bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study
Authors: E Jian-Yu , Lu Shou-En , Lin Yong , Graber Judith M. , Rotter David , Zhang Lanjing , Petersen Gloria M. , Demissie Kitaw , Lu-Yao Grace , Tan Xiang-Lin 
Published: June 2017

Abstract
Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.
Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders.
Results: Of 12,572 PDAC patients, 950 (7.56%) had used metformin alone, 4,506 (35.84%) had used statin alone, and 2,445 (19.45%) were dual users. Statin use was significantly associated with improved overall survival [HR, 0.94; 95% confidence interval (CI), 0.90–0.98], and survival was more pronounced in postdiagnosis statin users (HR, 0.69; 95% CI, 0.56–0.86). Metformin use was not significantly associated with overall survival (HR, 1.01; 95% CI, 0.94–1.09). No beneficial effect was observed for dual users (HR, 1.00; 95% CI, 0.95–1.05).
Conclusions: Our findings suggest potential benefits of statins on improving survival among elderly PDAC patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer.
Impact: Although more studies are needed to confirm our findings, our data add to the body of evidence on potential anticancer effects of statins. Cancer Epidemiol Biomarkers Prev; 26(8); 1225–32. ©2017 AACR.
Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer
Authors: Railkar Reema , Krane L. Spencer , Li Q. Quentin , Sanford Thomas , Siddiqui Mohammad Rashid , Haines Diana , Vourganti Srinivas , Brancato Sam J. , Choyke Peter L. , Kobayashi Hisataka , Agarwal Piyush K. 
Published: June 2017

Abstract
The use of light as a means of therapy for bladder cancer has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of phototherapy called photoimmunotherapy (PIT), which targets EGFR-expressing bladder cancer. Anti-EGFR antibody panitumumab was labeled with the photoabsorber (PA), IRDye 700Dx (IR700), to create a panitumumab-IR700 antibody–PA conjugate that is activated by near-infrared radiation (NIR). Bladder cancer tissue microarray (TMA) and bladder cancer cell lines were analyzed for expression of EGFR. Mechanism of PIT-induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. EGFR staining of TMAs showed that while most bladder cancers have expression of EGFR to a varying degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Panitumumab-IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Panitumumab alone, panitumumab-IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed toward cell death. NIR-PIT with panitumumab-IR700 reduced growth compared with only panitumumab-IR700–treated UMUC-5 xenograft tumors. PIT is a new targeted treatment for bladder cancer. Panitumumab-IR700–induced PIT selectively kills EGFR-expressing bladder cancer cells in vitro and in vivo and therefore warrants further therapeutic studies in orthotopic xenografts of bladder cancer and ultimately in patients. Mol Cancer Ther; 16(10); 2201–14. ©2017 AACR.
FBW7-Dependent Mcl-1 Degradation Mediates the Anticancer Effect of Hsp90 Inhibitors
Authors: Tong Jingshan , Tan Shuai , Nikolovska-Coleska Zaneta , Yu Jian , Zou Fangdong , Zhang Lin 
Published: June 2017

AbstractHeat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins and has shown promises in preclinical studies. However, the mechanism by which Hsp90 inhibitors kill tumor cells is not well-understood. Biomarkers associated with differential sensitivity and resistance to Hsp90 inhibitors remain to be identified. In this study, we found that colorectal cancer cells containing inactivating mutations of FBW7, a tumor suppressor and E3 ubiquitin ligase, are intrinsically insensitive to Hsp90 inhibitors. The insensitive colorectal cancer cells lack degradation of Mcl-1, a prosurvival Bcl-2 family protein. Hsp90 inhibition promotes GSK3β-dependent phosphorylation of Mcl-1, which subsequently binds to FBW7 and undergoes ubiquitination and proteasomal degradation. Specifically blocking Mcl-1 phosphorylation by genetic knock-in abrogates its degradation and renders in vitro and in vivo resistance to Hsp90 inhibitors, which can be overcame by Mcl-1–selective small-molecule inhibitors. Collectively, our findings demonstrate a key role of GSK3β/FBW7-dependent Mcl-1 degradation in killing of colorectal cancer cells by Hsp90 inhibitors and suggest FBW7 mutational status as a biomarker for Hsp90-targeted therapy. Mol Cancer Ther; 16(9); 1979–88. ©2017 AACR.
Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors
Authors: Nuotio Joel , Pitkänen Niina , Magnussen Costan G. , Buscot Marie-Jeanne , Venäläinen Mikko S. , Elo Laura L. , Jokinen Eero , Laitinen Tomi , Taittonen Leena , Hutri-Kähönen Nina , Lyytikäinen Leo-Pekka , Lehtimäki Terho , Viikari Jorma S. , Juonala Markus , Raitakari Olli T. 
Published: June 2017

Background—
Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures.

Methods and Results—

Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3–18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811;
P
=0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758;
P
<0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes.

Conclusions—
The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood.
Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke
Authors: Bunketorp-Käll Lina , Lundgren-Nilsson Åsa , Samuelsson Hans , Pekny Tulen , Blomvé Karin , Pekna Marcela , Pekny Milos , Blomstrand Christian , Nilsson Michael 
Published: June 2017

Background and Purpose—
Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke.

Methods—
Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants’ perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up.

Results—

One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79–9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00–13.66]), compared with controls (−0.5 [−3.20 to 2.28]);
P
=0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes.

Conclusions—
Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke.

Clinical Trial Registration—
URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059.
Alberico Gentili’s De iure belli: An Absolutist’s Attempt to Reconcile the jus gentium and the Reason of State Tradition
Authors: Vergerio Claire 
Published: June 2017

Abstract
Based on a detailed analysis of Gentili’s use of sources in De iure belli, this article argues that Gentili’s famous treatise on the laws of war is an incongruous attempt at reconciling an absolutist conception of sovereignty and a strong penchant for reason of state principles with an enduring commitment to the language of natural law and to its centrality in ordering relations between sovereigns.
Ḥalabi Arabic as a Contact Dialect in Jerusalem
Authors: Shachmon Ori 
Published: June 2017

This essay presents the main characteristics of a variety of Jerusalem Arabic, which was spoken in Jerusalem in the first half of the 20th century by Jews of North-Syrian origin, and also by others who conformed to this way of speech. The description provided is based on new evidence collected in 2012–2013 through interviews with elderly Jews who grew up in Jerusalem in the 1930s and 1940s. Growing up in mandatory Jerusalem, they mixed and socialized freely with their Christian and Muslim neighbors. Many of them heard the Arabic dialect of Aleppo at home, yet their home-dialect went through processes of linguistic accommodation, resulting in a contact variety which evidently differs from standard Jerusalem Arabic. Throughout this article I discuss a series of distinctive phonological, morphological, and lexical features, and discuss them vis-à-vis the standard dialect of Jerusalem and also in comparison with Aleppo Arabic. While many differences follow from the retention of substrate features in the language of the immigrants, this Jewish variety is by no means identical to any Syrian dialect. Rather, it is a contact dialect which emerged after the immigration to Jerusalem and which differs from Syrian Arabic in several prominent aspects. The linguistic analysis of the materials demonstrates the spread of features of the local dialect at the expense of others, as well as the emergence of fudged linguistic forms, which are identical neither to those of the local standard nor to those of the input dialect.The last section of this essay offers two full-length texts, demonstrating the Ḥalabi variety of Jerusalem Arabic (hereafter:ḥja) in its natural context.
Evaluation of the AMPS Boundary Layer Simulations on the Ross Ice Shelf, Antarctica, with Unmanned Aircraft Observations
Authors: Wille Jonathan D. , Bromwich David H. , Cassano John J. , Nigro Melissa A. , Mateling Marian E. , Lazzara Matthew A. 
Published: June 2017

AbstractAccurately predicting moisture and stability in the Antarctic planetary boundary layer (PBL) is essential for low-cloud forecasts, especially when Antarctic forecasters often use relative humidity as a proxy for cloud cover. These forecasters typically rely on the Antarctic Mesoscale Prediction System (AMPS) Polar Weather Research and Forecasting (Polar WRF) Model for high-resolution forecasts. To complement the PBL observations from the 30-m Alexander Tall Tower! (ATT) on the Ross Ice Shelf as discussed in a recent paper by Wille and coworkers, a field campaign was conducted at the ATT site from 13 to 26 January 2014 using Small Unmanned Meteorological Observer (SUMO) aerial systems to collect PBL data. The 3-km-resolution AMPS forecast output is combined with the global European Centre for Medium-Range Weather Forecasts interim reanalysis (ERAI), SUMO flights, and ATT data to describe atmospheric conditions on the Ross Ice Shelf. The SUMO comparison showed that AMPS had an average 2–3 m s−1 high wind speed bias from the near surface to 600 m, which led to excessive mechanical mixing and reduced stability in the PBL. As discussed in previous Polar WRF studies, the Mellor–Yamada–Janjić PBL scheme is likely responsible for the high wind speed bias. The SUMO comparison also showed a near-surface 10–15-percentage-point dry relative humidity bias in AMPS that increased to a 25–30-percentage-point deficit from 200 to 400 m above the surface. A large dry bias at these critical heights for aircraft operations implies poor AMPS low-cloud forecasts. The ERAI showed that the katabatic flow from the Transantarctic Mountains is unrealistically dry in AMPS.
The Sensitivity of Urban Meteorology to Soil Moisture Boundary Conditions: A Case Study in Melbourne, Australia
Authors: Jacobs Stephanie J. , Gallant Ailie J. E. , Tapper Nigel J. 
Published: June 2017

AbstractThe sensitivity of near-surface urban meteorological conditions to three different soil moisture initialization experiments under heat-wave conditions is investigated for the city of Melbourne, Australia. The Weather Research and Forecasting Model is used to simulate a domain over Melbourne and its surrounding rural areas. The experiments employ three suites of simulations. Two suites initialize the model with soil moisture from the top layer of the ERA-Interim soil moisture data with a 3-month and 24-h coupled spinup period, respectively. The third suite initializes the model with the arguably more realistic soil moistures from the Australian Water Availability Project (AWAP), which are an order of magnitude drier than the ERA-Interim data, again using a 24-h spinup period. The simulations employing the AWAP data are found to have smaller errors when compared with observations, with biases in urban maximum temperature reduced by 4.1°C and biases in the skin temperature reduced by 3.0°C relative to the biases of the 3-month-spinup experiment. Despite urban areas only having a small proportion of soil-covered surfaces, the results show that urban soils have a greater influence on urban near-surface temperatures at night, whereas rural soils have a greater influence on urban near-surface temperatures during the daytime.
Asymmetric Response of the Equatorial Pacific SST to Climate Warming and Cooling
Authors: Liu Fukai , Luo Yiyong , Lu Jian , Garuba Oluwayemi , Wan Xiuquan 
Published: June 2017

Abstract
The response of the equatorial Pacific Ocean to heat fluxes of equal amplitude but opposite sign is investigated using the Community Earth System Model (CESM). Results show a strong asymmetry in SST changes. In the eastern equatorial Pacific (EEP), the warming responding to the positive forcing exceeds the cooling response to the negative forcing, whereas in the western equatorial Pacific (WEP) it is the other way around and the cooling surpasses the warming. This leads to a zonal dipole asymmetric structure, with positive values in the east and negative values in the west. A surface heat budget analysis suggests that the SST asymmetry mainly results from the oceanic horizontal advection and vertical entrainment, with both of their linear and nonlinear components playing a role. For the linear component, its change appears to be more significant over the EEP (WEP) in the positive (negative) forcing scenario, favoring the seesaw pattern of the SST asymmetry. For the nonlinear component, its change acts to warm (cool) the EEP (WEP) in both scenarios, also favorable for the development of the SST asymmetry. Additional experiments with a slab ocean confirm the dominant role of ocean dynamical processes for this SST asymmetry. The net surface heat flux, in contrast, works to reduce the SST asymmetry through its shortwave radiation and latent heat flux components, with the former being related to the nonlinear relationship between SST and convection, and the latter being attributable to Newtonian damping and air–sea stability effects. The suppressing effect of shortwave radiation on SST asymmetry is further verified by partially coupled overriding experiments.
Sacrificial template method for the synthesis of three-dimensional nanofibrous 58S bioglass scaffold and its in vitro bioactivity and cell responses
Authors: Luo Honglin , Zhang Yang , Li Gen , Tu Junpin , Yang Zhiwei , Xiong Guangyao , Wang Zheren , Huang Yuan , Wan Yizao 
Published: June 2017

Three-dimensional nanofibrous scaffolds that morphologically mimic natural extracellular matrices hold great promises in tissue engineering and regenerative medicine due to their increased cell attachment and differentiation compared with block structure. In this work, for the first time, three-dimensional porous nanofibrous 58S bioglass scaffolds have been fabricated using a sacrificial template method. During the process, a natural three-dimensional nanofibrous bacterial cellulose was used as the sacrificial template on which precursor 58S glass was deposited via a sol-gel route. SEM and TEM results verify that the as-prepared 58S scaffolds can inherit the three-dimensional nanofibrous feature of bacterial cellulose. Pore structure characterizations by nitrogen adsorption-desorption and mercury intrusion porosimetry demonstrate that the 58S scaffolds are highly porous with a porosity of 75.1% and contain both mesopores (39.4 nm) and macropores (60 µm) as well as large BET surface area (127.4 m2 g−1). In vitro cell studies suggest that the 58S scaffold is bioactive and biocompatible with primary mouse osteoblast cells, suggesting that the nanofibrous structure of 58S is able to provide an appropriate environment for cellular functioning. These results strongly suggest that the three-dimensional nanofibrous 58S scaffold has great potential for application in bone tissue engineering and regenerative medicine.
Cutaneous lupus erythematosus and the risk of deep venous thrombosis and pulmonary embolism: A Danish nationwide cohort study
Authors: Ahlehoff O , Wu J J , Raunsø J , Kristensen S L , Khalid U , Kofoed K , Gislason G 
Published: June 2017

Background Venous thromboembolism (VTE) is a major public health concern. Lupus erythematosus (LE) is a chronic autoimmune disease ranging from localized cutaneous disease (CLE) to systemic involvement (SLE). Patients with SLE have an increased risk of venous thromboembolism (VTE), but little is known about the CLE-related risk of VTE. Methods To evaluate the risk of VTE in patients with SLE and CLE as compared to the general population, a retrospective cohort study was conducted. Incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) from multivariable Cox regression models were used to evaluate and compare the risk of VTE. Registries of hospitalizations, outpatient visits, and prescription drug use were studied to determine the risk of VTE in patients with CLE and SLE and the general population between 1997 and 2011. Results A total of 3234 patients with CLE and 3627 patients with SLE were identified and compared to 5,590,070 individuals in the reference population. The incidence rates per 1000 year of VTE were higher in patients with LE, i.e. 1.20, 3.06, and 5.24 for the reference population, CLE, and SLE, respectively. In adjusted models, both CLE (HR 1.39; 95% CI 1.10–1.78) and SLE (HR 3.32; 95% CI 2.73–4.03) were associated with a statistically significant increased risk of VTE, compared to the reference population. Conclusion In this nationwide study, both CLE and SLE were significant risk factors for VTE. The results add to our understanding of comorbidities in patients with LE, and call for further studies and increased awareness of thromboembolic complications in patients with CLE.
Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1−/− mice
Authors: Percopo Caroline M , Ma Michelle , Rosenberg Helene F 
Published: June 2017

Abstract
Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1−/− mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1−/− mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication. By contrast, CD8null mice, which are fully capable of clearing virus, are protected by Lp with no delayed lethal outcome, granulocyte recruitment to the airways, or induction of CCL7. Repeated administration of Lp to virus-infected Rag1−/− mice had no impact on delayed mortality. Moreover, administration of Lp to the respiratory mucosa resulted in no induction of IFN-α or -β in Rag1−/− or wild-type mice, and IFN-abR gene deletion had no impact on Lp-mediated protection. Overall, our findings indicate that although Lp administered to the respiratory tract has substantial impact on lethal virus-induced inflammation in situ, endogenous virus clearance mechanisms are needed to promote sustained protection. Our results suggest that a larger understanding of the mechanisms and mediators that limit acute virus-induced inflammation may yield new and useful therapeutic modalities.