bluuebunny/crossref_metadata_2025_split huggingface dataset:
Employment relations and dismissal regulations: Does employment legislation protect the health of workers?
Authors: Barlow Pepita , Reeves Aaron , McKee Martin , Stuckler David 
Published: February 2019

AbstractSociologists have long acknowledged that being in a precarious labour market position, whether employed or unemployed, can harm peoples' health. However, scholars have yet to fully investigate the possible contextual, institutional determinants of this relationship. Two institutions that were overlooked in previous empirical studies are the regulations that set minimum compensation for dismissal, severance payments, and entitlements to a period of notice before dismissal, notice periods. These institutions may be important for workers' health as they influence the degree of insecurity that workers are exposed to. Here, we test this hypothesis by examining whether longer notice periods and greater severance payments protect the health of labour market participants, both employed and unemployed. We constructed two cohorts of panel data before and during the European recession using data from 22 countries in the European Union Statistics on Income and Living Conditions (person years = 338,000). We find more generous severance payments significantly reduce the probability that labour market participants, especially the unemployed, will experience declines in self‐reported health, with a slightly weaker relationship for longer notice periods.
Preconceptional factors associated with haemoglobin concentration in early pregnancy: a community‐based cohort study in rural northeastern Tanzania
Authors: Schmiegelow Christentze , Msemo Omari Abdul , Møller Sofie Lykke , Nielsen Birgitte Bruun , Paulsen Cecilie Bøge , Ødum Lars , Theander Thor Grundtvig , Kavishe Reginald Adolph , Lusingu John Peter Andrea , Minja Daniel Thomas , Bygbjerg Ib Christian 
Published: February 2019

AbstractObjectiveMaternal anaemia in early pregnancy is associated with poor pregnancy outcomes. Furthermore, preconceptional health can influence the health during pregnancy. The aim of this study was to investigate which preconceptional factors were associated with haemoglobin (Hb) concentration in early pregnancy.MethodsIn Tanzania, 226 women were followed at preconception and during early pregnancy. Red blood cell (RBC) morphology, serum micronutrient concentration, demographic characteristics and health status were assessed in preconception and in early pregnancy. The association between preconceptional factors and Hb concentration in early pregnancy was investigated using simple and multiple linear regression analyses stratified by preconceptional anaemia status.ResultsMean Hb was 123 and 119 g/l before conception and during early pregnancy (median gestational age 53 days) respectively. Preconceptional mid‐upper arm circumference (MUAC) (adjusted coefficient (AC) 0.35 95%CI0.9–0.61) and preconceptional Hb concentration (AC0.45 95%CI0.36–0.54) were positively associated with early pregnancy Hb concentration, whereas preconceptional microcytic hypochromicRBCmorphology (AC−6.00 95%CI−9.56 to −2.44) was negatively associated with early pregnancy Hb concentration. In addition, treatment of preconceptional malaria was positively associated with early pregnancy Hb concentration (AC6.45 95%CI0.74–12.2) among women with preconceptional anaemia. In contrast, among preconceptional non‐anaemic women, only preconceptional Hb concentration and medium socio‐economic status was positively associated with early pregnancy Hb concentration.ConclusionsMid‐upper arm circumference (MUAC) and Hb measurements in preconception can help to detect women at increased risk of low Hb concentration in early pregnancy.
Evaluation of equine corneal disease using spectral domain optical coherence tomography (SD‐OCT)
Authors: Blanchard Allison , Barr Erin M. , Gilger Brian C. 
Published: February 2019

AbstractPurposeThe purpose of this case series is to evaluate the use of spectral domain optical coherence tomography (SD‐OCT) imaging in equine corneal disease to demonstrate the feasibility, diagnostic effectiveness, and limitations of this imaging modality.MethodsRetrospective study: Handheld SD‐OCT (Envisu, Bioptigen Inc, Morrisville, NC) was used for high‐resolution imaging of horses with corneal disease presenting to the North Carolina State University Equine Ophthalmology Service from 2013 to 2018.ResultsFourteen horses were included in this study, including six horses with corneal ulceration, three with stromal abscesses (SA), three with immune‐mediated keratitis (IMMK), and two with ocular neoplasms. High‐resolution images of the cornea were obtained using handheld SD‐OCT in standing horses; however, acquiring images was time‐consuming due to the inherent movement of the examiner and horse. Despite this, in horses with corneal ulcers, SA, and IMMK, SD‐OCT assisted with determining location of disease in the cornea (eg, superficial, mid‐stromal, endothelial) and if disruption of Descemet's membrane was present. In horses with neoplasia, the SD‐OCT helped to determine whether the cornea had neoplastic invasion from anterior chamber masses.ConclusionsResults from this retrospective study suggest that handheld SD‐OCT for imaging the cornea of horses is feasible and may be helpful in determining depth and extent of lesions in the cornea.
Effects of low-dose leucine supplementation on gastrocnemius muscle mitochondrial content and protein turnover in tumor-bearing mice
Authors: Lee Harold W. , Baker Ella , Lee Kevin M. , Persinger Aaron M. , Hawkins William , Puppa Melissa 
Published: February 2019

Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, which are key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Twenty male C57BL/6 mice were divided into 4 groups (n = 5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, and LLC+Leu. At 9–10 weeks of age, mice were inoculated and supplemented with 5% leucine (w/w) in the diet. C2C12 myotubes were treated with 2.5 mmol/L leucine and 25% LLC conditioned media to further elucidate the direct influence of the tumor and leucine on the muscle. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius were assessed via Western blot analysis. Gastrocnemius mass was decreased in LLC+Leu relative to LLC (p = 0.040). Relative protein synthesis rate was decreased in LLC mice (p = 0.001). No change in protein synthesis was observed in myotubes. Phosphorylation of STAT3 was decreased in the Leu group relative to the control in both mice (p = 0.019) and myotubes (p = 0.02), but did not significantly attenuate the inflammatory effect of LLC implantation (p = 0.619). LLC decreased markers of mitochondrial content; however, PGC-1α was increased in LLC+Leu relative to LLC (p = 0.001). While leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation, it was able to increase mitochondrial biogenesis signaling. Novelty This study provides novel insights on the effect of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Leucine increased signaling for mitochondrial biogenesis in the skeletal muscle. Leucine supplementation decreased inflammatory signaling in skeletal muscle.
STABILITY OF A STOCHASTICALLY PERTURBED MODEL OF INTRACELLULAR SINGLE-STRANDED RNA VIRUS REPLICATION
Authors: SHAIKHET LEONID , ELENA SANTIAGO F. , KOROBEINIKOV ANDREI 
Published: February 2019

Compared to the replication of double-stranded RNA and DNA viruses, the replication of single-stranded viruses requires the production of a number of intermediate strands that serve as templates for the synthesis of genomic-sense strands. Two theoretical extreme mechanisms for replication for such single-stranded viruses have been proposed; one extreme being represented by the so-called linear stamping machine and the opposite extreme by the exponential growth. Of course, real systems are more complex and examples have been described in which a combination of such extreme mechanisms can also occur: a fraction of the produced progeny resulting from a stamping-machine type of replication that uses the parental genome as template, whereas other fraction of the progeny results from the replication of other progeny genomes. Martínez et al. 1 , Sardanyés et al. 2 and Fornés et al. 3 suggested and analyzed a deterministic model of single-stranded RNA (ssRNA) virus intracellular replication that incorporated variability in the replication mechanisms. To explore how stochasticity can affect this mixed-model principal properties, in this paper, we consider the stability of a stochastically perturbed model of ssRNA virus replication within a cell. Using the direct Lyapunov method, we found sufficient conditions for the stability in probability of equilibrium states for this model. This result confirms that this heterogeneous model of single-stranded RNA virus replication is stable with respect to stochastic perturbations of the environment.
Soapstone in
Jugend
(Art Nouveau) architecture of northern European cities (1890s–1910s)
Authors: Bulakh Andrey , Selonen Olavi , Pirinen Heikki 
Published: February 2019

Abstract

Soapstone occurs in Finland within Precambrian greenstone belts in the eastern parts of the country. Nunnanlahti and other deposits near Lake Pielinen are the best known and most important of these occurrences. This soft stone is highly workable. Soapstone was one of the most popular ornamental rocks used in architecture of the
Jugend
(Art Nouveau) style in St Petersburg, Russia, Helsinki, Finland, and in other northern European cities at the end of the nineteenth and into the early twentieth centuries.
Role of ketone signaling in the hepatic response to fasting
Authors: Geisler Caroline E. , Ghimire Susma , Bogan Randy L. , Renquist Benjamin J. 
Published: February 2019

Ketosis is a metabolic adaptation to fasting, nonalcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G protein-coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism, we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production. To establish that rescue of ketone metabolic/endocrine signaling would restore the normal hepatic fasting response, we gave intraperitoneal injections of β-OH butyrate (5.7 mmol/kg) to HMGCS2 knockdown and control mice every 2 h for the final 9 h of a 16-h fast. In hypoketonemic, HMGCS2 knockdown mice, fasting more robustly increased mRNA expression of uncoupling protein 2 (UCP2), a protein critical for supporting fatty acid oxidation and ketogenesis. In turn, exogenous β-OH butyrate administration to HMGCS2 knockdown mice decreased fasting UCP2 mRNA expression to that observed in control mice. Also supporting feedback at the transcriptional level, β-OH butyrate lowered the fasting-induced expression of HMGCS2 mRNA in control mice. β-OH butyrate also regulates the glycemic response to fasting. The fast-induced fall in serum glucose was absent in HMGCS2 knockdown mice but was restored by β-OH butyrate administration. These data propose that endogenous β-OH butyrate signaling transcriptionally regulates hepatic fatty acid oxidation and ketogenesis, while modulating glucose tolerance.NEW & NOTEWORTHY Ketogenesis regulates whole body glucose metabolism and β-OH butyrate produced by the liver feeds back to inhibit hepatic β-oxidation and ketogenesis during fasting.
HIV and cardiovascular diseases risk: exploring the interplay between T-cell activation, coagulation, monocyte subsets, and lipid subclass alterations
Authors: Teer Eman , Joseph Danzil E. , Driescher Natasha , Nell Theo A. , Dominick Leanne , Midgley Natasha , Deshpande Gaurang , Page Martin J. , Pretorius Etheresia , Woudberg Nicholas J. , Lecour Sandrine , Glashoff Richard H. , Essop M. Faadiel 
Published: February 2019

Although rollout of combined antiretroviral treatment (cART) has blunted human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) onset, there is increased development of cardiovascular diseases (CVDs) in HIV-infected individuals. While most HIV-infected individuals on cART achieve viral suppression, this may not necessarily result in complete immunological recovery. This study therefore evaluated T-cell-mediated changes and coagulation markers in HIV-positive individuals to ascertain their potential to increase CVD risk. Eighty participants were recruited (Worcester, South Africa), and fasted blood was collected to evaluate: 1) immune activation (CD38 expression on CD4+and CD8+T cells) and thrombus formation [tissue factor (CD142)] on CD4+and CD8+T cells; 2) monocyte subpopulations (nonclassical, intermediate, and classical); and 3) classical regulatory T (Treg) cells with activation markers [glycoprotein A repetitions predominant (GARP) and special AT-rich sequence-binding protein 1 (SATB-1)]. High- and low-density lipoprotein subclasses (Lipoprint) were also determined. This study revealed four key findings for HIV-positive patients: 1) coexpression of the CD142 coagulation marker together with immune activation on both CD4+and CD8+T cells during chronic infection stages; 2) Treg cell activation and upregulated GARP and SATB-1 contributing to Treg dysfunction in chronic HIV; 3) proatherogenic monocyte subset expansion with significant correlation between T-cell activation and macrophage activation (marker: CD163); and 4) significant correlation between immune activation and lipid subclasses, revealing crucial changes that can be missed by traditional lipid marker assessments (LDL and HDL). These data also implicate lipopolysaccharide-binding protein as a crucial link between immune activation, lipid alterations, and increased CVD risk.NEW & NOTEWORTHY With combined antiretroviral treatment rollout, HIV-AIDS patients are increasingly associated with cardiovascular diseases onset. This study demonstrated the significant interplay between adaptive immune cell activation and monocyte/macrophage markers in especially HIV-positive individuals with virological failure and on second line treatment. Our data also show a unique link between immune activation and lipid subclass alterations, revealing important changes that can be missed by traditional lipid marker assessments (e.g., LDL and HDL).
A Novel Form of 4-1BBL Prevents Cancer Development via Nonspecific Activation of CD4+ T and Natural Killer Cells
Authors: Barsoumian Hampartsoum B. , Batra Lalit , Shrestha Pradeep , Bowen William S. , Zhao Hong , Egilmez Nejat K. , Gomez-Gutierrez Jorge G. , Yolcu Esma S. , Shirwan Haval 
Published: February 2019

AbstractCostimulation through 4-1BB (CD137) receptor generates robust CD8+ T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Here, we report that treatment with an oligomeric form of the ligand, SA-4-1BBL, as a single agent is able to protect mice against subsequent tumor challenge irrespective of the tumor type. Protection was long-lasting (&gt;8 weeks) and a bona fide property of SA-4-1BBL, as treatment with an agonistic antibody to the 4-1BB receptor was ineffective in generating immune protection against tumor challenge. Mechanistically, SA-4-1BBL significantly expanded IFNγ-expressing, preexisting memory-like CD44+CD4+ T cells and NK cells in naïve mice as compared with the agonistic antibody. In vivo blockade of IFNγ or depletion of CD4+ T or NK cells, but not CD8+ T or B cells, abrogated the immunopreventive effects of SA-4-1BBL against cancer. SA-4-1BBL as a single agent also exhibited robust efficacy in controlling postsurgical recurrences. This work highlights unexpected features of SA-4-1BBL as a novel immunomodulator with implications for cancer immunoprevention and therapy.Significance:This study demonstrates the unique and unexpected immunomodulatory features of SA-4-1BBL that bridge innate and adaptive immune responses with both preventive and therapeutic efficacy against cancer.
A PET Glutamate Analogue to Measure Cancer Cell Redox State and Oxidative Stress: Promise and Paradox
Authors: Lee Hsiaoju S. , Pantel Austin R. , Zhou Rong , Mankoff David A. 
Published: February 2019

Abstract
[18F]FSPG was shown to provide an indirect measure of the cellular redox state and may be used as an early indicator of therapy response to cancer therapies that cause oxidative stress. A somewhat paradoxical finding was that reduced [18F]FSPG cellular uptake was associated with either lower cellular concentrations of cystine or glutamate, despite opposing the transport of these substances in the Xc− antiporter, for which [18F]FSPG is also a substrate. Further studies of the kinetics of [18F]FSPG will help elucidate the factors mediating a decline in [18F]FSPG with oxidative stress.
See related article by McCormick et al, p. 853
ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Authors: Dillon Magnus T. , Bergerhoff Katharina F. , Pedersen Malin , Whittock Harriet , Crespo-Rodriguez Eva , Patin Emmanuel C. , Pearson Alex , Smith Henry G. , Paget James T.E. , Patel Radhika R. , Foo Shane , Bozhanova Galabina , Ragulan Chanthirika , Fontana Elisa , Desai Krisha , Wilkins Anna C. , Sadanandam Anguraj , Melcher Alan , McLaughlin Martin , Harrington Kevin J. 
Published: February 2019

AbstractPurpose:ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironment.Experimental Design: We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT). Gene expression analysis and flow cytometry were performed posttherapy.Results:Significant radiosensitization to RT by ATRi was observed alongside a marked increase in immune cell infiltration. We identified increased numbers of CD3+ and NK cells, but most of this infiltrate was composed of myeloid cells. ATRi plus radiation produced a gene expression signature matching a type I/II IFN response, with upregulation of genes playing a role in nucleic acid sensing. Increased MHC I levels were observed on tumor cells, with transcript-level data indicating increased antigen processing and presentation within the tumor. Significant modulation of cytokine gene expression (particularly CCL2, CCL5, and CXCL10) was found in vivo, with in vitro data indicating CCL3, CCL5, and CXCL10 are produced from tumor cells after ATRi + RT.Conclusions:We show that DNA damage by ATRi and RT leads to an IFN response through activation of nucleic acid–sensing pathways. This triggers increased antigen presentation and innate immune cell infiltration. Further understanding of the effect of this combination on the immune response may allow modulation of these effects to maximize tumor control through antitumor immunity.
Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion
Authors: Weissgerber Tracey L. , Garcia‐Valencia Oscar , Milic Natasa M. , Codsi Elizabeth , Cubro Hajrunisa , Nath Meryl C. , White Wendy M. , Nath Karl A. , Garovic Vesna D. 
Published: February 2019

Background
The endothelial glycocalyx is a vasoprotective barrier between the blood and endothelium. We hypothesized that glycocalyx degradation is present in preeclampsia, a pregnancy‐specific hypertensive disorder characterized by endothelial dysfunction and activation.

Methods and Results

We examined the sublingual glycocalyx noninvasively using sidestream dark field imaging in the third trimester among women with normotensive pregnancies (n=73), early (n=14) or late (n=29) onset preeclampsia, or gestational diabetes mellitus (n=21). We calculated the width of the glycocalyx that was permeable to red blood cells (called the
perfused boundary region
, a measure of glycocalyx degradation) and the percentage of vessels that were filled with red blood cells ≥50% of the time (a measure of microvascular perfusion). In addition, we measured circulating levels of glycocalyx components, including heparan sulfate proteoglycans, hyaluronic acid, and SDC1 (syndecan 1), in a subset of participants by
ELISA
. Repeated‐measures
ANOVA
was performed to adjust for vessel diameter and caffeine intake. Women with early onset preeclampsia showed higher glycocalyx degradation, indicated by a larger perfused boundary region (mean: 2.14 [95% CI, 2.05–2.20]), than the remaining groups (mean: normotensive: 1.99 [95% CI, 1.95–2.02],
P
=0.002; late‐onset preeclampsia: 2.01 [95% CI, 1.96–2.07],
P
=0.024; gestational diabetes mellitus: 1.97 [95% CI, 1.91–2.04],
P
=0.004). The percentage of vessels that were filled with red blood cells was significantly lower in early onset preeclampsia. These structural glycocalyx changes were accompanied by elevated plasma concentrations of the glycocalyx components, heparan sulfate proteoglycans and hyaluronic acid, in early onset preeclampsia compared with normotensive pregnancy.

Conclusions
Glycocalyx degradation and reduced microvascular perfusion are associated with endothelial dysfunction and activation and vascular injury in early onset preeclampsia.
Paippalādasaṃhitā 19.20.15–17. Against Wrinkles
Authors: Lelli Duccio 
Published: February 2019

Abstract
This article presents a critical edition, translation and commentary of a tr̥ca found in book 19 of the Paippalādasaṃhitā of the Atharvaveda. The hymn, which consists in a spell against wrinkles, pronounced by a woman who tries to ward off the signs of aging with the help of the goddess Indrāṇī, is remarkable both in term of content and from a linguistic point of view: it is the only hymn directed against wrinkles in the Vedic corpus and the role of the goddess Indrāṇī in the ritual confirms and broadens her sphere of influence related to female charm. Besides providing the earliest attestation of the word for ‘wrinkle’ váli-, the hymn contains two hapaxes, previously unattested forms of the perfect subjunctive and features of women’s speech. The article also includes a stylistic analysis that aims at illuminating the structure and poetics of the hymn.