bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma
Authors: Udumyan Ruzan , Montgomery Scott , Fang Fang , Almroth Henrik , Valdimarsdottir Unnur , Ekbom Anders , Smedby Karin E. , Fall Katja 
Published: May 2017

Abstract
Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70–0.90; P &lt; 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n = 517; adjusted HR, 0.60; 95% CI, 0.43–0.83; P = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35–0.83; P = 0.005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease. Cancer Res; 77(13); 3700–7. ©2017 AACR.
Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade
Authors: Gu Yi-Feng , Cohn Shannon , Christie Alana , McKenzie Tiffani , Wolff Nicholas , Do Quyen N. , Madhuranthakam Ananth J. , Pedrosa Ivan , Wang Tao , Dey Anwesha , Busslinger Meinrad , Xie Xian-Jin , Hammer Robert E. , McKay Renée M. , Kapur Payal , Brugarolas James 
Published: May 2017

Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1-deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1-deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1, in Pbrm1-deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells.
Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900–17. ©2017 AACR.
See related commentary by Leung and Kim, p. 802.
This article is highlighted in the In This Issue feature, p. 783
Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation
Authors: McRobb Lucinda S. , McGrath Kristine C.Y. , Tsatralis Tania , Liong Eleanore C. , Tan Joanne T.M. , Hughes Gillian , Handelsman David J. , Heather Alison K. 
Published: May 2017

Objective—
Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro.

Approach and Results—
Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERβ]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus independently of plaque growth or lipid levels and occurred in association with a site-specific decrease in the proportion of ERβ-positive intimal cells. Calcified lesions expressed collagen I and bone sialoprotein, with decreased matrix Gla protein. In vitro, E2 suppressed ERβ expression and increased VSMC mineralization, demonstrating increased collagen I and II, osteocalcin and bone sialoprotein, and reduced matrix Gla protein and osteopontin. Antagonism or RNA silencing of estrogen receptor alpha, ERβ, or both further increased VSMC mineralization.

Conclusions—
We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERβ activity.
Human Plasma Thioredoxin-80 Increases With Age and in ApoE
−/−
Mice Induces Inflammation, Angiogenesis, and Atherosclerosis
Authors: Couchie Dominique , Vaisman Boris , Abderrazak Amna , Mahmood Dler Faieeq Darweesh , Hamza Magda M. , Canesi Fanny , Diderot Vimala , El Hadri Khadija , Nègre-Salvayre Anne , Le Page Aurélie , Fulop Tamas , Remaley Alan T. , Rouis Mustapha 
Published: May 2017

Background:
Thioredoxin (TRX)-1, a ubiquitous 12-kDa protein, exerts antioxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces upregulation of proinflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a proinflammatory M1 phenotype.

Methods:
TRX1 and TRX80 plasma levels were determined with a specific ELISA. A disintegrin and metalloproteinase domain-containing protein (ADAM)-10, ADAM-17, and ADAM-10 activities were measured with SensoLyte 520 ADAM10 Activity Assay Kit, Fluorimetric, and InnoZyme TACE Activity Kit, respectively. Western immunoblots were performed with specific antibodies to ADAM-10 or ADAM-17. Angiogenesis study was evaluated in vitro with human microvascular endothelial cells-1 and in vivo with the Matrigel plug angiogenesis assay in mice. The expression of macrophage phenotype markers was investigated with real-time polymerase chain reaction. Phosphorylation of Akt, mechanistic target of rapamycin, and 70S6K was determined with specific antibodies. The effect of TRX80 on NLRP3 inflammasome activity was evaluated by measuring the level of interleukin-1β and -18 in the supernatants of activated macrophages with ELISA. Hearts were used for lesion surface evaluation and immunohistochemical studies, and whole descending aorta were stained with Oil Red O. For transgenic mice generation, the human scavenger receptor (SR-A) promoter/enhancer was used to drive macrophage-specific expression of human TRX80 in mice.

Results:

In this study, we observed a significant increase of plasma levels of TRX80 in old subjects compared with healthy young subjects. In parallel, an increase in expression and activity of ADAM-10 and ADAM-17 in old peripheral blood mononuclear cells compared with those of young subjects was observed. Furthermore, TRX80 was found to colocalize with tumor necrosis factor-α, a macrophage M1 marker, in human atherosclerotic plaque. In addition, TRX80 induced the expression of murine M1 macrophage markers through Akt2/mechanistic target of rapamycin–C1/70S6K pathway and activated the inflammasome NLRP3, leading to the release of interleukin-1β and -18, potent atherogenic cytokines. Moreover, TRX80 exerts a powerful angiogenic effect in both in vitro and in vivo mouse studies. Finally, transgenic mice that overexpress human TRX80 specifically in macrophages of apoE
−/−
mice have a significant increase of aortic atherosclerotic lesions.

Conclusions:
TRX80 showed an age-dependent increase in human plasma. In mouse models, TRX80 was associated with a proinflammatory status and increased atherosclerosis.
Water Budget and Intensity Change of Tropical Cyclones over the Western North Pacific
Authors: Gao Si , Zhai Shunan , Chen Baiqing , Li Tim 
Published: May 2017

AbstractThree satellite observational datasets and a reanalysis dataset during the period 2001–09 are used to examine four water budget components (total precipitable water, surface evaporation, precipitation, and column-integrated moisture flux convergence) associated with western North Pacific tropical cyclones (TCs) of different intensity change categories: rapidly intensifying, slowly intensifying, neutral, and weakening. The results show that surface evaporation plays an important role in storm rapid intensification (RI) and the highest evaporation associated with rapidly intensifying TCs is associated with the highest sea surface temperature. Total precipitable water in the outer environment, where moisture is mainly provided by surface evaporation, is also vital to storm RI because RI is favored when there is less dry air intruded into the storm circulation. The roles of surface evaporation and total precipitable water in storm RI are related to the enhanced convective available potential energy by moistening and warming the boundary layer. The largest amount of column-integrated moisture flux convergence associated with weakening TCs, which results in the heaviest precipitation, is because their strongest mean intensity promotes moisture transport. It is suggested that different water budget components play different roles in TC intensity change. The results agree with the notion that TC intensity change results from a competition between surface moisture and heat fluxes and low-entropy downdrafts into the boundary layer.
Aggressive Salivary Malignancies at Early Stage: Outcomes and Implications for Treatment
Authors: Eppsteiner Robert W. , Fowlkes Jonathan W. , Anderson Carryn M. , Robinson Robert A. , Pagedar Nitin A. 
Published: May 2017

Background: Few studies have examined whether the use of adjuvant treatment impacts survival for early stage high-grade salivary tumors. Methods: A retrospective review of the SEER database between 1973 and 2012 was performed. Patients with high-grade major salivary gland tumors including salivary duct carcinoma, carcinoma ex-pleomorphic adenoma, high-grade mucoepidermoid carcinoma, or adenocarcinoma, NOS were identified. Only stage I-II tumors were included. The impact of radiation status on observed and relative survival was examined. Results: Five hundred seventy-four patients with high-grade, early stage salivary tumors met inclusion criteria. Sixty-seven percent of patients received radiation therapy. There was no difference in observed or relative survival based on having received radiation. Conclusions: Adjuvant radiation is indicated for advanced stage tumors or early stage tumors with adverse features. For early stage tumors without adverse features, there was no survival benefit from radiation therapy. Adjuvant radiation should be decided on a case-by-case basis for these patients.
Is a Multidisciplinary Aerodigestive Clinic More Effective at Treating Recalcitrant Aerodigestive Complaints Than a Single Specialist?
Authors: Rotsides Janine M. , Krakovsky Gina M. , Pillai Dinesh K. , Sehgal Sona , Collins Maura E. , Noelke Carolyn E. , Bauman Nancy M. 
Published: May 2017

Objective: To determine the utility of a pediatric multidisciplinary aerodigestive clinic (ADC) in treating recalcitrant aerodigestive conditions. Methods: Longitudinal observational study of presenting complaints, evaluation, management, and outcome of patients seen during 12 monthly ADCs beginning August 2013. Results: Fifty-five patients were seen by the ADC team (otolaryngology/gastroenterology/pulmonology/speech pathology/nurse practitioner) and followed for a mean 17.6 months (range, 12-26 months). Mean age was 4.3 years (range, 0.5-19 years). All were seen by at least 1 specialist before ADC referral but without significant improvement. Chronic cough was the most common primary symptom (44%). Clinic evaluation included flexible nasopharyngolaryngoscopy (FFL, 53%) and pulmonary function testing (36%.) FFL influenced management in 79%. An operative procedure usually combined endoscopy was warranted in 58%. Endoscopy provided high diagnostic yield, detecting laryngeal cleft (8), adenoid hypertrophy (8), vocal cord dysfunction (4), pulmonary infection (4), reflux disease (3), laryngomalacia (3), tracheomalacia (2), cilia abnormality (2), celiac disease (1), Helicobacter pylori (1), duodenal web (1), and eosinophilic esophagitis (1). Outcome was available for 48 of 55 patients, with 73% reporting resolved to markedly improved symptoms and 27% minimal to no improvement. Conclusions: The ADC team approach resulted in resolved to markedly improved symptoms in 73% of patients whose symptoms persisted despite seeing a single specialist prior to referral.
Carbon monoxide inhalation induces headache in a human headache model
Authors: Arngrim Nanna , Schytz Henrik Winther , Britze Josefine , Vestergaard Mark Bitsch , Sander Mikael , Olsen Karsten Skovgaard , Olesen Jes , Ashina Messoud 
Published: May 2017

Introduction Carbon monoxide (CO) is an endogenously produced signalling molecule that has a role in nociceptive processing and cerebral vasodilatation. We hypothesized that inhalation of CO would induce headache and vasodilation of cephalic and extracephalic arteries. Methods In a randomized, double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0–10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial Doppler, diameter of the superficial temporal artery (STA) and radial artery (RA) by high-resolution ultrasonography and facial skin blood flow by laser speckle contrast imaging. Results Ten volunteers developed headache after CO compared to six after placebo. The area under the curve for headache (0–12 hours) was increased after CO compared with placebo ( p = 0.021). CO increased VMCA ( p = 0.002) and facial skin blood flow ( p = 0.012), but did not change the diameter of the STA ( p = 0.060) and RA ( p = 0.433). Conclusion In conclusion, the study demonstrated that CO caused mild prolonged headache but no arterial dilatation in healthy volunteers. We suggest this may be caused by a combination of hypoxic and direct cellular effects of CO.
Limits of Calcaneal Lengthening for Treating Planovalgus Foot Deformity in Children With Cerebral Palsy
Authors: Luo Chi-An , Kao Hsuan-Kai , Lee Wei-Chun , Yang Wen-E , Chang Chia-Hsieh 
Published: May 2017

Background: Calcaneal lengthening is used to correct symptomatic planovalgus foot deformity, but outcomes have been less satisfactory in children with cerebral palsy. This study aimed to define limits of calcaneal lengthening by analyzing the risk factors for undercorrection of deformity. Methods: We retrospectively reviewed 20 cases of children with cerebral palsy who underwent calcaneal lengthening of 30 planovalgus feet at a mean age of 11.9 years. Foot deformities were evaluated by the anteroposterior talo–first metatarsal angle (normal, 10 ± 7.0 degrees), lateral talo–first metatarsal angle (normal, 13 ± 7.5 degrees), and lateral calcaneal pitch angle (normal, 17 ± 6.0 degrees) on standing foot radiographs. Among these parameters, a corrected foot was defined as 2 or 3 parameters being corrected to within a normal range, and an undercorrected foot was only 1 or no parameter being corrected to within a normal range. Factors were compared between the corrected group and undercorrected group for significant predictors, and cutoff values of predictors were calculated for use as a clinical guideline. Results: Seventeen planovalgus feet were corrected satisfactorily by calcaneal lengthening, while the other 13 feet were undercorrected. Undercorrected feet had a greater preoperative anteroposterior talonavicular angle (33.7 vs 22.8 degrees, P = .001) and a smaller lateral calcaneal pitch (−1.7 vs 5.6 degrees, P = .03). A talonavicular angle of more than 24 degrees and calcaneal pitch less than −5 degrees were identified as cutoff values using a receiver operating characteristic curve. The predicted probability of undercorrection was 100% (9/9 feet) for 2 positive predictors, 50% (8/16 feet) for 1 positive predictor, and 0 (0/5 feet) for zero predictors. Conclusion: A talonavicular lateral subluxation of more than 24 degrees on the anteroposterior radiograph and a calcaneal pitch angle less than −5 degrees on the lateral radiograph were 2 independent predictors that could be used to identify a planovalgus deformity that would be beyond the corrective capacity of calcaneal lengthening to restore normal alignment. Level of Evidence Retrospective case control study, level III
Angiographic Analysis of Vascular Integrity After Percutaneous Closure Using Prostar XL Device During Transcatheter Aortic Valve Implantation
Authors: Lareyre Fabien , Raffort Juliette , Dommerc Carine , Benhammamia Mohamed , Bourlon François , Habib Yacoub , Mialhe Claude 
Published: May 2017

Introduction: Percutaneous closure devices are commonly used to achieve hemostasis during endovascular procedures including transcatheter aortic valve implantation (TAVI). The aim of our study was to investigate the quality of the percutaneous femoral arterial closure by Prostar XL device using a systematic peroperative angiographic control at the end of TAVI procedure. Materials and Methods: Two hundred seventeen consecutive patients (mean age: 84 [6.5]; 112 women and 105 men) undergoing TAVI with percutaneous transfemoral access were prospectively registered in our center. Preoperative computed tomography scan was performed, and mean femoral vessel diameter was 7.9 (0.9) mm. At the end of TAVI intervention, the hemostasis was systematically achieved using the percutaneous closure device Prostar XL, without selection of patients based on anatomical criteria. An angiography with front and oblique views was performed to evaluate the quality and the safety of the closure device. Success of the percutaneous closure was defined as the absence of hemorrhage and the restitution of the arterial anatomy. Complications related to the percutaneous closure were classified as stenosis, dissection at the puncture site, suture failure, misplacement, or persistent bleeding. Results: Twenty-three (10.6%) patients had complications related to arterial percutaneous closure—14 (60.8%) stenosis, 6 (26.1%) persistent bleeding, and 1 (4.3%) dissection. These lesions were accessible to endovascular treatment via a crossover procedure. One (4.3%) suture failure and 1 (4.3%) misplacement of the device, with a puncture site created above the femoral arch, were reported. The patient developed a retroperitoneal hematoma postoperatively and required transfusion of 2 units of red blood cells associated with a cutdown to remove hematoma and to repair the common femoral artery. Conclusion: Angiography after arterial percutaneous closure using Prostar XL device during TAVI allows detection and endovascular treatment of vascular complications and is associated with low rate of conversion to open surgery.
The Impact of Previous Athletic Experience on Current Physical Fitness in Former Collegiate Athletes and Noncollegiate Athletes
Authors: Simon Janet E. , Docherty Carrie L. 
Published: May 2017

Background: Physical activity performed at moderate intensity is associated with reduced risk of mortality, cardiovascular disease, hypertension, and some types of cancers. However, vigorous physical activity during participation in college athletics may increase the risk of injury, which might limit future physical activity levels. Purpose: To evaluate differences in current physical fitness levels between former Division I athletes and noncollegiate athletes. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: The sample was recruited from a large midwestern university alumni database and consisted of 2 cohorts: (1) former Division I athletes (n = 100; mean age, 53.1 ± 7.4 years) and (2) nonathletes who were active in college (n = 100; age, 51.4 ± 7.3 years). Individuals answered a demographics questionnaire and completed a physical fitness assessment consisting of 7 measures: percent body fat, 1-mile walk, sit-to-stand test, push-up, half sit-up test, sit and reach test, and back scratch test. Results: Performance was significantly worse for former Division I athletes compared with nonathletes for percent body fat (mean difference, 7.58%; F(1, 198) = 59.91; P < 0.01), mile time (mean difference, 2.42 minutes; F(1, 198) = 1.74; P = 0.03), sit-to-stand test (mean difference, 4.3 repetitions; F(1, 198) = 6.59; P = 0.01), and push-up test (mean difference, 8.9 repetitions; F(1, 198) = 7.35; P = 0.01). Conclusion: Former Division I athletes may be limited because of previous injury, inhibiting their ability to stay active later in life. Clinical Relevance: It is imperative that clinicians, coaches, and strength and conditioning specialists understand the possible future repercussions from competing at the Division I level.
Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus
Authors: Greenlee-Wacker Mallary C. , Kremserová Silvie , Nauseef William M. 
Published: May 2017

Key PointsPhenotypic features of human neutrophils after ingestion of CA-MRSA contrast with those of phagocytosis-induced apoptosis. Lysis of human neutrophils fed CA-MRSA requires active RIPK-3 but is independent of tumor necrosis factor α, active RIPK-1, and MLKL.
Quantification of HTLV-1 reverse transcriptase activity in ATL patients treated with zidovudine and interferon-α
Authors: Macchi Beatrice , Balestrieri Emanuela , Frezza Caterina , Grelli Sandro , Valletta Elena , Marçais Ambroise , Marino-Merlo Francesca , Turpin Jocelyn , Bangham Charles R. , Hermine Olivier , Mastino Antonio , Bazarbachi Ali 
Published: May 2017

Key Points
The therapeutic efficacy of the AZT and IFN combination in ATL presumably reflects the inhibition of RT-related functions. HTLV-1–RT activity from short-term cultured PBMCs may represent a predictive correlate of clinical response to AZT/IFN in ATL patients.
Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia
Authors: Renou Laurent , Boelle Pierre-Yves , Deswarte Caroline , Spicuglia Salvatore , Benyoucef Aissa , Calvo Julien , Uzan Benjamin , Belhocine Mohamed , Cieslak Agata , Landman-Parker Judith , Baruchel Andre , Asnafi Vahid , Pflumio Françoise , Ballerini Paola , Naguibneva Irina 
Published: May 2017

Key Points
TLX3 transactivates LINC00478, the host gene of oncogenic miR-125b-2 in T-ALL. TLX3 and miR-125b contribute to the differentiation arrest and the expansion of transformed T cells.