bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivation of cAMP Pathway by PDE4D Inhibition Represents a Novel Druggable Axis for Overcoming Tamoxifen Resistance in ER-positive Breast Cancer
Authors: Mishra Rasmi R. , Belder Nevin , Ansari Suhail A. , Kayhan Merve , Bal Hilal , Raza Umar , Ersan Pelin G. , Tokat Ünal M. , Eyüpoğlu Erol , Saatci Özge , Jandaghi Pouria , Wiemann Stefan , Üner Ayşegül , Cekic Caglar , Riazalhosseini Yasser , Şahin Özgür
Published: January 2018

Purpose: Tamoxifen remains an important hormonal therapy for ER-positive breast cancer; however, development of resistance is a major obstacle in clinics. Here, we aimed to identify novel mechanisms of tamoxifen resistance and provide actionable drug targets overcoming resistance.

Experimental Design: Whole-transcriptome sequencing, downstream pathway analysis, and drug repositioning approaches were used to identify novel modulators [here: phosphodiesterase 4D (PDE4D)] of tamoxifen resistance. Clinical data involving tamoxifen-treated patients with ER-positive breast cancer were used to assess the impact of PDE4D in tamoxifen resistance. Tamoxifen sensitization role of PDE4D was tested in vitro and in vivo. Cytobiology, biochemistry, and functional genomics tools were used to elucidate the mechanisms of PDE4D-mediated tamoxifen resistance.

Results: PDE4D, which hydrolyzes cyclic AMP (cAMP), was significantly overexpressed in both MCF-7 and T47D tamoxifen-resistant (TamR) cells. Higher PDE4D expression predicted worse survival in tamoxifen-treated patients with breast cancer (n = 469, P = 0.0036 for DMFS; n = 561, P = 0.0229 for RFS) and remained an independent prognostic factor for RFS in multivariate analysis (n = 132, P = 0.049). Inhibition of PDE4D by either siRNAs or pharmacologic inhibitors (dipyridamole and Gebr-7b) restored tamoxifen sensitivity. Sensitization to tamoxifen is achieved via cAMP-mediated induction of unfolded protein response/ER stress pathway leading to activation of p38/JNK signaling and apoptosis. Remarkably, acetylsalicylic acid (aspirin) was predicted to be a tamoxifen sensitizer using a drug repositioning approach and was shown to reverse resistance by targeting PDE4D/cAMP/ER stress axis. Finally, combining PDE4D inhibitors and tamoxifen suppressed tumor growth better than individual groups in vivo.

Conclusions: PDE4D plays a pivotal role in acquired tamoxifen resistance via blocking cAMP/ER stress/p38-JNK signaling and apoptosis. Clin Cancer Res; 24(8); 1987–2001. ©2018 AACR.
YAP-Induced PD-L1 Expression Drives Immune Evasion in BRAFi-Resistant Melanoma
Authors: Kim Min Hwan , Kim Chang Gon , Kim Sang-Kyum , Shin Sang Joon , Choe Eun Ah , Park Su-Hyung , Shin Eui-Cheol , Kim Joon
Published: January 2018

Activation of YAP, a Hippo pathway effector, is an important resistance mechanism to BRAF inhibitor (BRAFi) in melanoma. Emerging evidence also suggests that YAP is involved in suppression of the antitumor immune response. However, the potential direct impact of YAP activity on cytotoxic T-cell immune responses has not been explored yet. Here, we show that BRAFi-resistant melanoma cells evade CD8+ T-cell immune responses in a PD-L1–dependent manner by activating YAP, which synchronously supports melanoma cell survival upon BRAF inhibition. PD-L1 expression is elevated in BRAFi-resistant melanoma cells, in which YAP is robustly activated, and YAP knockdown decreases PD-L1 expression. In addition, constitutively active YAP (YAP-5SA) increases PD-L1 expression by binding to an upstream enhancer of the PD-L1 gene and potentiating its transcription. Both BRAFi-resistant and YAP-5SA–expressing melanoma cells suppress the cytotoxic function and cytokine production of Melan-A–specific CD8+ T cells, whereas anti–PD-1 antibody reverses the YAP-mediated T-cell suppression. Moreover, nuclear enrichment of YAP in clinical melanoma samples correlates with increased PD-L1 expression. Our findings show that YAP directly mediates evasion of cytotoxic T-cell immune responses in BRAFi-resistant melanoma cells by upregulating PD-L1, and targeting of YAP-mediated immune evasion may improve prognosis of melanoma patients. Cancer Immunol Res; 6(3); 255–66. ©2018 AACR.
Evaluation of Reproductive Concerns and Biographical Impact of Breast Cancer in Young Patients
Authors: Burgmann Maximiliane , Hermelink Kerstin , Farr Alex , van Meegen Friederike , Heiduschk Annika , Engel Jutta , Kolben Thomas , Degenhardt Tom , Ditsch Nina , Mahner Sven , Harbeck Nadia , Würstlein Rachel
Published: January 2018

Background: This study evaluates interventions offered to young breast cancer (BC) patients, including fertility preservation, genetic testing, and counseling for parenthood concerns, and analyzes the effect of BC on biographical issues. Methods: Women who were diagnosed with BC at the age of 18-40 years and who underwent treatment at the Breast Center, Ludwig-Maximilian University (LMU) in Munich between 2006 and 2013, were eligible for this study. Patients received a self-developed questionnaire which covered the following topics: fertility preservation, family planning, genetic testing, parenthood concerns and children's needs, partnership status, and employment situation. Results: Re-evaluating their initial decision on fertility preservation, 76.4% of patients reported satisfaction with their decision. After BC diagnosis, 45.8% reported to have maternal desire, but only 21.7% actually planned to have children. 41.7% of patients missed sufficient counseling regarding parenthood concerns. Analysis of individual employment situations showed that the time period until the return to work was longer in patients who received chemotherapy. The majority of patients (71.6%) did not report changes in their partnership status. Conclusion: Young BC survivors report a lack of communication related to parenthood concerns and future conception, but are satisfied with counseling regarding fertility preservation and genetics.
Porous Chitosan/Nano-Hydroxyapatite Composite Scaffolds Incorporating Simvastatin-Loaded PLGA Microspheres for Bone Repair
Authors: Li Yu , Zhang Zhanzhao , Zhang Zhiyong
Published: January 2018

The combination of bone tissue scaffolds with osteogenic induction factors is an effective strategy to facilitate bone healing processes. Here, chitosan (CS)/nano-hydroxyapatite (HA) scaffolds containing simvastatin (SIM)-loaded PLGA microspheres were fabricated by combining a freeze-drying technique with a modified water-oil-water emulsion method. The CS/HA weight ratio of 1:2 was selected by analyzing the effect of HA content on the micro-architecture, mechanical strength, and biocompatibility of the scaffold. Drug release kinetics showed that the SIM encapsulated in the scaffold was released in a sustained manner for up to 30 days. In vitro bioactivity study in rat bone marrow-derived mesenchymal stem cells showed that the SIM-loaded scaffolds had a strong ability in accelerating cell proliferation and inducing osteogenic differentiation. Moreover, an in vivo experiment using a rat calvarial defect model also documented that the SIM-loaded scaffolds had a remarkable effect on bone-promoting regeneration. The results of this study suggest that the SIM-loaded CS/HA scaffold is feasible and effective in bone repair and thus may provide a promising route for the treatment of critical-sized bone defects.
Lipid Metabolism in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Shu Yaqing , Qin Bing , Xu Yue , Sun Xiaobo , Chen Zheng , Wang Jia , Peng Lisheng , Qiu Wei , Lu Zhengqi , Wu Aimin
Published: January 2018

Objective: Lipid metabolism has been implicated in autoimmune disorders, but its relationship with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unclear. This study examined the association of serum lipids with anti-NMDAR encephalitis. Methods: Serum lipid profiles and C-reactive protein (CRP) were evaluated in 68 patients with anti-NMDAR encephalitis, and 68 age- and sex-matched healthy controls (CTLs). Follow-up evaluations were conducted 3 months after admission in 32 of the 68 patients. Modified Rankin scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated in all patients. Results: Compared with CTLs, patients with anti-NMDAR encephalitis had significantly lower serum high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels but significantly higher serum apoB levels and apoB/apoA-I ratios. Serum HDL and apoA-I were significantly and negatively associated with serum CRP levels, whereas serum aopB levels and apoB/apoA-I ratios were positively associated with age, CRP levels, and mRS scores. Follow-up evaluations revealed that serum total cholesterol, apoA-I, and HDL-C levels were significantly higher but mRS scores were significantly lower than those before treatment, and that the increased HDL-C levels were significantly and negatively correlated with decreased mRS scores. Conclusion: Serum HDL-C and apoA-I levels are reduced in the initial phase of anti-NMDAR encephalitis and recover after treatment. Further studies about the role of serum lipid in anti-NMDAR encephalitis are needed.
Acute Erythroderma in a Patient Receiving TNF-α-Blocking Therapy for Hidradenitis Suppurativa
Authors: Benhadou Farida , Hellgren Guillaume , Willaert Fabienne , del Marmol Véronique
Published: January 2018

Tumor necrosis factor-α (TNF-α) normally binds to TNF-α receptors, leading to the inflammatory response of autoimmune diseases. Adalimumab is a TNF-inhibiting, anti-inflammatory, biological medication which binds to TNF-α, thus reducing this inflammatory response. The use of TNF-α-inhibiting medication, such as adalimumab, being the first FDA-approved treatment for hidradenitis suppurativa, has drastically changed the management of dermatological diseases. One rarely reported manifestation that occurs as a side effect associated with the use of TNF-α-blocking agents is erythroderma. This study, for the first time, reports the case of a patient suffering from hidradenitis suppurativa with concomitant psoriasis, who developed a severe and acute erythrodermic rash after the start of adalimumab therapy.
Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status
Authors: Igawa Satoshi , Shirasawa Masayuki , Fukui Tomoya , Nishinarita Noriko , Sone Hideyuki , Ozawa Takahiro , Sugita Keisuke , Okuma Yuriko , Kurahayashi Shintaro , Ono Taihei , Sugimoto Ai , Mitsufuji Hisashi , Kubota Masaru , Katagiri Masato , Sasaki Jiichiro , Naoki Katsuhiko
Published: January 2018

Background: Previous studies have shown amrubicin to be an effective first- or second-line treatment option for small-cell lung cancer (SCLC). However, there have been few studies reporting the efficacy of platinum-based chemotherapy after amrubicin therapy. We aimed to evaluate the efficacy of platinum-based chemotherapy as second-line treatment for elderly patients and those with SCLC with poor performance status (PS) previously treated with amrubicin monotherapy. Methods: The records of SCLC patients who received platinum-based chemotherapy as a second-line chemotherapy after first-line treatment with amrubicin monotherapy were retrospectively reviewed and the treatment outcomes were evaluated. Results: A total of 48 patients were enrolled in this study. Forty-one patients (85%) received carboplatin plus etoposide. The overall response rate was 39.6%. The median progression-free survival and overall survival were 3.7 and 7.6 months, respectively. The efficacy of the platinum-based regimen did not differ with the type of relapse after amrubicin monotherapy. The most common adverse events were hematological toxicities, including grade 3 or 4 neutropenia (38%), leukopenia (33%), and thrombocytopenia (10%). Conclusions: Platinum-based chemotherapy is potentially a valid treatment option for elderly patients or those with extensive-stage SCLC with poor PS as second-line chemotherapy, who progressed after first-line treatment with amrubicin monotherapy.
Diagnostic Accuracy of a Bioluminescence System for the Assessment of Caries Activity on Occlusal Surfaces
Authors: Jablonski-Momeni Anahita , Moos Johanna , Sakhaei Manesh Vahid , Stoll Richard
Published: January 2018

Objective: Assessment of caries lesion activity is usually performed using visual-tactile criteria. A new approach is to use a system consisting of a photoprotein, which is specific for free calcium ions, along with an integrated camera that visualizes the elevated calcium ions on the lesion as a light signal (bioluminescence). This study aimed to evaluate the reproducibility and diagnostic accuracy of a newly developed bioluminescence system to assess caries lesion activity on occlusal surfaces in vitro. Materials and Methods: Ninety-four extracted permanent teeth with sound surfaces and both active and inactive caries lesions were included. The extent and activity of the investigation sites were classified visually according to the International Caries Detection and Assessment System. Digital images of the teeth were produced by the bioluminescence system and the images were analyzed for the presence of caries activity (the bioluminescent areas at the investigation sites). The images were reanalyzed after 4 weeks. Teeth were hemisected and methyl red dye was applied on the sections to validate lesion activity histologically. Results: Agreement between the bioluminescence readings was shown by κ values of 0.802–0.917. A significant positive correlation (p < 0.001) was found across all methods (rs 0.618–0.811). Sensitivity and specificity for activity assessment using histology as the gold standard (cut-off: active/inactive) were, respectively, 83.6 and 85.0% for the visual assessment, and 92.5 and 90.0% for the bioluminescence method. Comparison of areas under the receiver-operating characteristic curves showed no significant difference between the visual and bioluminescence systems (p = 0.094). Conclusion: The bioluminescence system demonstrated high in vitro reproducibility and good diagnostic accuracy for activity assessment of caries lesions on occlusal surfaces which were not significantly different from the values obtained in the visual assessment.
Clinical Outcomes of Myocardial Bridging versus No Myocardial Bridging in Patients with Apical Hypertrophic Cardiomyopathy
Authors: Zhai Shan-Shan , Fan Chao-Mei , An Shuo-Yan , Hang Fei , Yang Yin-Jian , Yan Li-Rong , Guo Xi-Ying , Li Yi-Shi
Published: January 2018

Objective: To determine the prevalence and clinical effects of myocardial bridging (MB) in patients with apical hypertrophic cardiomyopathy (AHCM). Methods: Angiograms from 212 AHCM patients were reviewed to identify MB. The patients were classified into 2 groups: AHCM with and AHCM without MB. We reviewed patient records on cardiovascular (CV) risk factors, symptoms, CV events, and CV mortality. Results: In all, 60 patients with MB and 100 without MB were included. Rates of angina (61.7 vs. 40%; p = 0.008), mimicking non-ST-segment elevation myocardial infarction (15 vs. 3%, p = 0.013), and Canadian Cardiovascular Society class III/IV angina (18.3 vs. 4%; p = 0.003) were higher in patients with MB than in those without. Mean follow-up periods (65.5 ± 50.5 vs. 64.4 ± 43.6 months, p = 0.378) and CV mortality (3.3 vs. 1%; p = 0.652) were similar in the 2 groups. Kaplan-Meier estimates demonstrated that CV event-free survival rates were lower in patients with MB than in those without (71.7 vs. 88%; p = 0.022). MB, late gadolinium enhancement, and female sex were independent risk factors for CV events in a multivariate Cox regression analysis adjusted for other risk factors. Conclusion: More serious symptoms and a higher risk of CV events were observed in AHCM patients with MB than in those without MB. CV mortality was similar in these 2 groups.
Sarcomatoid Tumor following Radium Treatment
Authors: Chakari Wahida , Pedersen Pilt Anette , Lock-Andersen Jørgen
Published: January 2018

Haemangiomas are benign skin lesions that usually regress spontaneously, but radiotherapy has previously been used to assist the regression and healing of the lesions. Radium and X-rays were used as a treatment for benign skin lesions such as haemangioma until the carcinogenic effect of ionising radiation in humans was described. We report a patient diagnosed with a sarcomatoid carcinoma. Her past history was of particular interest since she had received radium treatment for a haemangioma at the same location more than 70 years before.
The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-β1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients
Authors: Abu El Makarem Mona A. , El-Sagheer Ghada M. , Abu El-Ella Moustafa A.
Published: January 2018

Objective: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). Subjects and Methods: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-β1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. Results: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-β1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-β1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-β1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-β1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8). Conclusions: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-β1 but not through the activation of hepatic stellate cells.
Definition of Iron Deficiency Based on the Gold Standard of Bone Marrow Iron Staining in Heart Failure Patients
Authors: Grote Beverborg Niels , Klip IJsbrand T. , Meijers Wouter C. , Voors Adriaan A. , Vegter Eline L. , van der Wal Haye H. , Swinkels Dorine W. , van Pelt Joost , Mulder Andre B. , Bulstra Sjoerd K. , Vellenga Edo , Mariani Massimo A. , de Boer Rudolf A. , van Veldhuisen Dirk J. , van der Meer Peter
Published: January 2018

Background

The most commonly used definition of iron deficiency (ID; ferritin <100 ng/mL or ferritin 100–300 ng/mL and transferrin saturation [TSAT] <20%) has not been validated in patients with heart failure (HF). We aimed to define and validate the biomarker-based definition of ID in HF, using bone marrow iron staining as the gold standard. Second, we aimed to assess the prognostic value of the optimized definition.

Methods and Results

Bone marrow aspiration with iron staining was performed in 42 patients with HF and a reduced left ventricular ejection fraction (≤45%) undergoing median sternotomy for coronary artery bypass grafting. Patients were mostly male (76%) with mild-to-moderate HF and a mean age of 68±10 years. Bone marrow ID was found in 17 (40%) of the HF patients. The most commonly used definition of ID had a sensitivity of 82% and a specificity of 72%. A definition solely based on TSAT ≤19.8% or serum iron ≤13 µmol/L had a sensitivity of 94% and specificity of 84% and 88%, respectively (
P
<0.05 compared with the former definition). Subsequently, we assessed the incidence of all-cause mortality in 387 consecutive outpatient HF patients (left ventricular ejection fraction ≤45%). In these patients, TSAT ≤19.8% and serum iron ≤13 µmol/L, and not ferritin, were independently associated with mortality.

Conclusions

A TSAT ≤19.8% or a serum iron ≤13 µmol/L shows the best performance in selecting patients with ID and identifies HF patients at the highest risk of death. Our findings validate the currently used TSAT cutoff of <20% for the identification of ID in HF patients, but question the diagnostic value of ferritin.
Six-Year Changes in Physical Activity and the Risk of Incident Heart Failure
Authors: Florido Roberta , Kwak Lucia , Lazo Mariana , Nambi Vijay , Ahmed Haitham M. , Hegde Sheila M. , Gerstenblith Gary , Blumenthal Roger S. , Ballantyne Christie M. , Selvin Elizabeth , Folsom Aaron R. , Coresh Josef , Ndumele Chiadi E.
Published: January 2018

Background:

Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown.

Methods:

We evaluated 11 351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993–1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987–1989) and third ARIC visits and HF risk.

Results:

During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60–0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63–0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82–0.96).

Conclusions:

Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.
Long‐Term Outcome of Consecutive Patients With Previous Coronary Bypass Surgery, Treated With Newer‐Generation Drug‐Eluting Stents
Authors: van der Heijden Liefke C. , Kok Marlies M. , Zocca Paolo , Sen Hanim , Löwik Marije M. , Mariani Silvia , de Man Frits H. A. F. , Hartmann Marc , Stoel Martin G. , van Houwelingen K. Gert , Louwerenburg J. (Hans) W. , Linssen Gerard C. M. , Doggen Carine J. M. , Grandjean Jan G. , von Birgelen Clemens
Published: January 2018

Background

Percutaneous coronary intervention (
PCI
) in patients with previous coronary artery bypass grafting (
CABG
) is associated with adverse clinical events. Although newer generation drug‐eluting stents showed favorable short‐term safety profiles, there is a lack of long‐term outcome data. We evaluated the impact of previous
CABG
on 5‐year clinical outcomes of patients treated with
PCI
using newer‐generation drug‐eluting stents.

Methods and Results

In this patient‐level pooled analysis of the prospective TWENTE (The Real‐World Endeavor Resolute versus Xience V Drug‐Eluting Stent Study in Twente) trial and nonenrolled
TWENTE
registry, we assessed a consecutive series of patients who underwent
PCI
with newer‐generation drug‐eluting stents for non–
ST
‐segment–elevation acute coronary syndromes or stable angina. Of all 1709 patients, 202 (11.8%) had a history of
CABG
. Patients with previous
CABG
had significantly higher 5‐year rates of cardiac death (10.4% versus 4.3%;
P
<0.001) and target vessel revascularization (25.0% versus 8.1%;
P
<0.001). These differences remained statistically significant after adjustment for differences in baseline characteristics. Landmark analysis revealed that from 1‐ to 5‐year follow‐up, the rates of cardiac death (8.1% versus 3.2%;
P
<0.001) and target vessel revascularization (17.1% versus 5.9%;
P
<0.001) were significantly higher in patients with previous
CABG
. Among patients with a history of
CABG
,
PCI
of an obstructed vein graft was associated with a higher rate of 5‐year target vessel revascularization (
P
=0.003).

Conclusions

At 5‐year follow‐up after
PCI
with newer‐generation drug‐eluting stents, the risk of cardiac death and target vessel revascularization was significantly higher in patients with previous
CABG
. The target vessel revascularization rate was highest in patients who underwent
PCI
of obstructed vein grafts.
Hypertensive Disorders of Pregnancy and Offspring Cardiometabolic Health at Midchildhood: Project Viva Findings
Authors: Tripathi Ruby Reetika , Rifas‐Shiman Sheryl L. , Hawley Nicola , Hivert Marie‐France , Oken Emily
Published: January 2018

Background

Exposure to preeclampsia or gestational hypertension is associated with higher offspring systolic blood pressure (
SBP
), but less is known about associations with other cardiometabolic risk markers.

Methods and Results

We studied 1097 children from the Project Viva cohort born 1999‐2002. Exposures were preeclampsia or gestational hypertension and mean maternal
SBP
in each trimester from prenatal records. Outcomes were research measures in midchildhood (mean 8.0 years) of
SBP
, overall adiposity, and a global cardiometabolic risk score comprising measures of
SBP
, waist circumference, glycemia, and lipids. We conducted linear regression analyses adjusted for maternal characteristics and offspring sex and age. In adjusted models, maternal preeclampsia or gestational hypertension (n=98, 9.1%) versus normal blood pressure was associated with slightly higher offspring
SBP
z‐score (0.15 units; 95% confidence interval [CI] −0.03, 0.32) but otherwise predicted better cardiometabolic health markers including metabolic risk z‐score (−0.23 units; −95%
CI
0.44, −0.03) and several of its components as well as lower body mass index z‐score (−0.27 units; 95%
CI
−0.48, −0.06) and lower fat mass index (−0.91 kg/m
2
; 95%
CI
−1.35, −0.47). Similarly, higher mean third‐trimester maternal
SBP
was associated with higher offspring
SBP
z‐score (0.09 units per 10 mm Hg; 95%
CI
0.02, 0.16) and lower overall and central adiposity but not with biomarkers of metabolic risk. Results for second‐trimester
SBP
were generally similar. First‐trimester blood pressure was associated with higher offspring blood pressure but not with other outcomes.

Conclusions

Higher maternal late‐pregnancy
SBP
and hypertensive disorders of pregnancy were associated with higher offspring
SBP
but otherwise better cardiometabolic health.
EU Criminal Law and Its Legitimation: In Search for a Substantive Principle of Criminalisation
Authors: Peršak Nina
Published: January 2018

The increasing legislative activity in the field of eu criminal law has highlighted the need for a coherent and consistent approach to criminalisation, which has been acknowledged by the eu institutions themselves. One of the basic questions all legislators need to tackle, however, is what sorts of conduct can be (legitimately) criminalised. The aim of this article is, firstly, to examine the prevailing substantive criminalisation principle(s) in the eu Member States’ criminal law theories; secondly, to sketch an ideal criminalisation process, which although applicable at national level can be useful also at eu level, and thirdly, to inspect the existing criminal law grounds for criminalisation and the criminal policy orientations at eu level in order to find out what the underlying substantive criminalisation principle behind eu criminal law is or ought to be, alongside other principles that may act as ‘limiting factors’ within the criminalisation process.
Three new species of Pambolus (Braconidae: Pambolinae) from Mexico, with comments on the variation of P. oblongispina Papp
Authors: AGUILERA-URIBE MAGALI , MARTÍNEZ JUAN JOSÉ , ZALDÍVAR-RIVERÓN ALEJANDRO
Published: January 2018

Three species of the braconid genus Pambolus (Braconidae) are described from Mexico: P. jarocho sp. n., P. chinanteco sp. n. and P. bizelab sp. n. The external morphological variation in males and females of P. oblongispina Papp, previously known only by two females from Honduras and northern Mexico, is described based on material from Jalisco and Oaxaca in central and southeast Mexico. Molecular characterisation of the examined species was carried out based on the 28S nuclear ribosomal and the COI mitochondrial DNA gene markers.
Using the Atmospheric Radiation Measurement (ARM) Datasets to Evaluate Climate Models in Simulating Diurnal and Seasonal Variations of Tropical Clouds
Authors: Wang Hailong , Burleyson Casey D. , Ma Po-Lun , Fast Jerome D. , Rasch Philip J.
Published: January 2018

Long-term Atmospheric Radiation Measurement (ARM) datasets collected at the three tropical western Pacific (TWP) sites are used to evaluate the ability of the Community Atmosphere Model (CAM5) to simulate the various types of clouds, their seasonal and diurnal variations, and their impact on surface radiation. A number of CAM5 simulations are conducted at various horizontal grid spacing (around 2°, 1°, 0.5°, and 0.25°) with meteorological constraints from analysis or reanalysis. Model biases in the seasonal cycle of cloudiness are found to be weakly dependent on model resolution. Positive biases (up to 20%) in the annual mean total cloud fraction appear mostly in stratiform ice clouds. Higher-resolution simulations do reduce the positive bias in ice clouds, but they inadvertently increase the negative biases in convective clouds and low-level liquid clouds, leading to a positive bias in annual mean shortwave fluxes at the sites, as high as 65 W m−2 in the 0.25° simulation. Such resolution-dependent biases in clouds can adversely lead to biases in ambient thermodynamic properties and, in turn, produce feedback onto clouds. Both the model and observations show distinct diurnal cycles in total, stratiform, and convective cloud fractions; however, they are out of phase by 12 h and the biases vary by site. The results suggest that biases in deep convection affect the vertical distribution and diurnal cycle of stratiform clouds through the transport of vapor and/or the detrainment of liquid and ice. The approach used here can be easily adapted for the evaluation of new parameterizations being developed for CAM5 or other global or regional models.
The encouragement of bargaining in good faith – A behavioural approach
Authors: Fells Ray , Caspersz Donella , Leighton Catherine
Published: January 2018

The Fair Work Act, 2009 has provisions that require the parties to bargain in good faith. ‘Good faith’ is difficult to codify, and analysis of whether those who bargain comply with the provisions is typically conducted using a legal perspective. This article adopts a behavioural perspective by conducting negotiation simulations and shows that priming negotiators with good faith requirements has a positive impact on the way they negotiated. The article contributes to understanding the efficacy of the good faith bargaining provision in fostering productive enterprise bargaining outcomes. Thus, the article will be of interest to policy makers and practitioners including those in the Australian Government’s Fair Work Commission, as well as those interested in workplace bargaining.
Keeping Black Children Pushed Into, Not Pushed Out of, Classrooms: Developing a Race-Conscious Parent Engagement Project
Authors: Yull Denise , Wilson Marguerite
Published: January 2018

Black students in prekindergarten through Grade 12 (P-12) schools across the United States experience persistent educational disparities involving disproportionate disciplinary practices. This research study, using a qualitative methodological approach, describes and analyzes the impact of the Parent Mentor Program, which brings together Black parents, community members, school district personnel and university researchers working together to implement a race-conscious parent engagement project to transform the experiences of Black parents and Black children in the school district. Themes that emerged from the qualitative narratives include Black parents moving from marginalized outsiders to feeling accepted, teachers’ perspectives on the impact of the program, and the final theme—pushing kids into, not out of the classroom—which delineates the critical role of Black parents in addressing pervasive racialized disciplinary practices within school systems. Findings provide support for this culturally responsive innovative parent engagement program with Black parents based on a model that does not subscribe to a traditional framework of race neutrality and colorblindness situated in educational systems. This program instead proposes a race-conscious parent engagement model.
Does Self-Licensing Benefit Self-Regulation Over Time? An Ecological Momentary Assessment Study of Food Temptations
Authors: Prinsen Sosja , Evers Catharine , Wijngaards Leoniek , van Vliet Renée , de Ridder Denise
Published: January 2018

Self-licensing, employing reasons to justify indulgence, may help resolve the conflict between immediate temptations and long-term goals in favor of the former. It was hypothesized that this conflict-resolving potential of self-licensing may benefit self-regulation over time. With a momentary assessment design, we examined how self-licensing affects self-regulatory ability and the capacity to deal with subsequent self-regulatory conflicts. One hundred thirty-six female participants filled out surveys eight times per day for one week. Food temptation strength, conflict, resistance, and enactment were assessed, as well as license opportunity and perceived self-regulatory ability. When self-licensing opportunity was high (vs. low), a weaker association between temptation strength and conflict was observed. High license opportunity was associated with higher perceived self-regulatory ability for instances of low degrees of temptation enactment and predicted better handling of subsequent conflict after high degrees of prior temptation enactment. These results suggest that self-licensing can support self-regulation after initial failure.
Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease
Authors: Sato Shinpei , Kojima Daigo , Shimada Yasuyoshi , Yoshida Jun , Fujimato Kentaro , Fujiwara Shunrou , Kobayashi Masakazu , Kubo Yoshitaka , Yoshida Kenji , Terasaki Kazunori , Tsutsui Shouta , Miyoshi Kenya , Ogasawara Kuniaki
Published: January 2018

The present study examined whether preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease. Among 65 adult patients with ischemic moyamoya disease, 19 had misery perfusion in the precentral region on preoperative 15O positron emission tomography and underwent arterial bypass surgery for that region. Brain technetium-99 m-labeled ethyl cysteinate dimer single-photon emission computed tomography (SPECT) was preoperatively performed with and without hyperventilation challenge and relative cerebrovascular contractile reactivity to hypocapnia (RCVCRhypocap) (%/mmHg) was calculated in the precentral region. Development of cerebral hyperperfusion syndrome was determined using perioperative changes of symptoms and brain N-isopropyl-p-[123I]-iodoamphetamine SPECT performed after surgery. RCVCRhypocap was significantly lower in the 6 patients with cerebral hyperperfusion syndrome (−2.85 ± 1.10%/mmHg) than in the 13 patients without cerebral hyperperfusion syndrome (0.18 ± 1.97%/mmHg; p = 0.0050). Multivariate analysis demonstrated low RCVCRhypocap as an independent predictor of cerebral hyperperfusion syndrome (95% confidence interval, 0.04–0.96; p = 0.0433). Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease.
Preoperative Tibial Subchondral Bone Marrow Lesion Patterns and Associations With Outcomes After Isolated Meniscus Allograft Transplantation
Authors: Saltzman Bryan M. , Cotter Eric J. , Stephens Jeffrey P. , Cvetanovich Gregory L. , Madden Brett , Wang Kevin , Yanke Adam B. , Cole Brian J.
Published: January 2018

Background:

The association between preoperative tibial subchondral bone marrow lesion (BML) patterns and outcomes after isolated meniscus allograft transplantation (MAT) are unknown.

Purpose:

To determine (1) if a superior classification means exists (ie, high interrater reliability [IRR]) for grading tibial subchondral BML before isolated MAT and (2) whether quality and/or severity of preoperative tibial subchondral BML patterns was associated with clinical outcomes and/or failure rates after isolated MAT.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

All patients who underwent isolated MAT with a single surgeon between October 2006 and February 2017 were identified. Three means were evaluated to quantify the degree of subchondral BML in the affected tibial-sided compartment: Welsch et al, based on maximum diameter of the lesion; Costa-Paz et al, based on appearance and location of the lesion; and Filardo et al, based on severity of findings. IRR was generated and compared among the 3 classifications. The preoperative magnetic resonance imaging (MRI) subchondral BML grading scheme with the highest IRR was then used to assess for associations with postoperative outcomes for those patients with >2-year follow-up, per a Spearman correlation matrix with each reviewer’s grades.

Results:

In total, 60 MRI scans were available for subchondral BML grading. Grader 1 identified the presence of subchondral BML in the tibia of the affected compartment in 40 (66.7%) of the available MRI scans, as compared with 38 (63.3%) for grader 2. The calculated IRRs with the Welsch et al and Costa-Paz et al classifications were rated “strong/almost perfect” agreement. A significant correlation was demonstrated between grader 1 with the Welsch et al grading scheme and outcome measures of KOOS pain (Knee injury and Osteoarthritis Outcome Score; negative correlation, P = .05), WOMAC pain (Western Ontario and McMaster Universities Osteoarthritis Index; positive correlation, P = .026), and Marx Activity Rating Scale (negative correlation, P = .019). A significant correlation was demonstrated between grader 2 with the Costa-Paz et al grading scheme and postoperative satisfaction (positive correlation, P = .018). There were no significant differences in survivorship based on gradings.

Conclusion:

Nearly two-thirds of patients who undergo isolated MAT have subchondral BML on preoperative MRI. Our findings suggest that increasing BML size (Welsch et al) is correlated with worse postoperative pain measures (KOOS pain, WOMAC pain) and worse activity ratings (Marx Activity Rating Scale). Additionally, increasing disruption or depression of the normal contour of the cortical surface, with or without lesion contiguity with the subjacent articular surface (Costa-Paz et al), is correlated with greater postoperative satisfaction.
Transformed low-rank ANOVA models for high-dimensional variable selection
Authors: Jung Yoonsuh , Zhang Hong , Hu Jianhua
Published: January 2018

High-dimensional data are often encountered in biomedical, environmental, and other studies. For example, in biomedical studies that involve high-throughput omic data, an important problem is to search for genetic variables that are predictive of a particular phenotype. A conventional solution is to characterize such relationships through regression models in which a phenotype is treated as the response variable and the variables are treated as covariates; this approach becomes particularly challenging when the number of variables exceeds the number of samples. We propose a general framework for expressing the transformed mean of high-dimensional variables in an exponential distribution family via ANOVA models in which a low-rank interaction space captures the association between the phenotype and the variables. This alternative method transforms the variable selection problem into a well-posed problem with the number of observations larger than the number of variables. In addition, we propose a model selection criterion for the new model framework with a diverging number of parameters, and establish the consistency of the selection criterion. We demonstrate the appealing performance of the proposed method in terms of prediction and detection accuracy through simulations and real data analyses.
The Effects of a Culturally Tailored, Patient-Centered Psychosocial Intervention in South Korean Cancer Survivors
Authors: Kim Dohun , Chang Sun Ju , Lee Hyun Ok , Lee Seung Hee
Published: January 2018

This study aimed to develop a culturally tailored, patient-centered psychosocial intervention program and to investigate the effects of the program on health-related quality of life, sleep disturbance, and depression in cancer survivors. This was a one-group pretest and posttest design. A total of 19 cancer survivors participated in the program. The program was designed to have an 8-week duration with one class per week. Every class was composed of a 90-min education session and a 90-min exercise. Among the health-related quality of life subscales, the scores of global health status/quality of life, physical functioning, and emotional functioning at posttest were statistically increased than those at pretest. Fatigue scores significantly decreased, whereas no changes were observed in sleep disturbance or depression scores. The findings of this study suggested that a culturally tailored, patient-centered psychosocial intervention could be applied in clinical settings to improve health-related quality of life in cancer survivors.
Investigation of thermal indoor climate for a passive house in a sub-Arctic region using computational fluid dynamics
Authors: Risberg Daniel , Risberg Mikael , Westerlund Lars
Published: January 2018

There is currently an increasing trend in Europe to build passive houses. In order to reduce the cost of installation, an air-heating system may be an interesting alternative. Heat supplied through ventilation ducts located at the ceiling was studied with computational fluid dynamics technique. The purpose was to illustrate the thermal indoor climate of the building. To validate the performed simulations, measurements were carried out in several rooms of the building. Furthermore, this study investigated if a designed passive house located above the Arctic Circle could fulfil heat requirements for a Swedish passive house standard. Our results show a heat loss factor of 18.8 W/m2 floor area and an annual specific energy use of 67.9 kWh/m2 floor area, would fulfils the criteria. Validation of simulations through measurements shows good agreement with simulations if the thermal inertia of the building was considered. Calculation of heat losses from a building with a backward weighted moving average outdoor temperature produced correct prediction of the heat losses. To describe the indoor thermal climate correctly, the entire volume needs to be considered, not only one point, which normally is obtained with building simulation software. The supply airflow must carefully be considered to fulfil a good indoor climate.
Depoliticising addiction
Authors: Bujalski Michał , Hellman Matilda , Moskalewicz Jacek , Beccaria Franca , Rolando Sara
Published: January 2018

Aims:

The article presents an analysis of sources of information employed in mainstream print media reporting on addiction problems in Finland, Italy and Poland in the 1990s and 2000s.

Method:

A quantitative content analysis of frequency of different sources employed in articles in daily newspapers from Finland ( N = 258), Italy ( N = 296), and Poland ( N = 212) from the years 1991, 1998 and 2011. Semantic units were coded in Atlas.ti. The societal spheres represented were identified using a common coding scheme broadly inspired by Boltanski and Thévenot’s typology of polities of worth. Transformations were identified in line with van Leeuwen’s framework for trends in discourse salience over time.

Results:

The study highlights different patterns of coverage of addictions in the three countries. Over time, increased salience is given to the individuals affected by addictions and experts who represent biomedical sciences. This process occurred with varying intensity and expressiveness in all countries under study.

Conclusions:

Social and political sources were employed to less extent over time. The media focus seemed to shift to the affected individuals and scientific expertise. This confirms results from previous studies on a general move towards individualisation and an increased focus on more personal and technical aspects of addiction problems in the mass media.
Making market research work in Saudi Arabia
Authors: Aichner Thomas , Shaltoni Abdel Monim
Published: January 2018

Market research in the Kingdom of Saudi Arabia (KSA) is becoming increasingly important for mainly two reasons. First, because its population is growing with a significant shift to the younger generation of Millenials (Generation Y) and Post-Millenials (Generation Z) and, second, because the economy is moving away from its dependence on oil. Researchers from both national and foreign research agencies, companies, and higher education institutions are therefore required to consider these changes when studying Saudi consumers. Especially for those who are not familiar with the cultural and societal peculiarities of the KSA, we highlight some key considerations for survey design to get quality data. We argue that several issues remain sensitive, cultural factors such as power distance have great relevance, and, inter alia, give recommendations regarding sampling and interviewing respondents.
Evaluation of the oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population
Authors: Liu Ding , Liu Lei , Hu Zhongyang , Song Zhi , Wang Yaqin , Chen Zhiheng
Published: January 2018

Aim:

Type 2 diabetes mellitus is a polygenic metabolic disorder resulting from oxidative stress, the root cause of insulin resistance, β-cell dysfunction and impaired glucose tolerance. The aim of this study was to investigate the role of oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO in type 2 diabetes mellitus susceptibility in the Chinese Han population.

Methods:

A total of 396 type 2 diabetes mellitus patients and 678 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222, GPX1 rs1050450, GPX3 rs3828599 and MPO rs2107545 gene polymorphisms were genotyped.

Results:

We found one single-nucleotide polymorphism in the MPO gene was associated with type 2 diabetes mellitus susceptibility [rs2107545: odds ratio = 1.563 (1.166–2.096); p = 0.003], after adjusting for covariates. Furthermore, we also considered the likely complexity of effects of genetic and conventional risk factors in type 2 diabetes mellitus–related vascular complications, such as carotid plaques. Our analysis revealed that the GPX1 rs1050450 and MPO rs2107545 were significantly associated with increased risk of carotid plaques in type 2 diabetes mellitus patients.

Conclusion:

Our study presents novel evidence for main effects of MPO gene on type 2 diabetes mellitus susceptibility. Furthermore, our study supported the association between variants of oxidative stress–related genes ( GPX1 and MPO) and carotid plaques in type 2 diabetes mellitus patients, which indicated a modulation of type 2 diabetes mellitus–related vascular complication susceptibility by genetic predisposition.