bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models
Authors: Kossatz Susanne , Carney Brandon , Schweitzer Melanie , Carlucci Giuseppe , Miloushev Vesselin Z. , Maachani Uday B. , Rajappa Prajwal , Keshari Kayvan R. , Pisapia David , Weber Wolfgang A. , Souweidane Mark M. , Reiner Thomas
Published: January 2017

Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize a positron emission tomography (PET) probe for imaging DIPG in vivo. In human histological tissues, the probes target, PARP1, was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model, and probe uptake correlated to histologically determined tumor infiltration. Imaging with the sister fluorescence agent revealed that uptake was confined to proliferating, PARP1-expressing cells. Comparison with other imaging technologies revealed remarkable accuracy of our biomarker approach. We subsequently demonstrated that serial imaging of DIPG in mouse models enables monitoring of tumor growth, as shown in modeling of tumor progression. Overall, this validated method for quantifying DIPG burden would serve useful in monitoring treatment response in early phase clinical trials. Cancer Res; 77(8); 2112–23. ©2017 AACR.
Cancer Risk in Women Treated with Fertility Drugs According to Parity Status—A Registry-based Cohort Study
Authors: Reigstad Marte Myhre , Storeng Ritsa , Myklebust Tor Åge , Oldereid Nan Birgitte , Omland Anne Katerine , Robsahm Trude Eid , Brinton Louise Annette , Vangen Siri , Furu Kari , Larsen Inger Kristin
Published: January 2017

Background: Long-term safety of assisted reproductive techniques (ART) is of interest as their use is increasing. Cancer risk is known to be affected by parity. This study examined the risk of cancer after fertility treatment, stratified by women's parity.

Methods: Data were obtained from all women (n = 1,353,724) born in Norway between 1960 and 1996. Drug exposure data (2004–2014) were obtained from the Norwegian Prescription Database (drugs used in ART and clomiphene citrate). The Medical Birth Registry of Norway provided parity status. HRs were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer, and malignant melanoma.

Results: In 12,354,392 person-years of follow-up, 20,128 women were diagnosed with cancer. All-site cancer risk was 1.14 [95% confidence interval (95% CI), 1.03–1.26] and 1.10 (95% CI, 0.98–1.23) after clomiphene citrate and ART exposure, respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR, 2.49; 95% CI, 1.30–4.78; and HR, 1.62; 95% CI, 0.78–3.35) versus parous women (HR, 1.37; 95% CI, 0.64–2.96; and HR, 0.87; 95% CI, 0.33–2.27). Elevated risk of endometrial cancers was observed for clomiphene citrate exposure in nulliparous women (HR, 4.49; 95% CI, 2.66–7.60 vs. HR, 1.52; 95% CI, 0.67–3.42). Risk was elevated for breast cancer in parous women exposed to clomiphene citrate (HR, 1.26; 95% CI, 1.03–1.54) for thyroid cancer and among nulliparous women after ART treatment (HR, 2.19; 95% CI, 1.08–4.44).

Conclusions: Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity.

Impact: Continued monitoring of fertility treatments is warranted. Cancer Epidemiol Biomarkers Prev; 26(6); 953–62. ©2017 AACR.
The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer
Authors: Governa Valeria , Trella Emanuele , Mele Valentina , Tornillo Luigi , Amicarella Francesca , Cremonesi Eleonora , Muraro Manuele Giuseppe , Xu Hui , Droeser Raoul , Däster Silvio R. , Bolli Martin , Rosso Raffaele , Oertli Daniel , Eppenberger-Castori Serenella , Terracciano Luigi M. , Iezzi Giandomenica , Spagnoli Giulio C.
Published: January 2017

Purpose: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer–infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells.

Experimental Design: CD66b+ and CD8+ cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b+ cells were evaluated by flow cytometry. CD66b+/CD8+ cells crosstalk was investigated by in vitro experiments.

Results: CD66b+ cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8+ T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8+ T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8+ cell stimulation in the presence of CD66b+ cells results in increasing numbers of cells expressing CD45RO/CD62L “central memory” phenotype. Importantly, combined tumor infiltration by CD66b+ and CD8+ T lymphocytes is associated with significantly better prognosis, as compared with CD8+ T-cell infiltration alone.

Conclusions: Neutrophils enhance the responsiveness of CD8+ T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8+ T cells, suggesting that they might effectively promote antitumor immunity. Clin Cancer Res; 23(14); 3847–58. ©2017 AACR.
Bombesin Antagonist-Based Radiotherapy of Prostate Cancer Combined with WST-11 Vascular Targeted Photodynamic Therapy
Authors: Kim Kwanghee , Zhang Hanwen , La Rosa Stephen , Jebiwott Sylvia , Desai Pooja , Kimm Simon , Scherz Avigdor , O'Donoghue Joseph A. , Weber Wolfgang A. , Coleman Jonathan A.
Published: January 2017

Purpose: DOTA-AR, a bombesin-antagonist peptide, has potential clinical application for targeted imaging and therapy in gastrin-releasing peptide receptor (GRPr)–positive malignancies when conjugated with a radioisotope such as 90Y. This therapeutic potential is limited by the fast washout of the conjugates from the target tumors. WST-11 (Weizmann STeba-11 drug; a negatively charged water-soluble palladium-bacteriochlorophyll derivative, Tookad Soluble) vascular targeted photodynamic therapy (VTP) is a local ablation approach recently approved for use in early-stage prostate cancer. It generates reactive oxygen/nitrogen species within tumor blood vessels, resulting in their instantaneous destruction followed by rapid tumor necrosis. We hypothesize that the instantaneous arrest of tumor vasculature may provide a means to trap radiopharmaceuticals within the tumor, thereby improving the efficacy of targeted radiotherapy.

Experimental Design: GRPr-positive prostate cancer xenografts (PC-3 and VCaP) were treated with 90Y-DOTA-AR with or without VTP. The uptake of radioisotopes was monitored by Cherenkov luminescence imaging (CLI). The therapeutic efficacy of the combined VTP and 90Y-DOTA-AR in PC-3 xenografts was assessed.

Results: CLI of 90Y-DOTA-AR demonstrated longer retention of radiotracer within the VTP-treated PC-3 xenografts compared with the non–VTP-treated ones (P < 0.05) at all time points (24–144 hours) after 90Y-DOTA-AR injection. A similar pattern of retention was observed in VCaP xenografts. When 90Y-DOTA-AR administration was combined with VTP, tumor growth delay was significantly longer than for the control or the monotherapy groups.

Conclusions: Tumor vascular arrest by VTP improves 90Y-DOTA-AR retention in the tumor microenvironment thereby enhancing therapeutic efficacy. Clin Cancer Res; 23(13); 3343–51. ©2017 AACR.
Tumor-induced Stromal STAT1 Accelerates Breast Cancer via Deregulating Tissue Homeostasis
Authors: Zellmer Victoria R. , Schnepp Patricia M. , Fracci Sarah L. , Tan Xuejuan , Howe Erin N. , Zhang Siyuan
Published: January 2017

The tumor microenvironment (TME), the dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphologic and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAG) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect. FACS analysis of TAGs demonstrated an increased number of Lin−CD24+/CD49+ enriched mammary gland stem cells (MaSC), suggesting deregulated tissue homeostasis in TAGs. Comparative transcriptome analysis of TAGs and contralateral control glands coupled with meta-analysis on differentially expressed genes with two breast cancer stromal patient microarray datasets identified shared upregulation of STAT1. Knockdown of STAT1 in cancer-associated fibroblast (CAF) cocultured with human breast cancer cells altered cancer cell proliferation, indicating a role for STAT1 as a stromal contributor of tumorigenesis. Furthermore, depletion of STAT1 in CAFs significantly reduced periductal reactive fibrosis and delayed early breast cancer progression in vivo. Finally, cotreatment with fludarabine, a FDA-approved STAT1 activation inhibitor and DNA synthesis inhibitor, in combination with doxorubicin, showed enhanced therapeutic efficacy in treating mouse mammary gland tumors. Taken together, these results demonstrate that stromal STAT1 expression promotes tumor progression and is a potential therapeutic target for breast cancer.

Implications: Tumors induce stromal STAT1-dependent cytokine secretion that promotes tumor cell proliferation and can be targeted using clinically-approved inhibitors of STAT1. Mol Cancer Res; 15(5); 585–97. ©2017 AACR.
Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype
Authors: Ashkavand Zahra , O'Flanagan Ciara , Hennig Mirko , Du Xiuxia , Hursting Stephen D. , Krupenko Sergey A.
Published: January 2017

Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration, and survival in many cell types. Here, the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: noninvasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wntliver) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors. NMR-based metabolomics was used to quantitate 41 major metabolites in cells grown in folate-free medium versus standard medium. Each cell line demonstrated metabolic reprogramming when grown in folate-free medium. In E-Wnt, M-Wnt, and metM-Wntliver cells, 12, 29, and 25 metabolites, respectively, were significantly different (P < 0.05 and at least 1.5-fold change). The levels of eight metabolites (aspartate, ATP, creatine, creatine phosphate, formate, serine, taurine and β-alanine) were changed in each folate-restricted cell line. Increased glucose, decreased lactate, and inhibition of glycolysis, cellular proliferation, migration, and invasion occurred in M-Wnt and metM-Wntliver cells (but not E-Wnt cells) grown in folate-free versus standard medium. These effects were accompanied by altered levels of several folate-metabolizing enzymes, indicating that the observed metabolic reprogramming may result from both decreased folate availability and altered folate metabolism. These findings reveal that folate restriction results in metabolic and bioenergetic changes and a less aggressive cancer cell phenotype.

Implications: Metabolic reprogramming driven by folate restriction represents a therapeutic target for reducing the burden of breast cancer. Mol Cancer Res; 15(2); 189–200. ©2016 AACR.
Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex
Authors: Zawistowski Jon S. , Bevill Samantha M. , Goulet Daniel R. , Stuhlmiller Timothy J. , Beltran Adriana S. , Olivares-Quintero Jose F. , Singh Darshan , Sciaky Noah , Parker Joel S. , Rashid Naim U. , Chen Xin , Duncan James S. , Whittle Martin C. , Angus Steven P. , Velarde Sara Hanna , Golitz Brian T. , He Xiaping , Santos Charlene , Darr David B. , Gallagher Kristalyn , Graves Lee M. , Perou Charles M. , Carey Lisa A. , Earp H. Shelton , Johnson Gary L.
Published: January 2017

Targeting the dysregulated BRAF–MEK–ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRAF and MEK, resistance develops often involving nongenomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in patients with triple-negative breast cancer (TNBC) induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTK) comparing tumor samples before and after one week of treatment. In preclinical models, MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation, and p300 that drives transcriptional adaptation. Inhibition of the P-TEFb–associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts, and syngeneic mouse TNBC models. Pharmacologic targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance.

Significance: Widespread transcriptional adaptation to pharmacologic MEK inhibition was observed in TNBC patient tumors. In preclinical models, MEK inhibition induces dramatic genome-wide modulation of chromatin, in the form of de novo enhancer formation and enhancer remodeling. Pharmacologic targeting of P-TEFb complex members at enhancers is an effective strategy to durably inhibit such adaptation. Cancer Discov; 7(3); 302–21. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 235
Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation
Authors: Zhou Jingjiao , Qu Zhaoxia , Sun Fan , Han Lei , Li Liwen , Yan Shapei , Stabile Laura P. , Chen Lin-Feng , Siegfried Jill M. , Xiao Gutian
Published: January 2017

One of the most fundamental and challenging questions in the cancer field is how immunity in patients with cancer is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4+ T-helper (Th1) cells and CD8+ T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8+ T cells, enhancement of cytotoxicity toward CD4+ and CD8+ T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype. The deletion of myeloid STAT3 boosted antitumor immunity and suppressed lung tumorigenesis. These findings increase our understanding of immune programming in lung tumorigenesis and provide a mechanistic basis for developing STAT3-based immunotherapy against this and other solid tumors. Cancer Immunol Res; 5(3); 257–68. ©2017 AACR.
Significance of Vasculogenic Mimicry Formation in Gastric Carcinoma
Authors: Lv Jingfang , Sun Baocun , Sun Huizhi , Zhang Yanhui , Sun Junying , Zhao Xiulan , Gu Qiang , Dong Xueyi , Che Na
Published: January 2017

Background: The purpose of this study was to evaluate the clinical significance and prognostic roles of vasculogenic mimicry (VM) and elucidate their intrinsic association with molecular markers. Methods: 89 human gastric cancer cases with detailed follow-up and clinicopathologic data were collected. CD34/periodic acid-Schiff double staining was performed to validate the existence of VM. Immunohistochemistry was performed to explore the expression of different molecular factors. Results: VM was observed in 24 gastric cancer patients. They were prone to higher histological grade, hematogenous metastasis, distant recurrence, and chance of progression to stage III or IV (p < 0.05). The VM group had shorter overall and disease-free survival (p < 0.05). VM negativity was independently prognostic for prolonged overall or disease-free survival (p < 0.05). VM was positively associated with levels of matrix metalloproteinase-2, matrix metalloproteinase-9, vascular endothelial growth factor, and vascular endothelial growth factor receptor-1 (p < 0.05), but not with vascular endothelial growth factor receptor-2 (p > 0.05). Conclusion: VM should be regarded as a good marker to indicate pathobiological behaviors of gastric cancer. Using antibodies against matrix metalloproteinases, vascular endothelial growth factor, or vascular endothelial growth factor receptors could be strategies to counteract VM formation.
Increased Expression of miR-29a and Its Prognostic Significance in Patients with Cholangiocarcinoma
Authors: Deng Yingbin , Chen Yuxin
Published: January 2017

Background: This study aimed to examine the expression level and prognostic value of microRNA-29a (miR-29a) in human cholangiocarcinoma (CCA). Patients and Methods: The expression of miR-29a was measured in tissues collected from 125 CCA patients using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Survival analysis was carried out using the Kaplan-Meier method and log-rank test. The prognostic value of miR-29a was examined with Cox regression analysis. Results: The results of qRT-PCR demonstrated that miR-29a expression was significantly upregulated in CCA tissue samples compared with matched noncancerous samples. Overexpression of miR-29a was found to be correlated with lymph node metastasis, clinical stage, and differentiation of CCA. The Kaplan-Meier survival curves suggested that patients with high miR-29a levels had poor overall survival compared to those with low miR-29a expression. From the results of the Cox regression analysis, we considered increased miR-29a expression to be an independent prognostic factor for patients with CCA. Conclusion: Our study data demonstrated that upregulated miR-29a expression is associated with progression of CCA and might act as a prognostic biomarker in CCA patients.
Two Cases of Proliferative Diabetic Retinopathy with Marked Sheathing of the Retinal Arteries following Vitrectomy
Authors: Nishikawa Yuko , Morishita Seita , Nakamura Kimitoshi , Fukumoto Masanori , Suzuki Hiroyuki , Tajiri Kensuke , Sato Takaki , Kobayashi Takatoshi , Kida Teruyo , Oku Hidehiro , Ikeda Tsunehiko
Published: January 2017

Purpose: The aim of this paper was to report 2 patients (3 eyes) with proliferative diabetic retinopathy (PDR) who showed marked sheathing of the retinal arterioles that was ultimately attributed to calcification following vitrectomy. Cases: Case 1 involved a 65-year-old female with PDR who underwent bilateral vitrectomy for traction retinal detachment. Postoperatively, bilateral retinal redetachment (reRD) was observed. Sheathing of the retinal arterioles was observed at the same time, yet was not apparent preoperatively. Case 2 involved a 71-year-old female with PDR who underwent vitrectomy for vitreous hemorrhage. Postoperatively, reRD was observed, and fundus findings showed sheathing of the retinal arterioles. In both patients, silicone oil tamponade and retinopexy were performed at reoperation, but sheathing of the retinal arterioles persisted postoperatively. Fluorescein fundus angiography showed that retinal blood flow was maintained, and no vessel leakage occurred. In addition, no sheathing of the retinal veins was observed. Optical coherence tomography (OCT) showed a higher intensity for retinal arterioles with sheathing than for normal retinal arterioles. Conclusion: Vessel sheathing in our 2 patients (3 eyes) differed from the sheathing seen in vasculitis. Based on the hyperintensity on OCT, this sheathing may have been due to retinal artery calcification induced by hypoxia and inflammation associated with reRD.
Does Extremely Low Birth Weight Predispose to Low-Renin Hypertension?
Authors: Raaijmakers Anke , Zhang Zhen-Yu , Claessens Jolien , Cauwenberghs Nicholas , van Tienoven Theun Pieter , Wei Fang-Fei , Jacobs Lotte , Levtchenko Elena , Pauwels Steven , Kuznetsova Tatiana , Allegaert Karel , Staessen Jan A.
Published: January 2017

Low birth weight and prematurity are risk factors for hypertension in adulthood. Few studies in preterm or full-term born children reported on plasma renin activity (PRA). We tested the hypothesis that renin might modulate the incidence of hypertension associated with prematurity. We enrolled 93 prematurely born children with birth weight <1000 g and 87 healthy controls born at term, who were all examined at ≈11 years. Renal length and glomerular filtration rate derived from serum cystatin C were 0.28 cm (95% confidence interval, 0.09–0.47) and 11.5 mL/min per 1.73 m
2
(6.4–16.6) lower in cases, whereas their systolic/diastolic blood pressure (BP) was 7.5 mm Hg (4.8–10.3)/4.0 mm Hg (2.1–5.8) higher (
P
<0.001 for all). The odds of having systolic prehypertension or systolic hypertension associated with extreme low birth weight were 6.43 (2.52–16.4;
P
<0.001) and 10.9 (2.46–48.4;
P
=0.002). Twenty-four hours of urinary sodium excretion was similar in cases and controls (102.1 versus 106.8 mmol;
P
=0.47). Sodium load per nephron was estimated as sodium excretion divided by kidney length (mmol/cm). PRA was 0.54 ng/mL per hour (0.23–0.85;
P
=0.001) lower in cases. PRA, systolic BP, and sodium load were available in 43 cases and 56 controls. PRA decreased with systolic BP (slope −0.022 ng/mL per hour/
−
mm Hg
;
P
=0.048), but was unrelated to sodium load (slope +0.13 mmol/cm
−
mm Hg
;
P
=0.54). The slope of PRA on systolic BP was similar (
P
=0.17) in cases and controls. In conclusion, extremely low birth weight predisposes young adolescents to low-renin hypertension, but does not affect the inverse association between PRA and BP.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02147457.
Lower Extremity Peripheral Artery Disease and Quality of Life Among Older Individuals in the Community
Authors: Wu Aozhou , Coresh Josef , Selvin Elizabeth , Tanaka Hirofumi , Heiss Gerardo , Hirsch Alan T. , Jaar Bernard G. , Matsushita Kunihiro
Published: January 2017

Background

Evidence regarding the association of lower extremity peripheral arterial disease with quality of life (
QOL
) is mainly from selected clinical populations or relatively small clinical cohorts. Thus, we investigated this association in community‐derived populations.

Methods and Results

Using data of 5115 participants aged 66 to 90 years from visit 5 (2011‐2013) of the Atherosclerosis Risk in Communities Study, we quantified the associations of ankle‐brachial index (
ABI
) with several
QOL
parameters, including 12‐item Short‐Form Health Survey (
SF
‐12), after accounting for potential confounders using linear and logistic regression models. Peripheral arterial disease defined by an
ABI
<0.90 (n=402), was independently associated with a low
SF
‐12 Physical Component Summary score (−3.26 [95%
CI
−5.60 to −0.92]), compared to the
ABI
reference 1.10 to 1.19 (n=1900) but not with the Mental Component Summary score (−0.07 [−2.21 to 2.06]). A low
ABI
was significantly associated with poorer status of all
SF
‐12 physical domains (physical functioning, role‐physical, bodily pain, and general health) but only vitality out of 4 mental domains. Similarly, low
ABI
values were more consistently associated with other physically related
QOL
parameters (leisure‐time exercise/activity/walking) than mentally related parameters (significant depressive symptoms and hopeless feeling). Lower physical
QOL
was observed even in individuals with borderline low
ABI
(0.90 to 0.99; n=426).

Conclusions

Low
ABI
(even borderline) was independently associated with poor
QOL
, especially for physical components, in community‐dwelling older adults.
QOL
is a critical element for older adults, and thus, further studies are warranted to assess whether peripheral arterial disease‐specific management can improve
QOL
in older populations.
Post–Glucose Load Measures of Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke
Authors: Pan Yuesong , Jing Jing , Chen Weiqi , Zheng Huaguang , Jia Qian , Mi Donghua , Li Hao , Zhao Xingquan , Liu Liping , Wang Chunxue , Gaisano Herbert Y. , He Yan , Wang Yilong , Wang Yongjun
Published: January 2017

Background

Insulin resistance is associated with an increased risk of cardiovascular events in the general population. This study aimed to estimate the association between post–glucose load measures of insulin resistance and prognosis of nondiabetic patients with ischemic stroke.

Methods and Results

Data were derived from the
ACROSS
‐China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry. Patients with ischemic stroke without a history of diabetes mellitus were included. Two post–glucose load measures of insulin sensitivity, the insulin sensitivity indices
ISI
(composite) and the
ISI
0,120
, were calculated. Outcomes included stroke recurrence, all‐cause death, and poor functional outcome at 12 months. Among 1203 patients, 63.3% were male with an average age of 62.1 years. At 12 months, 168 (14.4%) patients had recurrent stroke, 111 (9.2%) had died, and 288 (24.4%) had poor outcome. After adjustment for potential covariates, the first quartile of the
ISI
(composite) was associated with increased 12‐month stroke recurrence (adjusted hazard ratio 2.02, 95% CI 1.28–3.18,
P
=0.003), death (adjusted hazard ratio 2.78, 95%
CI
1.59–4.86,
P
<0.001), and poor outcome (adjusted odds ratio 2.67, 95%
CI
1.69–4.21,
P
<0.001) compared with the fourth quartile. Similar results were observed for the
ISI
0,120
but with a larger magnitude of association. Using a multivariable regression model with restricted cubic spline, we found an L‐shaped association between the insulin sensitivity indices and the risk of each end point.

Conclusions

In this large‐scale registry, post–glucose load measures of insulin resistance with the
ISI
(composite) and the
ISI
0,120
were associated with 12‐month poor outcomes of nondiabetic patients with ischemic stroke.
Impact of Rehabilitation on Outcomes in Patients With Ischemic Stroke
Authors: Yagi Maiko , Yasunaga Hideo , Matsui Hiroki , Morita Kojiro , Fushimi Kiyohide , Fujimoto Masashi , Koyama Teruyuki , Fujitani Junko
Published: January 2017

Background and Purpose—

We aimed to examine the concurrent effects of timing and intensity of rehabilitation on improving activities of daily living (ADL) among patients with ischemic stroke.

Methods—

Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with ischemic stroke at admission who received rehabilitation (n=100 719) from April 2012 to March 2014. Early rehabilitation was defined as that starting within 3 days after admission. The average rehabilitation intensity per day was calculated as the total units of rehabilitation during hospitalization divided by the length of hospital stay. A multivariable logistic regression analysis with multiple imputation and an instrumental variable analysis were performed to examine the association of early and intensive rehabilitation with the proportion of improved ADL score.

Results—

The proportion of improved ADL score was higher in the early and intensive rehabilitation group. The multivariable logistic regression analysis showed that significant improvements in ADL were observed for early rehabilitation (odds ratio: 1.08; 95% confidence interval: 1.04–1.13;
P
<0.01) and intensive rehabilitation of >5.0 U/d (odds ratio: 1.87; 95% confidence interval: 1.69–2.07;
P
<0.01). The instrumental variable analysis showed that an increased proportion of improved ADL was associated with early rehabilitation (risk difference: 2.8%; 95% confidence interval: 2.0–3.4%;
P
<0.001) and intensive rehabilitation (risk difference: 5.6%; 95% confidence interval: 4.6–6.6%;
P
<0.001).

Conclusions—

The present results suggested that early and intensive rehabilitation improved ADL during hospitalization in patients with ischemic stroke.
Strange Bedfellows?
Authors: Steen Sheldon
Published: January 2017

This paper offers a comparative analysis of two people in situations of seemingly contested allegiances: David Brog and Josephus. While the two come from wildly disparate contexts, they nonetheless employ strikingly similar rhetorical strategies as they justify their cooperation with a group to which they would otherwise appear to be categorically opposed. In this paper I examine, compare, and contrast the rhetorical strategies of both, with particular attention to strategies of legitimation (both internal and external), their reconstructions of history, and how each minimizes the importance of apocalypticism. While there is certainly more that distinguishes the two than unites them, this comparative analysis will hopefully give insight into how people navigate complex identities, particularly when those identities, at least from an outsider’s perspective, would appear to be in conflict.
Uncertainty Perpetuated? The Pitfalls of a Weakly Institutionalized Party System in Kyrgyzstan
Authors: Doolotkeldieva Asel , Wolters Alexander
Published: January 2017

The parliamentary elections in Kyrgyzstan in October 2015 garnered widespread approval from commentators for the level of fairness and freedom maintained throughout the campaign. However, the results of the vote do not provide a clear indication of the current state of affairs of parliamentarism in the republic. Focusing on the commercialization of party lists, we argue that neither identity politics nor the logic of neopatrimonialism adequately explain the dynamics of political competition in Kyrgyzstan. Instead, we see perpetual uncertainty emerging from contradicting yet increasing attempts to harness the capital of privatized party lists and to impose discipline. Eventually, and beyond short-term threats of an emerging super-presidentialism, Kyrgyzstan risks suffering from hollow parliamentarism, with political parties persistently failing to supply legislative initiatives with substantial agendas and adequate professionals. The weakly institutionalized political parties and their short-sighted electoral strategies undermine both the parliamentary system and its political pluralism.
Labor of Love: Amateurs and Lay-expertise Legitimation in the Early U.S. Radio Field
Authors: Croidieu Grégoire , Kim Phillip H.
Published: January 2017

Many actors claim to be experts of specialized knowledge, but for this expertise to be perceived as legitimate, other actors in the field must recognize them as authorities. Using an automated topic-model analysis of historical texts associated with the U.S. amateur radio operator movement between 1899 and 1927, we propose a process model for lay-expertise legitimation as an alternative to professionalization. While the professionalization account depends on specialized work, credentialing, and restrictive jurisdictional control by powerful field actors, our model emphasizes four mechanisms leading to lay-expert recognition: building an advanced collective competence, operating in an unrestricted public space, providing transformational social contributions, and expanding an original collective role identity. Our analysis shows how field expertise can be achieved outside of professional spaces by non-professionalized actors who master activities as a labor of love. Our work also reveals that lay-expertise recognition depends on the interplay between collective identities and collective competence among non-professional actors, and it addresses the shifting power dynamics when professional and non-professional actors coexist and strive for expertise recognition.
“If Chemists Don’t Do It, Who Is Going To?” Peer-driven Occupational Change and the Emergence of Green Chemistry
Authors: Howard-Grenville Jennifer , Nelson Andrew J. , Earle Andrew G. , Haack Julie A. , Young Douglas M.
Published: January 2017

We investigate the emergence and growth of “green chemistry”—an effort by chemists to encourage other chemists to reduce the health, safety, and environmental impacts of chemical products and processes—to explore how occupational members, absent external triggers for change, influence how their peers do their work. Using extensive interviews, archival data, and observations, we find that advocates simultaneously advanced different frames that specified the utility of making the change: (1) a normalizing frame, positioning green chemistry as consistent with mainstream chemistry innovation; (2) a moralizing frame, positioning it as an ethical imperative; and (3) a pragmatizing frame, positioning it as a tool that could help chemists tackle problems they encountered in their day-to-day work. Each frame resonated differently with chemists in their various occupational roles. Though this pluralistic approach generated broad acceptance of the change effort, it also exposed tensions, which threatened the coherence of the change. Advocates’ diverse responses to these tensions contribute to a persistent state of pluralism and dynamism in the change effort. We uncover a process through which occupational members generate and sustain change, show how occupational heterogeneity can enable and delimit change, and show how well-meaning efforts to “moralize” occupational work can heighten resistance, inhibiting the very changes that enable experts to address urgent societal problems.
Own Gender, Sibling’s Gender, Parent’s Gender
Authors: Grigoryeva Angelina
Published: January 2017

Research on the gender division of family labor largely focuses on housework and childcare in spousal couples. This article advances scholarship by examining the gender division of elderly parent care in sibling groups. Using the Health and Retirement Study, a nationally representative survey of elderly Americans, I find that caregiving to elderly parents varies not only by an adult child’s own gender, but also by the gender of the siblings with whom caregiving is shared and by the gender of the parent to whom care is provided. The salience of an adult child’s gender manifests in two primary ways: not only do daughters provide more care than do sons to their elderly parents, but daughters’ caregiving is also more elastic with respect to their own and their parents’ attributes than is sons’ caregiving. With respect to the gender of the siblings, sons provide relatively less care if they have sisters, whereas daughters provide relatively more care if they have brothers. With respect to the gender of the parent, sons provide relatively more care to fathers, and daughters provide relatively more care to mothers. Finally, analyses did not reveal changes over time.
Histamine Applied Topically to the Nasal Mucosa Increases the Transmucosal Nitrous Oxide Exchange for the Middle Ear
Authors: Teixeira Miriam S. , Alper Cuneyt M. , Martin Brian S. , Cetin Selma , El-Wagaa Jenna A. , Doyle William J.
Published: January 2017

Objective:

Determine if the middle ear transmucosal nitrous oxide (N2O) exchange rate is affected by nasal inflammation caused by topical application of histamine.

Methods:

In a randomized, double-blind, crossover study, 20 adults were challenged intranasally with histamine (5 mg) and placebo on separate occasions. At each session, the subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure, and blood O2 saturation were monitored, and bilateral middle ear pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the middle ear pressure-time function for the 50% N2O:50% O2 breathing period, which is a measure of the transmucosal N2O exchange-constant. The effects of challenge substance, session, and period on the measured vital signs and of treatment, session, ear disease history, and test ear on the pressure-time slopes were evaluated using repeated measures ANOVAs.

Results:

The post-challenge total symptom score and the slope of the middle ear pressure-time function were greater after histamine when compared to placebo challenge. Of the signs, only heart rate was affected, responding to challenge substance and study period.

Conclusion:

The transmucosal N2O exchange rate for the middle ear is increased during inflammation caused by nasal histamine exposure.
Standoff Laser-Induced Breakdown Spectroscopy (LIBS) Using a Miniature Wide Field of View Spatial Heterodyne Spectrometer with Sub-Microsteradian Collection Optics
Authors: Barnett Patrick D. , Lamsal Nirmal , Angel S. Michael
Published: January 2017

A spatial heterodyne spectrometer (SHS) is described for standoff laser-induced breakdown spectroscopy (LIBS) measurements. The spatial heterodyne LIBS spectrometer (SHLS) is a diffraction grating based interferometer with no moving parts that offers a very large field of view, high light throughput, and high spectral resolution in a small package. The field of view of the SHLS spectrometer is shown to be ∼1° in standoff LIBS measurements. In the SHLS system described here, the collection aperture was defined by the 10 mm diffraction gratings in the SHS and standoff LIBS measurements were made up to 20 m with no additional collection optics, corresponding to a collection solid angle of 0.2 μsr, or f/2000, and also using a small telescope to increase the collection efficiency. The use of a microphone was demonstrated to rapidly optimize laser focus for 20 m standoff LIBS measurements.
Variable Selection for Survival Data under Weibull Distribution
Authors: Das Ujjwal
Published: January 2017

In a wide spectrum of natural and social sciences, very often one encounters a large number of predictors for time to event data. An important task is to select right ones, and thereafter carry out the analysis. The [Formula: see text] penalized regression, known as ”least absolute shrinkage and selection operator (LASSO)” has become a popular approach for predictor selection in last two decades. The LASSO regression involves a penalizing parameter (commonly denoted by [Formula: see text]) that controls the extent of penalty, and hence plays a crucial role in identifying the right covariates. In this article, we propose an information theory-based method to determine the value of [Formula: see text] under the accelerated failure time (AFT) model with extreme value distribution. Furthermore, an efficient algorithm is discussed in the same context. We demonstrate the usefulness of our method through an extensive simulation study.
Influence Diagnostics in Modified Liu-type Estimator
Authors: Emami Hadi , Emami Mostafa
Published: January 2017

In regression, it is of interest to detect anomalous observations that exert an unduly large influence on the least squares (LS) analysis. Frequently, the existence of influential data is complicated by the presence of collinearity (see, e.g., Walker and Birch  [1] ). Very little work has been done, however, on the possible effects that collinearity can have on the influence of an observation. While dealing with multicollinearity some new type of Liu estimator is proposed. When modified Liu-type estimator (MLE) is used to mitigate the effects of multicollinearity, the influence of observations can be drastically modified. In this article, we propose approximate case deletion formula to detect influential points in MLE. As an illustrative example, a real dataset is analyzed.
The Pediatrician and the Prevention of Adolescent Pregnancy: Should the Pediatrician Provide Contraceptive Care for Sexually Active Teen-agers?
Authors: Wilcox Allen J. , Mcanarney Elizabeth R.
Published: January 2017

Some unplanned adolescent pregnancies may be averted through education and preventive services provided by the teen-ager's physician. This paper discusses the need for such services, and reviews the current literature concerning issues surrounding adolescent contraception-professional acceptability, legality, public attitudes, morality, and appropriateness to the pediatrician's role. The authors conclude that recent developments make the pediatrician's involvement in adolescent sexuality counseling entirely feasible.
A Test of General Strain Theory in South Korea: A Focus on Objective/Subjective Strains, Negative Emotions, and Composite Conditioning Factors
Authors: Moon Byongook , Morash Merry
Published: January 2017

Few tests of General Strain Theory (GST) have examined the relative effects of objective and subjective strains on delinquency and the mediating effects of situational-based negative emotions linking strains to delinquency. With a sample of approximately 800 Korean adolescents, the present study tests a model that includes five key objective and the corresponding subjective strains identified as most predictive of delinquency, and situational-based anger and depression in response to each strain. Regardless of whether conceptualized as objective or subjective, three strains (teachers’ punishment, gender discrimination, and criminal victimization) have positive effects on delinquent behaviors. No indicators of situational-based anger and depression (except anger in response to victimization in a negative direction) have direct effects on delinquency or have mediating effects linking strains to delinquency. The results provide limited support for GST’s specification of the relatively greater effects of subjective than objective strains on delinquency and mediating effects of situational-based negative emotions. Theoretical implications are discussed.
Construct Validity for a Measure of Generalized Expectancy of Task Success
Authors: Motowidlo Stephan J.
Published: January 2017

This report presents results of correlational analyses bearing on the construct validity of the Estimate of Self-Competence (ESC) scale which was designed to measure generalized expectancy of task success. Three groups of university students completed the ESC and a variety of other measures. People with high ESC scores report stronger expectations of performing well in a university course if they apply effort, are more internal in their locus of control, and score higher on measures of self-assurance and self-confidence. They have self-perceptions similar to those of people with high levels of ability even though they may not possess more ability than people with low ESC scores. Although they tend to score somewhat higher on a measure of social desirability, it does not account for these findings. In addition, the ESC is correlated with other scales that seem to measure facets of drive and task-related motivation. Taken together, these results provide evidence for the validity of the ESC as a measure of generalized expectancy of task success.
Guidelines for Item Selection in Inventories Yielding Score Profiles
Authors: Meir Elchanan I. , Gati Itamar
Published: January 2017

In many personality and interest inventories a score profile, rather than a single score, is attributed to each subject. Six applicable criteria are suggested for use in examining the adequacy of items in such inventories. Two of these criteria relate to the response distribution on each item, two to the internal consistency of the items and two to the discriminative value of the items.
The Use and Misuse of Factor Scores in Multiple Regression Analysis
Authors: Fleming James S.
Published: January 2017

Kukuk and Baty (1979) have been critical of the use of factor scores as predictors in multiple regression analysis. The present paper, while in disagreement with certain of Kukuk and Baty's conclusions, also finds the perfunctory use of factor scores in conjunction with regression analysis to be inappropriate for many, or even most, purposes. It is suggested that factoring methods are most suitable for independent variable sets when some consideration has been given to the nature of the domain which is implied by the predictors.
Analyzing the Distractors of Multiple-Choice Test Items or Partitioning Multinomial Cell Probabilities with Respect to a Standard
Authors: Wilcox Rand R.
Published: January 2017

When analyzing the distractors of multiple-choice test items, it is sometimes desired to determine which of the distractors has a small probability of being chosen by a typical examinee. At present, this problem is handled in an informal manner. In particular, using an arbitrary number of examinees, the probabilities associated with the distractors are estimated and then sorted according to whether the estimated values are above or below a known constant p0 In this paper a more formal framework for solving this problem is described. The first portion of the paper considers the problem from the point of view of designing an experiment. The solution is based on a procedure similar to an indifference zone formulation of a ranking and election problem. A later section considers methods that might be employed in a retrospective study. Brief consideration is also given to how an analysis might proceed when a test item has been altered in some way.
On the Law of Comparative Judgment: Scaling with Intransitive Observers and Multidimensional Stimuli
Authors: Bruce Hull R. , Buhyoff Gregory J.
Published: January 2017

Intransitivities in observers' preference judgments for multidimensional natural landscape scenes are examined. Thurstone's Law of Comparative Judgment (LCJ) psychophysical scaling routine is used to scale landscape preference. Both the method of Rank Ordering (RO) and the method of Paired Comparisons (PC) are used to gather the raw data necessary for scaling. The preference metric derived from the PC data which allows intransitivities to occur, is compared to the metric derived from the RO data, which does not allow observer intransitivity. Analysis indicates that an observer's expressed ordinal preferences derived from his PC data differs from that obtained from his RO data. Analysis also indicates that intransitivity exist to a moderate degree in each individual's expressed preferences and that this intransitivity is related to the differences between the two sets of ordinal preferences. However, very little difference exists between the two, LCJ derived, interval preference metrics obtained from group PC data and group RO data.
The Reliability and Factorial Validity of the Questionnaire on the Quality of Relationships in Hospitals
Authors: Turner Carol J. , Willis Robert J.
Published: January 2017

An instrument developed to measure communication, collegiality, and climate related to the quality of relationships in hospitals is described. Entitled the Questionnaire on the Quality of Relationships in Hospitals (QQRH), the 62 item questionnaire was administerd to 345 employees at two non-profit, general hospitals. The reliability of the questionnaire was estimated by using coefficient alpha. The validity of the separate scales was evaluated through factor analysis. Finally, the questionnaire differentiated between and among subgroups in the sample that were assumed to have more or less positive attitudes. On the basis of this evidence, the QQRH is recommended to estimate employee attitudes about the quality of relationships in hospitals.