bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of β-Catenin Cooperates with Loss of Pten to Drive AR-Independent Castration-Resistant Prostate Cancer
Authors: Patel Rachana , Brzezinska Elspeth A. , Repiscak Peter , Ahmad Imran , Mui Ernest , Gao Meiling , Blomme Arnaud , Harle Victoria , Tan Ee Hong , Malviya Gaurav , Mrowinska Agata , Loveridge Carolyn J. , Rushworth Linda K. , Edwards Joanne , Ntala Chara , Nixon Colin , Hedley Ann , Mackay Gillian , Tardito Saverio , Sansom Owen J. , Leung Hing Y.
Published: November 2019

Inhibition of the androgen receptor (AR) is the main strategy to treat advanced prostate cancers. AR-independent treatment-resistant prostate cancer is a major unresolved clinical problem. Patients with prostate cancer with alterations in canonical WNT pathway genes, which lead to β-catenin activation, are refractory to AR-targeted therapies. Here, using clinically relevant murine prostate cancer models, we investigated the significance of β-catenin activation in prostate cancer progression and treatment resistance. β-Catenin activation, independent of the cell of origin, cooperated with Pten loss to drive AR-independent castration-resistant prostate cancer. Prostate tumors with β-catenin activation relied on the noncanonical WNT ligand WNT5a for sustained growth. WNT5a repressed AR expression and maintained the expression of c-Myc, an oncogenic effector of β-catenin activation, by mediating nuclear localization of NFκBp65 and β-catenin. Overall, WNT/β-catenin and AR signaling are reciprocally inhibited. Therefore, inhibiting WNT/β-catenin signaling by limiting WNT secretion in concert with AR inhibition may be useful for treating prostate cancers with alterations in WNT pathway genes.

Significance:

Targeting of both AR and WNT/β-catenin signaling may be required to treat prostate cancers that exhibit alterations of the WNT pathway.
Prediagnostic Allostatic Load as a Predictor of Poorly Differentiated and Larger Sized Breast Cancers among Black Women in the Women's Circle of Health Follow-Up Study
Authors: Xing Cathleen Y. , Doose Michelle , Qin Bo , Lin Yong , Plascak Jesse J. , Omene Coral , He Chunyan , Demissie Kitaw , Hong Chi-Chen , Bandera Elisa V. , Llanos Adana A.M.
Published: November 2019

Background:

Few studies have empirically tested the association of allostatic load (AL) with breast cancer clinicopathology. The aim of this study was to examine the association of AL, measured using relevant biomarkers recorded in medical records before breast cancer diagnosis, with unfavorable tumor clinicopathologic features among Black women.

Methods:

In a sample of 409 Black women with nonmetastatic breast cancer who are enrolled in the Women's Circle of Health Follow-Up Study, we estimated prediagnostic AL using two measures: AL measure 1 [lipid profile–based—assessed by systolic and diastolic blood pressure (SBP, DBP), high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, and glucose levels; waist circumference; and use of diabetes, hypertension, or hypercholesterolemia medication] and AL measure 2 (inflammatory index–based—assessed by SBP, DBP, glucose, and albumin levels; estimated glomerular filtration rate; body mass index; waist circumference; and use of medications previously described). We used Cohen's statistic to assess agreement between the two AL measures and multivariable logistic models to assess the associations of interest.

Results:

AL measures 1 and 2 moderately agreed (κ = 0.504). Higher prediagnostic AL predicted higher grade (poorly differentiated vs. well/moderately differentiated) using AL measure 1 [OR = 2.16; 95% confidence interval (CI), 1.18–3.94] and AL measure 2 (OR = 1.60; 95% CI, 1.02–2.51), and larger tumor size (≥2 cm vs. <2 cm; OR = 1.58; 95% CI, 1.01–2.46) using AL measure 2 only.

Conclusions:

Elevated prediagnostic AL might contribute to more unfavorable breast cancer clinicopathology.

Impact:

Addressing elevated prediagnostic levels of AL has potentially important clinical implications.
Reproductive and Hormonal Factors and Risk of Ovarian Cancer by Tumor Dominance: Results from the Ovarian Cancer Cohort Consortium (OC3)
Authors: Huang Tianyi , Townsend Mary K. , Wentzensen Nicolas , Trabert Britton , White Emily , Arslan Alan A. , Weiderpass Elisabete , Buring Julie E. , Clendenen Tess V. , Giles Graham G. , Lee I-Min , Milne Roger L. , Onland-Moret N. Charlotte , Peters Ulrike , Sandler Dale P. , Schouten Leo J. , van den Brandt Piet A. , Wolk Alicja , Zeleniuch-Jacquotte Anne , Tworoger Shelley S.
Published: November 2019

Background:

Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells.

Methods:

We pooled data from 9 prospective studies participating in the Ovarian Cancer Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance.

Results:

Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer (Pheterogeneity = 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors (Pheterogeneity = 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors (Pheterogeneity = 0.08).

Conclusions:

These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin.

Impact:

Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.
Hepatitis C Virus Infection and the Temporal Trends in the Risk of Liver Cancer: A National Register-Based Cohort Study in Sweden
Authors: Batyrbekova Nurgul , Aleman Soo , Lybeck Charlotte , Montgomery Scott , Duberg Ann-Sofi
Published: November 2019

Background:

In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims of this study were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV infection between 1990 and 2015.

Methods:

The HCV cohort (n = 52,853) was compared with a matched non-HCV comparison cohort (n = 523,649). Both the national Cancer Register (CR) and Cause of Death Register (DR) were used for follow-up. The crude and age-standardized PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as HRs using stratified Cox hazards regression.

Results:

There were 1,609 with PLC diagnosis in the HCV cohort; the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013 while remaining low and stable in the comparison cohort. In the HCV cohort, the age-standardized PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 [95% confidence interval (CI), 1.54–3.75] in 2000 and 3.31 (2.51–4.12) in 2014. The highest SIR was 73 (65.9–79.5) among those infected for 35 to 40 years; and the highest HR was 65.9 (55.9–77.6) for men and 62.2 (31.9–121.1) for women.

Conclusions:

There was a considerable increase in PLC incidence over time and an extremely high relative risk in the population with HCV infection for more than 35 years.

Impact:

The national HCV-associated PLC incidence should be monitored in future studies to evaluate the effect of direct-acting antiviral (DAA) treatment.
Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study
Authors: Smith Jenny L. , Ries Rhonda E. , Hylkema Tiffany , Alonzo Todd A. , Gerbing Robert B. , Santaguida Marianne T. , Eidenschink Brodersen Lisa , Pardo Laura , Cummings Carrie L. , Loeb Keith R. , Le Quy , Imren Suzan , Leonti Amanda R. , Gamis Alan S. , Aplenc Richard , Kolb E. Anders , Farrar Jason E. , Triche Timothy J. , Nguyen Cu , Meerzaman Daoud , Loken Michael R. , Oehler Vivian G. , Bolouri Hamid , Meshinchi Soheil
Published: November 2019

Purpose:

A cryptic inv(16)(p13.3q24.3) encoding the CBFA2T3–GLIS2 fusion is associated with poor outcome in infants with acute megakaryocytic leukemia. We aimed to broaden our understanding of the pathogenesis of this fusion through transcriptome profiling.

Experimental Design:

Available RNA from children and young adults with de novo acute myeloid leukemia (AML; N = 1,049) underwent transcriptome sequencing (mRNA and miRNA). Transcriptome profiles for those with the CBFA2T3–GLIS2 fusion (N = 24) and without (N = 1,025) were contrasted to define fusion-specific miRNAs, genes, and pathways. Clinical annotations defined distinct fusion-associated disease characteristics and outcomes.

Results:

The CBFA2T3–GLIS2 fusion was restricted to infants <3 years old (P < 0.001), and the presence of this fusion was highly associated with adverse outcome (P < 0.001) across all morphologic classifications. Further, there was a striking paucity of recurrent cooperating mutations, and transduction of cord blood stem cells with this fusion was sufficient for malignant transformation. CBFA2T3–GLIS2 positive cases displayed marked upregulation of genes with cell membrane/extracellular matrix localization potential, including NCAM1 and GABRE. Additionally, miRNA profiling revealed significant overexpression of mature miR-224 and miR-452, which are intronic miRNAs transcribed from the GABRE locus. Gene-set enrichment identified dysregulated Hippo, TGFβ, and hedgehog signaling, as well as NCAM1 (CD56) interaction pathways. Therapeutic targeting of fusion-positive leukemic cells with CD56-directed antibody–drug conjugate caused significant cytotoxicity in leukemic blasts.

Conclusions:

The CBFA2T3–GLIS2 fusion defines a highly refractory entity limited to infants that appears to be sufficient for malignant transformation. Transcriptome profiling elucidated several highly targetable genes and pathways, including the identification of CD56, providing a highly plausible target for therapeutic intervention.
Coaltered Ras/B-raf and TP53 Is Associated with Extremes of Survivorship and Distinct Patterns of Metastasis in Patients with Metastatic Colorectal Cancer
Authors: Datta Jashodeep , Smith J. Joshua , Chatila Walid K. , McAuliffe John C. , Kandoth Cyriac , Vakiani Efsevia , Frankel Timothy L. , Ganesh Karuna , Wasserman Isaac , Lipsyc-Sharf Marla , Guillem Jose , Nash Garrett M. , Paty Philip B. , Weiser Martin R. , Saltz Leonard B. , Berger Michael F. , Jarnagin William R. , Balachandran Vinod , Kingham T. Peter , Kemeny Nancy E. , Cercek Andrea , Garcia-Aguilar Julio , Taylor Barry S. , Viale Agnes , Yaeger Rona , Solit David B. , Schultz Nikolaus , D'Angelica Michael I.
Published: November 2019

Purpose:

We aimed to investigate genomic correlates underlying extremes of survivorship in metastatic colorectal cancer and their applicability in informing survival in distinct subsets of patients with metastatic colorectal cancer.

Experimental Design:

We examined differences in oncogenic somatic alterations between metastatic colorectal cancer cohorts demonstrating extremes of survivorship following complete metastasectomy: ≤2-year (n = 17) and ≥10-year (n = 18) survivors. Relevant genomic findings, and their association with overall survival (OS), were validated in two independent datasets of 935 stage IV and 443 resected stage I–IV patients.

Results:

In the extremes-of-survivorship cohort, significant co-occurrence of KRAS hotspot mutations and TP53 alterations was observed in ≤2-year survivors (P < 0.001). When validating these findings in the independent cohort of 935 stage IV patients, incorporation of the cumulative effect of any oncogenic Ras/B-raf (i.e., either KRAS, NRAS, or BRAF) and TP53 alteration generated three prognostic clusters: (i) TP53-altered alone (median OS, 132 months); (ii) Ras/B-raf–altered alone (65 months) or Ras/B-raf- and TP53 pan-wild-type (60 months); and (iii) coaltered Ras/B-raf–TP53 (40 months; P < 0.0001). Coaltered Ras/B-raf–TP53 was independently associated with mortality (HR, 2.47; 95% confidence interval, 1.91–3.21; P < 0.001). This molecular profile predicted survival in the second independent cohort of 443 resected stage I–IV patients. Coaltered Ras/B-raf–TP53 was associated with worse OS in patients with liver (n = 490) and lung (n = 172) but not peritoneal surface (n = 149) metastases. Moreover, coaltered Ras/B-raf–TP53 tumors were significantly more likely to involve extrahepatic metastatic sites with limited salvage options.

Conclusions:

Genomic analysis of extremes of survivorship following colorectal cancer metastasectomy identifies a prognostic role for coaltered Ras/B-raf–TP53 and its association with distinct patterns of colorectal cancer metastasis.
TCR Repertoire Diversity of Peripheral PD-1+CD8+ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non–Small Cell Lung Cancer
Authors: Han Jiefei , Duan Jianchun , Bai Hua , Wang Yuqi , Wan Rui , Wang Xin , Chen Si , Tian Yanhua , Wang Di , Fei Kailun , Yao Zhuoran , Wang Shuhang , Lu Zhimin , Wang Zhijie , Wang Jie
Published: November 2019

T-cell receptor (TCR)–based biomarkers might predict patient response to immune checkpoint blockade (ICB) but need further exploration and validation for that use. We sequenced complementarity-determining region 3 of TCRβ chains isolated from PD-1+ CD8+ T cells to investigate its value for predicting the response to anti–programmed cell death 1 (PD-1)/PD-ligand 1 (PD-L1) therapy in patients with non–small cell lung cancer (NSCLC). Two independent patient cohorts (cohort A, n = 25; cohort B, n = 15) were used as discovery and validation sets, respectively. Pre- and post-ICB peripheral blood samples were collected. In cohort A, patients with high PD-1+ CD8+ TCR diversity before ICB treatment showed better response to ICB and progression-free survival (PFS) compared with patients with low diversity [6.4 months vs. 2.5 months, HR, 0.39; 95% confidence interval (CI), 0.17–0.94; P = 0.021]. The results were validated in cohort B. Pre-ICB PD-1+ CD8+ TCR diversity achieved an optimal Youden's index of 0.81 (sensitivity = 0.87 and specificity = 0.94) for differentiating the ICB response in the merged dataset (cohort A plus cohort B). Patients with increased PD-1+ CD8+ TCR clonality after ICB treatment had longer PFS (7.3 months vs. 2.6 months, HR, 0.26; 95% CI, 0.08–0.86; P = 0.002) than those with decreased clonality. Thus, TCR diversity and clonality in peripheral blood PD-1+ CD8+ T cells may serve as noninvasive predictors of patient response to ICB and survival outcomes in NSCLC.
Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration
Authors: He Jinghu , Xing Junjie , Yang Xiaohong , Zhang Chenxin , Zhang Yixiang , Wang Hao , Xu Xiaodong , Wang Hantao , Cao Yi , Xu Haonan , Zhang Chuansen , Wang Chen , Yu Enda
Published: November 2019

Objective: Colorectal cancer (CRC) remains a major cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 2 (PSMC2) plays vital roles in regulating cell cycle and transcription and has been confirmed to be a gene potentially associated with some human tumors. However, the expression correlation and molecular mechanism of PSMC2 in CRC are still unclear. This study aimed to investigate the role of PSMC2 in malignant behaviors in CRC. Methods: The high protein levels of PSMC2 in CRC samples were identified by tissue microarray analysis. Lentivirus was used to silence PSMC2 in HCT116 and RKO cells; MTT and colony formation assay were performed to determine cell proliferation. Wound healing and Transwell assay were used to detect cell migration and invasion. Flow cytometry assay was applied to detect cell cycle and apoptosis. Result: The results showed that, among the 96 CRC patients, the expression of PSMC2 was a positive correlation with the clinicopathological features of the patients with CRC. Furthermore, the low PSMC2 expression group showed a higher survival rate than the high PSMC2 expression group. The expression levels of PSMC2 in cancer tissue were dramatically upregulated compared with adjacent normal tissues. In vitro, shPSMC2 was designed to inhibit the expression of PSMC2 in CRC cells. Compared with shCtrl, silencing of PSMC2 significantly suppressed cell proliferation, decreased single cell colony formation, enhanced apoptosis, and accelerated G2 phase and/or S phase arrest. Conclusion: Survival analysis indicated that high expression of PSMC2 in the CRC samples was associated with poorer survival rate than low expression of PSMC2, while the anti-tumor effect of PSMC2 silencing was also confirmed at the cellular level in vitro. Our results suggested that PSMC2 potentially worked as a regulator for CRC, and the silencing of PSMC2 may be a therapeutic strategy for CRC.
Chronisch-spontane Urtikaria: Viel hilft manchmal eben doch viel
Authors: Sondermann Wiebke
Published: November 2019

The recommended dose of omalizumab for the treatment of chronic spontaneous urticaria (CSU) is 300 mg every 4 weeks, but there is no recommendation for patients who do not benefit from this dose. Our aim is to present the experiences on the use of doses of omalizumab higher than those recommended for CSU patients and to propose a protocol for updosing. This was a retrospective analysis of patients treated with omalizumab for CSU from 2 urticaria centers in Istanbul and Barcelona. The weekly urticaria activity score and/or the Urticaria Control Test (UCT) were used to monitor response. In Barcelona, a stepwise updosing regimen was preferred (450 mg first, then increasing to 600 mg), while in Istanbul, direct updosing to 600 mg was chosen. In Istanbul, 81 (88%) patients were treated with 300 mg, while 11 (12%) received 600 mg of omalizumab. In Barcelona, 7 (8.8%), 45 (56.3%), 17 (21.3%), and 11 (13.8%) patients received 150, 300, 450, and 600 mg of omalizumab, respectively. Urticaria control was achieved in 82.6% of the patients with 300 mg and in 8.7% of the patients with 600 mg in Istanbul, while it was achieved with 150 mg in 10%, with 300 mg in 48.8%, with 450 mg in 16.3%, and with 600 mg in 6.3% of the patients in Barcelona. In total, 123 (71.5%) patients responded to 150-300 mg and 26 (15.1%) to 450-600 mg. When responders to 150-300 mg (n = 123) were compared with responders to 450-600 mg (n = 26), BMI was found to be higher, and pre-omalizumab UCT was found to be lower in patients receiving updosed omalizumab (p = 0.029). Baseline data of the patients, especially BMI and pre-oma UCT, might be useful to determine if the patient will require higher doses of omalizumab. We recommend a stepwise approach starting from 450 mg and then updosing to 600 mg in CSU patients who do not respond or partially respond to 300 mg of omalizumab after 3-6 months of treatment.
Is 123I-MIBG Scintigraphy Beneficial or Excessive for the Diagnosis of Parkinson’s Disease in the Early Phase?
Authors: Ikeda Tokunori , Ikenoshita Susumu , Sakamoto Fumi , Shiraishi Shinya , Nakahara Keiichi , Masuda Teruaki , Yamashita Satoshi
Published: November 2019

Introduction/Objective: In most cases, abnormal cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy increases the probability of a diagnosis of Parkinson’s disease (PD) in patients with parkinsonian features. In our study, we validated the additional value of 123I-MIBG scintigraphy beyond providing information on neurological findings and response to dopaminergic therapy for the diagnosis of PDin the early phase. Methods: We investigated 77 cases of PD (Hoehn and Yahr Stages I–III) and 73 cases of atypical parkinsonian disorder (APD), including 35 patients with multiple system atrophy, 19 with corticobasal syndrome, and 19 with progressive supranuclear palsy. Two multiple logistic regression models were developed to predict the probability of PD based on APD. Common covariates were resting tremor, vertical supranuclear palsy, apraxia, cerebellar symptoms, and response to dopaminergic therapy with MIBG scintigraphy (reference model) or without it (MIBG-added model). The net reclassification index (NRI) was examined and net benefit using decision curve analysis was performed to examine the additional clinical value of MIBG scintigraphy. Finally, we estimated the cost-effectiveness of MIBG scintigraphy. Results: The MIBG-added model significantly improved the ability to classify PD or APD compared with the reference model (NRI index 1.390, p < 0.001). However, the decision curve of the reference model ranked equally with the MIBG-added model up to a risk threshold of 0.8. In addition, MIBG scintigraphy was not cost-effective. Conclusions: Although MIBG scintigraphy has statistical usefulness for PD diagnosis, there may be little additional benefit in the early phase of PD beyond the neurological findings and response to dopaminergic therapy regarding clinical effectiveness and cost-effectiveness. It may be of greatest value when neurological findings that do not match PD are observed during the clinical course.
Serial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway and Total Mortality, Cause‐Specific Mortality, and Cardiovascular Diseases in the Cardiovascular Health Study
Authors: Lai Heidi T.M. , de Oliveira Otto Marcia C. , Lee Yujin , Wu Jason H.Y. , Song Xiaoling , King Irena B. , Psaty Bruce M. , Lemaitre Rozenn N. , McKnight Barbara , Siscovick David S. , Mozaffarian Dariush
Published: November 2019

Background

Synthesized fatty acids (
FA
s) from de novo lipogenesis may affect cardiometabolic health, but longitudinal associations between serially measured de novo lipogenesis–related fatty acid biomarkers and mortality or cardiovascular disease (
CVD)
are not well established.

Methods and Results

We investigated longitudinal associations between de novo lipogenesis–related fatty acids with all‐cause mortality, cause‐specific mortality, and incident
CVD
among 3869 older US adults, mean (
SD
) age 75 (5) years and free of prevalent
CVD
at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n‐7), stearic (18:0), oleic acid (18:1n‐9), and other risk factors were serially measured at baseline, 6 years, and 13 years. All‐cause mortality, cause‐specific mortality, and incident fatal and nonfatal
CVD
were centrally adjudicated. Risk was assessed in multivariable‐adjusted Cox models with time‐varying
FA
s and covariates. During 13 years, median follow‐up (maximum 22.4 years), participants experienced 3227 deaths (1131
CVD
, 2096 non‐
CVD
) and 1753 incident
CVD
events. After multivariable adjustment, higher cumulative levels of 16:0, 16:1n‐7, and 18:1n‐9 were associated with higher all‐cause mortality, with extreme‐quintile hazard ratios (95%
CI
s) of 1.35 (1.17–1.56), 1.40 (1.21–1.62), and 1.56 (1.35–1.80), respectively, whereas higher levels of 18:0 were associated with lower mortality (hazard ratio=0.76; 95%
CI
=0.66–0.88). Associations were generally similar for
CVD
mortality versus non‐
CVD
mortality, as well as total incident
CVD
. Changes in levels of 16:0 were positively, and 18:0 inversely, associated with all‐cause mortality (hazard ratio=1.23, 95%
CI
=1.08–1.41; and hazard ratio=0.78, 95%
CI
=0.68–0.90).

Conclusions

Higher long‐term levels of 16:0, 16:1n‐7, and 18:1n‐9 and changes in 16:0 were positively, whereas long‐term levels and changes in 18:0 were inversely, associated with all‐cause mortality in older adults.
Pigment Epithelial‐Derived Factor Deficiency Accelerates Atherosclerosis Development via Promoting Endothelial Fatty Acid Uptake in Mice With Hyperlipidemia
Authors: Wang Haiping , Yang Yanfang , Yang Ming , Li Xinghui , Tan Jing , Wu Yandi , Zhang Yuling , Li Yuanlong , Hu Bo , Deng Shijie , Yang Fengmin , Gao Saifei , Li Hui , Yang Zhenyu , Chen Hui , Cai Weibin
Published: November 2019

Background

Endothelial cell injury, induced by dyslipidemia, is the initiation of atherosclerosis, resulting in an imbalance in endothelial fatty acid (
FA
) transport. Pigment epithelial‐derived factor (
PEDF
) is an important regulator in lipid metabolism. We hypothesized that
PEDF
is involved in endothelium‐mediated
FA
uptake under hyperlipidemic conditions.

Methods and Results

Circulating
PEDF
levels were higher in patients with atherosclerotic cardiovascular disease than in normal individuals. However, decreasing trends of serum
PEDF
levels were confirmed in both wild‐type and apolipoprotein E–deficient mice fed a long‐term high‐fat diet. Apolipoprotein E–deficient/PEDF‐deficient mice were generated by crossing PEDF‐deficient mice with apolipoprotein E–deficient mice, and then mice were fed with 24, 36, or 48 weeks of high‐fat diet. Greater increases in body fat and plasma lipids were displayed in
PEDF
‐deficient mice. In addition,
PEDF
deficiency in mice accelerated atherosclerosis, as evidenced by increased atherosclerotic plaques, pronounced vascular dysfunction, and increased lipid accumulation in peripheral tissues, whereas injection of adeno‐associated virus encoding
PEDF
exerted opposite effects. Mechanistically,
PEDF
inhibited the vascular endothelial growth factor B paracrine signaling by reducing secretion of protein vascular endothelial growth factor B in peripheral tissue cells and decreasing expression of its downstream targets in endothelial cells, including its receptors (namely, vascular endothelial growth factor receptor‐1 and neuropilin‐1), and FA transport proteins 3 and 4, to suppress endothelial
FA
uptake, whereas
PEDF
deletion in mice activated the vascular endothelial growth factor B signaling pathway, thus causing markedly increased lipid accumulation.

Conclusions

Decreasing expression of
PEDF
aggravates atherosclerosis by significantly impaired vascular function and enhanced endothelial
FA
uptake, thus exacerbating ectopic lipid deposition in peripheral tissues.
Systematic Review and Meta‐Analysis of Medication Reviews Conducted by Pharmacists on Cardiovascular Diseases Risk Factors in Ambulatory Care
Authors: Martínez‐Mardones Francisco , Fernandez‐Llimos Fernando , Benrimoj Shalom I. , Ahumada‐Canale Antonio , Plaza‐Plaza José Cristian , S. Tonin Fernanda , Garcia‐Cardenas Victoria
Published: November 2019

Background

Pharmacists‐led medication reviews (
MRs
) are claimed to be effective for the control of cardiovascular diseases; however, the evidence in the literature is conflicting. The main objective of this meta‐analysis was to analyze the impact of pharmacist‐led
MRs
on cardiovascular disease risk factors overall and in different ambulatory settings while exploring the effects of different components of
MRs
.

Methods and Results

Searches were conducted in PubMed, Web of Science, Embase, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library Central Register of Controlled Trials database. Randomized and cluster randomized controlled trials of pharmacist‐led
MRs
compared with usual care were included. Settings were community pharmacies and ambulatory clinics. The classification used for
MRs
was the Pharmaceutical Care Network Europe as basic (type 1), intermediate (type 2), and advanced (type 3). Meta‐analyses in therapeutic goals used odds ratios to standardize the effect of each study, and for continuous data (eg, systolic blood pressure) raw differences were calculated using baseline and final values, with 95%
CI
s. Prediction intervals were calculated to account for heterogeneity. Sensitivity analyses were conducted to test the robustness of results. Meta‐analyses included 69 studies with a total of 11 644 patients. Sample demographic characteristics were similar between studies.
MRs
increased control of hypertension (odds ratio, 2.73; 95% prediction interval, 1.05–7.08), type 2 diabetes mellitus (odds ratio, 3.11; 95% prediction interval, 1.17–5.88), and high cholesterol (odds ratio, 1.91; 95% prediction interval, 1.05–3.46). In ambulatory clinics,
MRs
produced significant effects in control of diabetes mellitus and cholesterol. For community pharmacies, systolic blood pressure and low‐density lipoprotein values decreased significantly. Advanced
MRs
had larger effects than intermediate
MRs
in diabetes mellitus and dyslipidemia outcomes. Most intervention components had no significant effect on clinical outcomes and were often poorly described.
CIs
were significant in all analyses but prediction intervals were not in continuous clinical outcomes, with high heterogeneity present.

Conclusions

Intermediate and advanced
MRs
provided by pharmacists may improve control of blood pressure, cholesterol, and type 2 diabetes mellitus, as statistically significant prediction intervals were found. However, most continuous clinical outcomes failed to achieve statistical significance, with high heterogeneity present, although positive trends and effect sizes were found. Studies should use a standardized method for
MRs
to diminish sources of these heterogeneities.
Public Opinion and the Legitimacy of Global Private Environmental Governance
Authors: Neuner Fabian G.
Published: November 2019

The rise of global private environmental governance has inspired substantial research assessing whether organizations like the International Organization for Standardization (ISO) and the Forest Stewardship Council (FSC) are legitimate. These organizations address global challenges and help overcome collective action problems, but public opposition can severely curb their effectiveness. Yet, we do not know whether the public supports such organizations and perceives them as legitimate. This article draws on diverse political science literatures to outline why a focus on public opinion is important. The article tests two competing arguments explaining potential opposition toward organizations like the ISO and the FSC: accounts centered on the role of sincere preferences over the legitimate locus of authority and on the influence of domestic elite rhetoric. Results suggest that public opinion is generally positive and that elite rhetoric about a potential democratic deficit rather than simple information about the bodies’ governance structures decreases favorability.
The Role of Customary Land Ownership in Land-Use Conversion in the Peri-urban of Bukittinggi, Indonesia
Authors: Darwin Ira Safitri , Winarso Haryo , Zulkaidi Denny
Published: November 2019

Taluak is located in the peri-urban area of the city of Bukittinggi, in Agam Regency, West Sumatra, Indonesia. Bukittinggi is rapidly expanding into this peri-urban area. Due to a lack of sound land-use regulations, the growing population and increasing development are encroaching into the peri-urban area. In 1999, the administrative area of Bukittinggi was formally expanded to include some of the surrounding land that had previously been part of Agam Regency. However, although the physical development of the city has encroached into parts of Agam Regency, including Taluak, the communities of the village refused to be administratively included in Bukittinggi. One of their reasons for this refusal is a belief that such urbanization will harm the culture and traditions of the village. This article aims to explain how the communities of Taluak have resisted the formal expansion of Bukittinggi to include them in order to maintain their culture and traditions of land management and to estimate how long such resistance can survive. The article also explains how the process of land conversion in Taluak is carried out, particularly the conversion from rural use into urban use, which creates rurban (rural-urban) areas.
How Does Faith Feel?
Authors: Schultz Callan
Published: November 2019

Research on emotion in anthropology has been supplanted by an ethnographic turn toward ‘subjectivity’, ‘embodiment’, ‘personhood’, and ‘experience’. In this article, I explore how these interrelated modes of analysis can help ethnographers to better understand the cultural processes that constitute how people feel. I show that among my Christian Dusun interlocutors in Ranau, Malaysian Borneo, the interactive engagement between subjects and their environment determined the vectors of emotional possibility in terms of belief. The intersection of religious objects (God, the Holy Spirit, Satan) and mutual obligations in the community produce what I refer to as the ‘faith network’. I trace these collective attachments to consider how ‘believing in’ regulates feeling in relation to situations of crisis, impasse, and tragedy. The combined efforts of my interlocutors, I suggest, created an active commitment that pulsated through the faith network, which sustained an intensive and defining mode of their relational experience.
PREFACE: Proceedings of the 13th International Symposium on Trichoptera
Authors: MAJECKA KATARZYNA , MAJECKI JANUSZ , MORSE JOHN
Published: November 2019

The 13th International Symposium on Trichoptera took place in Bialowieża, Poland, in 22-27 June 2009, but the idea to organize the symposium there was evoked 3 years earlier.  When, at the end of the symposium in Mexico City, Professor Hans Malicky suggested that the next symposium take place in Poland, the first question we asked ourselves was, “Where could we organize it?”  That night we were discussing this issue with several colleagues and Wolfram Mey said, “Why not do it in Białowieża?” The idea was tempting.  In the last 2 decades Trichoptera symposia were organized in big cities. The last one even took place in one of the largest cities of the world—Mexico City. By contrast, Białowieża is just a small village; but for researchers it is paradise. The significance of this last natural European forest for science is reflected in the presence of many scientific institutions there. And so, we decided that Bialowieża would be a perfect venue for our symposium.
Annotated checklist of Hongkong Lichens
Authors: Aptroot André , Seaward Mark R.D.
Published: November 2019

An annotated checklist of the lichens of Hong Kong, based on all available literature reports and specimens, including those recently collected by the authors, is presented. In total, 261 species are reported, of which 176 are new records for Hong Kong, 132 of which are new for China, 43 are new for East Asia, and 27 are new for Asia. The lichen vegetation is mainly tropical, as is shown by the distribution patterns of the identified species: 53 species are cosmopolitan, 40 northern temperate, 122 pantropical, 17 paleotropical and 29 endemic to tropical East Asia. With regard to substrata, 129 species are corticolous, 148 saxicolous, 17 foliicolous and 19 terricolous. Four species are newly described: Anisomeridium conorostratum Aptroot, A. hydei Aptroot, Caloplaca pulicarioides Aptroot and Placidiopsis poronioides Aptroot. The flora is rather poor in species; for example, no Caliciales have been found. In the past, the numbers of species of several groups such as the Graphidaceae, Heterodermia and Xanthoparmelia have been overestimated, whereas few pyrenocarps have been reported. The flora of wet granitic outcrops is surprisingly well developed in Hong Kong. Although not a single Peltula species was reported before, six species were identified, including one that was previously only known from Africa. In addition, several other cyanophilic genera are present, such as Euopsis, Psorotichia, Pyrenopsis and, most unexpectedly, Vestergrenopsis, each with one species. A comparison between old and recent records shows that many Lobarion species are now extinct. The drastic decline of species of the Lobarion vegetation indicates that air pollution and other habitat disturbances, mainly deforestation, to which these species are very sensitive, are seriously threatening the lichen biodiversity of Hong Kong.
New records and additions to the hepatic flora of Uganda 2.
Authors: Pócs Tamás , Lye Kåre Arnstein
Published: November 2019

82 liverwort taxa are recorded from Uganda, of which 24 are new to the flora of the country. Colura hedbergiana, Colura kilimanjarica and Harpalejeunea fischeri found on Mt. Elgon, were previously known only from their type locality on Mt. Kilimanjaro or on Mt. Karisimbi. A Madagascan-Mascarene species, Plagiochila boryana was also found on Mt.Elgon. Its only known previous locality in continental Africa was Mt. Kilimanjaro.
The status of Thamnobryum maderense (Kindb.) Hedenäs and T. fernandesii C. Sergio
Authors: Frahm Jan-Peter , Sabovljevic Marko
Published: November 2019

Th. maderense was regarded either as synonymous with Th. alopecurum, as a variety of the latter and also as a good species. A morphological study revealed that it clearly distinguished from Th. alopecurum by four ranked instead of eight-ranked leaves and thus deserves full rank of a species. Th. fernandesii has eight-ranked leaves and is therefore more related to Th. alopecurum than to Th. maderense. A comparison of the sequences of the Internal Transcribed Spacer of the nuclear ribosomal DNA region in the tree species supports the morphological evidence. Previous molecular studies of Th. maderense (showing almost no differences to Th. alopecurum) were based on misidentifications. The status of Th. fernandesii is not clear. The multistratose leaves with broad costa indicate that it is a mutant as proved in several other cases by molecular methods. It differs, however, genetically too much from Th. alopecurum that it cannot be interpreted as a mutant of the latter.
Proceedings of the Ninth International Polychaete Conference

Authors: MACIOLEK N. J. , BLAKE J. A.
Published: November 2019

Table of Content
Preface
Authors: MACIOLEK N. J. , BLAKE J. A.
Published: November 2019

The Ninth International Polychaete Conference (IPC) was held 12–17 August 2007 in Portland, Maine, USA, at the Conference Center of the Holiday Inn by the Sea. Kevin Eckelbarger and Linda Healy of the Darling Marine Center, University of Maine, Walpole, Maine, and James Blake and Nancy Maciolek of AECOM (formerly ENSR) Environment’s Marine & Coastal Center in Woods Hole, Massachusetts, organized and planned the activities for the Conference. Dan Dauer of Old Dominion University, Norfolk, Virginia, organized the judging for student awards and identified proposals for future conferences.
Monticellina (Polychaeta: Cirratulidae) from the Pacific coast of Costa Rica with descriptions of six new species

Authors: DEAN HARLAN K. , BLAKE JAMES A.
Published: November 2019

Eight species of Monticellina are described from intertidal and subtidal sites on the Pacific coast of Costa Rica. Six of these species, M. acunai sp. nov., M. antelaxa sp. nov., M. carrikeri sp. nov., M. elongata sp. nov., M. giribeti sp. nov., and M. setosa sp. nov. are new to science while M. cryptica Blake, 1996 and M. tesselata (Hartman, 1960) have been previously described from California. M. acunai sp. nov. has a wide prostomium, a peristomium with four annulations and denticulate capillary setae with numerous well-developed teeth in both the notopodium and neuropodium. M. antelaxa sp. nov. has a small prostomium, a wide peristomium with three annulations, and a double row of denticulate neurosetae with long fibrillar teeth. M. carrikeri sp. nov. has a wide prostomium, a wide peristomium with three annulations, and denticulate neurosetae with a narrow base and an expanded midsection with numerous, scattered, small teeth. M. elongata sp. nov. has a wide prostomium, an elongate peristomium with six annulations, the first segment joined with the first setiger, and denticulate capillary noto- and neurosetae with coarse teeth. M. giribeti sp. nov. has a wide prostomium, an elongate peristomium with five annulations, an asetigerous first segment joined with the peristomium, and denticulate capillary noto- and neurosetae with fine teeth. M. setosa sp. nov. has a small prostomium, a wide peristomium with five annulations, nuchal organs present within narrow indentations of the overlying peristomium, and denticulate capillary neurosetae with fine teeth. Morphological characteristics that may aid in the differentiation of species within the genus are discussed.
Surface analyses of biocements from Pectinaria gouldii (Polychaeta: Pectinariidae) and Phragmatopoma lapidosa (Polychaeta: Sabellariidae)

Authors: DEAN MARIA , WELCH JOHN , BRANDT CASSIDY , TAUER THOMAS
Published: November 2019

Pectinaria gouldii and Phragmatopoma lapidosa are marine polychaetes that reside in protective structures built from sand grains bound together using proteinaceous cement secreted from specialized glands. P. gouldii constructs a solitary, ice-cream-cone-like structure. The smaller, gregarious P. lapidosa forms a large, reef-like mound. This study investigates the physical features of these two polychaete biocements, linking structure and function in two marine environments.      The surface structures of hydrated biocement samples were analyzed using atomic force microscopy (AFM), and the surface structures and composition of dehydrated biocement samples were analyzed using scanning electron microscopy (SEM) and electron dispersive spectroscopy (EDS). Atomic force analyses indicate that (in their native states) the surface roughness, adhesion, and stiffness of P. gouldii biocement are greater than P. lapidosa biocement. The surface of P. gouldii resembled “cottage cheese,” while the surface of P. lapidosa had smoother features. SEM revealed “popped bubble” features that indicated a solid foam-like material for both biocements. EDS confirmed the presence of calcium, magnesium, and phosphorous in both biocements, with varying amounts of these three elements at different locations on the same sample.
Ecology and biology of chemoreception in polychaetes
Authors: LINDSAY SARA M.
Published: November 2019

Nervous system and sensory structure morphologies provide useful information for reconstructing phylogenetic relationships among the Polychaeta, Annelida, and Arthropoda. With the more common use of indirect immunocytochemistry and laser scanning confocal microscopy methods, the detailed information available from morphological studies has increased. Despite this wealth of information, developing an integrated understanding of the ecology, physiology, morphology, and molecular mechanisms of sensory systems in polychaetes remains a challenge.      For many marine organisms, including polychaetes, chemical signals and chemoreception mediate numerous ecologically important behaviors including defense, reproduction, recruitment, and feeding, yet the mechanism of chemoreception in polychaetes has not been well described. This review summarizes research on the ecology and biology of polychaete chemoreception, particularly as it mediates reproduction, recruitment, and feeding, discusses the chemosensory structures of polychaetes, and describes recent advances in our understanding of chemoreception mechanisms in polychaetes.
Obituary Torleif Holthe (1946–2007)
Authors: BAKKEN TORKILD , SNELI JON-ARNE
Published: November 2019

Professor Emeritus Torleif Holthe passed away on Friday, 22 June 2007 at the age of 61. Torleif had for the last few years suffered from deteriorating health after a stroke eight years ago. He never fully recovered and had several more strokes during the following years. Then in early June he had another that he did not survive.
Obituary Nathan Wendell Riser (1920–2006)

Authors: ECKELBARGER KEVIN J.
Published: November 2019

Professor Nathan Wendell Riser died at his home in Swampscott, Massachusetts on Wednesday July 26, 2006 at the age of 86. He was known to his colleagues as “Pete” and to his graduate students as “Doc.” He was born in Salt Lake City, Utah, in 1920 where he completed secondary school in 1937. After attending the University of Utah for three years he transferred to the University of Illinois, Champagne, where he earned his B.S. degree in zoology in 1941. He enlisted in the military in 1942 and served as a Navy Corpsman in the Navy Medical Corp where he saw action in the Pacific Theater of WWII. He was discharged in 1945 and entered graduate school at Stanford University where he conducted research at the Hopkins Marine Station in Pacific Grove, California. He earned an M.S. degree in 1948 and a Ph.D. in 1949 on the biology of tetraphyllidean cestodes associated with sharks and rays (“The morphology and systematic position of some little known Tetraphyllideans”) under the direction of Prof. Tage Skogsberg.
Limoniidae (Diptera) in the Upper Jurassic of Shar Teg, Mongolia
Authors: LUKASHEVICH ELENA D.
Published: November 2019

A diverse Late Jurassic crane fly assemblage is described from Shar Teg locality (SW Mongolia), viz. Architipula krzeminskii n.sp., A. ampla n.sp., Mesotipula sigmoidea n.sp., ?M. brevicella n.sp., M. (Metatipula n.subgen.) continens n.sp., Tipunia undata n.sp., T. jorgi n.sp., Cretolimonia jurassica n.sp., C. pygmaea n. sp., Eotipulina sharategica n.sp., E. paula n.sp., E. evidens n.sp. and Eotipuloptera sp. The genus Praearchitipula Kalugina, 1985 is transferred to Pediciidae; it is the first Mesozoic record of this family (Middle Jurassic of Siberia). One species originally included in Praearchitipula is transferred to Mesotipula: M. parvula (Kalugina, 1985) n.comb. from the Middle Jurassic of Siberia.
New species and immatures of crane flies of subgenus Formotipula Matsumura from Taiwan (Diptera: Tipulidae: Tipula)

Authors: YOUNG CHEN W.
Published: November 2019

Taiwanese species of the crane fly subgenus Tipula (Formotipula) Matsumura, 1916, are reviewed.  Tipula (Formotipula) argentea, new species, is described and figured. The only other previously known Taiwanese species, Tipula (Formotipula) holoserica (Matsumura, 1916), is redescribed. The external anatomy of the last instar larva and pupa of T. (F.) holoserica is described and illustrated, with a brief discussion of the biology of the larva.
Tenuipalpidae of China: a review of progress
Authors: ZHANG ZHI-QIANG
Published: November 2019

This paper reviews the taxonomic research on the family Tenuipalpidae in China, with an updated checklist of 56 species belonging to nine genera.  Major contributions to the Chinese fauna of the Tenuipalpidae were made by Ma En-Pei and his colleagues, who discovered and described over 20 species, Wang Hui-Fu and her colleagues, who described 10 species from China, and Yin Sui-Gong and students, who added five new species.  There have been relatively few studies on the biology and control of the Tenuipalpidae in China and these are briefly reviewed.
A review of progress on the systematics and biology of the family Cheyletidae in China, with a checklist of the Chinese cheyletids
Authors: XIA BIN
Published: November 2019

This paper reviews the taxonomic research on the family Cheyletidae in China, with an updated checklist of 48 species belonging to 24 genera. The most important contributions to the Chinese fauna of these mites were made by Tseng Yi-Hsiung, who recognized and described ten species from Taiwan, Lin Jianzhen, who described seven species from Fujian, and Xia Bin, who added five new species. A few studies on the biology and ecology of Cheyletidae in China are briefly reviewed.
Psoroptidia (Acari: Astigmatina) of China: a review of research progress
Authors: WANG ZI-YING , FAN QING-HAI
Published: November 2019

Research history of the taxonomy, morphology, biology and ecology of the Psoroptidia in China until 31 Dec 2009 was summarized. A checklist of 70 species, 1 subspecies and 11 varieties, in 49 genera of 20 families and a checklist of mites unidentified to species of 8 families are provided.