bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of interleukin-10 promoter polymorphisms with serofast state after syphilis treatment
Authors: Pastuszczak Maciej , Jakiela Bogdan , Wojas-Pelc Anna 
Published: October 2018

ObjectivesRecent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence ofTreponema palliduminfection despite adequate treatment, resulting in a serofast state. The objective of this study was to determine whether enhanced interleukin (IL)-10-related response during earlyT. palliduminfection increased the risk of serofast syphilis.MethodsTwoIL10gene promoter polymorphisms affecting IL-10 production (−1082A>G [rs1800896], −592C>A [rs1800872]) and serum levels of IL-10 were measured in 80 patients with early syphilis before and 6 months after penicillin treatment and in 24 healthy volunteers (control group).ResultsAfter 6 months, patients were stratified based on serological response into two groups: (1) serofast state (n = 28) and (2) serologically cured (n = 52). Pretreatment and post-treatment serum IL-10 levels were significantly higher in patients who remained serofast compared with those who had a serological cure (p<0.001). The GG genotype of the −1082A>G (rs1800896) polymorphism and the CC genotype of the −592C>A (rs1800872) polymorphism were significantly correlated with higher serum IL-10 levels. Moreover, the OR for remaining serofast for carriers of these genotypes was 16.2 (95% CI: 4.1 to 65.0, p<0.0001) and 2.9 (95% CI: 1.4 to 5.9, p=0.002), respectively.ConclusionsWe showed that a pronounced anti-inflammatory immune response may be an important predictor for the serofast state. Additionally, host-related factors such as polymorphisms of immune regulatory genes may influence the risk of remaining serofast after syphilis therapy.
Joint management format at the mixed-surgical intermediate care unit: an interrupted time series analysis
Authors: Plate Joost D J , Peelen Linda M , Leenen Luke P H , Houwert R Marijn , Hietbrink Falco 
Published: October 2018

BackgroundThe management format of the mixed-surgical intermediate care unit (IMCU) affects its performance. A format of combined supervision of surgeons with additional critical care certifications and admitting specialists, named the “joint format”, may herein be a promising new model of specialized critical care. This study aims to assess the performance of the joint management format.MethodsThis observational cohort study compared three IMCU management formats at the stand-alone, mixed-surgical IMCU of a tertiary referral hospital using interrupted time series analyses. All admissions from 2001 until 2015 were included. Predetermined criteria for performance (utilization, efficiency, and safety) were applied to three different management format periods: open (2001–2006), closed (2006–2011), and joint (2011–2015) formats.ResultsA total of 8894 admissions were analyzed. In terms of case load (utilization), there was an overall increase in the number of surgical patients (0.25%/year) (p<0.001), age (0.38/year) (p<0.001), and readmissions from the ward (0.16%/year) (p<0.001) and from the intensive care unit (ICU) (0.17%/year) (p=0.014). In terms of efficiency, the admission duration decreased (1.58 hours/year) (p<0.001). Transfer to the ICU within 24  hours, readmission within 24  hours from the ward, and unplanned mortality (eg, safety) did not change over time.DiscussionAt a time of increasingly complex case load, the joint format at the mixed-surgical IMCU is an efficient and safe management format in which the admitting specialist continues to provide specialized care. Specialty-specific supervision at IMCUs is a safe option which should be considered in healthcare policy decisions.Level of evidenceLevel IV.
Syntectonic quartz vein evolution during progressive deformation
Authors: Lloyd Geoffrey E. 
Published: October 2018

Abstract
Two models to explain the progressive deformation of syntectonic quartz veins are derived from conventional theories for simple and pure shears. The simple-shear model is based on reorientation and changes in length of linear vein elements, and predicts initial orientations of veins for imposed shear strains, elongations and strain ratios. The pure-shear model considers changes in length of lines variably orientated relative to the maximum compression direction, and yields estimates of elongation strains and strain ratios. Expectations of both models are different, as illustrated by analysis of quartz veins from the Rhoscolyn Anticline, Anglesey, NW Wales. The simple-shear model recognizes three distinct initial orientations, which predict different strains across the fold; the pure-shear model suggests veins were initially sub-parallel to the principal compression direction and predicts effectively constant strains across the fold. In addition, both models predict different patterns of fold vergence: for simple shear, vergence depends on magnitude and direction of shearing and may exhibit complex patterns; for pure shear, vergence patterns are predicted to be essentially constant. In general, the predictions of either model are critically dependent on the origin of the veins, particularly relative to the formation of the Rhoscolyn Anticline.
TGFβ-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1
Authors: Lambies Guillem , Miceli Martina , Martínez-Guillamon Catalina , Olivera-Salguero Rubén , Peña Raúl , Frías Carolina-Paola , Calderón Irene , Atanassov Boyko S. , Dent Sharon Y. R. , Arribas Joaquín , García de Herreros Antonio , Díaz Víctor M. 
Published: October 2018

Abstract

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box–specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance.

Significance:
These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.
Host Characteristics and Risk of Incident Melanoma by Breslow Thickness
Authors: Li Wen-Qing , Cho Eunyoung , Wu Shaowei , Li Suyun , Matthews Natalie H. , Qureshi Abrar A. 
Published: October 2018

Abstract

Background:
Several host characteristics, including pigmentary traits (hair color, sunburn susceptibility and tanning ability), number of common nevi (moles), and family history of melanoma, have been associated with risk of melanoma.

Methods:
We prospectively examined the associations between host characteristics and risk of incident melanoma by Breslow thickness (≤1 mm, thin melanoma; or &gt;1 mm, “thicker melanoma”) based on the Nurses' Health Study (NHS, n = 86,380 women), NHS II (n = 104,100 women), and Health Professionals Follow-up Study (HPFS, n = 46,934 men).

Results:
During 22–30 years' follow-up, a total of 1,813 incident melanoma cases were identified with information on Breslow thickness, 1,392 (76.8%) of which had thin melanoma. No significant differences were observed for thin and thicker melanoma in associations with hair color, sunburn susceptibility, and tanning ability. However, we found significant differences for the association with family history of melanoma, with a higher risk estimate for thicker melanoma [HR = 2.55; 95% confidence interval (CI): 1.91–3.42] than thin melanoma (HR = 1.59; 95% CI: 1.21–2.08; Pheterogeneity = 0.02). Interestingly, women and men displayed differential associations between nevi count and risk of melanoma by Breslow thickness, with the association appearing stronger for thicker melanoma than thin melanoma in men (Pheterogeneity = 0.01), but not in women.

Conclusions:
Individuals with family history of melanoma may be more likely to develop thicker melanoma. Men with high number of common nevi may tend to develop thicker melanoma, which was not found for women.

Impact:
The findings further stress the risk of thicker melanoma for individuals with a family history of melanoma and men with a high nevi count.
LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis
Authors: Wang Hongxiang , Song Xiao , Huang Qilin , Xu Tao , Yun Dapeng , Wang Yuqi , Hu Lingna , Yan Yong , Chen Hongyan , Lu Daru , Chen Juxiang 
Published: October 2018

Abstract

Background:
LGALS3 promotes tumor progression in diverse cancers. However, the involvement of LGALS3 in glioblastoma has not yet been broadly illuminated.

Methods:
Microarray was performed to detect the gene expression profiles of radioresistance in T98G cells and identified a universally upregulated gene, LGALS3. The impact of LGALS3 on the survival of glioblastoma cells facing ionizing irradiation or temozolomide was investigated by the Cell Counting Kit-8 (CCK-8). A total of 120 glioblastoma cases were collected to analyze the relationship between LGALS3 expression and patient prognosis. Another 961 patients with glioma and 1,351 healthy controls were recruited to study the association of SNPs across the LGALS3 gene with glioblastoma susceptibility. The functional SNP sites were also studied in cellular experiments.

Results:
An effective protection of LGALS3 from ionizing irradiation or temozolomide-induced cell death in T98G and U251 cells was found. In addition, high expression of LGALS3 could work as an independent risk factor for survival of patients with glioblastoma. Two SNP sites (rs4644 and rs4652) across the LGALS3 gene were associated with increased risk for glioblastoma, and the C allele of rs4652 and the A allele of rs4644 could enhance glioblastoma resistance to radio-chemotherapy, but not cell proliferation.

Conclusions:
Our results suggest that LGALS3 is an important biomarker influencing glioblastoma risk and prognosis and a potential target for treating the malignancy, especially ones with resistance against the standard therapy.

Impact:
LGALS3 promotes glioblastoma cells' resistance to ionizing irradiation and temozolomide and predicts poor prognosis. Targeting LGALS3 may limit the therapeutic resistance in glioblastoma and increase patient survival.
Leveraging Breadth and Depth: Strategies to Characterize Population Diversity to Address Cancer Disparities in the DF/HCC Catchment Area
Authors: McCloud Rachel Faulkenberry , Bekalu Mesfin Awoke , Maddox Nicole , Minsky Sara J. , Viswanath K. 
Published: October 2018

Abstract

Background:
NCI-Designated Cancer Centers provide key cancer research, prevention, and treatment services to members of their catchment area. Characterization of these areas may be complex given the diverse needs of the populations within, particularly those from low socioeconomic position (SEP). The purpose of this paper is to describe the characterization of the Dana-Farber/Harvard Cancer Center (DF/HCC) catchment area through using a two-pronged approach.

Methods:
Participants (n = 1,511) were recruited through (i) an online, probability-based survey (n = 1,013) and (ii) a supplementary, in-person survey from priority groups (African Americans, Latinos, blue-collar workers, low SEP, homeless; n = 498) within Massachusetts. Study staff worked closely with community partners across the state to reach individuals who may not usually be included in online surveys.

Results:
There were several differences across samples, with the community-based sample having a higher percentage of low SEP, low education, African Americans, and Latinos compared with the online sample. Differences were also noted in the cancer-related behaviors of the samples, with the community-based sample having higher rates of smoking, particularly within those who were homeless or make less than $20,000 per year. Fewer community-based subgroups were current with cancer screenings, and more showed more indication of potential communication inequalities compared with statewide estimates.

Conclusions:
The sampling strategy used to characterization of the DF/HCC catchment area provided broad, statewide estimates and additional focus on vulnerable populations, highlighting several potential areas for intervention.

Impact:
This study provides data to highlight the value of using multiple sampling strategies when characterizing cancer center catchment areas.
Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs
Authors: Christmas Brian J. , Rafie Christine I. , Hopkins Alexander C. , Scott Blake A. , Ma Hayley S. , Cruz Kayla A. , Woolman Skylar , Armstrong Todd D. , Connolly Roisin M. , Azad Nilo A. , Jaffee Elizabeth M. , Roussos Torres Evanthia T. 
Published: October 2018

AbstractImmune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor cells (MDSCs), whose functioning prohibits both T-cell activation and infiltration. We attempted to sensitize these tumors to ICI using epigenetic modulation to target MDSC trafficking and function to foster a less immunosuppressive TME. We showed that combining a histone deacetylase inhibitor, entinostat (ENT), with anti–PD-1, anti–CTLA-4, or both significantly improved tumor-free survival in both the HER2/neu transgenic breast cancer and the Panc02 metastatic pancreatic cancer mouse models. Using flow cytometry, gene-expression profiling, and ex vivo functional assays, we characterized populations of tumor-infiltrating lymphocytes (TILs) and MDSCs, as well as their functional capabilities. We showed that addition of ENT to checkpoint inhibition led to significantly decreased suppression by granulocytic MDSCs in the TME of both tumor types. We also demonstrated an increase in activated granzyme-B–producing CD8+ T effector cells in mice treated with combination therapy. Gene-expression profiling of both MDSCs and TILs identified significant changes in immune-related pathways. In summary, addition of ENT to ICI significantly altered infiltration and function of innate immune cells, allowing for a more robust adaptive immune response. These findings provide a rationale for combination therapy in patients with immune-resistant tumors, including breast and pancreatic cancers.
High Genetic Risk Scores of <b><i>ASIC2, MACROD2, CHRM3</i></b>, and <b><i>C2orf83</i></b> Genetic Variants Associated with Polycystic Ovary Syndrome Impair Insulin Sensitivity and Interact with Energy Intake in Korean Women
Authors: Kim Sung-Hoon , Liu Meiling , Jin Hyun Seok , Park Sunmin 
Published: October 2018

<b><i>Background:</i></b> We explored the genetic variants that were associated with polycystic ovary syndrome (PCOS) by genome-wide association study (GWAS) and evaluated the association of genetic risk scores (GRS) of the selected genetic variants with insulin resistance and the interaction of the GRS with nutrient intake to develop insulin resistance. <b><i>Methods:</i></b> The 6 genetic variants involved in brain and nervous system (acid sensing ion channel subunit 2 rs8071961, rs1988598, and rs16589, macro domain containing 2 rs7262810 CHRM3 rs1867265 and chromosome 2 open reading frame 83 rs11889798) were selected from a GWAS of the PCOS study. GRS of the 6 single nucleotide polymorphisms was calculated in 3,723 Korean women in the Ansan/Ansung cohort of KARE study. <b><i>Results:</i></b> Fasting serum insulin and C-reactive protein (CRP) levels, homeostasis model assessment of insulin resistance (HOMA-IR), and psychological stress levels were significantly higher in the high-GRS group than the low-GRS group. However, serum-free T4 levels were significantly lower in the high-GRS group. HOMA-IR and CRP were higher OR (1.129 and 1.382) in the high-GRS group than the low-GRS group after adjusted for covariates. There was a significant interaction between GRS and daily energy intake (<i>p</i> = 0.004). The OR (1.233) for HOMA-IR was higher in the high-GRS group than the low-GRS group only in the group with lower energy intakes based on estimated energy requirement. <b><i>Conclusion:</i></b> Women with high-GRS for PCOS had increased risk of insulin resistance and low energy intake did not protect against the elevation of insulin resistance in women with high GRS. Low energy intake might be protective against PCOS in carriers with low and medium GRS.
Prevention of Stent Thrombosis in Rats by a Direct Oral Factor Xa Inhibitor Edoxaban
Authors: Morishima Yoshiyuki , Honda Yuko , Kamisato Chikako 
Published: October 2018

<b><i>Background/Aims:</i></b> Stent thrombosis is a serious complication after percutaneous coronary intervention and femoropopliteal endovascular intervention. The aim of this study was to determine the antithrombotic effects of a direct factor Xa inhibitor edoxaban alone or in combination with antiplatelet agents in a rat model of stent thrombosis. <b><i>Methods:</i></b> Stainless steel stents (4 stents per rat) were placed in an extracorporeal arteriovenous shunt. The shunt was inserted into the carotid artery and the jugular vein in each rat to circulate blood. Stent thrombosis was induced by exposing the stents to arterial blood for 30 min. Protein content of the thrombus was measured. Edoxaban and antiplatelet agents (aspirin, clopidogrel, and ticagrelor) were orally administered before the thrombus induction. <b><i>Results:</i></b> Edoxaban (0.3–3 mg/kg), clopidogrel (1–10 mg/kg), aspirin (10–100 mg/kg), and ticagrelor (0.3–3 mg/kg) exerted significant and dose-dependent antithrombotic effects in a rat stent thrombosis model. The effect of edoxaban was comparable to that of antiplatelet agents. The combination of submaximal doses of edoxaban and clopidogrel or aspirin significantly potentiated the antithrombotic effects compared with antiplatelet agents alone. <b><i>Conclusion:</i></b> These results suggest that edoxaban alone and in combination with clopidogrel or aspirin are promising antithrombotic therapies for the prevention of stent thrombosis.
Halal Dating and Norwegian Youth Culture
Authors: Bøe Marianne 
Published: October 2018

Abstract
Through conversations with Norwegian youth of Muslim background, this article explores how such young people negotiate religious identity, intimacy and sexuality within Norwegian youth culture. In light of recent statistics on marriage patterns in Norway, it further investigates norms and approaches significant to these youths’ choices. Marriage and intimate relationships are central to how this study’s participants connect the expectations of their minority background with the norms of Norwegian society. Some choose to engage in informal religious marriages—such as “halal dating”—while others are in love relationships and define for themselves the boundaries of what is and is not allowed.
A Frame for Turkey’s Foreign Policy via the Diyanet in the Balkans
Authors: Öztürk Ahmet Erdi , Gözaydın İştar 
Published: October 2018

Abstract
This article deals with Turkey’s increasing involvement and activism in the Balkans between 2002 and 2016, under the government of the Justice and Development Party. The central focus is Turkey’s pliable state apparatus; the Presidency of Religious Affairs and its activities in the region. The article therefore aims to answer the following questions: Why does Turkey use these various state apparatuses specifically as a foreign policy tool and how does their influence differ from country to country? What factors determine the scope of activity of Turkish transnational state apparatuses in the case of each country? And, how do local actors and public opinion respond to Turkey’s newly-emerging activities in the region?
Influence of Atmospheric Rivers on Mountain Snowpack in the Western United States
Authors: Goldenson N. , Leung L. R. , Bitz C. M. , Blanchard-Wrigglesworth E. 
Published: October 2018

AbstractIn the coastal mountains of western North America, most extreme precipitation is associated with atmospheric rivers (ARs), narrow bands of moisture originating in the tropics. Here we quantify how interannual variability in atmospheric rivers influences snowpack in the western United States in observations and a model. We simulate the historical climate with the Model for Prediction Across Scales (MPAS) with physics from the Community Atmosphere Model, version 5 [CAM5 (MPAS-CAM5)], using prescribed sea surface temperatures. In the global variable-resolution domain, regional refinement (at ~30 km) is applied to our region of interest and upwind over the northeast Pacific. To better characterize internal variability, we conduct simulations with three ensemble members over 30 years of the historical period. In the Cascade Range, with some exceptions, winters with more atmospheric river days are associated with less snowpack. In California’s Sierra Nevada, winters with more ARs are associated with greater snowpack. The slope of the linear regression of observed snow water equivalent (SWE) on reanalysis-based AR count has the same sign as that arrived at using the model, but is statistically significant in observations only for California. In spring, internal variance plays an important role in determining whether atmospheric river days appear to be associated with greater or less snowpack. The cumulative (winter through spring) number of atmospheric river days, on the other hand, has a relationship with spring snowpack, which is consistent across ensemble members. Thus, the impact of atmospheric rivers on winter snowpack has a greater influence on spring snowpack than spring atmospheric rivers in the model for both regions and in California consistently in observations.