bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of the Family Resilience (FaRE) Questionnaire: an observational study in Italy
Authors: Faccio Flavia , Gandini Sara , Renzi Chiara , Fioretti Chiara , Crico Chiara , Pravettoni Gabriella
Published: June 2019

Objective

Develop and validate an instrument to assess family resilience and, more specifically, the family dynamics and resources, estimating the adaptation flexibility to cancer disease. Cohesion, communication, coping style and relational style were considered as critical functional areas in the construction of the instrument.

Design

Two cross-sectional studies. Study 1: identification of factorial structure of the questionnaire in two samples with different cancer sites. Study 2: validation of the questionnaire in patients with cancer in two different phases of their therapeutic pathway.

Participants and setting

A total of 213 patients with a histologically confirmed non-metastatic breast or prostate cancer and 209 caregivers were recruited for the two studies from an oncological hospital in Italy.

Outcome measures

The Resilience Scale for Adults and the Family Resilience (FaRE) Questionnaire, developed by the researchers, were administered to all patients and caregivers who gave consent.

Results

In study 1, the 60-item version of the FaRE Questionnaire underwent discriminant and construct validity, internal consistency and factorial analysis. Comparisons between patient and caregiver populations showed that patients perceived higher levels of family resources (p=0.048) and that patients with prostate cancer perceived less social support compared with patients with breast cancer (p=0.002). Factor analysis demonstrated four domains: communication and cohesion, perceived social support, perceived family coping, and religiousness and spirituality. In study 2, the validity and factorial structure of the final scale, composed of 24 items, were confirmed. The Cronbach alpha of all subscales was above 82. Normative values for patients with breast cancer can provide indications of family resilience levels.

Conclusions

Preliminary findings showed acceptable psychometric properties for the FaRE Questionnaire to evaluate family resilience in oncological patients and their caregivers. Further research should test its sensibility to change to assess its use as a psychoemotional monitoring tool and its validity in other medical contexts.
Glossary of health equity in the context of environmental public health practice
Authors: Rideout Karen , Oickle Dianne
Published: June 2019

Health equity is increasingly present as an overarching goal in public health policy frameworks across the globe. Public health actions to support health equity are challenging because solutions to the root causes of health inequities often lie outside of the health sector, and a specific role for environmental public health practitioners has not been clearly articulated. The regulatory nature of the environmental public health profession means that their role is particularly ambiguous. Still, environmental public health practitioners are well situated to identify and respond to factors that contribute to health inequities because of their role as front-line professionals who interact with a wide cross-sector of the population. This Glossary, rooted primarily in the Canadian context but drawing on lessons from elsewhere, describes environmental public health regulatory practice in relation to health equity, including approaches that practitioners can use to contribute to addressing the social determinants of health.
Beyond pathology: women’s lived experiences of melancholy and mourning in infertility treatment
Authors: de Boer Marjolein Lotte , Bondevik Hilde , Solbraekke Kari Nyheim
Published: June 2019

Throughout history, melancholy and mourning are predominantly understood within the tradition of psychopathology. Herein, melancholy is perceived as an ailing response to significant loss, and mourning as a healing experience. By taking the philosophies of Freud, Ricoeur and Kristeva together with relevant social scientific research as a theoretical framework and by drawing on women’s accounts of melancholy and mourning in infertility treatment, we offer an exploration of melancholy and mourning beyond this pathological ailing/healing logic. We do so by asking what it means for women to actually live with melancholy and mourning in infertility treatment. In answering this question, we show that women in infertility treatment may have different kinds of melancholic longings: they desire their lost time as a pregnant woman, lost love life and lost future. Within these longings, women derive their sense of self predominantly from their lost past: they understand themselves as the mothers or lovers they once were or could have been. We further reveal that some of these women attempt to escape this dwelling of identity and mourn their losses by (re)narrating their pasts or through performing rituals. While these results show how melancholy and mourning are coshaped in relation to these women’s embodied, temporal, sociocultural and material lived context, they also give insight into how melancholy and mourning may be understood beyond infertility treatment. We reveal how the binary dynamic between melancholy and mourning is inherently ambiguous: melancholy instigates a joyous painfulness, something that is or is not overcome through the agonising exertion of mourning. We show, moreover, that underlying this melancholy/mourning dynamic is a pressing and uncontrollable reality of not being able to make (sufficient) sense of oneself. At the end of this work, then, we argue that it follows out of these conclusions’ urgency to have context-sensitive compassionate patience with those who live with melancholy and mourning.
Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis
Authors: Teixeira Vítor , Mohammad Aladdin J , Jones Rachel B , Smith Rona , Jayne David
Published: June 2019

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA) is a subset of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis with distinct pathophysiological mechanisms, clinical features and treatment responses. Rituximab is a licensed therapy for granulomatosis with polyangiitis and microscopic polyangiitis but there is limited experience of rituximab in EGPA.

Methods

EGPA patients from a tertiary centre who received rituximab for mostly refractory EGPA or in whom cyclophosphamide was contra indicated were studied. A standardised dataset was collected at time of initial treatment and every 3 months for 24 months. Response was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and partial response as ≥50% reduction in BVAS from baseline. Remission was defined as a BVAS of 0 on prednisolone dose ≤5 mg.

Results

Sixty-nine patients (44 female) received rituximab between 2003 and 2017. Improvement (response and partial response) was observed in 76.8% of patients at 6 months, 82.8% at 12 months and in 93.2% by 24 months, while relapses occurred in 54% by 24 months, with asthma being the most frequent manifestation. The median BVAS decreased from 6 at baseline to 1 at 6 months, and 0 at 12 and 24 months. Prednisolone dose (mg/day, median) decreased from 12.5 to 7, 7.5 and 5 at 6, 12 and 24 months, respectively. ANCA positive patients had a longer asthma/ear, nose and throat (ENT) relapse-free survival time and a shorter time to remission.

Discussion

Rituximab demonstrated some efficacy in EGPA and led to a reduction in prednisolone requirement, but asthma and ENT relapse rates were high despite continued treatment. The ANCA positive subset appeared to have a more sustained response on isolated asthma/ENT exacerbations.
Characteristics of Northern Irish cattle herds without bovine tuberculosis infection
Authors: Milne Georgina , Graham Jordon , Allen Adrian R , Lahuerta‐Marin Angela , McCormick Carl M , Presho Eleanor , Skuce Robin A , Byrne Andrew
Published: June 2019

Background

Despite ongoing eradication efforts, bovine tuberculosis (bTB) is endemic in cattle herds in Northern Ireland (NI). This disease has serious implications for the economy, farming and animal welfare. Previous research identified a population of herds which have remained free from bTB infection for 10 years (2004–2014). Understanding the characteristics of these herds may have important implications for eradication efforts, such as spatially targeted interventions.

Methods

A cluster analysis and a retrospective case–control analysis was conducted to compare bTB‐ free herds with herds which experienced prolonged infection (ie, bTB breakdowns lasting more than ≥ 365 days).

Results

Only small, localised clusters of herds which have remained free from bTB were revealed, thus limiting the potential for spatially targeted interventions. The results illustrated the importance of herd size to disease status; over 27 per cent of the bTB‐free herds had up to 10 animals. However, the data also showed that there were no inward movements in the year before the bTB skin test in those herds which remained free from bTB.

Conclusions

Attention should therefore be given to the cattle movement network in NI to better understand the risk associated with cattle purchasing.
Capture, ingestion, and egestion of microplastics by suspension-feeding bivalves: a 40-year history
Authors: Ward J. Evan , Rosa Maria , Shumway Sandra E.
Published: June 2019

In aquatic environments, suspension-feeding bivalve molluscs are exposed to a manifold of natural and anthropogenically derived particles, including micro- and nanoplastics. Plastic particles interact with feeding and digestive organs and can produce negative effects. As a result of these effects and the potential transfer of microplastics to higher trophic levels, including humans, there has been renewed interest in the ingestion of plastic particles by different species of bivalves. Many recent studies, however, have ignored the ability of bivalves to select among particles both pre- and post-ingestively. Neglecting to consider the factors that mediate particle capture, ingestion, and egestion can lead to erroneous data and conclusions. This paper outlines the current state of knowledge of particle processing by bivalves, and demonstrates how it relates to studies utilizing plastic particles. In particular, the effects of particle size, shape, and surface properties on capture, preferential ingestion, post-ingestive sorting, and egestion are summarized. The implications of particle selection for the use of bivalves as bioindicators of microplastic pollution in the environment are discussed. Only through a full understanding of the types of plastic particles ingested and egested by bivalves can internal exposure, toxic effects, and trophic transfer of microplastics be assessed adequately.
Time-lapsed shear-wave velocity (Vs) tomographic images and stress in sand surrounding displacement pile during setup
Authors: Wu Yuxin , Chow Jun Kang , Wu Jimmy , Wang Yu-Hsing
Published: June 2019

This study reports model pile tests designed to characterize the underlying mechanisms of driven pile setup in dry sand by means of stress measurement with the tactile pressure sensors and spatio-temporal, shear-wave velocity (Vs) distributions using an automated high-speed tomographic imaging system. The pile-load test results demonstrate a distinct increase in the pile shaft resistance after pile setup. The measured stress and Vs in the soil surrounding the pile suggest the increase in the radial effective stress during pile loading [Formula: see text], as a result of the aging-induced stiffness increase, is the dominant mechanism of pile setup. The spatio-temporal evolution of Vs distributions reveals that during initial aging (before pile installation), Vs is similar at any distance to the pile shaft and exhibits a similar aging rate S0 in terms of stiffness increases. After pile installation, the soil exhibits a higher aging rate S1. In addition, the ratio S1/S0 decreases with increasing distance from the pile shaft. A lower initial Vs and a higher aging rate S1 are also observed for the measurements at the three sensing layers of different depths, suggesting that more soils disturbed by pile installation tend to recover at a relative higher aging rate.
Field temperature and moisture loads from a building envelope as the basis for accelerated aging of barrier membranes
Authors: Riahinezhad Marzieh , Eve Augusta , Armstrong Marianne , Collins Peter , Masson J.-F.
Published: June 2019

Temperature and relative humidity (RH) data within the building envelope of a single-family home at the National Research Council of Canada’s Canadian Centre for Housing Technology were collected over five years. We report on the distribution, rate of change, and the limits of temperature and moisture variations for south-easting wall and south-facing wall and roof systems to better understand the in-situ environmental conditions to which building materials and components typical of homes in North America may be subjected. Over an average year, wall temperature varied from −25 °C to +45 °C, and temperature followed a bimodal distribution, with maxima at 0 °C to 5 °C and 15 °C to 20 °C. Each maximum represented about 1100 h of field exposure. Roof temperatures, which spanned a temperature range from −35 °C to 75 °C, did not show a Gaussian distribution but were characterized as being multi-modal. From values of temperature and RH, absolute moisture contents within the building envelope were found to range between 1 and 55 g/m3, with the most common values being 6–8 g/m3. The application of this information is discussed and related to the development of realistic accelerated aging conditions to obtain a more accurate durability assessment of building envelope materials used in Canadian dwellings.
Measure-valued solutions to size-structured population model of prey controlled by optimally foraging predator harvester
Authors: Jabłoński Jȩdrzej , Wrzosek Dariusz
Published: June 2019

Radon-measure-valued solutions to a size structured population model of the McKendrick–von Foerster-type are analytically studied under general assumptions on individuals’ growth, birth and mortality rates. The model is used to describe changes in size structure of zooplankton when prey size-dependent mortality rate is a consequence of a planktivorous fish foraging in low prey-density environment (commonly found in predator-controlled populations). The model of foraging is based on the optimization of the rate of net energy intake as a function of predator speed. Mortality is defined as an operator on a metric space of nonnegative Radon measures equipped with the bounded Lipschitz distance. The solutions to the size structured model of zooplankton population are studied analytically and numerically. Numerical solutions (derived using the Escalator Boxcar Train (EBT)-like schema), in particular those starting from Dirac deltas corresponding to distinct cohorts, exhibit regularization in time and convergence to the same stationary state.
Crystallization in the hexagonal lattice for ionic dimers
Authors: Friedrich Manuel , Kreutz Leonard
Published: June 2019

We consider finite discrete systems consisting of two different atomic types and investigate ground-state configurations for configurational energies featuring two-body short-ranged particle interactions. The atomic potentials favor some reference distance between different atomic types and include repulsive terms for atoms of the same type, which are typical assumptions in models for ionic dimers. Our goal is to show a two-dimensional crystallization result. More precisely, we give conditions in order to prove that energy minimizers are connected subsets of the hexagonal lattice where the two atomic types are alternately arranged in the crystal lattice. We also provide explicit formulas for the ground-state energy. Finally, we characterize the net charge, i.e. the difference of the number of the two atomic types. Analyzing the deviation of configurations from the hexagonal Wulff shape, we prove that for ground states consisting of [Formula: see text] particles the net charge is at most of order [Formula: see text] where the scaling is sharp.
Mice with finitely many Woodin cardinals from optimal determinacy hypotheses
Authors: Müller Sandra , Schindler Ralf , Woodin W. Hugh
Published: June 2019

We prove the following result which is due to the third author. Let [Formula: see text]. If [Formula: see text] determinacy and [Formula: see text] determinacy both hold true and there is no [Formula: see text]-definable [Formula: see text]-sequence of pairwise distinct reals, then [Formula: see text] exists and is [Formula: see text]-iterable. The proof yields that [Formula: see text] determinacy implies that [Formula: see text] exists and is [Formula: see text]-iterable for all reals [Formula: see text]. A consequence is the Determinacy Transfer Theorem for arbitrary [Formula: see text], namely the statement that [Formula: see text] determinacy implies [Formula: see text] determinacy.
Geometric measures of discordlike quantum correlations based on Tsallis relative entropy
Authors: Li Weijing
Published: June 2019

A kind of new geometric measure of quantum correlations is formulated. The proposed formulation is in terms of the quantum Tsallis relative entropy and can naturally be viewed as a one-parameter extension quantum discordlike measure that satisfies all requirements of a good measure of quantum correlations. It is of an elegant analytic expression and contains several existing good quantum correlation measures as special cases. The partial coherence measure is also investigated.
Piezoresponse force microscopy and dielectric spectroscopy study of Ba0.6Sr0.4TiO3 thin films
Authors: Czekaj Dionizy , Lisińska-Czekaj Agata
Published: June 2019

Research on synthesis, characterization and determination of processing — structure — property relationships of commercially important ferroelectric thin films has been performed. The sol–gel type solution deposition technique was applied to produce good quality thin films of [Formula: see text][Formula: see text]TiO3 (BST60/40) chemical composition on the stainless steel substrates. The thin films were characterized in terms of their microstructure, crystal structure, phase composition, piezoelectric and dielectric properties. It was found that the BST60/40 thin film adopted the cubic structure at room temperature with an elementary cell parameter [Formula: see text] Å. Morphology of the thin film surface was studied with Atomic Force Microscopy (AFM). Average roughness of the thin films surface was found ([Formula: see text]m). Piezoresponse Force Microscopy (PFM) was applied for the thin film characterization. Active piezoelectric regions were found in BST60/40 thin film. Therefore, dielectric response measured at room temperature was studied in assumption of piezoelectric electric equivalent circuit.
Hierarchical Clustering
Authors: Cohen-addad Vincent , Kanade Varun , Mallmann-trenn Frederik , Mathieu Claire
Published: June 2019

Hierarchical clustering is a recursive partitioning of a dataset into clusters at an increasingly finer granularity. Motivated by the fact that most work on hierarchical clustering was based on providing algorithms, rather than optimizing a specific objective, Dasgupta framed similarity-based hierarchical clustering as a combinatorial optimization problem, where a “good” hierarchical clustering is one that minimizes a particular cost function [23]. He showed that this cost function has certain desirable properties: To achieve optimal cost, disconnected components (namely, dissimilar elements) must be separated at higher levels of the hierarchy, and when the similarity between data elements is identical, all clusterings achieve the same cost.

We take an axiomatic approach to defining “good” objective functions for both similarity- and dissimilarity-based hierarchical clustering. We characterize a set of
admissible
objective functions having the property that when the input admits a “natural” ground-truth hierarchical clustering, the ground-truth clustering has an optimal value. We show that this set includes the objective function introduced by Dasgupta.

Equipped with a suitable objective function, we analyze the performance of practical algorithms, as well as develop better and faster algorithms for hierarchical clustering. We also initiate a beyond worst-case analysis of the complexity of the problem and design algorithms for this scenario.
Verification of Hierarchical Artifact Systems
Authors: Deutsch Alin , Li Yuliang , Vianu Victor
Published: June 2019

Data-driven workflows, of which IBM’s Business Artifacts are a prime exponent, have been successfully deployed in practice, adopted in industrial standards, and have spawned a rich body of research in academia, focused primarily on static analysis. The present work represents a significant advance on the problem of artifact verification by considering a much richer and more realistic model than in previous work, incorporating core elements of IBM’s successful Guard-Stage-Milestone model. In particular, the model features task hierarchy, concurrency, and richer artifact data. It also allows database key and foreign key dependencies, as well as arithmetic constraints. The results show decidability of verification and establish its complexity, making use of novel techniques including a hierarchy of Vector Addition Systems and a variant of quantifier elimination tailored to our context.
Systemic Interferon-γ Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a Phase 0 Clinical Trial
Authors: Zhang Shihong , Kohli Karan , Black R. Graeme , Yao Lu , Spadinger Sydney M. , He Qianchuan , Pillarisetty Venu G. , Cranmer Lee D. , Van Tine Brian A. , Yee Cassian , Pierce Robert H. , Riddell Stanley R. , Jones Robin L. , Pollack Seth M.
Published: June 2019

Interferon-γ (IFNγ) has been studied as a cancer treatment with limited evidence of clinical benefit. However, it could play a role in cancer immunotherapy combination treatments. Despite high expression of immunogenic cancer–testis antigens, synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) have a cold tumor microenvironment (TME), with few infiltrating T cells and low expression of major histocompatibility complex class I (MHC-I). We hypothesized that IFNγ treatment could drive inflammation in a cold TME, facilitating further immunotherapy. We conducted a phase 0 clinical trial treating 8 SS or MRCL patients with weekly systemic IFNγ. We performed pre- and posttreatment biopsies. IFNγ changed the SS and MRCL TME, inducing tumor-surface MHC-I expression and significant T-cell infiltration (P < 0.05). Gene-expression analysis suggested increased tumor antigen presentation and less exhausted phenotypes of the tumor-infiltrating T cells. Newly emergent antigen-specific humoral and/or T-cell responses were found in 3 of 7 evaluable patients. However, increased expression of PD-L1 was observed on tumor-infiltrating myeloid cells and in some cases tumor cells. These findings suggest that systemic IFNγ used to convert SS and MRCL into “hot” tumors will work in concert with anti–PD-1 therapy to provide patient benefit.
Critical Thinking as Discourse
Authors: Kuhn Deanna
Published: June 2019

Less than it is an individual ability or skill, critical thinking is a dialogic practice people engage in and commit to, initially interactively and then in interiorized form with the other only implicit. An argument depends for its meaning on how others respond. In advancing arguments, well-practiced thinkers anticipate their defeasibility as a consequence of others’ objections, in addition to envisioning their own potential rebuttals. Whether in external or interiorized form, the dialogic process creates something new, while itself undergoing development. This perspective may be useful in sharpening the definition of the construct of critical thinking and in so doing help to bring together the largely separate strands of work examining it as a theoretical construct, a measurable skill, and an educational objective. Implications for education follow. How might critical thinking as a shared practice be engaged within educational settings in ways that will best support its development? One step is to privilege frequent practice of direct peer-to-peer discourse. A second is to take advantage of the leveraging power of dialogue as a bridge to individual argument – one affording students’ argumentative writing a well-envisioned audience and purpose. Illustrations of this bridging power are presented. Finally, implications for assessment of critical thinking are noted and a case made for the value of commitment to a high standard of critical thinking as a shared and interactive practice.
Effects of Bardoxolone Methyl on Magnesium in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Authors: Rizk Dana V. , Silva Arnold L. , Pergola Pablo E. , Toto Robert , Warnock David G. , Chin Melanie P. , Goldsberry Angie , O’Grady Megan , Meyer Colin J. , McCullough Peter A.
Published: June 2019

Background: Treatment with bardoxolone methyl (Bard) in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate with concurrent reductions in serum magnesium. We analyzed data from several trials to characterize reductions in magnesium with Bard. Methods: BEACON randomized patients (n = 2,185) with type 2 diabetes (T2DM) and stage 4 chronic kidney disease (CKD) 1:1 to receive Bard (20 mg) or placebo once daily. In a separate open-label study, magnesium levels from 24-hour urine and sublingual epithelial cell samples were analyzed in patients with stage 3b-4 CKD and T2DM administered 20 mg Bard for 56 consecutive days. Results: BEACON patients randomized to Bard experienced significant reductions in serum magnesium from baseline relative to patients randomized to placebo (–0.17 mEq/L, 95% CI –0.18 to –0.60 mEq/L; p < 0.001). A separate study showed intracellular and urinary magnesium levels were unchanged with Bard treatment. Conclusions: Bard treatment results in significant decreases in serum magnesium that are not associated with changes in intracellular and urinary magnesium levels, indicating that magnesium decreases are not due to renal magnesium wasting or total body magnesium depletion. Importantly, the decreases in serum magnesium with Bard are not associated with adverse effects on QT interval.
Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease
Authors: Okada Yuki , Uehara Shinichiro , Shibata Mikiko , Koh Hideo , Oue Keiko , Kambe Hiroshi , Morimoto Michio , Sato Kyoko Kogawa , Hayashi Tomoshige
Published: June 2019

Background: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. Methods: A prospective cohort study of 9,116 middle-aged nondiabetic ­Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1–23.0 g ethanol/day), moderate drinkers (23.1–46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. Results: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11–1.70), 1.58 (95% CI 1.28–1.95), 2.27 (95% CI 1.86–2.77), and 3.12 (95% CI 2.56–3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46–0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. Conclusions: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.
Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats
Authors: Hurley Matthew M. , Anderson Eden M. , Chen Christopher , Maunze Brian , Hess Evan M. , Block Megan E. , Patel Neerali , Cooper Zane , McCoy Riley , Dabra Tanya , Conley William , Reilly Michael J. , Hearing Matthew , Choi SuJean
Published: June 2019

Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce feeding behavior and alter metabolism when administered into the VMN in a pattern similar to that of leptin. In the current study, we examined whether leptin and PACAP actions in the VMN share overlapping pathways in the regulation of energy balance. Interestingly, PACAP administration into the VMN increased STAT3 phosphorylation and SOCS3 mRNA expression, both of which are hallmarks of leptin receptor activation. In addition, BDNF mRNA expression in the VMN was increased by both leptin and PACAP administration. Moreover, antagonizing PACAP receptors fully reversed the behavioral and cellular effects of leptin injections into the VMN. Electrophysiological studies further illustrated that leptin-induced effects on VMN neurons were blocked by antagonizing PACAP receptors. We conclude that leptin dependency on PACAP signaling in the VMN suggests a potential common signaling cascade, allowing a tonically and systemically secreted neuropeptide to be more precisely regulated by central neuropeptides.
Targeted Deletion of Hepatocyte
Abca1
Increases Plasma HDL (High-Density Lipoprotein) Reverse Cholesterol Transport via the LDL (Low-Density Lipoprotein) Receptor
Authors: Bashore Alexander C. , Liu Mingxia , Key Chia-Chi C. , Boudyguina Elena , Wang Xianfeng , Carroll Caitlin M. , Sawyer Janet K. , Mullick Adam E. , Lee Richard G. , Macauley Shannon L. , Parks John S.
Published: June 2019

Objective:

The role of hepatocyte Abca1 (ATP binding cassette transporter A1) in trafficking hepatic free cholesterol (FC) into plasma versus bile for reverse cholesterol transport (RCT) is poorly understood. We hypothesized that hepatocyte Abca1 recycles plasma HDL-C (high-density lipoprotein cholesterol) taken up by the liver back into plasma, maintaining the plasma HDL-C pool, and decreasing HDL-mediated RCT into feces.

Approach and Results:

Chow-fed hepatocyte-specific
Abca1
knockout (HSKO) and control mice were injected with human HDL radiolabeled with
125
I-tyramine cellobiose (
125
I-TC; protein) and
3
H-cholesteryl oleate (
3
H-CO).
125
I-TC and
3
H-CO plasma decay, plasma HDL
3
H-CO selective clearance (ie,
3
H-
125
I fractional catabolic rate), liver radiolabel uptake, and fecal
3
H-sterol were significantly greater in HSKO versus control mice, supporting increased plasma HDL RCT. Twenty-four hours after
3
H-CO-HDL injection, HSKO mice had reduced total hepatic
3
H-FC (ie,
3
H-CO hydrolyzed to
3
H-FC in liver) resecretion into plasma, demonstrating Abca1 recycled HDL-derived hepatic
3
H-FC back into plasma. Despite similar liver LDLr (low-density lipoprotein receptor) expression between genotypes, HSKO mice treated with LDLr-targeting versus control antisense oligonucleotide had slower plasma
3
H-CO-HDL decay, reduced selective
3
H-CO clearance, and decreased fecal
3
H-sterol excretion that was indistinguishable from control mice. Increased RCT in HSKO mice was selective for
3
H-CO-HDL, since macrophage RCT was similar between genotypes.

Conclusions:

Hepatocyte Abca1 deletion unmasks a novel and selective FC trafficking pathway that requires LDLr expression, accelerating plasma HDL-selective CE uptake by the liver and promoting HDL RCT into feces, consequently reducing HDL-derived hepatic FC recycling into plasma.
MARK4 (Microtubule Affinity-Regulating Kinase 4)-Dependent Inflammasome Activation Promotes Atherosclerosis—Brief Report
Authors: Clement Marc , Chen Xiao , Chenoweth Hannah L. , Teng Zhongzhao , Thome Sarah , Newland Stephen A. , Harrison James , Yu Xian , Finigan Alison J. , Mallat Ziad , Li Xuan
Published: June 2019

Objective:

MARK4 (microtubule affinity-regulating kinase 4) regulates NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3) inflammasome activation. The aim of the study is to examine the role of MARK4 in hematopoietic cells during atherosclerosis.

Methods and Results:

We show increased MARK4 expression in human atherosclerotic lesions compared with adjacent areas. MARK4 is coexpressed with NLRP3, and they colocalize in areas enriched in CD68-positive but α-SMA (α-smooth muscle actin)–negative cells. Expression of MARK4 and NLRP3 in the atherosclerotic lesions is associated with the production of active IL (interleukin)-1β and IL-18. To directly assess the role of hematopoietic MARK4 in NLRP3 inflammasome activation and atherosclerotic plaque formation,
Ldlr
(low-density lipoprotein receptor)-deficient mice were lethally irradiated and reconstituted with either wild-type or
Mark4
-deficient bone marrow cells, and were subsequently fed a high-fat diet and cholesterol diet for 9 weeks.
Mark4
deficiency in bone marrow cells led to a significant reduction of lesion size, together with decreased circulating levels of IL-18 and IFN-γ (interferon-γ). Furthermore,
Mark4
deficiency in primary murine bone marrow–derived macrophages prevented cholesterol crystal–induced NLRP3 inflammasome activation, as revealed by reduced caspase-1 activity together with reduced production of IL-1β and IL-18.

Conclusions:

MARK4-dependent NLRP3 inflammasome activation in the hematopoietic cells regulates the development of atherosclerosis.
Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke
Authors: Deng Yiming , Chen Duanduan , Wang Luyao , Gao Feng , Jin Bo , Lv Hong , Zhang Guojun , Sun Xuan , Liu Lian , Mo Dapeng , Ma Ning , Song Ligang , Huo Xiaochuan , Yan Tianyi , Miao Zhongrong
Published: June 2019

Background and Purpose—

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke.

Methods—

We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke.

Results—

We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1.

Conclusions—

We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.
Carotid Plaque Inflammation Imaged by
18
F-Fluorodeoxyglucose Positron Emission Tomography and Risk of Early Recurrent Stroke
Authors: Kelly Peter J. , Camps-Renom Pol , Giannotti Nicola , Martí-Fàbregas Joan , Murphy Sean , McNulty Jonathan , Barry Mary , Barry Patrick , Calvet David , Coutts Shelagh B. , Cronin Simon , Delgado-Mederos Raquel , Dolan Eamon , Fernández-León Alejandro , Foley Shane , Harbison Joseph , Horgan Gillian , Kavanagh Eoin , Marnane Michael , McDonnell Ciaran , O’Donohoe Martin , Sharma Vijay , Walsh Cathal , Williams David , O’Connell Martin
Published: June 2019

Background and Purpose—

Plaque inflammation contributes to stroke and coronary events.
18
F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid
18
F-FDG uptake and early recurrent stroke.

Methods—

We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid
18
F-FDG PET/computed tomography angiography,
18
F-FDG uptake was expressed as maximum standardized uptake value (SUV
max
) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUV
max
with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only.

Results—

In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUV
max
was 2.2 (CI, 1.1–4.5;
P
=0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1–4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98–5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUV
max
was higher in patients with all recurrence (
P
<0.0001) and post-PET recurrence (
P
=0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41–3.39;
P
<0.001) and for post-PET recurrent stroke was 4.57 (CI, 1.5–13.96;
P
=0.008). Recurrent stroke risk increased across SUV
max
quartiles (log-rank
P
=0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59–0.78) and for post-PET recurrence was 0.80 (CI, 0.64–0.96).

Conclusions—

Plaque inflammation-related
18
F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed,
18
F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.
Preliminary investigation of antimicrobial activity of the skin secretions of frogs from Bangladesh
Authors: Islam Md. Sirajul , Rahman Md. Mokhlesur , Rahaman Md. Mizanur
Published: June 2019

Amphibians, like some animals and plants, defend themselves against various pathogenic organisms by producing and secreting various peptides and small molecules from granular skin glands. In this study, we evaluated for the first time, the antibiotic activity of the skin secretions of 8 different frog species (Euphlyctis cyanophlyctis, E. hexadactylus, Fejervarya teraiensis, F. asmati, F. syhadrensis, Hoplobatrachus tigerinus, Microhyla ornata and Polypedates leucomystax) from Bangladesh. These secretions were collected by a nonlethal approach through chemical stimulation and the antibacterial activity was evaluated by broth macrodilution method against some Gram-positive and Gram-negative bacteria. Our study revealed that all the skin secretions (8 out of 8) from the selected frogs have antimicrobial activity against Gram-positive bacteria and 7 out of 8 skin secretions possess antibacterial activity against Gram-negative bacteria tested. Further analysis of data showed that these secretions are significantly more effective against Gram-positive bacteria than Gram-negative bacteria.
Ocimum sebrabergensis (Lamiaceae), a new species from Namibia
Authors: SWANEPOEL WESSEL , VAN JAARSVELD ERNST J.
Published: June 2019

Ocimum sebrabergensis, here described as new species, has a restricted range and is only known from the Zebra Mountains within the Kaokoveld Centre of Endemism, northwestern Namibia. These shrubs grow on clayey soil among greyish black rocks of anorthosite. Diagnostic characters for O. sebrabergensis include the mauve-coloured corolla with four orbicular lobes on the posterior lip and the calyx which has the lateral lobes of the anterior lip asymmetric lanceolate. Ocimum sebrabergensis is placed in Ocimum subg. Ocimum sect. Hiantia subsect. Hiantia ser. Serpyllifolium. A comparison of some of the more prominent morphological features to differentiate between O. sebrabergensis and its possible nearest relatives, O. burchellianum and O. fimbriatum, are provided. Based on IUCN Red List categories and criteria, a conservation assessment of Vulnerable (VU D1) is recommended for the new species.
Isotrema plagiostomum (Aristolochiaceae), a new species from Guangdong, South China
Authors: ZHOU XIN-XIN , JIANG GUO-BIN , ZHU XIN-XIN , LIU ZI-YUE , HUANG YI , WANG GANG-TAO , WANG RUI-JIANG
Published: June 2019

Isotrema plagiostomum X. X. Zhou & R. J. Wang, a new species of Isotrema (Aristolochiaceae) from Guangdong, south China, is described and illustrated for the first time. It is similar to I. thwaitesii in the morphology of the obliquely truncated calyx limb, but differs by the habit, leaf shape, inflorescence position and splitting extent of calyx limb. It is evaluated as CR according to the IUCN categories and criteria.
The most latent cladoceran in the Holarctic revealed—sinking Unapertura Sarmaja-Korjonen, Hakojärvi & Korhola, 2000 into the genus Rhynchotalona Norman, 1903 (Branchiopoda: Cladocera: Chydoridae)
Authors: VAN DAMME KAY , NEVALAINEN LIISA
Published: June 2019

The morphology of one of the smallest chydorid cladocerans in the world, Unapertura latens Sarmaja-Korjonen, Hakojärvi & Korhola, 2000 (Branchiopoda: Cladocera: Anomopoda) is studied herein. External features and postabdomen of the adult parthenogenetic female are discussed in detail for the first time, based on an intact specimen from northern Finland. Originally described on Quaternary fossil remains, we investigate the validity of the monotypic genus Unapertura and its position within the Aloninae subfamily, in particular in relation to Rhynchotalona Norman, 1903. As a result, we rename the taxon as Rhynchotalona latens comb. nov., based on morphology. The species, a glacial relict, seems one of the rarest cladocerans in contemporary waters in Finland, yet intact specimens are clearly overlooked and recent remains in surface sediments suggest an Arctic-Alpine distribution in oligotrophic habitats in the Holarctic.
On a collection of brachyuran crabs from Lakshadweep, Indian Ocean (Crustacea: Decapoda: Brachyura)
Authors: DEVI S. SUVARNA , MENDOZA JOSE C. E. , RAVINESH R. , BABU K. K. IDRESS , KUMAR A. BIJU , NG PETER K. L.
Published: June 2019

The crab fauna (Crustacea: Brachyura) of Lakshadweep (Laccadives), a group of Indian islands in the western Indian Ocean is updated, using material from the intertidal and shallow subtidal areas collected between 2012 and 2015. Fifty-three species were recorded during this study, of which 17 species are newly recorded from the islands, and three are also new records for India. A total of 169 species of brachyuran crabs are now known from Lakshadweep. The taxonomy of Elamena gracilis Borradaile, 1903 (Hymenosomatidae) is clarified and stabilized by the designation of a lectotype.
CMIP5 Models’ Ability to Capture Observed Trends under the Influence of Shifts and Persistence: An In-Depth Study on the Colorado River Basin
Authors: Tamaddun Kazi Ali , Kalra Ajay , Kumar Sanjiv , Ahmad Sajjad
Published: June 2019

This study evaluated the ability of phase 5 of the Coupled Model Intercomparison Project (CMIP5) to capture observed trends under the influence of shifts and persistence in their data distributions. A total of 41 temperature and 25 precipitation CMIP5 simulation models across 22 grid cells (2.5° × 2.5° squares) within the Colorado River basin were analyzed and compared with the Climate Research Unit Time Series (CRU-TS) observed datasets over a study period of 104 years (from 1901 to 2004). Both the modeled simulations and observations were tested for shifts, and the time series before and after the shifts were analyzed separately for trend detection and quantification. Effects of several types of persistence were accounted for prior to both the trend and shift detection tests. The mean significant shift points (SPs) of the CMIP5 temperature models across the grid cells were found to be within a narrower range (between 1957 and 1968) relative to the CRU-TS observed SPs (between 1924 and 1985). Precipitation time series, especially the CRU-TS dataset, had a lack of significant SPs, which led to an inconsistency between the models and observations since the number of grid cells with a significant SP was not comparable. The CMIP5 temperature trends, under the influence of shifts and persistence, were able to match the observed trends very satisfactorily (within the same order of magnitude and consistent direction). Unlike the temperature models, the CMIP5 precipitation models detected SPs that were earlier than the observed SPs found in the CRU-TS data. The direction (as well as the magnitude) of trends, before and after significant shifts, was found to be inconsistent between the modeled simulations and observed precipitation data. Shifts, based on their direction, were found either to strengthen or to neutralize the preexisting trends in both the model simulations and the observations. The results also suggest that the temperature and precipitation data distributions were sensitive to different types of persistence—such sensitivity was found to be consistent between the modeled and observed datasets. The study detected certain biases in the CMIP5 models in detecting the SPs (tendency of detecting shifts earlier for precipitation and later for temperature than the observed shifts) and also in quantifying the trends (overestimating the trend slopes)—such insights may be helpful in evaluating the efficacy of the simulation models in capturing observed trends under uncertainties and natural variabilities.