bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the utility of cystatin C as a confirmatory test of chronic kidney disease across the age range in middle-aged and older community-dwelling adults
Authors: Canney Mark , Sexton Donal J , O’Leary Neil , Healy Martin , Kenny Rose Anne , Little Mark A , O’Seaghdha Conall M
Published: January 2018

Background

Cystatin C has been proposed as a confirmatory test of chronic kidney disease (CKD). This is most applicable to older individuals with CKD, the majority of whom have a creatinine-based estimated glomerular filtration rate (eGFR) of 45–59 mL/min/1.73 m2(CKD stage 3a). We sought to examine the utility of cystatin C as a confirmatory test of CKD across the age range in the general population of older adults.

Methods

Cross-sectional analysis of 5386 participants from The Irish Longitudinal Study on Ageing, a cluster-sampled national cohort of community-dwelling adults aged ≥50 years. Cystatin C and creatinine were measured simultaneously using standardised assays. Using generalised additive models, we modelled the distributions of creatinine and cystatin C per year of age from four distributional parameters: location, dispersion, skewness, kurtosis. Among participants with CKD stage 3a, we estimated the predicted probability of cystatin C eGFR <60 mL/min/1.73 m2(‘confirmed CKD’) as a function of age.

Results

Median age was 62 years, 53% were female and median cystatin C eGFR was 80 mL/min/1.73 m2. We observed progressive variability in cystatin C with increasing age. Compared with creatinine, cystatin C levels rose sharply beyond the age of 65. Among participants with CKD stage 3a (n=463), the predicted probability of ‘confirmed CKD’ increased steadily with age, from 15% at age 50 to 80% at age 80.

Conclusions

The clinical utility of cystatin C may be maximised in middle-aged individuals, in whom the distribution of cystatin C is less variable than older adults, and the pretest probability of confirming CKD is lower.
Stroke-induced immunosuppression and poststroke infection
Authors: Shi Kaibin , Wood Kristofer , Shi Fu-Dong , Wang Xiaoying , Liu Qiang
Published: January 2018

Infections occur commonly after stroke and are strongly associated with an unfavourable functional outcome of these patients. Approaches for effective management of poststroke infection remain scarce, presenting an urgent need for preventive anti-infection strategies for patients who have suffered a stroke. Emerging evidence indicates that stroke impairs systemic immune responses and increases the susceptibility to infections, suggesting that the modification of impaired immune defence could be beneficial. In this review, we summarised previous attempts to prevent poststroke infections using prophylactic antibiotics and the current understanding of stroke-induced immunosuppression. Further elucidation of the immune mechanisms of stroke will pave the way to tailored design of new treatment to combat poststroke infection via modifying the immune system.
Global evidence on the effect of point-of-sale display bans on smoking prevalence
Authors: He Yanyun , Shang Ce , Huang Jidong , Cheng Kai-Wen , Chaloupka Frank J
Published: January 2018

Background

Since Iceland became the first country to impose a ban on point-of-sale (POS) tobacco product displays in 2001, 20 countries have implemented POS display bans as of 2016. This study examined the effect that POS display bans have on smoking prevalence.

Methods

Data were sourced from Euromonitor International and the WHO MPOWER package for 2007–2014 from 77 countries worldwide. generalised linear models with country and year fixed effects were estimated to analyse the effect of POS display bans on smoking prevalence.

Results

Having a POS display ban reduced overall adult daily smoking, male smoking and female smoking by about 7%, 6% and 9%, respectively.

Conclusions

Having a POS display ban is likely to reduce smoking prevalence and generate public health benefits.
Predicting weed and lowbush blueberry biomass using the point intercept method
Authors: Lévesque Josée-Anne , Bradley Robert L. , Bellemare Mireille , Lafond Jean , Paré Maxime C.
Published: January 2018

Lowbush blueberry is an important crop in the Saguenay–Lac-Saint-Jean region of Quebec. Accurate evaluation of agronomic practices currently requires destructive sampling and loss of productive fields. We showed that the point intercept method is a rapid and reliable nondestructive alternative for predicting biomass and yield of lowbush blueberry and competing species.
Response of growth, yield, and quality of pea shoots to supplemental light-emitting diode lighting during winter greenhouse production
Authors: Kong Yun , Llewellyn Dave , Zheng Youbin
Published: January 2018

Low natural light levels during the winter months are a major limiting factor for greenhouse production in northern regions. To determine the effects of supplemental lighting (SL) on winter greenhouse production of pea shoots, crop growth, yield, and quality were investigated under the treatments of supplemental photosynthetic photon flux density (PPFD) of 50, 80, 110, and 140 μmol m−2 s−1, all with a 16 h photoperiod, plus a no-SL control treatment, inside a Canadian greenhouse from December to March. Light-emitting diodes with a red to blue PPFD ratio of 4:1 and peak wavelengths at 665 and 440 nm were used for the lighting treatment. During the trial period, the average natural daily light integral (DLI) inside the greenhouse was 5.3 mol m−2 d−1 and the average daily temperature was around 13 °C. Compared with the no-SL control, SL of 50–140 μmol m−2 s−1 increased stem length and leaf number before the first harvest and promoted the cumulative yield (kg m−2) of pea shoots throughout the five harvest times. The total yield (kg m−2) of five harvests and weekly average stem extension rate were proportional to supplemental PPFD within the range of 0–140 μmol m−2 s−1; however, SL of 50–80 μmol m−2 s−1, corresponding to total (natural + supplemental) DLI of 8.1–9.8 mol m−2 d−1, resulted in the best integrated quality based on the evaluation of individual fresh mass, soluble solids content, succulence, and firmness. Therefore, a total DLI ranging between 8.1 and 9.8 mol m−2 d−1 can be suggested as a target for winter greenhouse production of pea shoots under conditions similar to this trial.
AAC Bloomfield barley
Authors: Khanal Raja , Choo Thin Meiw , Martin Richard , Xue Allen , Beek Sharon Ter , MacDonald Douglas , Scott Peter
Published: January 2018

AAC Bloomfield is a six-row spring feed barley (Hordeum vulgare L.) cultivar with high yield, high test weight, high seed weight, and good lodging resistance. It performed well in the Maritime Six-Row Barley Registration and Recommendation Test (2013–2016) before being registered in 2017. AAC Bloomfield was developed by the Ottawa Research and Development Centre, Agriculture and Agri-Food Canada, Ottawa, ON. AAC Bloomfield is recommended for barley growing areas in the Maritime provinces.
Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration
Authors: Scarlett Kisha A. , White El-Shaddai Z. , Coke Christopher J. , Carter Jada R. , Bryant Latoya K. , Hinton Cimona V.
Published: January 2018

G-protein–coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro. However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro. Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease.

Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728–39. ©2018 AACR.
Centriole Overduplication is the Predominant Mechanism Leading to Centrosome Amplification in Melanoma
Authors: Denu Ryan A. , Shabbir Maria , Nihal Minakshi , Singh Chandra K. , Longley B. Jack , Burkard Mark E. , Ahmad Nihal
Published: January 2018

Centrosome amplification (CA) is common in cancer and can arise by centriole overduplication or by cell doubling events, including the failure of cell division and cell–cell fusion. To assess the relative contributions of these two mechanisms, the number of centrosomes with mature/mother centrioles was examined by immunofluorescence in a tissue microarray of human melanomas and benign nevi (n = 79 and 17, respectively). The centrosomal protein 170 (CEP170) was used to identify centrosomes with mature centrioles; this is expected to be present in most centrosomes with cell doubling, but on fewer centrosomes with overduplication. Using this method, it was determined that the majority of CA in melanoma can be attributed to centriole overduplication rather than cell doubling events. As Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication, the hypothesis that PLK4 overexpression contributes to centriole overduplication was evaluated. PLK4 is significantly overexpressed in melanoma compared with benign nevi and in a panel of human melanoma cell lines (A375, Hs294T, G361, WM35, WM115, 451Lu, and SK-MEL-28) compared with normal human melanocytes. Interestingly, although PLK4 expression did not correlate with CA in most cases, treatment of melanoma cells with a selective small-molecule PLK4 inhibitor (centrinone B) significantly decreased cell proliferation. The antiproliferative effects of centrinone B were also accompanied by induction of apoptosis.

Implications: This study demonstrates that centriole overduplication is the predominant mechanism leading to centrosome amplification in melanoma and that PLK4 should be further evaluated as a potential therapeutic target for melanoma treatment. Mol Cancer Res; 16(3); 517–27. ©2018 AACR.
Characterization and Evidence of the miR-888 Cluster as a Novel Cancer Network in Prostate
Authors: Hasegawa Tsuyoshi , Glavich Garrison J. , Pahuski Mary , Short Aleena , Semmes O. John , Yang Lifang , Galkin Vitold , Drake Richard , Esquela-Kerscher Aurora
Published: January 2018

Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive class of approximately 22 nucleotide noncoding RNAs, are often aberrantly expressed in tissues and fluids from prostate cancer patients, but the mechanisms of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly understood. Here, miR-888 was identified as a novel prostate factor that promotes proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on human chromosome Xq27.3. Moreover, as miR-888 maps within HPCX1, a locus associated with susceptibility and/or hereditary prostate cancer, it was hypothesized that additional miRNA cluster members also play functional roles in the prostate. Expression analysis determined that cluster members were similarly elevated in metastatic PC3-ML prostate cells and their secreted exosomes, as well as enriched in expressed prostatic secretions urine-derived exosomes obtained from clinical patients with high-grade prostate cancer. In vitro assays revealed that miR-888 cluster members selectively modulated PC3-derived and LNCaP cell proliferation, migration, invasion, and colony formation. Mouse xenograft studies verified miR-888 and miR-891a as pro-oncogenic factors that increased prostate tumor growth in vivo. Further analysis validated RBL1, KLF5, SMAD4, and TIMP2 as direct miR-888 targets and that TIMP2 is also coregulated by miR-891a. This study provides the first comprehensive analysis of the entire miR-888 cluster and reveals biological insight.

Implications: This work reveals a complex noncoding RNA network in the prostate that could be developed as effective diagnostic and therapeutic tools for advanced prostate cancer. Mol Cancer Res; 16(4); 669–81. ©2018 AACR.
BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism
Authors: Vázquez-Arreguín Karina , Maddox Jessica , Kang Jinsuk , Park Dongju , Cano Reuben R. , Factor Rachel E. , Ludwig Thomas , Tantin Dean
Published: January 2018

The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 protein levels correlate positively with tumor aggressiveness and inversely with BRCA1. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism and restrict tumorigenicity. Mol Cancer Res; 16(3); 439–52. ©2018 AACR.
Novel Intergenically Spliced Chimera, NFATC3-PLA2G15, Is Associated with Aggressive T-ALL Biology and Outcome
Authors: Bond Jonathan , Tran Quang Christine , Hypolite Guillaume , Belhocine Mohamed , Bergon Aurélie , Cordonnier Gaëlle , Ghysdael Jacques , Macintyre Elizabeth , Boissel Nicolas , Spicuglia Salvatore , Asnafi Vahid
Published: January 2018

Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically spliced chimeric RNAs (ISC) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA sequencing was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens (n = 24), and candidate T-ALL–related ISCs were identified (n = 55; a median of 4/patient). In-depth characterization of the NFATC3-PLA2G15 chimera, which was variably expressed in primary T-ALL, was performed. Functional assessment revealed that the fusion had lower activity than wild-type NFATC3 in vitro, and T-ALLs with elevated NFATC3-PLA2G15 levels had reduced transcription of canonical NFAT pathway genes in vivo. Strikingly, high expression of the NFATC3-PLA2G15 chimera correlated with aggressive disease biology in murine patient-derived T-ALL xenografts, and poor prognosis in human T-ALL patients. Mol Cancer Res; 16(3); 470–5. ©2018 AACR.
Epigenetic Reprogramming of Pericentromeric Satellite DNA in Premalignant and Malignant Lesions
Authors: Brückmann Nadine Heidi , Pedersen Christina Bøg , Ditzel Henrik Jørn , Gjerstorff Morten Frier
Published: January 2018

Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms. Furthermore, the data reveal that polycomb bodies are exclusive to premalignant and malignant cells, being absent in normal cells. For instance, polycomb bodies are present in melanocytic cells of nevi and conserved in primary and metastatic melanomas. Deposition of polycomb on the 1q12 satellite DNA in melanoma development correlated with reduced DNA methylation levels. In agreement with this, inhibition of DNA methyltransferases, with the hypomethylating agent guadecitabine (SGI-110), was sufficient for polycomb body formation on pericentromeric satellites in primary melanocytes. This suggests that polycomb bodies form in cancer cells with global DNA demethylation to control the stability of pericentromeric satellite DNA. These results reveal a novel epigenetic perturbation specific to premalignant and malignant cells that may be used as an early diagnostic marker for detection of precancerous changes and a new therapeutic entry point.

Implications: Pericentromeric satellite DNA is epigenetically reprogrammed into polycomb bodies as a premalignant event with implications for transcriptional activity and genomic stability. Mol Cancer Res; 16(3); 417–27. ©2018 AACR.
Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells Following PI3K–Akt Inhibition
Authors: Damrauer Jeffrey S. , Phelps Stephanie N. , Amuchastegui Katie , Lupo Ryan , Mabe Nathaniel W. , Walens Andrea , Kroger Benjamin R. , Alvarez James V.
Published: January 2018

Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously, it was observed that the proapoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans. However, the mechanistic underpinnings on how Par-4 expression is regulated are unclear. Here, it is demonstrated that Par-4 is transcriptionally upregulated following treatment with multiple drugs targeting the PI3K–Akt–mTOR signaling pathway, and identify the Forkhead family of transcription factors as mediators of this upregulation. Mechanistically, Foxo3a directly binds to the Par-4 promoter and activates its transcription following inhibition of the PI3K–Akt pathway. This Foxo-dependent Par-4 upregulation limits the long-term survival of residual cells following treatment with therapeutics that target the PI3K–Akt pathway. Taken together, these results indicate that residual breast cancer tumor cell survival and recurrence requires circumventing Foxo-driven Par-4 upregulation and suggest that approaches to enforce Par-4 expression may prevent residual cell survival and recurrence. Mol Cancer Res; 16(4); 599–609. ©2018 AACR.
Differential Regulation of LET-7 by LIN28B Isoform–Specific Functions
Authors: Mizuno Rei , Chatterji Priya , Andres Sarah , Hamilton Kathryn , Simon Lauren , Foley Shawn W. , Jeganathan Arjun , Gregory Brian D. , Madison Blair , Rustgi Anil K.
Published: January 2018

The RNA-binding protein LIN28B plays an important role in development, stem cell biology, and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short isoforms. Although studies have revealed the functions of the LIN28B-long isoform in tumorigenesis, the role of the LIN28B-short isoform remains unclear and represents a major gap in the field. The LIN28B-long and -short isoforms are expressed in a subset of human colorectal cancers and adjacent normal colonic mucosa, respectively. To elucidate the functional and mechanistic aspects of these isoforms, colorectal cancer cells (Caco-2 and LoVo) were generated to either express no LIN28B or the -short or -long isoform. Interestingly, the long isoform suppressed LET-7 expression and activated canonical RAS/ERK signaling, whereas the short isoform did not. The LIN28B-long isoform–expressing cells demonstrated increased drug resistance to 5-fluorouracil and cisplatin through the upregulation of ERCC1, a DNA repair gene, in a LET-7–dependent manner. The LIN28B-short isoform preserved its ability to bind pre-let-7, without inhibiting the maturation of LET-7, and competed with the LIN28B-long isoform for binding to pre-let-7. Coexpression of the short isoform in the LIN28B-long isoform–expressing cells rescued the phenotypes induced by the LIN28B-long isoform.

Implications: This study demonstrates the differential antagonistic functions of the LIN28B-short isoform against the LIN28B-long isoform through an inability to degrade LET-7, which leads to the novel premise that the short isoform may serve to counterbalance the long isoform during normal colonic epithelial homeostasis, but its downregulation during colonic carcinogenesis may reveal the protumorigenic effects of the long isoform. Mol Cancer Res; 16(3); 403–16. ©2018 AACR.
Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells
Authors: Patel Priyank , Tsiperson Vladislav , Gottesman Susan R.S. , Somma Jonathan , Blain Stacy W.
Published: January 2018

Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib, have shown clinical efficacy, but primary or secondary resistance has emerged as a problem. To develop more effective therapeutic approaches, investigation is needed into the mechanisms of resistance or adaption. Here, it is demonstrated that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested breast cancer cells, suggesting that inhibition of both kinases is required to achieve durable response. In addition, a novel strategy is described to inhibit tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2 and CDK4. p27Kip1 is a required assembly factor for cyclin–CDK4 complexes, but it must be phosphorylated on residue Y88 to open or activate the complex. The Brk-SH3 peptide, ALT, blocks p27 Y88 phosphorylation, inhibiting CDK4. Nonphosphorylated p27 is no longer a target for ubiquitin-mediated degradation and this stabilized p27 now also inhibits CDK2 activity. Thus, ALT induction inhibits both the kinase that drives proliferation (CDK4) and the kinase that mediates resistance (CDK2), causing a potent and long-lasting cell-cycle arrest. ALT arrests growth of all breast cancer subgroups and synergizes with palbociclib to increase cellular senescence and to cause tumor regression in breast cancer xenograft models. The use of ALT demonstrates that both CDK4 and CDK2 need to be inhibited if long-term efficacy is to be achieved and represents a novel modality to inhibit breast cancer cells.

Implications: Modulating tyrosine phosphorylation of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in breast cancer and suggests that phospho-p27 status may serve as a biomarker for patients that are responsive to CDK4/6 inhibition. Mol Cancer Res; 16(3); 361–77. ©2018 AACR.
Heart Failure in Pregnant Women
Authors: Mogos Mulubrhan F. , Piano Mariann R. , McFarlin Barbara L. , Salemi Jason L. , Liese Kylea L. , Briller Joan E.
Published: January 2018

Background

Heart failure (HF) is a leading cause of maternal morbidity and mortality in the United States, but prevalence, correlates, and outcomes of HF-related hospitalization during antepartum, delivery, and postpartum periods remain unknown. The objective was to examine HF prevalence, correlates, and outcomes among pregnancy-related hospitalizations among women 13 to 49 years of age.

Methods and Results

We used the 2001 to 2011 Nationwide Inpatient Sample. Rates of HF were calculated by patient and hospital characteristics. Survey logistic regression was used to estimate adjusted odds ratios representing the association between HF and each outcome, stratified by antepartum, delivery, and postpartum periods. Joinpoint regression was used to describe temporal trends in HF and in-hospital mortality. Over 50 million pregnancy-related hospitalizations were analyzed. The overall rate of HF was 112 cases per 100 000 pregnancy-related hospitalizations. Although postpartum encounters represented only 1.5% of pregnancy-related hospitalizations, ≈60% of HF cases occurred postpartum, followed by delivery (27.3%) and antepartum (13.2%). Among postpartum hospitalizations, there was a significant 7.1% (95% confidence interval, 4.4–9.8) annual increase in HF from 2001 to 2006, followed by a steady rate through 2011. HF rates among antepartum hospitalizations increased on average 4.9% (95% confidence interval, 3.0–6.8) annually from 2001 to 2011. Women with a diagnosis of HF were more likely to experience adverse maternal outcomes, as reflected by outcome-specific adjusted odds ratios during antepartum (2.7–25), delivery (6–195), and postpartum (1.5–6.6) periods.

Conclusions

HF is associated with increased risk of maternal mortality and morbidities. During hospitalization, high-risk mothers need to be identified and surveillance programs developed before discharge.
Increased Levels of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Ischemic Stroke and Transient Ischemic Attack
Authors: Skarpengland Tonje , Skjelland Mona , Kong Xiang Yi , Skagen Karolina , Holm Sverre , Otterdal Kari , Dahl Christen P. , Krohg‐Sørensen Kirsten , Sagen Ellen L. , Bjerkeli Vigdis , Aamodt Anne Hege , Abbas Azhar , Gregersen Ida , Aukrust Pål , Halvorsen Bente , Dahl Tuva B.
Published: January 2018

Background

Soluble lectin‐like oxidized low‐density lipoprotein receptor‐1 (
sLOX
‐1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma
sLOX
‐1 levels and vascular carotid plaque
LOX
‐1 (ie,

OLR
1

) gene expression in patients with ischemic stroke and transient ischemic attack (
TIA
) with particular focus on their relation to time since symptom onset.

Methods and Results

Plasma
sLOX
‐1 (n=232) and carotid plaque

OLR
1

gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81). Patients were categorized according to presence of acute ischemic stroke or transient ischemic attack (n=35) ≤7 days, >7 days ≤3 months (n=90), >3 months (n=40), or no reported symptoms before study inclusion (n=67). Our major findings were the following: (1) Patients with carotid atherosclerosis had increased plasma
sLOX
‐1 levels as compared with controls. (2) Plaque

OLR
1

mRNA
levels were increased in carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common iliac arteries of organ donors, n=10). (3) There were no differences in
sLOX
plasma levels or

OLR
1

gene expression when analyzed according to the time since relevant cerebral ischemic symptoms. (4) Also patients with severe carotid atherosclerosis without any previous ischemic events had raised
sLOX
‐1 levels. (5) Immunostaining showed colocalization between
LOX
‐1 and macrophages within the carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by atrial fibrillation (n=22) had comparable raised
sLOX
‐1 levels.

Conclusions

sLOX
‐1 levels are elevated in patients with ischemic stroke and transient ischemic attack independent of cause and time since the ischemic event.
Offerings of Women in the Transformation of African Higher Education: A Retrospective Overview
Authors: Potokri Onoriode Collins , Perumal Juliet
Published: January 2018

This article presents an unusual concrete insight to African higher education transformation. The purpose is to examine the roles of African women mainly Charlotte Maxeke, a South African, in the transformation of higher education and to identify the legacy these transformation offerings translate into for women. It is organized as follows: first, the origin of transformation in higher education systems to global massification of education in the background section is traced. Second, in an attempt to understand as a means of examining the roles of women in the transformation of higher education, existing literature as evidence is engaged. Two crucial issues—challenges for African higher education transformation and women’s role in higher education development in Africa—were reviewed analytically toward transformation of higher education. Third, empowerment theory, as suitable theory for the reasonable accomplishment of the purpose of this article, is presented. Last, the theory was applied to the discussions justifying the conclusion. The methodology used is both descriptive and exploratory. The article divulges that women had always being fanatical about empowerment of themselves and others because women had at some points in history contributed to developmental alterations of African higher education given their enormous offerings or contributions. Obviously, as revealed in this article, while risking their lives in an Apartheid/colonial regime where death could visit anyone who opposes the government at any time, their offerings or roles include financial commitment; empowerment advocacy and knowledge enchanting.
Shake and Bake: Exploring Drug Producers’ Adaptability to Legal Restrictions Through Online Methamphetamine Recipes
Authors: Vidal Sabrina , Décary-Hétu David
Published: January 2018

Despite numerous regulations, methamphetamine consumption persists; its availability has even increased in the United States. Methamphetamine is produced in small labs and super labs that are differentiated by the quantity of drug they generate and by how they are embedded in trafficking networks. The stagnant statistics regarding methamphetamine consumption and lab seizures suggest that laws have been ineffective, partly due to the producers’ adaptability. To understand this adaptation, methamphetamine recipes collected online will be analyzed through a qualitative methodology. Emphasis will be placed on the impact of the American legislation toward synthetic drug production. This article describes how methamphetamine producers have adapted to get around the regulations. The producers synthesize the regulated precursors by extracting them from processed products. To comply with the quotas imposed by law, the producers limit their quantities used. This article suggests that producers keep abreast of legislations and perfect the recipes accordingly.
The Effectiveness of Preoperative Preparation for Improving Perioperative Outcomes in Children and Caregivers
Authors: Lin Chia-Jung , Liu Hsin-Ping , Wang Pei-Ya , Yu Mei-Hua , Lu Mei-Chun , Hsieh Ling-Yu , Lin Tzu-Chia
Published: January 2018

Most children experience significant anxiety during the preoperative period. Greater preoperative anxiety may be related to a higher incidence of negative behaviors. This study aimed to develop a family-centered preoperative preparation program and to evaluate the effects of this program on children’s preoperative emotional behaviors, postoperative behavior, and posthospital behavior, and on caregiver anxiety. A prospective, randomized controlled study was conducted. The population consisted of children who underwent minor surgery and their caregivers. The control group received standard care, and the experimental group received standard care plus preoperative preparation, which included a tour, a cartoon video depicting a boy’s surgical journey, and familiarization with medical equipment. Children’s emotional behaviors and caregiver anxiety were measured at the preoperative visit, in the preoperative holding area, and at induction of anesthesia. Postoperative behavior was measured when children were in the recovery room, and the researcher also contacted caregivers 2 weeks after the surgery to assess the children’s behavior at home. A linear mixed-effects model results showed that as the surgery approached, the experimental group had fewer and more stable preoperative emotional behaviors (least squares means of preoperative emotional behaviors from preoperative visit to induction of anesthesia = 10.01-10.95). However, the control group exhibited significantly increased preoperative emotional behaviors as the surgery approached (least squares means of preoperative emotional behaviors from the preoperative visit to induction of anesthesia = 7.87-12.23). Family-centered preoperative preparation can effectively improve children’s negative emotional behaviors from their time in the preoperative holding area to the induction of anesthesia.
Validation of the Ceredigion Youth Screening Tool
Authors: Norris Gareth , Griffith Gwyn , West Megan
Published: January 2018

Evidence suggests that only a small minority of youth offenders will continue their behaviour in the longer term and largely independent of any interventions they may receive (Bateman, 2011; Haines & Case, 2015). Hence, “screening out” this larger low-risk cohort could have a positive impact upon the individual through a reduction in stigmatisation/labelling and free up resources for higher risk clients. This article outlines development of the Ceredigion Youth Screening Tool (CYSTEM)—developed and tested to address the two facets of criminality and vulnerability—closely aligned to the eight key risk indicators identified in the Risk-Needs-Responsivity (R-N-R) literature (Andrews & Bonta, 2010). Initial results with two cohorts of 372 young people indicate good convergent and discriminative validity in screening out the lowest level referrals, while also identifying 90% of potential future offenders. More importantly, CYSTEM is able to screen out approximately 35% of the low-risk offenders that are unlikely to require formal evaluation and/or intervention. It is suggested that the streamlining of this process using CYSTEM reduces demand on staff time and decreases the stigmatisation of young people referred for minor offences. Potential improvements to the tool and future developments in statistical risk prediction are also discussed.
Examination of an in vitro methodology to evaluate the biomechanical performance of nucleus augmentation in axial compression
Authors: Sikora Sebastien NF , Miles Danielle E , Tarsuslugil Sami , Mengoni Marlène , Wilcox Ruth K
Published: January 2018

Intervertebral disc degeneration is one of the leading causes of back pain, but treatment options remain limited. Recently, there have been advances in the development of biomaterials for nucleus augmentation; however, the testing of such materials preclinically has proved challenging. The aim of this study was to develop methods for fabricating and testing bone-disc-bone specimens in vitro for examining the performance of nucleus augmentation procedures. Control, nucleotomy and treated intervertebral disc specimens were fabricated and tested under static load. The nucleus was removed from nucleotomy specimens using a trans-endplate approach with a bone plug used to restore bony integrity. Specimen-specific finite element models were developed to elucidate the reasons for the variations observed between control specimens. Although the computational models predicted a statistically significant difference between the healthy and nucleotomy groups, the differences found experimentally were not significantly different. This is likely due to variations in the material properties, hydration and level of annular collapse. The deformation of the bone was also found to be non-negligible. The study provides a framework for the development of testing protocols for nucleus augmentation materials and highlights the need to control disc hydration and the length of bone retained to reduce inter-specimen variability.
Iterative lagged asymmetric responses in strategic management and long-range planning
Authors: Simandan Dragos
Published: January 2018

Actors in competitive environments are bound to decide and act under conditions of uncertainty because they rarely have accurate foreknowledge of how their opponents will respond and when they will respond. Just as a competitor makes a move to improve their standing on a given variable relative to a target competitor, she should expect the latter to counteract with an iterative lagged asymmetric response, that is, with a sequence of countermoves ( iteration) that is very different in kind from its trigger ( asymmetry) and that will be launched at some unknown point in the future ( time lag). The paper explicates the broad relevance of the newly proposed concept of “iterative lagged asymmetric responses” to the social study of temporality and to fields as diverse as intelligence and counterintelligence studies, strategic management, futures studies, military theory, and long-range planning. By bringing out in the foreground and substantiating the observation that competitive environments place a strategic premium on surprise, the concept of iterative lagged asymmetric responses makes a contribution to the never-ending and many-pronged debate about the extent to which the future can be predicted.
Impact of the Elderly on Household Health Expenditure in Bihar and Kerala, India
Authors: Loutfi David , Lévesque Jean-Frédéric , Mukherjee Subrata
Published: January 2018

Ageing in India is leading to an increase in chronic diseases. Given the limited health insurance coverage, this could lead to a variety of economic- and access-related consequences for the households. Against this backdrop, this article aims at examining the impact of the presence of the elderly on household health expenditure, avoidance of treatment, loss of income and use of alternate sources of funding to pay for care. The article uses data from 2004 National Sample Survey Organisation survey on healthcare for two Indian states, namely, Bihar and Kerala. The rate of catastrophic health expenditure (CHE) is found to be higher in Kerala and is associated with a higher proportion of households having elderly members, who, in turn, have higher incidence of chronic disease. While the presence of elderly in the household, incidence of chronic disease and treatment from private sources are linked to CHE, our results suggest that other groups, such as households without elderly, may simply be delaying the economic consequences of paying for healthcare by borrowing. Though the ageing population is leading to increased health expenditure for households due to increased chronic illness, the impact of using private treatment is much less clear.
Examining States’ Responses to the IDEA Special Factors Requirements for DHH Students
Authors: Luft Pamela , Amiruzzaman Stefanie
Published: January 2018

Deaf and hard-of-hearing (DHH) students have exhibited deficient language competencies and low academic achievement for over four decades. As a result, Individuals With Disabilities Education Act (IDEA) 2004 requires schools to address special language and communication factors through each student’s Individualized Education Program (IEP). States have responded in a variety of ways with several that supplement their IEPs using a communication plan. This article examined states’ IEP or communication plan templates to identify the format and specificity with which they addressed these requirements. The IDEA language was parsed into distinct items to allow ratings using a Likert-type scale. The analyses performed descriptive, t test, and ANOVA comparisons on the forms posted on states’ website. Those states using a communication plan had significantly higher ratings overall. Kentucky’s form was the most highly rated IEP and identified each required item. Most state IEP forms identified these factors more generally with a majority rated as only minimally specified. Use of a communication plan or IEP form that incorporates IDEA language similar was the most effective strategy. Overt specificity ensures that DHH students’ language and communication needs are being met in the educational environment and facilitates states’ oversight in meeting their educational responsibilities.
Predictors of Participant Perceptions of Facilitated Individualized Education Program Meeting Success
Authors: Goldman Samantha E. , Mason Carolyn Q.
Published: January 2018

Facilitated Individualized Education Program (FIEP) meetings present one option for early, alternative dispute resolution in special education. Although it has been suggested that this process may be useful in resolving disputes and improving relationships, these hypotheses have not been directly addressed. In this study, we used individual participant feedback data collected by a northwestern state over a 2-year period to answer the following research questions: (a) What are the perceived outcomes of FIEP meetings in terms of agreement, reduced future use of procedural safeguards, and improved relationships between school staff and family? and (b) What are the predictors of these positive participant perceptions of the outcomes of FIEP meetings? We found that respondents perceived FIEP meetings to be successful, with more than half of respondents reporting an outcome of full agreement by all team members, 44% reporting reduced future use of procedural safeguards, and 42% reporting an improved relationship between school staff and family following the meeting. Using multilevel models, we found that perceived facilitator quality was a significant predictor of all three positive outcomes, even after controlling for significant meeting characteristics such as region and year. Given these initial findings, we also provide implications for research, practice, and policy.
Slippage of Tightrope Button in Syndesmotic Fixation of Weber C Malleolar Fractures: A Case Series
Authors: Ibnu Samsudin Mas’uud , Yap Ming Quan Wayne , Wei Luong Ang , Kwek Ernest Beng Kee
Published: January 2018

Background:

Tightrope fixation is an emerging technique for syndesmotic fixation with promising results. However, our case series highlights the slippage of Tightrope buttons as a complication of suture button syndesmotic fixation of Weber C malleolar fractures using limited contact dynamic compression (LCDCP) plates.

Methods:

We report a series of cases from our database in which slippage of the Tightrope button through the LCDCP holes in Weber C malleolar fractures was noted. We measured the medial clear space (MCS), tibiofibular clear space (TFCS), and distal tibiofibular overlap (DTFO) and computed the largest change in these measurements from the first postoperative follow-up radiographs. Patient records were reviewed for persistent symptoms that could be attributed to the loss of syndesmotic fixation and stability.

Results:

Follow-up radiographs of 3 patients showed a slippage of the Tightrope button through the LCDCP holes. Two of the patients reported persistent ankle pain and swelling with prolonged activity. The mean increases in MCS and TFCS among these patients were 0.7 (±0.081) mm and 1.5 (±0.798) mm, respectively. The mean decrease in DTFO was 2.2 (±0.864) mm. We next highlight 3 patients with Weber C malleolar fractures who underwent suture button syndesmotic fixation using double-stacked one-third tubular plates instead of the LCDCP.

Conclusion:

This case series reported Tightrope button slippage as an early complication of syndesmotic fixation of Weber C malleolar fractures. We propose the use of double-stacked one-third tubular plates instead of the LCDCP to avoid this complication.

Level of Evidence:

Level V, expert opinion.
Decoding Science: Development and Evaluation of a Science Communication Training Program Using a Triangulated Framework
Authors: Rodgers Shelly , Wang Ze , Maras Melissa A. , Burgoyne Suzanne , Balakrishnan Bimal , Stemmle Jon , Schultz Jack C.
Published: January 2018

The authors describe a science communication training called “Decoding Science” and the steps taken to develop and assess program effectiveness. Evaluation is based on a triangulated framework involving feedback from graduate student trainees, faculty trainers, and ordinary citizens who are not specialists in the field. Three cohorts of graduate STEM (science, technology, engineering, math) students participated in the training in Spring 2016 ( N = 18), Fall 2016 ( N = 11), and Spring 2017 ( N = 14). Analysis of these evaluations indicates significant improvements in trainees’ communication of science. We conclude that our triangulated approach can be useful in science communication training.
Testing Links Among Uncertainty, Affect, and Attitude Toward a Health Behavior
Authors: Fung Timothy K. F. , Griffin Robert J. , Dunwoody Sharon
Published: January 2018

This study examines the conceptual linkages between individuals’ uncertainty judgments and affective reactions (worry and anger) within the context of an environmental health risk. It uses data from a longitudinal study of people’s reactions to the risks of eating contaminated fish from the Great Lakes that employed the risk information seeking and processing model and incorporates a set of variables from the full model, which includes preventive behavior. Findings support the model and indicate that worry and anger strongly influenced uncertainty judgments but worry and anger influenced attitudes toward fish avoidance and information insufficiency differently.
The Possible Use of Preoperative Natriuretic Peptides for Discriminating Low Versus Moderate-High Surgical Risk Patient
Authors: Vetrugno Luigi , Orso Daniele , Matellon Carola , Giaccalone Marilù , Bove Tiziana , Bignami Elena
Published: January 2018

Perioperative risk scores for patients undergoing noncardiac surgery are generally considered inaccurate, poor, or, at best, modest. We propose estimating a patient’s pretest and posttest probability of cardiac morbidity and death using the preoperative scoring system plus the negative likelihood ratio from brain natriuretic peptide (BNP) or N-terminal proB-type natriuretic peptide (NT-proBNP) plasma levels. Our clinical challenge scenario showed a pretest probability of postoperative major cardiac complications with the patient risk factor as 6.6% for the Revised Cardiac Risk Index and between 1% and 5% (intermediate risk) per the recent European Society of Cardiology and the European Society of Anesthesiologist guidelines for surgical risk estimation. In fact, the American College of Cardiology and the American Heart Association guidelines consider the same surgical procedure for elevated risk. The posttest probability takes advantage of a negative likelihood ratio from BNP plasma levels, with patient risk factor reduced to 0.8% and surgical risk to 1.1%. In the same way, the pretest American College of Surgeons National Surgical Quality Improvement Program score decreased from 18.8% to 3.5% for severe complications and from 0.9% to 0.1% for death at ≤90 days. Following noncardiac surgery, postoperative complications and mortality are often cardiac in nature. The negative likelihood ratio of BNP and NT-proBNP plasma levels provides a quick, low-cost tool for recognizing and reclassifying the cardiovascular risk of those undergoing noncardiac surgery, thereby singling out low- versus moderate-high-risk surgical patients.