bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives: Using Results from HRSA's Health Workforce Simulation Model to Examine the Geography of Primary Care
Authors: Streeter Robin A. , Zangaro George A. , Chattopadhyay Arpita
Published: January 2017

Objective

Inform health planning and policy discussions by describing Health Resources and Services Administration's (HRSA's) Health Workforce Simulation Model (HWSM) and examining the HWSM's 2025 supply and demand projections for primary care physicians, nurse practitioners (NPs), and physician assistants (PAs).

Data Sources

HRSA's recently published projections for primary care providers derive from an integrated microsimulation model that estimates health workforce supply and demand at national, regional, and state levels.

Principal Findings

Thirty‐seven states are projected to have shortages of primary care physicians in 2025, and nine states are projected to have shortages of both primary care physicians and PAs. While no state is projected to have a 2025 shortage of primary care NPs, many states are expected to have only a small surplus.

Conclusions

Primary care physician shortages are projected for all parts of the United States, while primary care PA shortages are generally confined to Midwestern and Southern states. No state is projected to have shortages of all three provider types. Projected shortages must be considered in the context of baseline assumptions regarding current supply, demand, provider‐service ratios, and other factors. Still, these findings suggest geographies with possible primary care workforce shortages in 2025 and offer opportunities for targeting efforts to enhance workforce flexibility.
Clinical and pathological evaluation of patients with prostate and colorectal cancer five or more years after curative resection
Authors: Lee Jung Nam , Park Yeon Ho , Han Jung , Baek Jeong‐Heum , Park Sung Won , Lee Won‐Suk
Published: January 2017

Aim

The survival of men diagnosed with colorectal cancer (CRC) has improved over time, and the current 5‐year overall survival rate is 65.1 per cent. The long survival of patients with CRC raises issues regarding risk of a second primary prostate cancer and the need for continued proper surveillance. The aim of the study was to evaluate the incidence of prostate cancer in a uniform CRC population.

Patients and Methods

Between September 2007 and September 2012, 347 patients with curatively‐resected CRC who have had a follow‐up duration of more than 3 years at Gachon Medical Center were included in this study.

Results

The incidence of synchronous or metachronous prostate cancer in addition to CRC was 4.3 per cent (15 patients). The time interval between CRC to prostate tumour in ranged from 0.1 to 5.5 years. Fourteen patients (93.3 per cent) were greater than 65 years of age. There were only two synchronous prostate cancers (0.6 per cent) among the CRC patients.

Conclusion

Due to the increased survival of CRC, continued surveillance could be necessary.
Factors affecting outcomes in traumatic liver injury: A retrospective study
Authors: Lee Kit‐Fai , Chong Charing Ching‐Ning , Yeung Janice Hiu‐Hung , Cheung Nai‐Kwong , Siu Eva Yin‐Yu , Cheung Yue‐Sun , Wong John , Lai Paul Bo‐San
Published: January 2017

Aim

To achieve better outcomes, nonoperative management (NOM) and damage control surgery (DCS) are now recommended for traumatic liver injury. The aim of the present study was to review the outcomes of patients suffering from liver trauma and to determine the factors affecting the outcomes, with emphasis on NOM and DCS.

Patients and Methods

This was a retrospective cohort study for liver trauma patients from a single centre. The outcomes were compared between two equal consecutive periods: period A (2001–2007) and period B (2008–2014).

Results

There were 116 patients, with a mean age of 38.1 years and a male predominance (61.2 per cent). Approximately 57 per cent of patients suffered from grade III or higher liver injury. The mean Injury Severity Score (ISS) was 32.3. The 90‐day mortality was 20.7 per cent. During period B, the 90‐day mortality was significantly lowered (6/56 vs 18/60, P = 0.010) with less liver operations (13/56 vs 26/60, P = 0.022) and more hepatic angiography ± embolization (7/56 vs 0/60, P = 0.005). The proportion of DCS was similar, but more hepatectomies were performed in period B (4/13 vs 0/26, P = 0.009). Multivariate analysis revealed that ISS grade, age and sex were predictors for 90‐day mortality.

Conclusions

Reduced mortality was seen in traumatic liver injury accomplished by increased NOM, but not DCS.
Diagnostic accuracy of sialendoscopy referenced to current imaging modalities
Authors: Ng Siu‐Kwan , Chan Jason Ying‐Kuen , Wong Eddy Wai‐Yeung , Vlantis Alexander Chris
Published: January 2017

Aim

The aim of the present study was to determine the accuracy of diagnostic sialendoscopy in patients with suspected obstructive salivary duct disease referenced to current imaging modalities.

Patients and Methods

A retrospective study of patients with symptoms suggestive of obstructive salivary duct disease who underwent one or more imaging modalities, and then sialendoscopy at an academic hospital, were reviewed. The radiological and sialendoscopic findings were compared, and the diagnostic accuracy of various imaging modalities was determined using sialendoscopy as a reference.

Results

Seventy‐five sialendoscopies were performed in 68 patients (39 females, 29 males). Obstructive lesions were identified in 71 of the 75 sialendoscopies; 18 stones and 53 nonstone obstructive lesions were identified. Imaging consisting of plain X‐ray (n = 4), radiosialography (n = 18), ultrasonography (n = 58), computed tomography (n = 13) and magnetic resonance imaging (n = 10) detected disease in 25, 70.6, 69.1, 69.2 and 100 per cent of diseased ducts, respectively.

Conclusion

Sialendoscopy is more sensitive, and thus more useful, in diagnosing obstructive salivary duct disease in symptomatic patients than current imaging modalities. Symptomatic patients with negative imaging should be considered for sialendoscopy when therapy, such as stone retrieval or stricture dilation, can instituted at the time of diagnosis.
Abiotic effects on the distributions of major insect species in agricultural fields
Authors: Eo Jinu , Kim Myung‐Hyun , Na Young‐Eun , Oh Young‐Ju , Park Sangkyu
Published: January 2017

We compared how abiotic factors affect the regional distributions of four insect groups (Dermaptera, Formicidae, Orthoptera and Diptera). Insects were collected using a pitfall trap from 36 agricultural field sites, and 31 933 individuals encompassing 139 species were observed. The distribution pattern of dominant species was not obviously different among the four groups. Species richness (H′) of Orthoptera showed a negative and positive correlation with precipitation and sunlight duration, respectively. Longitudinal zonation was the main distribution pattern of many dominant species. Overall, canonical correspondence analysis showed that temperature and precipitation were closely associated with the distribution of Orthoptera, but not that of Formicidae, implying that Formicidae may be affected less by abiotic factors compared to other taxonomic groups. Some orthopteran species such as Dianemobius nigrofasciatus and Polionemobius mikado showed a negative correlation with temperature. We suggest that these species can be categorized as susceptible to climate change. Our results also implied that the association between climate variables and distribution of insects should be evaluated at a species level.
MicroRNA profile analysis in the liver fibrotic tissues of chronic hepatitis B patients
Authors: Chen Rong , Wu Jun Cheng , Liu Ting , Qu Ying , Lu Lun Gen , Xu Ming Yi
Published: January 2017

OBJECTIVE

We aimed to identify the features of microRNA (miRNA) at different fibrotic stages in patients with hepatitis B virus (HBV)‐related liver fibrosis.

METHODS

Liver tissues were collected from 40 chronic hepatitis B (CHB) patients at fibrotic stages S0–4. Microarrays of miRNAs and genomic informatics analysis were performed.

RESULTS

In total, 105 miRNAs were differentially expressed in fibrotic tissues (S1–4 groups) compared with no fibrotic tissues (S0 group; P < 0.05). Combined with three classifications, 17 differential miRNAs were found to be closely related to fibrotic stages (over twofold change and P < 0.05). Five miRNAs had a signature that correlated with serum biochemical parameters and liver inflammatory grades. The receiver operating characteristic (ROC) curve showed that six miRNAs performed excellently in the diagnosis of liver fibrosis, with the area under the ROC curve (AUROC) over 0.8; among them hsa‐miR‐214‐3p had the highest AUROC (0.867). Gene ontology functions of differential miRNAs mainly involved in the cellular and developmental processes, localization, biological regulation, binding, transcriptional regulator and organelle. We also found that 23 novel signaling pathways were dysregulated in the liver fibrosis.

CONCLUSIONS

MiRNA profile signature, including 17 differential miRNAs and 23 dysregulated signaling pathways, was associated with liver fibrosis. Hepatic inflammatory grades were correlated with the differential miRNA. Some miRNAs can be used for the diagnosis of liver fibrosis.
Probabilistic Flood Inundation Forecasting Using Rating Curve Libraries
Authors: Buahin Caleb A. , Sangwan Nikhil , Fagan Cassandra , Maidment David R. , Horsburgh Jeffery S. , Nelson E. James , Merwade Venkatesh , Rae Curtis
Published: January 2017

One approach for performing uncertainty assessment in flood inundation modeling is to use an ensemble of models with different conceptualizations, parameters, and initial and boundary conditions that capture the factors contributing to uncertainty. However, the high computational expense of many hydraulic models renders their use impractical for ensemble forecasting. To address this challenge, we developed a rating curve library method for flood inundation forecasting. This method involves pre‐running a hydraulic model using multiple inflows and extracting rating curves, which prescribe a relation between streamflow and stage at various cross sections along a river reach. For a given streamflow, flood stage at each cross section is interpolated from the pre‐computed rating curve library to delineate flood inundation depths and extents at a lower computational cost. In this article, we describe the workflow for our rating curve library method and the Rating Curve based Automatic Flood Forecasting (RCAFF) software that automates this workflow. We also investigate the feasibility of using this method to transform ensemble streamflow forecasts into local, probabilistic flood inundation delineations for the Onion and Shoal Creeks in Austin, Texas. While our results show water surface elevations from RCAFF are comparable to those from the hydraulic models, the ensemble streamflow forecasts used as inputs to RCAFF are the largest source of uncertainty in predicting observed floods.
Differences Between Treatment‐Seeking and Nontreatment‐Seeking Alcohol‐Dependent Research Participants: An Exploratory Analysis
Authors: Rohn Matthew C.H. , Lee Mary R. , Kleuter Samuel B. , Schwandt Melanie L. , Falk Daniel E. , Leggio Lorenzo
Published: January 2017

Background

Alcoholism is a chronic relapsing disorder with complex behavioral and functional heterogeneity. To date, attempts to characterize subgroups of alcohol‐dependent (AD) individuals have largely been focused on categorical distinctions based on behaviors such as ability to abstain, age of onset, and drinking motives, but these have failed to yield predictors of treatment response and disease course. The distinction between AD individuals who are or are not interested in treatment holds significant implications for interpreting results of human laboratory studies with nontreatment seekers and clinical trials with treatment‐seeking AD patients. However, despite their crucial role in alcohol‐related research, these 2 groups are poorly defined. In this exploratory analysis, we attempt to better define the phenotypic differences between these 2 experimentally relevant populations.

Methods

We analyzed data from AD individuals who participated in screening protocols to evaluate their suitability for participation in either treatment or nontreatment research studies at NIAAA. Scores on individual measures from a battery of behavioral, neuropsychological, and blood laboratory measures were compared between those who presented seeking treatment for AD and those who were not seeking treatment. Differences in each measure were assessed between the 2 groups. In addition, we explored whether significant differences were apparent when drinking behavior was used as a covariate.

Results

Treatment seekers manifested more impairment compared to nontreatment seekers on a wide variety of measures in the following categories: alcohol drinking, personality, impulsivity, trauma/stress, cognition, aggression, mood, and liver enzyme tests. Treatment seekers endorsed a greater number of AD criteria. Several measures including elevations in liver enzyme tests remained significantly different between the 2 groups when average daily alcohol consumption per drinking day was used as a covariate.

Conclusions

Treatment‐seeking, compared to nontreatment‐seeking AD subjects who present for alcohol‐related research studies, differ in characteristics beyond the quantity of alcohol consumption. Implications of these differences with respect to clinical research for treatments of AD are discussed.
Imbalance between pro‐apoptotic and pro‐survival factors in human retinal pericytes in diabetic‐like conditions
Authors: Beltramo Elena , Arroba Ana I. , Mazzeo Aurora , Valverde Angela M. , Porta Massimo
Published: January 2017

Purpose

Loss of pericytes is one the key events in the pathogenesis of diabetic retinopathy. We have previously demonstrated that human retinal pericytes (HRP) are more vulnerable to intermittent than stable high glucose concentrations, with an increase in apoptosis. Our aim was to explore the expression of molecules involved in pro‐apoptotic and survival pathways in pericytes cultured in stable/intermittent high glucose and/or hypoxia, to clarify the mechanisms of action of these diabetic‐like stressing stimuli.

Methods

Human retinal pericytes (HRP) were exposed intermittently at 48‐hr intervals to high/physiological glucose for 8 days (intHG) and/or hypoxia over the last 48 hr. Control cells were kept in stable physiological and high glucose. Cell proliferation and apoptosis were assessed. The expression of pro‐apoptotic and pro‐survival molecules was evaluated by Western blotting. Caspase‐8 translocation from the cytoplasm into the nucleus was checked by Western blotting of nuclear versus cytoplasmic fractions and immunofluorescence.

Results

Hypoxia, alone and combined with intHG, increased HRP apoptosis and decreased proliferation. Pro‐apoptotic molecules increased in HRP cultured in these conditions, while some survival markers decreased. Conversely, in stable HG, pro‐apoptotic molecules were stable or even decreased, and survival factors increased. Translocation of caspase‐8 from cytoplasm into nucleus indicates a primary role for this molecule in inducing apoptosis.

Conclusion

Diabetic‐like conditions are able to stimulate pericyte apoptosis through activation of pro‐apoptotic molecules, leading to an imbalance between pro‐apoptotic and survival signalling pathways, with caspase‐8 playing a pivotal role. Our identification of such intermediates could help finding new therapeutic approaches for the prevention of diabetic retinopathy.
Literature review on cancer risk in children born after fertility treatment suggests increased risk of haematological cancers
Authors: Reigstad Marte M. , Oldereid Nan B. , Omland Anne K. , Storeng Ritsa
Published: January 2017

Medically assisted fertility treatment, including assisted reproductive technology (ART), is increasingly being used and the subsequent child health outcomes are of interest. Some studies have suggested an elevated risk of somatic morbidity, while others have reported an elevated cancer risk. This review summarises the literature on fertility treatments and childhood cancer, based on 23 cohort and case–control studies.

Conclusion

The findings varied, but reassuring results on overall childhood cancer and fertility treatment were observed. However, some studies suggested an elevated risk of haematological cancers. More large population‐based studies are needed, and the growing population of ART children should be monitored.
Policy of feeding very preterm infants with their mother's own fresh expressed milk was associated with a reduced risk of bronchopulmonary dysplasia
Authors: Dicky Odile , Ehlinger Virginie , Montjaux Nathalie , Gremmo‐Féger Gisèle , Sizun Jacques , Rozé Jean‐Christophe , Arnaud Catherine , Casper Charlotte ,   the EPIPAGE 2 Nutrition Study Group,   the EPINUTRI Study Group
Published: January 2017

Aim

Since 2005, the French Food Safety Agency has recommended that very preterm or low‐birthweight babies should be fed with pasteurised, expressed breastmilk, and feeding policies on this vary widely in French neonatal units. We investigated the differences between using a mother's expressed milk, in fresh or pasteurised forms, for very preterm infants.

Methods

This observational multicentre study analysed data on 926 very preterm infants: 636 from neonatal units who used the mother's own fresh milk and 290 who used the mother's milk after pasteurisation. We analysed necrotising enterocolitis, bronchopulmonary dysplasia, in‐hospital mortality, late‐onset sepsis, weight gain, length of hospital stay, the duration of parenteral nutrition and the duration of enteral feeding with a nasogastric tube. Multivariate analyses were conducted to assess the impact of maternal milk policies.

Results

After adjustment, there was a reduced risk of bronchopulmonary dysplasia in the fresh milk group with an odds ratio of 0.40 and 95% confidence interval of 0.27–0.67 (p < 0.001). No other statistically significant differences were observed.

Conclusion

Feeding very preterm infants with their mother's expressed fresh milk was associated with a reduced risk of bronchopulmonary dysplasia, and further investigations are needed to evaluate the clinical impact of this practice.
Gender differences in exposure and vulnerability to psychosocial and behavioral factors of suicide attempt among Korean adolescents
Authors: Jeon Gyeong‐Suk , Choi Kyungwon , Cho Sung‐il
Published: January 2017

Introduction

This study examined gender differences in suicide attempts and their association with exposure and vulnerability to psychosocial, behavioral, and structural factors among Korean adolescents.

Methods

Data of 74 854 adolescents, taken from the 2010 Korea Youth Risk Behavior Survey, were used. Logistic regression analysis was used to assess the contribution of differential exposure to psychosocial, behavioral, and structural factors for gender differences of suicidal attempt.

Results

Gender differences were observed in the degree of exposure to the various factors. Females were more likely to report psychosocial problems, whereas males were more likely to report experience of smoking and drinking alcohol and to engage in vigorous physical activity. Stress and unhappiness were significantly associated with suicide attempts in both males and females, and gender differences in these variables were nonsignificant. Depressive symptoms were associated with a higher risk of suicide attempts, and this relationship was significantly stronger for males. The effects of cigarette smoking and risky drinking were significantly stronger in females.

Discussion

Greater exposure to perceived stress, feelings of unhappiness, depression, and higher vulnerability of smoking and heavy drinking accounted for higher suicide attempts of female adolescents. Higher exposure to health‐related behaviors and greater vulnerability to depressive symptoms in male were also noted. In conclusion, differences in exposure and vulnerability to psychosocial and behavioral factors may partly explain gender differences in suicide attempts among Korean adolescents.
Buchnera aphidicola of the birch blister aphid, Hamamelistes betulinus (Horváth, 1896) (Insecta, Hemiptera, Aphididae: Hormaphidinae): molecular characterization, transmission between generations and its geographic significance
Authors: Wegierek Piotr , Michalik Anna , Wieczorek Karina , Kanturski Mariusz , Kobiałka Michał , Śliwa Karolina , Szklarzewicz Teresa
Published: January 2017

The birch blister aphid Hamamelistes betulinus, like most aphids, is host to obligate symbiotic bacterium Buchnera aphidicola. Ultrastructural and molecular analyses did not reveal the presence of secondary symbionts in the body of H. betulinus. The bacteria Buchnera aphidicola are transmitted to the next generation vertically (maternally). The bacteria released from the cytoplasm of the bacteriocyte to the haemolymph migrate to the embryo at the cellular blastoderm stage, through the opening at its posterior pole. Next, the bacteria enter the cytoplasm of newly formed bacteriocytes. The concept of the relationship between the geographic distribution of Hormaphidini aphids and the presence/absence of bacterium Buchnera aphidicola is discussed.
5‐fluorouracil causes endothelial cell senescence: potential protective role of glucagon‐like peptide 1
Authors: Altieri Paola , Murialdo Roberto , Barisione Chiara , Lazzarini Edoardo , Garibaldi Silvano , Fabbi Patrizia , Ruggeri Clarissa , Borile Silvia , Carbone Federico , Armirotti Andrea , Canepa Marco , Ballestrero Alberto , Brunelli Claudio , Montecucco Fabrizio , Ameri Pietro , Spallarossa Paolo
Published: January 2017

Background and Purpose

5‐fluorouracil (5FU) and its prodrug, capecitabine, can damage endothelial cells, whilst endothelial integrity is preserved by glucagon‐like peptide 1 (GLP‐1). Here, we studied the effect of 5FU on endothelial senescence and whether GLP‐1 antagonizes it.

Experimental Approach

EA.hy926 cells were exposed to 5FU or sera from patients taking capecitabine, with or without pre‐incubation with GLP‐1. Senescence was identified by expression of senescence‐associated β‐galactosidase and p16INK4a and reduced cell proliferation. Soluble vascular cell adhesion molecule‐1 (sVCAM‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1) and CD146 (marker of endothelial injury) were measured by ELISA before and at completion of capecitabine chemotherapy. RT‐PCR, western blotting, functional experiments with signalling inhibitors and ERK1/2 silencing were performed to characterize 5FU‐induced phenotype and elucidate the pathways underlying 5FU and GLP‐1 activity.

Key Results

Both 5FU and sera from capecitabine‐treated patients stimulated endothelial cell senescence. 5FU‐elicited senescence occurred via activation of p38 and JNK, and was associated with decreased eNOS and SIRT‐1 levels. Furthermore, 5FU up‐regulated VCAM1 and TYMP (encodes enzyme activating capecitabine and 5FU), and sVCAM‐1 and CD146 concentrations were higher after than before capecitabine chemotherapy. A non‐significant trend for higher ICAM1 levels was also observed. GLP‐1 counteracted 5FU‐initiated senescence and reduced eNOS and SIRT‐1 expression, this protection being mediated by GLP‐1 receptor, ERK1/2 and, possibly, PKA and PI3K.

Conclusions and Implications

5FU causes endothelial cell senescence and dysfunction, which may contribute to its cardiovascular side effects. 5FU‐triggered senescence was prevented by GLP‐1, raising the possibility of using GLP‐1 analogues and degradation inhibitors to treat 5FU and capecitabine vascular toxicity.

Linked Articles

This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc
Bisperoxovandium (pyridin‐2‐squaramide) targets both PTEN and ERK1/2 to confer neuroprotection
Authors: Zhang Zhi‐Feng , Chen Juan , Han Xin , Zhang Ya , Liao Hua‐Bao , Lei Rui‐Xue , Zhuang Yang , Wang Ze‐Fen , Li Zhiqiang , Chen Jin‐Cao , Liao Wei‐Jing , Zhou Hai‐Bing , Liu Fang , Wan Qi
Published: January 2017

Background and Purpose

We and others have shown that inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or activating ERK1/2 confer neuroprotection. As bisperoxovanadium compounds are well‐established inhibitors of PTEN, we designed bisperoxovandium (pyridin‐2‐squaramide) [bpV(pis)] and determined whether and how bpV(pis) exerts a neuroprotective effect in cerebral ischaemia–reperfusion injury.

Experimental Approach

Malachite green‐based phosphatase assay was used to measure PTEN activity. A western blot assay was used to measure the phosphorylation level of Akt and ERK1/2 (p‐Akt and p‐ERK1/2). Oxygen–glucose deprivation (OGD) was used to injure cultured cortical neurons. Cell death and viability were assessed by LDH and MTT assays. To verify the effects of bpV(pis) in vivo, Sprague–Dawley rats were subjected to middle cerebral artery occlusion, and brain infarct volume was measured and neurological function tests performed.

Key Results

bpV(pis) inhibited PTEN activity and increased p‐Akt in SH‐SY5Y cells but not in PTEN‐deleted U251 cells. bpV(pis) also elevated p‐ERK1/2 in both SH‐SY5Y and U251 cells. These data indicate that bpV(pis) enhances Akt activation through PTEN inhibition but increases ERK1/2 activation independently of PTEN signalling. bpV(pis) prevented OGD‐induced neuronal death in vitro and reduced brain infarct volume and promoted functional recovery in stroke animals. This neuroprotective effect of bpV(pis) was blocked by inhibiting Akt and/or ERK1/2.

Conclusions and Implications

bpV(pis) confers neuroprotection in OGD‐induced injury in vitro and in cerebral ischaemia in vivo by suppressing PTEN and activating ERK1/2. Thus, bpV(pis) is a bi‐target neuroprotectant that may be developed as a drug candidate for stroke treatment.
Conceptual pathways and institutional barriers for urban physical geography: A response to Ashmore and Dodson
Authors: Conway Tenley M.
Published: January 2017

Key Messages

Growing urban physical geography research will focus the discipline on the places where most Canadians live and work, potentially raising the visibility of the discipline.

Urban physical geography can look to urban ecology for conceptual models to help advance urban physical geography research.

Funding institutions and undergraduate programs represent barriers for urban physical geography in Canada.
Investigation of the bindings of a class of inhibitors with GSK3β kinase using thermodynamic integration MD simulation and kinase assay
Authors: Hsu Chia‐Jen , Hsu Wen‐Chi , Lee Der‐Jay , Liu An‐Lun , Chang Chia‐Ming , Shih Huei‐Jhen , Huang Wun‐Han , Lee‐Chen Guey‐Jen , Hsieh‐Li Hsiu Mei , Lee Guan‐Chiun , Sun Ying‐Chieh
Published: January 2017

GSK3β kinase is a noteworthy target for discovery of the drugs that will be used to treat several diseases. In the effort to identify a new inhibitor lead compound, we utilized thermodynamic integration (TI)‐molecular dynamics (MD) simulation and kinase assay to investigate the bindings between GSK3β kinase and five compounds that were analogous to a known inhibitor with an available crystal structure. TI‐MD simulations of the first two compounds (analogs 1 and 2) were used for calibration. The computed binding affinities of analogs 1 and 2 agreed well with the experimental results. The rest three compounds (analogs 3–5) were newly obtained from a database search, and their affinity data were newly measured in our labs. TI‐MD simulations predicted the binding modes and the computed ΔΔG values have a reasonably good correlation with the experimental affinity data. These newly identified inhibitors appear to be new leads according to our survey of GSK3β inhibitors listed in recent review articles. The predicted binding modes of these compounds should aid in designing new derivatives of these compounds in the future.
The Role of Generic Language in the Early Development of Social Categorization
Authors: Rhodes Marjorie , Leslie Sarah‐Jane , Bianchi Lydia , Chalik Lisa
Published: January 2017

Classifying people into categories not only helps humans simplify a complex social world but also contributes to stereotyping and discrimination. This research examines how social categorization develops by testing how language imbues with meaning otherwise arbitrary differences between people. Experimental studies (N = 129) with 2‐year‐olds showed that generic language—language that refers to abstract kinds—guides the development of social categorization. Toddlers learned a new category after hearing generic language about individuals who shared an arbitrary perceptual feature but not after hearing matched specific language, simple labels, or plural (but nongeneric) language about the same set of individuals. These findings show how subtle linguistic cues shape the development of social categorization.
Sleep Tight, Act Right: Negative Affect, Sleep and Behavior Problems During Early Childhood
Authors: Cremone Amanda , de Jong Desiree M. , Kurdziel Lauri B. F. , Desrochers Phillip , Sayer Aline , LeBourgeois Monique K. , Spencer Rebecca M. C. , McDermott Jennifer M.
Published: January 2017

Temperamental negative affect and insufficient sleep have been independently associated with behavior problems during early childhood. However, it is unknown whether these factors interact to contribute to behavioral difficulties in young children. The current study examined the interactions between temperamental negative affect and both sleep onset time and sleep midpoint, assessed by actigraphy, in predicting externalizing and internalizing behaviors in a sample of 117 children (34–69 months of age). Children with high temperamental negative affect and either later sleep onset time or later sleep midpoint were more likely to exhibit externalizing and internalizing behaviors. These results emphasize the association between temperamental negative affect and behavioral difficulties, particularly for children with insufficient sleep.
Words to Sleep On: Naps Facilitate Verb Generalization in Habitually and Nonhabitually Napping Preschoolers
Authors: Sandoval Michelle , Leclerc Julia A. , Gómez Rebecca L.
Published: January 2017

A nap soon after encoding leads to better learning in infancy. However, whether napping plays the same role in preschoolers' learning is unclear. In Experiment 1 (N = 39), 3‐year‐old habitual and nonhabitual nappers learned novel verbs before a nap or a period of wakefulness and received a generalization test examining word extension to novel actors after 24 hr. Only habitual and nonhabitual nappers who napped after learning generalized 24 hr later. In Experiment 2 (N = 40), children learned the same verbs but were tested within 2–3 min of training. Here, habitual and nonhabitual nappers retained the mappings but did not generalize. The results suggest that naps consolidate weak learning that habitual and nonhabitual nappers would otherwise forget over periods of wakefulness.
Experiences in microarray‐based evaluation of developmental disabilities and congenital anomalies
Authors: Ozyilmaz B. , Kirbiyik O. , Koc A. , Ozdemir T.R. , Kaya O.O. , Guvenc M.S. , Erdoğan K.M. , Kutbay Y.B.
Published: January 2017

Background

Chromosomal microarray analysis is the first‐tier test for the evaluation of developmental disabilities and congenital anomalies. In this report, we present CMA results of 971 patient and 301 parent samples.

Materials and Methods

Among 971 patient samples, 133 (13.6%) had pathogenic variants.

Results

While analyzing, an “in‐house” variant database was also used besides other databases. Owing to this, we have found chance to report the most frequent benign variants in Turkish population.

Conclusion

With the additional data we acquired in this study, we also emphasized the high potential of CMA in revealing single gene disorders and novel gene‐phenotype associations as well as copy number variations.
Clinicopathological relevance of antithyroglobulin antibodies in low‐risk papillary thyroid cancer
Authors: Morand G.B. , da Silva S.D. , Mlynarek A.M. , Black M.J. , Payne R.J. , Hier M.P.
Published: January 2017

Objective

The extent of initial surgical management in papillary thyroid cancer (PTC) is controversial. We examined whether the presence of perioperative antithyroglobulin antibodies (TGA) could predict long‐term recurrence and occurrence of adverse features among a homogenous group of patients with PTC.

Methods

The clinical features of patients with PTC treated at a single institution (Jewish General Hospital, McGill University, Montreal, Canada) were obtained from the medical records, and all clinicopathologic information was reviewed. Only low‐risk PTC without clinical evidence of nodal disease before surgery and treated with 30 mCi of radioactive iodine was included in the study.

Results

The chart review retrieved 361 patients with a median follow‐up of 85.0 months (Q25‐Q75 73‐98). Forty‐two (11.6%) patients had presence of perioperative TGA. Perioperative TGAs were associated with present extrathyroidal extension (P=.005), unsuspected nodal disease (P=.001) and autoimmune thyroiditis (P<.0001). Overall, 17 (4.7%) patients experienced locoregional recurrence. Perioperative TGAs were a significant predictor of recurrence in univariable (P=.021) but not in multivariable analysis (P=.13).

Conclusion

Presence of perioperative TGAs is associated with aggressive histological features and the presence of thyroiditis. Detection of TGA perioperatively may encourage surgeons to consider more extensive initial surgery.
Swallowing outcomes for patients with oropharyngeal squamous cell carcinoma treated with primary (chemo)radiation therapy receiving either prophylactic gastrostomy or reactive nasogastric tube: A prospective cohort study
Authors: Goff D. , Coward S. , Fitzgerald A. , Paleri V. , Moor J.W. , Patterson J.M.
Published: January 2017

Objectives

There is currently no consensus on the optimal feeding route for an oropharyngeal squamous cell cancer (OPSCC) patient without pre‐existing dysphagia undergoing chemoradiotherapy. This study aimed to compare the swallowing outcomes for OPSCC patients fed via either prophylactic RIG (pRIG) or reactive nasogastric tube (rNGT).

Design

A prospective cohort study.

Setting

Four head and neck cancer centres in the North of England Cancer Network.

Participants

Fifty‐three participants with OPSCC, on a normal diet pre‐(chemo) radiotherapy.

Main outcome measure

Swallowing outcomes for patients with rNGT and pRIG were compared using the following outcome measures administered prospectively at pre‐treatment, three and 12 months post‐treatment: MD Anderson Dysphagia Inventory (MDADI), Performance Status Scales (Normalcy of Diet), timed water swallow test.

Results

Twenty‐three patients received pRIG while 30 were planned for a rNGT. No differences in demographics were found between the groups. The rNGT group had a clinically significant higher score on MDADI at 12 months post‐treatment. No significant difference was found on a timed water swallow test or diet texture scale.

Conclusions

There is no statistical difference for swallowing outcomes in either group. However, patients’ in the rNGT group reported a clinically meaningful difference at 1 year, with a trend for them to do better across all measures. Neither group returned to their baseline swallowing function. Further research with a larger sample size is indicated.
An institutional perspective on corruption in transition economies
Authors: Alon Anna , Hageman Amy M.
Published: January 2017

Manuscript Type

Empirical

Research Question/Issue

Companies operating in transition economies encounter a broad range of potential challenges. In the area of tax, firms make direct tax payments but may also encounter unofficial tax costs in the form of bribery or extortion. We focus on institutional determinants, including formal rules, informal rules, and enforcement, to examine conditions under which firms are more likely to encounter these transactions. We operationalize formal rules as rule‐based trust and informal rules as dispositional trust.

Research Findings/Insights

Based on a sample of over 5000 firms representing 20 transition economies, we show that when rule‐based trust is high, the presence of tax enforcement activities in the form of visits and inspections by tax officials does not change the relationship between rule‐based trust and unofficial payments. However, when dispositional trust is low, unofficial payments are more likely if verification activities occur.

Theoretical/Academic Implications

We adopt a more holistic view and focus on the joint consideration of different institutional determinants and firm outcomes. In doing so, the article demonstrates the complexity of firms’ tax environments where enforcement mechanisms can have unwelcome consequences, and, under certain conditions, create conditions for the persistence of corruption.

Practitioner/Policy Implications

This paper highlights the importance of the institutional landscape, especially considering the history of institutional voids in many transition economies. The results have implications for corporate governance and caution regulators and practitioners to consider institutional complexities when implementing reforms or establishing businesses in transition economies.
Diagnostic value of soluble B7‐H4 and carcinoembryonic antigen in distinguishing malignant from benign pleural effusion
Authors: Jing Xiaogang , Wei Fei , Li Jing , Dai Lingling , Wang Xi , Jia Liuqun , Wang Huan , An Lin , Yang Yuanjian , Zhang Guojun , Cheng Zhe
Published: January 2017

Objective

To explore the diagnostic value of joint detection of soluble B7‐H4 (sB7‐H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE).

Methods

A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme‐linked immunosorbent assay was applied to examine the levels of sB7‐H4 in pleural effusion and meanwhile CEA concentrations were detected by electro‐chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7‐H4 and CEA in pleural effusion. The correlation between sB7‐H4 and CEA levels was analyzed by Pearson's product‐moment.

Results

The concentrations of sB7‐H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7‐H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7‐H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7‐H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7‐H4 was correlated with CEA level (r = .770, P = .000).

Conclusions

sB7‐H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7‐H4 and CEA could improve the diagnostic sensitivity and specificity for MPE.
Urbanization may limit impacts of an invasive predator on native mammal diversity
Authors: Reichert Brian E. , Sovie Adia R. , Udell Brad J. , Hart Kristen M. , Borkhataria Rena R. , Bonneau Mathieu , Reed Robert , McCleery Robert
Published: January 2017

Aim

Our understanding of the effects of invasive species on faunal diversity is limited in part because invasions often occur in modified landscapes where other drivers of community diversity can exacerbate or reduce the net impacts of an invader. Furthermore, rigorous assessments of the effects of invasive species on native communities that account for variation in sampling, species‐specific detection and occurrence of rare species are lacking. Invasive Burmese pythons (Python molurus bivittatus) may be causing declines in medium‐ to large‐sized mammals throughout the Greater Everglades Ecosystem (GEE); however, other factors such as urbanization, habitat changes and drastic alteration in water flow may also be influential in structuring mammal communities. The aim of this study was to gain an understanding of how mammal communities simultaneously facing invasive predators and intensively human‐altered landscapes are influenced by these drivers and their interactions.

Location

Florida, USA.

Methods

We used data from trail cameras and scat searches with a hierarchical community model that accounts for undetected species to determine the relative influence of introduced Burmese pythons, urbanization, local hydrology, habitat types and interactive effects between pythons and urbanization on mammal species occurrence, site‐level species richness, and turnover.

Results

Python density had significant negative effects on all species except coyotes. Despite these negative effects, occurrence of some generalist species increased significantly near urban areas. At the community level, pythons had the greatest impact on species richness, while turnover was greatest along the urbanization gradient where communities were increasingly similar as distance to urbanization decreased.

Main conclusions

We found evidence for an antagonistic interaction between pythons and urbanization where the impacts of pythons were reduced near urban development. Python‐induced changes to mammal communities may be mediated near urban development, but elsewhere in the GEE, pythons are likely causing a fundamental restructuring of the food web, declines in ecosystem function, and creating complex and unpredictable cascading effects.
Inferential biases linked to unobservable states in complex occupancy models
Authors: Mosher Brittany A. , Bailey Larissa L. , Hubbard Ben A. , Huyvaert Kathryn P.
Published: January 2017

Modeling of species distributions has undergone a shift from relying on equilibrium assumptions to recognizing transient system dynamics explicitly. This shift has necessitated more complex modeling techniques, but the performance of these dynamic models has not yet been assessed for systems where unobservable states exist. Our work is motivated by the impacts of the emerging infectious disease chytridiomycosis, a disease of amphibians that is associated with declines of many species worldwide. Using this host‐pathogen system as a general example, we first illustrate how misleading inferences can result from failing to incorporate pathogen dynamics into the modeling process, especially when the pathogen is difficult or impossible to survey in the absence of a host species. We found that traditional modeling techniques can underestimate the effect of a pathogen on host species occurrence and dynamics when the pathogen can only be detected in the host, and pathogen information is treated as a covariate. We propose a dynamic multistate modeling approach that is flexible enough to account for the detection structures that may be present in complex multistate systems, especially when the sampling design is limited by a species’ natural history or sampling technology. When multistate occupancy models are used and an unobservable state is present, parameter estimation can be influenced by model complexity, data sparseness, and the underlying dynamics of the system. We show that, even with large sample sizes, many models incorporating seasonal variation in vital rates may not generate reasonable estimates, indicating parameter redundancy. We found that certain types of missing data can greatly hinder inference, and we make study design recommendations to avoid these issues. Additionally, we advocate the use of time‐varying covariates to explain temporal trends in the data, and the development of sampling techniques that match the biology of the system to eliminate unobservable states when possible.
Comparison of clinicopathological characteristics between T‐cell prolymphocytic leukemia and peripheral T‐cell lymphoma, not otherwise specified
Authors: Kawamoto Keisuke , Miyoshi Hiroaki , Yanagida Eriko , Yoshida Noriaki , Kiyasu Junichi , Kozai Yasuji , Morikita Tatsuma , Kato Takeharu , Suzushima Hitoshi , Tamura Shinobu , Muta Tsuyoshi , Kato Koji , Eto Tetsuya , Seki Ritsuko , Nagafuji Koji , Sone Hirohito , Takizawa Jun , Seto Masao , Ohshima Koichi
Published: January 2017

Objectives

T‐cell prolymphocytic leukemia (T‐PLL) is a very rare, aggressive T‐cell neoplasm. Peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T‐PLLandPTCL‐NOS.

Methods

We analyzed 15 T‐PLLand 91PTCL‐NOSpatients and also compared clinical features between T‐PLLandPTCL‐NOSwith leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared.

Results

T‐PLL cells were smaller in size than those ofPTCL‐NOSwith leukemic presentation (P=.0068); moreover,PTCL‐NOScells with leukemic presentation were smaller than those ofPTCL‐NOSwithout leukemic presentation (P=.0017). Immunophenotypic patterns in T‐PLLandPTCL‐NOSwere similar. Five‐year overall survival rates of T‐PLLand allPTCL‐NOSpatients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T‐PLLandPTCL‐NOSwith leukemic presentation had essentially equivalent characteristics.

Conclusion

T‐PLL andPTCL‐NOSmay share common biological and clinical characteristics in Japanese patients.
Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia
Authors: Mori Naoki , Ohwashi‐Miyazaki Mari , Yoshinaga Kentaro , Okada Michiko , Shiseki Masayuki , Motoji Toshiko , Tanaka Junji
Published: January 2017

Objectives

We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML.

Methods

We performed methylation‐specific PCR (MS‐PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS‐PCR, PCR‐single‐strand conformation polymorphism, and real‐time reverse transcriptase PCR were also analyzed. K‐562 cells were grown in the presence of 5‐Aza‐dC and trichostatin A.

Results

Methylation of the PRDM2, RUNX3, and TP73 genes was detected in 24/60 (40%), 21/61 (34%), and 28/60 (47%) patients, respectively. Methylation of all three genes was detected in 19/59 (32%) patients. Methylation was more frequent in BC than in CP. Oxidative MS‐PCR analysis detected 5‐mC in the PRDM2, RUNX3, and TP73 genes in 10/22 (45%), 15/21 (71%), and 16/26 (62%) samples with methylation detected by MS‐PCR, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K‐562 cells induced growth suppression, demethylation, and reexpression of the PRDM2 and RUNX3 genes.

Conclusion

Multiple tumor suppressor genes on 1p were inactivated in CML by methylation.