bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of longitudinal health‐related quality‐of‐life change in children with asthma from low‐income families: a report from the PROMIS® Pediatric Asthma Study
Authors: Li Z. , Leite W. L. , Thompson L. A. , Gross H. E. , Shenkman E. A. , Reeve B. B. , DeWalt D. A. , Huang I.‐C.
Published: September 2016

Background

How the longitudinal asthma control status and other socio‐demographic factors influence the changes of health‐related quality of life (HRQOL) among asthmatic children, especially from low‐income families, has not been fully investigated.

Objectives

This study aimed to describe the trajectories of asthma‐specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio‐demographic factors into consideration.

Methods

A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma‐specific HRQOL was assessed using the Patient‐Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL.

Results

Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio‐demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non‐Hispanic White children.

Conclusions

Vulnerable socio‐demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children.
Abnormal vocal cord movement in patients with and without airway obstruction and asthma symptoms
Authors: Low K. , Ruane L. , Uddin N. , Finlay P. , Lau K. K. , Hamza K. , Holmes P. W. , Hamilton G. , Bardin P. G.
Published: September 2016

Background

Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction – VCD) leading to asthma‐like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics, but it is not known if PVCM is detectable in all patients with asthma‐like symptoms and if the condition is more often associated with abnormal lung function.

Objective

We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms, or if PVCM is related to airflow limitation and/or other disease characteristics.

Methods

Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n = 155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionnaires were administered and skin prick testing was carried out. PVCM was quantified using dynamic 320‐slice computerized tomography of the larynx. Groups were divided into patients with FEV1 ≥ 80% predicted or FEV1 < 80% predicted and FEV1/FVC < 0.7. ATS/ERS definitions of severity were also applied and evaluated. Detection of PVCM in the groups was compared and analyses performed to identify features associated with PVCM.

Results

Overall (n = 155), PVCM was detected in 42 cases (27.1%). Patients with FEV1 < 80% predicted had PVCM more often (25/68, 36.8%) than individuals with normal spirometry (17/87, 19.5%; P = 0.016). PVCM was associated with older age (P = 0.003) and with Nijmegen scores > 20 (P = 0.04). Patients with FEV1 < 80% predicted plus Nijmegen scores > 20 were more likely to have PVCM (OR = 9.3, P = 0.02).

Conclusions and Clinical Relevance

Paradoxical vocal cord movement is more often associated with asthma symptoms accompanied by airflow limitation and dysfunctional breathing. Further studies are needed to determine whether PVCM is induced by dysfunctional breathing practices and/or airway obstruction. How PVCM links with symptomatic asthma and VCD also requires evaluation.
Incidental finding of a true human tail in an adult: a case report
Authors: Robinson Caitlin G. , Duke Taylor C. , Allison Ashley W.
Published: September 2016

True human tails are rare vestigial structures that are typically removed in childhood. Here a case is presented in which an inconspicuous sacrococcygeal tail was incidentally discovered in late adulthood. A 56‐year‐old man with no significant past medical history presented to a dermatology clinic with a chief complaint of a hyperpigmented lesion on his central back. However, on full body skin exam, a separate flesh‐colored 0.7 cm × 0.5 cm appendage was discovered in the midline sacrococcygeal region. This lesion had been present and unchanged since childhood. This particular lesion was removed via shave biopsy. Microscopic exam found it to be consistent with a diagnosis of a true human tail. There were no apparent involved spinal cord structures, and no further treatment was thought to be necessary. Human tails are congenital anomalies associated with occult spinal lesions in about 50% of cases. Therefore, it is in these patients' best interest to thoroughly evaluate for spinal cord involvement prior to biopsy. There is a relative lack of literature published on the topic, and a greater awareness of human tails would be helpful to ensure their inclusion in a differential diagnosis for persistent sacrococcygeal lesions in patients of any age.
Disease biology and histopathology of bronze leaf disease: a threat to cultivated aspens, white poplars and their hybrids
Authors: Ostry M. E. , Moore M. J. , Jacobs J. J. , Smith J. A. , Anderson N. A.
Published: September 2016

Bronze leaf disease (BLD) of species and hybrids of aspens, grey and white poplars (Genus Populus, section Populus) is a systemic disease incited by the fungus Apioplagiostoma populi (E.K. Cash & A.M. Waterman) M.E. Barr that results in a characteristic bronze to dark brown pigmentation of infected leaves in late summer and early fall. Branches on affected trees die over a period of several years, disfiguring trees and eventually leading to mortality of susceptible trees planted in landscapes. In this study, we describe the histopathology of the disease and fungus development relative to external symptoms on affected trees. A. populi hyphae were observed in leaf vessels, lateral veins and xylem vessels of stems and roots of affected trees. Hyphae were also observed in veins and vessels of asymptomatic leaves. Xylem vessels of growth rings on dead branches were completely occluded with A. populi near the vascular cambium and together with the ray parenchyma were stained a bronze colour. Evidence of putative toxin damage to mesophyll cells, not colonized by hyphae, was observed and may contribute to the characteristic tissue staining observed. The development of the fungus was consistent with previous reports, but in this study, we report additional details including perithecial development and ascospore release from predominantly abaxial leaf surfaces. We also report for the first time the isolation and growth of the pathogen in pure culture and systemic infection of roots.
Thermocline deepening boosts ecosystem metabolism: evidence from a large‐scale lake enclosure experiment simulating a summer storm
Authors: Giling Darren P. , Nejstgaard Jens C. , Berger Stella A. , Grossart Hans‐Peter , Kirillin Georgiy , Penske Armin , Lentz Maren , Casper Peter , Sareyka Jörg , Gessner Mark O.
Published: September 2016

Extreme weather events can pervasively influence ecosystems. Observations in lakes indicate that severe storms in particular can have pronounced ecosystem‐scale consequences, but the underlying mechanisms have not been rigorously assessed in experiments. One major effect of storms on lakes is the redistribution of mineral resources and plankton communities as a result of abrupt thermocline deepening. We aimed at elucidating the importance of this effect by mimicking in replicated large enclosures (each 9 m in diameter, ca. 20 m deep, ca. 1300 m3 in volume) a mixing event caused by a severe natural storm that was previously observed in a deep clear‐water lake. Metabolic rates were derived from diel changes in vertical profiles of dissolved oxygen concentrations using a Bayesian modelling approach, based on high‐frequency measurements. Experimental thermocline deepening stimulated daily gross primary production (GPP) in surface waters by an average of 63% for >4 weeks even though thermal stratification re‐established within 5 days. Ecosystem respiration (ER) was tightly coupled to GPP, exceeding that in control enclosures by 53% over the same period. As GPP responded more strongly than ER, net ecosystem productivity (NEP) of the entire water column was also increased. These protracted increases in ecosystem metabolism and autotrophy were driven by a proliferation of inedible filamentous cyanobacteria released from light and nutrient limitation after they were entrained from below the thermocline into the surface water. Thus, thermocline deepening by a single severe storm can induce prolonged responses of lake ecosystem metabolism independent of other storm‐induced effects, such as inputs of terrestrial materials by increased catchment run‐off. This highlights that future shifts in frequency, severity or timing of storms are an important component of climate change, whose impacts on lake thermal structure will superimpose upon climate trends to influence algal dynamics and organic matter cycling in clear‐water lakes.
4‐n‐butylresorcinol enhances proteolytic degradation of tyrosinase in B16F10 melanoma cells
Authors: Lee S.‐J. , Son Y. H. , Lee K. B. , Lee J.‐H. , Kim H.‐J. , Jeong E. M. , Park S. C. , Kim I.‐G.
Published: September 2016

Objective

4‐n‐butylresorcinol is a competitive inhibitor of tyrosinase and has been used as an antimelanogenic agent. However, its inhibition mechanism in intact cells is not fully understood. To elucidate the cellular mechanism, we compared in vitro and in vivo inhibitory effects of 4‐n‐butylresorcinol on tyrosinase activity.

Methods

B16F10 melanoma cells were cultured in media containing α‐MSH in the presence or absence of 4‐n‐butylresorcinol. Tyrosinase mRNA levels, protein levels and activity in B16F10 cells were compared by real‐time PCR, immunostaining combined with western blot and colorimetric analysis, respectively. Melanin concentration was measured by colorimetry both in the cells and in the media. Tyrosinase glycosylation and proteolytic degradation were analysed by immunoblotting after cells were treated with Endo H/PNGase F and E64/proteasome inhibitors, respectively.

Results

4‐n‐butylresorcinol inhibited tyrosinase activity and melanin synthesis more effectively in intact cells than in cell lysates. Western blotting and real‐time RT‐PCR showed that 4‐n‐butylresorcinol reduced protein levels, but not mRNA levels, of tyrosinase in B16F10 cells. 4‐n‐butylresorcinol showed no effect on the processing of tyrosinase glycosylation or on trafficking to melanosomes. However, treatment of B16F10 cells with E64 or proteasome inhibitor abrogated the 4‐n‐butylresorcinol‐induced decrease of tyrosinase. Moreover, 4‐n‐butylresorcinol activated p38 MAPK, resulting in increased ubiquitination of tyrosinase.

Conclusion

4‐n‐butylresorcinol inhibits melanogenesis by enhancing proteolytic degradation of tyrosinase as well as competitive binding to tyrosinase. These findings will help to develop new, effective and safe chemicals for the treatment of hyperpigmentation disorders.
Genome‐wide nucleotide diversity of hatchery‐rearedAtlantic andMediterranean strains of brown troutSalmo truttacompared to wildMediterranean populations
Authors: Leitwein M. , Gagnaire P.‐A. , Desmarais E. , Guendouz S. , Rohmer M. , Berrebi P. , Guinand B.
Published: September 2016

A genome‐wide assessment of diversity is provided for wild Mediterranean brown troutSalmo truttapopulations from headwater tributaries of the Orb River and from Atlantic and Mediterranean hatchery‐reared strains that have been used for stocking. Double‐digest restriction‐site‐associatedDNAsequencing (dd‐RADseq) was performed and the efficiency ofde novoand reference‐mapping approaches to obtain individual genotypes was compared. Large numbers of single nucleotide polymorphism (SNP) markers with similar genome‐wide distributions were discovered using both approaches (196 639v.121 016SNPs, respectively), withc.80% of the loci detectedde novobeing also found with reference mapping, using the Atlantic salmonSalmo salargenome as a reference. Lower mapping density but larger nucleotide diversity (π) was generally observed near extremities of linkage groups, consistent with regions of residual tetrasomic inheritance observed in salmonids. Genome‐wide diversity estimates revealed reduced polymorphism in hatchery strains (π= 0·0040 andπ= 0·0029 in Atlantic and Mediterranean strains, respectively) compared to wild populations (π= 0·0049), a pattern that was congruent with allelic richness estimated from microsatellite markers. Finally, pronounced heterozygote deficiency was found in hatchery strains (AtlanticFIS= 0·18; MediterraneanFIS= 0·42), indicating that stocking practices may affect the genetic diversity in wild populations. These new genomic resources will provide important tools to define better conservation strategies inS. trutta.
[18F]JNJ42259152 binding to phosphodiesterase 10A, a key regulator of medium spiny neuron excitability, is altered in the presence of cyclic AMP
Authors: Ooms Maarten , Attili Bala , Celen Sofie , Koole Michel , Verbruggen Alfons , Van Laere Koen , Bormans Guy
Published: September 2016

Phosphodiesterase 10A (PDE10A) is a key regulator of medium spiny neuron excitability. Therefore, it plays an important role in the regulation of motor, reward, and cognitive processes. Despite the interest in PDE10A as a drug and positron emission tomography (PET) imaging target, little is known about the regulation of PDE10A enzymatic activity. This study aimed to further investigate the role of cAMP in the regulation of PDE10A activity and PDE10A PET imaging. Using [18F]JNJ42259152 as radioligand, we investigated alterations in PDE10A binding secondary to changes in cAMP levels. An in vitro striatum homogenate binding assay was developed to determine KD and Bmax of [18F]JNJ42259152. Homogenate binding was assessed after addition of increasing concentrations of exogenous cAMP (1, 10, and 100 μM). Rats were treated using JNJ49137530 and rolipram to induce in vivo alterations of cAMP. The effect of the induced cAMP alterations on PDE10A binding was assessed by comparing [18F]JNJ42259152 microPET studies after treatment to microPET studies acquired at baseline conditions prior to treatment. In vitro binding affinity of [18F]JNJ42259152 was higher in the presence of cAMP compared to baseline conditions (KD = 3.17 ± 0.91 nM with 10 μM cAMP vs. KD = 6.62 ± 0.7 nM at baseline). Inhibition of PDE4 using rolipram significantly increased [18F]JNJ42259152 binding (BPND = 2.61 ± 0.50 vs. 1.91 ± 0.36 at baseline). Administration of the PDE2 inhibitor JNJ49137530 significantly increased PDE10A binding potential (BPND = 2.74 ± 0.22 vs. 2.05 ± 0.16 at baseline). Our data indicate an important role for cAMP in the regulation of PDE10A activity. Additionally, our data show a profound interaction between several PDEs in striatum.

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In vitro complement activation, adherence to red blood cells and induction of mononuclear cell cytokine production by four strains of Aggregatibacter actinomycetemcomitans with different fimbriation and expression of leukotoxin
Authors: Damgaard C. , Reinholdt J. , Palarasah Y. , Enevold C. , Nielsen C. , Brimnes M. K. , Holmstrup P. , Nielsen C. H.
Published: September 2016

Background and Objective

The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro‐atherogenic, and complement‐mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs).

Material and Methods

Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence‐labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis. The levels of IgG to A. actinomycetemcomitans serotype b were quantified by ELISA, as was consumption of complement.

Results

The JP2 clone variants HK 1651 and, to a lesser extent, HK 2092, consumed complement efficiently, while HK 2108 (= strain Y4) consumed complement poorly. Nonetheless, the four tested strains adhered equally well to RBCs in the presence of autologous serum, without causing RBC lysis. The JP2 clone variant HK 2092, selectively lacking LtxA production, induced higher production of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and IL‐10 by MNCs than did the other three strains, while the four strains induced similar production of IL‐12p70. RBCs facilitated the HK 2092‐induced production of TNF‐α and IL‐1β, and IL‐6 was enhanced by RBCs, and this facilitation could be counteracted by blockade of complement receptor 3 (CD11b/CD18).

Conclusion

Our data suggest that the JP2 clone of A. actinomycetemcomitans, most closely resembled by the variant HK 1651, activates complement well, while strain Y4, represented by HK 2108, activates complement poorly. However, all strains of A. actinomycetemcomitans adhere to RBCs and, when capable of producing LtxA, prevent production of inflammatory cytokines by MNCs. This “immunologically silent” immune adherence may facilitate systemic spread and atherogenesis.
Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence
Authors: Agossa K. , Dendooven A. , Dubuquoy L. , Gower‐Rousseau C. , Delcourt‐Debruyne E. , Capron M.
Published: September 2016

Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle‐related risk factors. Despite this intriguing pathogenic parallel, large‐scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up‐to‐date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease.
Commodifying Indigeneity: How the Humanization of Birth Reinforces Racialized Inequality in Mexico
Authors: Vega Rosalynn Adeline
Published: September 2016

This article examines the humanized birth movement in Mexico and analyzes how the remaking of tradition—the return to traditional birthing arts (home birth, midwife‐assisted birth, natural birth)—inadvertently reinscribes racial hierarchies. The great irony of the humanized birth movement lies in parents’ perspective of themselves as critics of late capitalism. All the while, their very rejection of consumerism bolsters ongoing commodification of indigenous culture and collapses indigeneity, nature, and tradition onto one another. While the movement is quickly spreading across Mexico, indigenous women and their traditional midwives are largely excluded from the emerging humanized birth community. Through ethnographic examples, the article suggests that indigenous individuals are agentive actors who appropriate cards in decks stacked against them. Examples of resistance emerge within a context of power and political economy that often capitalizes on images of indigeneity while obscuring the lives, experiences, and opinions of indigenous people.
Microinfarcts in an older population‐representative brain donor cohort (MRC CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease
Authors: Ince P. G. , Minett T. , Forster G. , Brayne C. , Wharton S. B. ,   the Medical Research Council Cognitive Function and Ageing Neuropathology Study
Published: September 2016

Introduction

Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population‐representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD).

Methods

Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected.

Results

36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05–1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11–3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts.

Conclusion

Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis.
When more is better: how data sharing would accelerate genomic selection of crop plants
Authors: Spindel Jennifer E. , McCouch Susan R.
Published: September 2016

Genomic selection is proving an effective new strategy for increasing breeding efficiency in a wide variety of cereal species – the staple crops that feed the world. A preponderance of studies, reviewed here, has confirmed that the more correlated phenotypic and environmental data that are used to feed genomics‐assisted breeding models, the better the prediction accuracies of the models and the more useful the breeding outcomes. We argue that based on these empirical results, new alliances to share data across genomic selection breeding programs are critical to the rapid development and deployment of new crop varieties.
Application of an epitope‐based allocation system in pediatric kidney transplantation
Authors: Kausman Joshua Y. , Walker Amanda M. , Cantwell Linda S. , Quinlan Catherine , Sypek Matthew P. , Ierino Francesco L.
Published: September 2016

Donor–recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope‐based allocation approach to prospectively exclude donors with high‐level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m2, no episodes of rejection, and time to transplant 6.55 months. HLA‐A, HLA‐B, HLA‐DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope‐based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow‐up and larger numbers, but has the potential to reduce anti‐HLA sensitization and improve both graft survival and opportunities for future retransplantation.
The role of hemiparasitic plants: influencing tallgrass prairie quality, diversity, and structure
Authors: DiGiovanni Jane P. , Wysocki William P. , Burke Sean V. , Duvall Melvin R. , Barber Nicholas A.
Published: September 2016

Wood betony, Orobanchaceae (Pedicularis canadensis) and bastard toadflax, Santalaceae (Comandra umbellata) are two root‐hemiparasitic plant species found in tallgrass prairie communities. Natural resource managers are interested in utilizing these species as “pseudograzers” in grasslands to reduce competitively dominant grasses and thereby increase ecological diversity and quality in prairie restorations and urban plantings. We performed an observational field study at 5 tallgrass prairie sites to investigate the association of hemiparasite abundance with metrics of phylogenetic and ecological diversity, as well as floristic quality. Although no reduction in C4 grasses was detected, there was a significant association between hemiparasite abundance and increased floristic quality at all 5 sites. Hemiparasite abundance and species richness were positively correlated at one restoration site. In a greenhouse mesocosm experiment, we investigated response to parasitism by P. canadensis in 6 species representing different plant functional groups of the tallgrass prairie. The annual legume partridge pea, Fabaceae (Chamaecrista fasciculata) had the greatest significant dry biomass reduction among 6 host species, but the C4 grass big bluestem, Poaceae (Andropogon gerardii) had significantly greater aboveground biomass when grown with the hemiparasite. Overall, host species biomass as a total community was significantly reduced in mesocosms, consistent with other investigations that demonstrate influence on community structure by hemiparasitic plant species. Although hemiparasites were not acting as pseudograzers, they have the potential to influence community structure in grassland restorations and remnants.
Part I––Comparing Noncancer Chronic Human Health Reference Values: An Analysis of Science Policy Choices
Authors: Holman Elizabeth , Francis Royce , Gray George
Published: September 2016

The goal of this study was to systematically evaluate the choices made in deriving a chronic oral noncancer human health reference value (HHRV) for a given chemical by different organizations, specifically those from the U.S. Environmental Protection Agency, Health Canada, RIVM (the Netherlands), and the U.S. Agency for Toxic Substances and Disease Registry. This analysis presents a methodological approach for comparing both the HHRVs and the specific choices made in the process of deriving an HHRV across these organizations. Overall, across the 96 unique chemicals and 171 two‐way organizational comparisons, the HHRV agreed approximately 26% of the time. A qualitative method for identifying the primary factors influencing these HHRV differences was also developed, using arrays of HHRVs across organizations for the same chemical. The primary factors identified were disagreement on the critical or principal study and differential application of the total uncertainty factor across organizations. Of the cases where the total UF was the primary factor influencing HHRV disagreement, the database UF had the greatest influence.
Depressive symptoms in patients with wounds: A cross‐sectional study
Authors: Zhou Kehua , Jia Peng
Published: September 2016

Depression slows wound healing in patients with chronic wounds. The prevalence of depressive symptoms differs in the literature and the current understandings of factors related to depression in patients with wounds have been limited. To investigate the prevalence of depressive symptoms and the associated factors in patients with wounds, we performed this retrospective study in which depressive symptoms were evaluated with the Patient Health Questionnaire 9‐item (PHQ‐9). Valid PHQ‐9 scores were collected from 222 patients (112 males and 110 females; age: 64.1 ± 15.8) out of 260 consecutive patients evaluated at an outpatient physical therapy wound clinic during 2012–2015. The proportion of patients with minimal to severe depressive symptoms was 81.5% [80.8% in patients with venous leg ulcers (VLUs) and 82.0% in non‐VLUs]; 22.1% patients with wounds had scored positive for depression (moderate to severe depressive symptoms). Specific proportions of positive depression screening were 26.6% in patients with VLUs and 18.8% in non‐VLU patients, and 14.1 and 40.0% in patients with wounds <90 and ≥ 90 days as of initial examination, respectively. PHQ‐9 scores were significantly decreased from 5.85 ± 6.01 at initial examination to 3.42 ± 4.35 at last visit (p < 0.001). The odds of a positive depression screening was 3.20 (95% CI = [1.49, 6.87]) in patients with wounds ≥ 90 days (vs. < 90 days) and 2.53 (95% CI = [1.26, 5.08]) in patients with pain related to the wounds (vs. without pain), after patients’ age, gender, and race were controlled for. No difference was found in proportions of positive depression screening between VLUs and other wound diagnoses. Depressive symptoms were common in patients with wounds, especially in patients with wounds ≥90 days and with pain related to the wounds at initial examination. Therefore, clinicians should take into consideration patients’ mental status upon management of wounds.
VISUALIZATION AND CENTRALITY MEASUREMENT OF SOCIAL NETWORK ANALYSIS
Authors: Sulaiman Sarina , Abdul Rahim Nor Amalina , Mohd Hashim Siti Zaiton , Ahmad Nor Bahiah
Published: September 2016

Social networks have increased in popularity and play an important role in people's life nowadays. Hundreds of millions of people participate in social networks and the number is growing day by day. Social networks have become a useful tool and help people in every field of life such as in education, politics and business. Social networks give people the idea of knowing and interacting with each other, experiencing the power of sharing and being connected with people from different places and countries. The purpose of this study is to analyse the behaviour of actors in a network, the graph and the relationship between actors in social networks. The researcher expects to use the technique of Social Network Analysis with Organisation Risk Analyser (ORA) tool to analyse the data. Three different types of dataset are analysed in the form of network visualisation and centrality measurement. The results reveal the hidden relationships and clusters in the network, and indicate which nodes provide better performance for each centrality measure.
Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer
Authors: Ouwerkerk Janneke P. , van der Ark Kees C. H. , Davids Mark , Claassens Nico J. , Finestra Teresa Robert , de Vos Willem M. , Belzer Clara
Published: September 2016

Akkermansia muciniphila
colonizes the mucus layer of the gastrointestinal tract, where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how
A. muciniphila
is able to survive and grow at this oxic-anoxic interface, its oxygen tolerance and response and reduction capacities were studied.
A. muciniphila
was found to be oxygen tolerant. On top of this, under aerated conditions,
A. muciniphila
showed significant oxygen reduction capacities and its growth rate and yield were increased compared to those seen under strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Thereafter, genes related to respiration were expressed, including those coding for the cytochrome
bd
complex, which can function as a terminal oxidase. The functionality of
A. muciniphila
cytochrome
bd
genes was proven by successfully complementing cytochrome-deficient
Escherichia coli
strain ECOM4. We conclude that
A. muciniphila
can use oxygen when it is present at nanomolar concentrations.

IMPORTANCE
This article explains how
Akkermansia muciniphila
, previously described as a strictly anaerobic bacterium, is able to tolerate and even benefit from low levels of oxygen. Interestingly, we measured growth enhancement of
A. muciniphila
and changes in metabolism as a result of the oxygen exposure. In this article, we discuss similarities and differences of this oxygen-responsive mechanism with respect to those of other intestinal anaerobic isolates. Taken together, we think that these are valuable data that indicate how anaerobic intestinal colonizing bacteria can exploit low levels of oxygen present in the mucus layer and that our results have direct relevance for applicability, as addition of low oxygen concentrations could benefit the
in vitro
growth of certain anaerobic organisms.
BCL-2 system analysis identifies high-risk colorectal cancer patients
Authors: Lindner Andreas U , Salvucci Manuela , Morgan Clare , Monsefi Naser , Resler Alexa J , Cremona Mattia , Curry Sarah , Toomey Sinead , O'Byrne Robert , Bacon Orna , Stühler Michael , Flanagan Lorna , Wilson Richard , Johnston Patrick G , Salto-Tellez Manuel , Camilleri-Broët Sophie , McNamara Deborah A , Kay Elaine W , Hennessy Bryan T , Laurent-Puig Pierre , Van Schaeybroeck Sandra , Prehn Jochen H M
Published: September 2016

Objective

The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC).

Design

Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project.

Results

High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling.

Conclusions

DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors.
CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke
Authors: Sallustio Fabrizio , Motta Caterina , Pizzuto Silvia , Diomedi Marina , Giordano Angela , D'Agostino Vittoria Carla , Samà Domenico , Mangiafico Salvatore , Saia Valentina , Legramante Jacopo Maria , Konda Daniel , Pampana Enrico , Floris Roberto , Stanzione Paolo , Gandini Roberto , Koch Giacomo
Published: September 2016

Background

Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy.

Methods

Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals.

Results

Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0–2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome.

Conclusions

CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.
Experiences with Macroprudential Policy — Five Case Studies
Authors: Darbar Salim M. , Wu Xiaoyong
Published: September 2016

This paper presents case studies of macroprudential policy in five jurisdictions (Hong Kong SAR, the Netherlands, New Zealand, Singapore, and Sweden). The case studies describe the institutional framework, its evolution, the use of macroprudential tools, and the circumstances under which the tools have been used. The paper shows how macroprudential policy is conducted under a heterogeneous set of institutional frameworks. In all cases, macroprudential tools have been used to address risks in the housing market. In addition, some of them have moved to enhance the resilience of their banks to more general cyclical and structural risks.
MGD011, A CD19 x CD3 Dual-Affinity Retargeting Bi-specific Molecule Incorporating Extended Circulating Half-life for the Treatment of B-Cell Malignancies
Authors: Liu Liqin , Lam Chia-Ying K. , Long Vatana , Widjaja Lusiana , Yang Yinhua , Li Hua , Jin Linda , Burke Steve , Gorlatov Sergey , Brown Jennifer , Alderson Ralph , Lewis Margaret D. , Nordstrom Jeffrey L. , Koenig Scott , Moore Paul A. , Johnson Syd , Bonvini Ezio
Published: September 2016

Purpose: CD19, a B-cell lineage-specific marker, is highly represented in B-cell malignancies and an attractive target for therapeutic interventions. MGD011 is a CD19 x CD3 DART bispecific protein designed to redirect T lymphocytes to eliminate CD19-expressing cells. MGD011 has been engineered with a modified human Fc domain for improved pharmacokinetic (PK) properties and designed to cross-react with the corresponding antigens in cynomolgus monkeys. Here, we report on the preclinical activity, safety and PK properties of MGD011.

Experimental Design: The activity of MGD011 was evaluated in several in vitro and in vivo models. PK, safety and pharmacodynamic activity was also assessed in dose-escalation and repeat-dose studies of MGD011 administered once weekly in cynomolgus monkeys.

Results: MGD011 mediated killing of human B-cell lymphoma lines by human or cynomolgus monkey PBMCs as well as autologous B-cell depletion in PBMCs from both species. MGD011-mediated killing was accompanied by target-dependent T-cell activation and expansion, cytokine release and upregulation of perforin and granzyme B. MGD011 demonstrated antitumor activity against localized and disseminated lymphoma xenografts reconstituted with human PBMCs. In cynomolgus monkeys, MGD011 displayed a terminal half-life of 6.7 days; once weekly intravenous infusion of MGD011 at doses up to 100 μg/kg, the highest dose tested, was well tolerated and resulted in dose-dependent, durable decreases in circulating B cells accompanied by profound reductions of B lymphocytes in lymphoid organs.

Conclusions: The preclinical activity, safety and PK profile support clinical investigation of MGD011 as a therapeutic candidate for the treatment of B-cell malignancies. Clin Cancer Res; 23(6); 1506–18. ©2016 AACR.
BIRC6 Targeting as Potential Therapy for Advanced, Enzalutamide-Resistant Prostate Cancer
Authors: Luk Iris Sze Ue , Shrestha Raunak , Xue Hui , Wang Yuwei , Zhang Fang , Lin Dong , Haegert Anne , Wu Rebecca , Dong Xin , Collins Colin C. , Zoubeidi Amina , Gleave Martin E. , Gout Peter W. , Wang Yuzhuo
Published: September 2016

Purpose: Enzalutamide resistance has emerged as a major problem in the management of castration-resistant prostate cancer (CRPC). Research on therapy resistance of CRPCs has primarily focused on the androgen receptor pathway. In contrast, there is limited information on antiapoptotic mechanisms that may facilitate the treatment resistance. The inhibitor of apoptosis proteins (IAP) family is well recognized for its role in promoting treatment resistance of cancers by inhibiting drug-induced apoptosis. Here, we examined whether BIRC6, an IAP family member, has a role in enzalutamide resistance of CRPCs and could provide a therapeutic target for enzalutamide-resistant CRPC.

Experimental Design: Use of enzalutamide-resistant CRPC models: (i) the transplantable, first high-fidelity LTL-313BR patient-derived enzalutamide-resistant CRPC tissue xenograft line showing primary enzalutamide resistance, (ii) MR42D and MR49F CRPC cells/xenografts showing acquired enzalutamide resistance. Specific BIRC6 downregulation in these models was produced using a BIRC6-targeting antisense oligonucleotide (ASO-6w2). Gene expression was determined by qRT-PCR and gene expression profiling. Molecular pathways associated with growth inhibition were assessed via gene enrichment analysis.

Results: Of eight IAPs examined, BIRC6 was the only one showing elevated expression in both enzalutamide-resistant CRPC models. Treatment with ASO-6w2 markedly suppressed growth of LTL-313BR xenografts and increased tumor apoptosis without inducing major host toxicity. Pathway enrichment analysis indicated that GPCR and matrisome signaling were the most significantly altered pathways. Furthermore, ASO-6w2 inhibited expression of prosurvival genes that were upregulated in the LTL-313BR line.

Conclusions: BIRC6 targeting inhibited the growth of enzalutamide-resistant CRPC models and may represent a new option for clinical treatment of advanced, enzalutamide-resistant prostate cancer. Clin Cancer Res; 23(6); 1542–51. ©2016 AACR.
Identification of Keratin 19–Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18F-Fluorodeoxyglucose Positron Emission Tomography
Authors: Kawai Takayuki , Yasuchika Kentaro , Seo Satoru , Higashi Tatsuya , Ishii Takamichi , Miyauchi Yuya , Kojima Hidenobu , Yamaoka Ryoya , Katayama Hokahiro , Yoshitoshi Elena Yukie , Ogiso Satoshi , Kita Sadahiko , Yasuda Katsutaro , Fukumitsu Ken , Nakamoto Yuji , Hatano Etsuro , Uemoto Shinji
Published: September 2016

Purpose: The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with 18F-fluorodeoxyglucose (18F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19+ HCC-CSCs can be tracked using 18F-FDG-PET.

Experimental Design: K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent 18F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19+/K19− patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter–driven enhanced GFP, 18F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19+/K19− cells.

Results: In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19+ cells displayed significantly higher 18F-FDG uptake than K19− cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates 18F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.

Conclusions: 18F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs. Clin Cancer Res; 23(6); 1450–60. ©2016 AACR.
Cícero Dias e as danças do nordeste
Authors: Andrade Mário De
Published: September 2016

Mário de Andrade apresenta um conjunto de aquarelas de Cícero Dias, baseadas em motivos coreográficos pernambucanos. O tema das aquarelas inspira considerações sobre as origens e a evolução das músicas e “danças folclóricas brasileiras”, como o maracatu, os bumbas, os cabocolinhos e as danças antifolclóricas, semi-eruditas e popularescas, como o frevo e o samba
O tribunal do sertão "Os Chefes"
Authors: Roncari Luiz
Published: September 2016

“O tribunal do sertão” é um ensaio que tematiza a formação do herói, a possibilidade e a dificuldade da incorporação das instituições modernas pelos costumes arcaicos. O autor nos mostra como a narrativa roseana, na composição das suas personagens, explora esse embate entre moderno/arcaico, e desvenda a própria alegorização do Brasil
Ordem e desordem em "Fora da ordem"
Authors: Lopes Ivã Carlos , Tatit Luiz
Published: September 2016

Este trabalho pretendeu demonstrar que o sentido formulado com os recursos da canção popular provém simultaneamente de suas faces lingüística e melódica. A partir da análise da composição “Fora da Ordem”, de Caetano Veloso, verificou-se que tanto as situações de precipitação e atropelo quanto os sinais de um certo arranjo natural dos conteúdos expressos pela letra migram para o setor melódico da canção, onde recebem um reforço dos tratamentos entoativo e musical. Em outros termos, este artigo sugere que, por meio de técnicas particulares de organização, letra e melodia revezam-se para garantir à canção o seu sentido homogêneo.
Modelos em movimento: os contos de Machado de Assis
Authors: Dixon Paul
Published: September 2016

Quanto à questão da caracterização, as declarações teóricas de Machado de Assis são consistentes e mostram um compromisso com uma veracidade psicológica. Ao mesmo tempo as dúvidas machadianas sobre a escola Realista se m anifestam num método de caracterização diferente das práticas normais de criar indivíduos verossímeis. O interesse de Machado, amplamente demonstrado nos contos, é mais relacional e consiste em construir quadros de personalidades ou perspectivas contrastantes. Freqüentemente a relação contrária de personagens sugere teorias opostas. A natureza categórica de tais dicotomias, porém, geralmente é problem atizada através de recursos com o o duplo