications for anticoagulation are more likely to receive a DES than a BMS, even among those at high predicted risk of both stroke and bleeding.
Regulation of IL-17A expression in mice following subacute ozone exposure

Abstract Exposure to subacute ozone (O3) causes pulmonary neutrophil recruitment. In mice, this recruitment requires IL-17A. Ozone also causes expression of IL-23 and IL-1, which can induce IL-17A. The purpose of this study was to examine the hypothesis that IL-23 and IL-1 contribute to IL-17A expression and subsequent neutrophil recruitment after subacute O3 exposure. Wild-type, IL-23−/−, and Flt3l−/− mice were exposed to air or 0.3 ppm O3 for 72 h. Flt3l−/− mice lack conventional dendritic cells (cDC) that can express IL-23 and IL-1. Other wild-type mice were pre-treated with saline or the IL-1R1 antagonist anakinra prior to O3 exposure. After exposure, bronchoalveolar lavage (BAL) was performed and lung tissue harvested. The results indicated that pulmonary Il17a mRNA abundance and IL-17A+ F4/80+ cells were significantly reduced in O3-exposed IL-23−/− vs in wild-type mice. In contrast, anakinra had no effect on Il23a or Il17a pulmonary mRNA abundance or on BAL concentrations of the neutrophil survival factor G-CSF, but anakinra did reduce BAL neutrophil numbers, likely because anakinra also reduced BAL IL-6. Compared to air, O3 caused a significant increase in DC numbers in wild-type, but not in Flt3−/− mice. However, there was no significant difference in Il23a or Il17a mRNA abundance or in BAL neutrophil count in O3-exposed Flt3−/− vs in wild-type mice. From these results, it was concluded that IL-23 but not IL-1 contributes to the IL-17A expression induced by subacute O3 exposure. Induction of IL-23 by O3 does not appear to require cDC.
Segregating bodily isomerism or heterotaxy: potential echocardiographic correlations of morphological findings

Abstract Background Bodily isomerism, also referred to as heterotaxy, involves predominantly the thoracic organs, although other organs are usually abnormally positioned. Previously assessed on the basis of splenic anatomy, it is now understood that isomerism is better segregated on the basis of atrial appendage morphology. This allows for anticipation of associated findings. We aimed to assess the accuracy of segregation based on the morphology of the atrial appendages and other structures more easily identified by echocardiography. Methods We reviewed postmortem specimens of hearts from the archives at four institutions categorised as obtained from patients with “heterotaxy”. The cardiac structures were analysed using sequential segmental analysis. Non-cardiac structures were also examined if available. Statistical analyses were performed to compare differences in the settings of right as opposed to left isomerism. Results Specimens were available from 188 patients. Of these, 57 had left isomerism, and 131 had right isomerism. Atrial appendages were isomeric in all patients. A coronary sinus was found only in left isomerism, whereas a terminal crest, or a Eustachian valve, was found only in right isomerism. Interruption of the inferior caval vein was associated with left isomerism, whereas totally anomalous pulmonary venous connection was associated with right isomerism. Conclusion Isomerism is uniformly segregated on the basis of the morphology of the atrial appendages, itself defined by the extent of the pectinate muscles. Other features such as the presence of a coronary sinus and systemic venous return can further help with such segregation of isomerism.
Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient Management in Rectal Cancer

BACKGROUND: Few publications exist regarding gadolinium-enhanced sequences in rectal MRI. None have evaluated its potential impact on patient management. OBJECTIVE: This study aimed to assess whether gadolinium-enhanced sequences, including dynamic contrast enhancement, change radiologic interpretation and clinical management of rectal cancer. DESIGN: This is a retrospective analysis of 100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and with gadolinium-enhanced sequences. Treatment plans were rendered based on each radiologic interpretation for each case by a single experienced surgeon. Differences in radiologic interpretation and management were statistically analyzed. SETTINGS: The study was conducted at the Memorial Sloan Kettering Cancer Center. PATIENTS: Patients undergoing rectal MRI between 2011 and 2015 for baseline tumor staging and/or postneoadjuvant restaging were included. MAIN OUTCOME MEASURES: Primary outcome measures were changes in radiologic tumor stage, tumor margins, and surgical planning with the use of gadolinium at baseline and postneoadjuvant time points. RESULTS: At baseline, tumor downstaging occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium. Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal fascia were not statistically different with gadolinium. However, in 7 patients, differences could have resulted in treatment changes, accounted for by changes in relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2), or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and anal verge (in centimeters) were statistically smaller with gadolinium (p = 0.0017 and p = 0.0151) but could not have resulted in clinically significant treatment changes. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The use of gadolinium at baseline MRI could have altered treatment in 24% of patients because of differences in tumor stage or position. Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances to sphincters, which could influence surgical decision for sphincter-preserving rectal resection. See Video Abstract at http://links.lww. com/DCR/A444.
A Randomized Comparative Study of 24- and 6-Hour Infusion of Nafamostat Mesilate for the Prevention of Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective Randomized Comparison Trial

Objectives Although prolonged intravenous infusion (24 hours) of nafamostat mesilate is effective for the prevention of post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, it requires hospitalization and is expensive. The aim of this study was to compare the efficacy of 24- versus 6-hour intravenous infusion of 20 mg nafamostat mesilate for the prevention of post-ERCP pancreatitis (PEP). Methods A total of 382 patients who underwent ERCP were randomly assigned into 2 groups: 24 hours or 6 hours. In both groups, nafamostat mesilate (20 mg) infusion was initiated up to an hour before ERCP and continued for either 24 or 6 hours. Results The overall incidence of pancreatitis was 2.4% (9/371). The rates of PEP following 24- and 6-hour infusion were 2.8% (5/179) and 2.1% (4/192), respectively (P = 0.744). No significant difference was observed in the severity of pancreatitis between the groups. On multivariate analysis, increasing pancreatic duct cannulations (odds ratio, 1.685; 95% confidence interval, 1.036–2.741; P = 0.036) was identified as a statistically significant risk factor of PEP. Conclusions No difference was found in the incidence of PEP regardless of the duration of nafamostat mesilate infusion. Therefore, 6-hour infusion of 20 mg nafamostat mesilate may be useful for the prevention of PEP in an outpatient setting.
Echocardiographic Techniques of Deformation Imaging in the Evaluation of Maternal Cardiovascular System in Patients with Complicated Pregnancies

Cardiovascular diseases (CVD) represent the leading cause of maternal mortality and morbidity. Knowledge of CVD in women is constantly evolving and data are emerging that female-specific risk factors as complications of pregnancy are conditions associated with an increased risk for the long-term development of CVD. Echocardiography is a safe and effective imaging technique indicated in symptomatic or asymptomatic pregnant women with congenital heart diseases who require close monitoring of cardiac function. Deformation imaging is an echocardiographic technique used to assess myocardial function by measuring the actual deformation of the myocardium through the cardiac cycle. Speckle-tracking echocardiography (STE) is a two-dimensional (2D) technique which has been found to be more accurate than tissue Doppler to assess both left ventricular (LV) and right ventricular (RV) myocardial function. The use of 2D STE however might present some technical issues due to the tomographic nature of the technique and the motion in the three-dimensional space of the myocardial speckles. This has promoted the use of 3D STE to track the motion of the speckles in the 3D space. This review will focus on the clinical value of the new echocardiographic techniques of deformation imaging used to assess the maternal cardiovascular system in complicated pregnancies.
A lectin receptor kinase as a potential sensor for extracellular nicotinamide adenine dinucleotide in Arabidopsis thaliana

Nicotinamide adenine dinucleotide (NAD+) participates in intracellular and extracellular signaling events unrelated to metabolism. In animals, purinergic receptors are required for extracellular NAD+ (eNAD+) to evoke biological responses, indicating that eNAD+ may be sensed by cell-surface receptors. However, the identity of eNAD+-binding receptors still remains elusive. Here, we identify a lectin receptor kinase (LecRK), LecRK-I.8, as a potential eNAD+ receptor in Arabidopsis. The extracellular lectin domain of LecRK-I.8 binds NAD+ with a dissociation constant of 436.5 ± 104.8 nM, although much higher concentrations are needed to trigger in vivo responses. Mutations in LecRK-I.8 inhibit NAD+-induced immune responses, whereas overexpression of LecRK-I.8 enhances the Arabidopsis response to NAD+. Furthermore, LecRK-I.8 is required for basal resistance against bacterial pathogens, substantiating a role for eNAD+ in plant immunity. Our results demonstrate that lectin receptors can potentially function as eNAD+-binding receptors and provide direct evidence for eNAD+ being an endogenous signaling molecule in plants. DOI: http://dx.doi. org/10.7554/eLife.25474. 001
Quit Methods Used by American Smokers, 2013–2014

This report describes the quit methods used in the past 12 months by current and former smokers in the baseline Population Assessment of Tobacco and Health (PATH) Study during 2013–2014. Descriptive statistics were used to report the use of single and two or more quit methods; survey weights were used to compute population estimates. Logistic regression was used to estimate the association between past year former smokers and single quit method, including individual characteristics. Results: Of 11,402 current smokers and 4919 former smokers, 4541 had tried and 839 had quit in the past 12 months. Unaided quit attempts were the most common; the number was almost as high as all single methods combined (n = 1797 and n = 1831 respectively). The most frequently used single method was help from friends and family (n = 676) followed by e-cigarettes (n = 587). Use of e-cigarettes was the only method with higher odds of users being a former smoker than unaided attempts (OR = 1.42, 95% CI 1.12–1.81). Current use of e-cigarettes among current (34%) and former (54%) smokers was significantly higher than current use of nicotine replacement therapy (NRT). Conclusions: In 2013–2014 e-cigarettes were used by American adult smokers as quit-smoking aids more frequently than NRT products or prescription drugs.
Orbital fibrous histiocytoma mimicking cavernous hemangioma on dynamic contrast-enhanced MRA imaging.

Orbital lesions include a broad spectrum of tumors, vascular abnormalities, and inflammatory conditions. High-resolution imaging has become an invaluable tool toward formulating an accurate diagnosis, and facilitates proper counseling regarding appropriate interventions. Imaging may guide whether partial excision to minimize damage to orbital structures, or en bloc removal to prevent potential recurrence, as seen in mesenchymal tumors, is indicated. , Recently, dynamic contrast-enhanced magnetic resonance angiography (MRA) has demonstrated use in helping differentiate orbital vascular lesions. This imaging modality uses rapid MRI acquisition to provide noninvasive, dynamic flow information with high spatial resolution. However, even with modern imaging, reaching a diagnosis prior to histopathological analysis can be challenging. We present a case of orbital fibrous histiocytoma that appeared nearly identical to cavernous hemangioma on dynamic contrast-enhanced MRA.
Sucralfate and basic fibroblast growth factor promote endothelial cell proliferation around porous alloplastic implants in vitro.

Enhanced ingrowth of fibrovascular tissue into alloplastic orbital implants is clinically desirable. Basic fibroblast growth factor (bFGF) is an angiogenic factor that promotes proliferation of endothelial cells. Sucralfate is known to bind bFGF and render it stable by protecting it from degradation. To test the ability of bFGF to stimulate endothelial cell proliferation, porous orbital implants coated with a sustained-release and bioactively-stabilized preparation of the angiogenic peptide bFGF were studied. Hydroxyapatite (HA) and porous polyethylene (PP) implant discs (15 x 3 mm) were coated with sustained-release polymer polyhydroxyethylmethacrylate (hydron), sucralfate (a bFGF stabilizer), hydron plus or hydron/sucralfate plus bFGF. Discs were placed in tissue culture wells plated with 50,000 endothelial cells/well. After 5 days, cells were trypsinized and counted electronically using a Coulter counter. Statistical analysis was performed using unpaired Student's t-test. Implant discs coated with hydron/sucralfate/bFGF had significantly increased endothelial cell proliferation compared to discs coated with hydron alone or hydron/sucralfate (p < 0.05). There was no significant difference in the degree of enhanced proliferation between the HA and PP implants treated with hydron/sucralfate/bFGF (p > 0.05). Minimal proliferation occurred around discs treated with hydron alone or hydron/sucralfate. Coating both HA and PP orbital implants with the sustained-release form of sucralfate/bFGF promoted endothelial cell proliferation in vitro. The enhanced proliferation with hydron/sucralfate/bFGF warrants further exploration in an in vivo model.
Associations Between Periodontitis and Chronic Obstructive Pulmonary Disease: The 2010 to 2012 Korean National Health and Nutrition Examination Survey.

BACKGROUND The aim of this study is to examine whether oral hygiene and self-care, particularly in periodontal health, are associated with chronic obstructive pulmonary disease (COPD) in the Korean population. METHODS Data from the Korean National Health and Nutrition Examination Survey from 2010 to 2012 were used to assess the community periodontal index (CPI) of 5,878 participants (normal lung function: n = 5,181; obstructive spirometric pattern: n = 697) aged ≥40 years, who underwent spirometry. RESULTS Participants with COPD brushed their teeth less frequently and used the following less frequently: 1) dental floss and/or interdental brush; 2) mouthwash; and 3) electric toothbrush (P <0.001). Prevalence of periodontitis in patients with COPD (58.1%) was significantly higher than in those without COPD (34.0%, P <0.001). Number of teeth was significantly lower in patients with COPD compared with controls. Decayed-missing-filled tooth index was significantly lower in patients with COPD. This study shows risk of COPD by periodontal severity. Periodontitis (CPI 3 and 4) was associated in males with COPD after adjustment for: 1) age; 2) income; 3) education; 4) smoking; 5) alcohol consumption; 6) exercise; 7) body mass index; 8) toothbrushing frequency; 9) diabetes mellitus; and 10) number of teeth (CPI 3: relative risk [RR] = 1.38, 95% confidence interval [CI] = 1.12 to 2.05; CPI 4: RR = 1.23, 95% CI = 1.06 to 1.56). CONCLUSION Findings of this cross-sectional study suggest that COPD in males may be associated with severe periodontitis and indicates the importance of promoting dental care in patients with COPD.
Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray

Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu opioid receptors (MORs), and the N-methyl-d-aspartate subunit receptor (NR1) in the periaqueductal gray (PAG), since both of these receptors can regulate PAG activity. No changes in endogenous opioid peptides in met- and leu-enkephalin or β-endorphin levels were observed within the PAG. However, MOR immunoreactivity was significantly decreased in the ventral PAG in the endometriosis group. Endometriosis reduced by 20% the number of neuronal profiles expressing MOR and reduced by 40% the NR1 profiles. Our results suggest that endometriosis is associated with subtle variations in opioidergic and glutamatergic activity within the PAG, which may have implications for pain processing.
4D assessment of fetal brain function in diabetic patients

Abstract Objective: To assess whether there is a difference in the behavior of fetuses of pregnant women with diabetes under treatment with insulin, compared to fetuses of pregnant women without diabetes. Materials and methods: Kurjak’s antenatal neurodevelopmental test (KANET) – a method that, by application of four-dimensional (4D) ultrasound, assesses fetal behavior in a similar way that neonatologists perform a neurological assessment in newborns – was applied from 28 to 38 weeks of gestation to 40 pregnancies with pre-existing diabetes mellitus or gestational diabetes mellitus (GDM) requiring insulin (diabetic group) and to 40 non-diabetic cases, with otherwise low-risk pregnancies (non-diabetic group). Results: There were no statistically significant differences regarding maternal age (30.5±5.1 years for diabetic group vs. 29.8±6.2 years for non-diabetic group) and gestational age (32±1.6 weeks for the diabetic group compared to 33±1.2 weeks for the non-diabetic group). After analysis of the results obtained from application of KANET to each group, results of KANET had higher scores in the non-diabetic group. Conclusion: It appears that there are differences in the fetal behavior between diabetic and non-diabetic fetuses, and also the specific parameters – movements that were different between the two groups were identified.