bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta‐analysis of three‐in‐one single capsule bismuth‐containing quadruple therapy for the eradication of Helicobacter pylori
Authors: Nyssen Olga P. , McNicholl Adrian G. , Gisbert Javier P.
Published: February 2019

Background

Bismuth‐containing quadruple therapy has been suggested as first‐line and rescue alternative for Helicobacter pylori eradication. Our objective was to perform a meta‐analysis evaluating the efficacy and safety of single capsule Pylera® (bismuth, metronidazole, and tetracycline) plus a proton‐pump inhibitor (PPI) in any line of treatment.

Methods

Studies were selected up to October 2018. Outcomes were eradication and adverse events (AEs) rates pooled using the generic inverse variance method.

Results

In total, 30 studies (6482 patients) were included in the systematic review. The intention‐to‐treat (ITT) efficacy was 90% (95% CI: 87%‐92%, 21 studies, I2 = 88%) in first‐line therapy, 89% (95% CI: 86%‐93%, 12 studies, I2 = 78%) in second‐line and 82% (95% CI: 78%‐87%, nine studies, I2 = 60%) in third‐line; with no differences by the type or dosage of PPI used. For metronidazole‐resistant infection, the ITT efficacy as first‐line therapy was 93% (95% CI: 90%‐96%, six studies, I2 = 0%). In second‐line therapies where patients had been previously treated with clarithromycin, the ITT efficacy was 90% (95% CI: 87%‐93%, 11 studies, I2 = 78%). The overall incidence of AEs was 43% (95% CI: 35%‐50%, 24 studies, I2 = 92%) and they were mostly mild. In nearly 3% of the cases, treatment was interrupted due to AEs.

Conclusions

A 10‐day treatment with Pylera® achieved an effective eradication rate of approximately 90% both in first‐ and second‐line therapy. This applies regardless of the type and dose of the PPI, in patients with clarithromycin‐ or metronidazole‐resistant strains, and in those previously treated with clarithromycin.
Developing education materials for caregivers of culturally and linguistically diverse patients: Insights from a qualitative analysis of caregivers' needs, access and understanding of information
Authors: Schaffler Jamie L. , Tremblay Sarah , Laizner Andréa M. , Lambert Sylvie
Published: February 2019

Objectives

To explore the information needs of caregivers of culturally and linguistically diverse (CALD) patients, and how they access and understand health information related to the management of their care person's chronic illness(es).

Background

Caregivers of CALD patients experience greater unmet needs compared to the general caregiver population. They experience many challenges in identifying resources and accessing formal supports to aid in self‐management behaviours.

Methods

Eleven caregivers were recruited from outpatient clinics in Québec, Canada. Consenting caregivers participated in one face‐to‐face or phone interview. A qualitative descriptive design and inductive content analysis were used to identify themes.

Results

Caregivers described a “village” approach to caregiving in which more than one individual was involved in patient care. The specific roles ascribed to caregivers defined their information needs. Caregivers described two categories of information needs: perceived and unperceived. Perceived information needs were explicit, and centred on the medical management of illnesses. Unperceived needs were unrecognized knowledge gaps that emerged during interviews and focused on self‐care.

Conclusion

Although caregivers' perceived needs are often met, their unperceived needs remain unmet. Health‐care providers should perform need assessments to identify caregivers' unperceived needs, with the aims of providing culturally competent care and ongoing support.
Should businesses use religious cues in advertising? A comparison of consumer perceptions across Christianity and Islam
Authors: Zehra Saman , Minton Elizabeth
Published: February 2019

While religious cues are used in advertising efforts, research has yet to adequately understand perceived motives behind such religious cue use and how this influences consumers’ evaluations of a brand. Thus, this research addresses this gap through two studies examining cue measures, businesses’ motives for using cues, consumer affect, and brand evaluations. Specifically, Study 1 (an exploratory study) explores evaluations and associations evoked by religious cues representative of Christianity, Islam, Buddhism, and Hinduism. Study 2 narrows down the focus to Christianity and Islam to probe the outcome of religious cue use on businesses employing them in their advertisements. Specifically, Study 2 finds that consumers perceive businesses’ motives behind religious cue use as primarily trying to reach a specific target market but also as trying to witness and communicating reverence to God. Surprisingly, religious cue condition (Christian, Muslim, or none) did not directly influence business evaluations. Further analysis revealed that when affect toward the ad with religious cue was included in the model, that Muslim cue condition had a significant influence on affect, and such affect significantly influenced business evaluations. Interestingly, no similar effect could be established for the Christian condition. Discussion builds on the theory of visual rhetoric. Implications for marketing practice are also provided. The studies are limited by data collection only in the United States.
Social protection clusters in sub‐Saharan Africa
Authors: Clement Jessica
Published: February 2019

Sub‐Saharan Africa is expected to face the highest population growth rates leading up to 2060, yet this region faces uncertainties concerning how to cope with this demographic boom. Social protection has been a central theme in the political economic literature on advanced democracies, but little research has focused on the current social protection systems in sub‐Saharan Africa. Using a latent profile analysis, four clusters of social protection regimes were found in the region. The clusters range from groups with strong social protection and positive welfare outcomes to a cluster with poor social protection and weak welfare outcomes.
Airway macrophages as the guardians of tissue repair in the lung
Authors: Puttur Franz , Gregory Lisa G , Lloyd Clare M
Published: February 2019

The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.
Higher levels of B‐cell mutation in the early germinal centres of an inefficient secondary antibody response to a variant influenza haemagglutinin
Authors: Tennant Richard K. , Holzer Barbara , Love John , Tchilian Elma , White Harry N.
Published: February 2019

Designing improved vaccines against mutable viruses such as dengue and influenza would be helped by a better understanding of how the B‐cell memory compartment responds to variant antigens. Towards this we have recently shown, after secondary immunization of mice with a widely variant dengue virus envelope protein with only 63% amino acid identity, that IgM+ memory B cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein. Here, further investigation of memory responses to variant proteins, using more closely related influenza virus haemagglutinins (HA) that were 82% identical, produced a variant‐induced boost response in the GC dominated by highly mutated B cells that failed, not efficiently improving serum avidity even in the presence of extra adjuvant, and that was worse than a primary response. This supports a hypothesis that over a certain level of antigenic differences, cross‐reactive memory B‐cell populations have reduced competency for affinity maturation. Combined with our previous observations, these findings also provide new parameters of success and failure in antibody memory responses.
On secular stagnation and low interest rates: Demography matters
Authors: Ferrero Giuseppe , Gross Marco , Neri Stefano
Published: February 2019

Nominal and real interest rates in advanced economies have been declining since the mid‐1980s and reached historically low levels after the outbreak of the global financial crisis. Understanding why interest rates have fallen is of utmost importance for monetary policy. This paper focuses on one of the factors contained within the ‘secular stagnation’ view: adverse demographic developments. The empirical analysis shows that these developments have exerted a downward pressure on real interest rates in the euro area in the last decade. Building on the projections of the dependency ratios produced by the European Commission, we show that the foreseen changes in the age composition of the population may continue exerting downward pressure on real interest rates.
Impact of multidisciplinary foot care team on outcome of diabetic foot ulcer in term of lower extremity amputation at a tertiary care unit in Karachi, Pakistan
Authors: Riaz Musarrat , Miyan Zahid , Waris Nazish , Zaidi Syed I.H. , Tahir Bilal , Fawwad Asher , Basit Abdul
Published: February 2019

To compare the outcomes of diabetic foot ulcers (DFU) in terms of healing and lower extremity amputation (LEA) rate before and after training of multidisciplinary foot care team (MDFCT). Subjects were categorised into two groups; Group‐A cases seen between 1997 and 2006 (before upgrading of training and services of MDFCT) and Group‐B cases seen between 2007 and 2016 (after upgrading of training and services of MDFCT). Baseline demographic characteristics, biochemical results, and outcomes of DFU in terms of healing or amputation were analysed by using statistical package social science (SPSS) version 20. Total 7994 DFU cases seen, 888 in group A and 7106 in group B. Mean age of patients was 53.80 ± 10.40 years and mean haemoglobin (HbA1c) was 10.12 ± 2.44. Overall, decreasing trends of amputations were observed from baseline 27.5% to 3.92% during the period of 20 years. In group A, 479 (78.8%) subjects healed completely compared with 3806 (89.1%) in group B. Significant reduction in toe amputations ([13.81%] vs [8.11%]) and below knee amputations [(5.26%) vs (1.82%)] were seen. Similarly, rates of above knee amputation ([1.80%] vs [0.35%] P‐value 0.008) in two groups was also significant. Significant improvement was observed in outcomes of DFU in terms of amputation through multidisciplinary team approach.
On the diagnosis and treatment of cutaneous and soft tissue tumours misdiagnosed as scars: Lessons from four cases
Authors: Wang Yinmin , Yang Feng , Wu Xiao L. , Liu Fei , Jin Rui , Gu Chuan , Ni Tao , Wang Xi , Yang Qun , Luo Xusong , Yang Jun
Published: February 2019

Some types of skin and soft tissue tumours may be misdiagnosed as scars because of the scar‐like manifestation or the history of injury. It is generally believed that injuries will activate wound healing, ultimately ending in fibrosis. Because of the tumour‐promoting properties of both the microenvironment of the wound and the wound‐healing process that may go awry, there is a likelihood that injuries may trigger tumour growth. From 2012 to 2016, we treated four patients who underwent unsuccessful treatments because of the misdiagnosis of scars or keloids. Upon the pathological diagnoses of skin and soft tissue tumours in the four cases, extended resection of the tumours was performed. Recurrence was not observed up to the last follow up. Since then, soft tissue tumours have much greater visibility and are considered during diagnosis if a wound is presented with the atypical appearance of scar after injuries. Under these circumstances, biopsy should be conducted.
Extended surgical safety margins and ulceration are associated with an improved prognosis in pleomorphic dermal sarcomas
Authors: Persa O.D. , Loquai C. , Wobser M. , Baltaci M. , Dengler S. , Kreuter A. , Volz A. , Laimer M. , Emberger M. , Doerler M. , Mauch C. , Helbig D.
Published: February 2019

Background

Pleomorphic dermal sarcomas (PDS) are frequent UV‐induced sarcomas of the skin of intermediate grade malignant potential. Despite the fact that PDS have a noteworthy potential to recur (up to 28%) as well as to metastasize (up to 20%), there are no specific clinical guidelines with respect to follow‐up these patients. Moreover, little is known about clinical, histological or molecular prognostic factors in PDS.

Objective

The aim of the present study was to identify risk factors to predict relapse in a large multicentre sample cohort of PDS which could aid to optimize personalized treatment recommendations regarding surgical safety margins and adjuvant radiotherapy.

Methods

Patients with a diagnosis of PDS were selected from nine European institutions based on the histopathologic criteria described by Fletcher. Clinicopathologic and follow‐up data were collected and statistically analysed calculating univariate hazard ratios with 95% confidence intervals by use of the Cox proportional‐hazards model and a significance level of P < 0.05. Patients with an incomplete excision of the tumour were excluded.

Results

Univariate Cox regression analysis of possible prognostic factors for progression‐free survival (PFS) performed in 92 patients revealed that an excision margin of <2 cm is significantly associated with relapse of PDS [hazard ratio 4.478 (95% CI 1.536–13.055), P = 0.006]. Ulceration of the tumour was associated with a significantly better prognosis [0.396 (0.174–0.904), P = 0.028] whereas adjuvant radiotherapy did not reach statistical significance to improve prognosis in patients with PDS [0.775 (0.231–2.593), P = 0.679]. Gender, age, immunosuppression, intratumoural necrosis, tumour location, vertical thickness or horizontal diameter did not significantly influence PFS in PDS.

Conclusion

We identified surgical safety margins of <2 cm and absence of ulceration as risk factors for relapse in patients with PDS. These findings may be implemented into both the primary treatment as well as the further monitoring of patients with PDS.
Urinary neutrophil gelatinase‐associated lipocalin in dogs with stable or progressive kidney disease
Authors: Kim Yoojin M. , Polzin David J. , Rendahl Aaron , Granick Jennifer L.
Published: February 2019

Background

Active kidney injury may play a role in chronic kidney disease (CKD) progression in dogs. Neutrophil gelatinase‐associated lipocalin (NGAL), a novel tubular kidney injury biomarker, may help differentiate progressive CKD from stable CKD in dogs.

Objectives

To determine if urinary NGAL : creatinine ratio (UNCR) differentiates stable and progressive CKD in dogs. We hypothesized that UNCR would be higher in dogs with progressive CKD versus stable CKD.

Animals

Twenty‐one healthy control dogs, 22 with prerenal azotemia, 19 with stable CKD, 30 with progressive CKD, and 27 with acute kidney injury (AKI).

Methods

Prospective study. Azotemic (serum creatinine concentration >1.6 mg/dL) dogs or nonazotemic AKI dogs were enrolled and classified into 4 groups: (1) prerenal azotemia, (2) stable CKD, (3) progressive CKD, and (4) AKI. Urinary NGAL was measured by ELISA and UNCR compared among groups. Urine protein : creatinine ratio (UPC) in dogs with stable and progressive CKD was compared to UNCR for differentiating CKD groups.

Results

UNCR was significantly higher in dogs with progressive CKD than stable CKD. UNCR of the prerenal azotemia group was significantly lower than that of the progressive CKD and AKI groups. No significant difference was found in UNCR between stable CKD and prerenal azotemia groups. ROC curve analysis of UNCR for differentiating progressive CKD from stable CKD resulted in an AUC of 0.816 (95% confidence interval [CI], 0.673‐0.959), greater than that of UPC (0.696; 95% CI, 0.529‐0.863).

Conclusions and Clinical Importance

Urinary NGAL could be helpful to predict the risk of progression in dogs with CKD.
The marrow stem cell niche in normal and malignant hematopoiesis
Authors: Kaushansky Kenneth , Zhan Huichun
Published: February 2019

The hematopoietic niche is composed of endothelial cells, mesenchymal stromal cells of several types, and megakaryocytes, and functions to support the survival, proliferation, and differentiation of normal hematopoietic stem cells (HSCs). An abundance of evidence from a range of hematological malignancies supports the concept that the niche also participates in the pathogenesis of malignant hematopoiesis, differentially supporting malignant stem or progenitor cells over that of normal blood cell development. In 2005, patients with myeloproliferative neoplasms were reported to harbor an acquired, activating, missense V617F mutation of the cytokine‐signaling Janus kinase (JAK)‐2, JAK2V617F, present in virtually all patients with polycythemia vera and half of patients with essential thrombocythemia and primary myelofibrosis. Using both in vitro and in vivo methods, several investigators have shown that in addition to driving cytokine‐independent proliferation in HSCs, JAK2V617F contributes to these neoplasms by altering the hematopoietic niche. The role of both endothelial cells and megakaryocytes bearing JAK2V617F will be presented, which involves altering cytokine production within the niche, resulting in their differential support of mutant kinase–bearing stem cells over their normal counterparts, and imparting relative radiation resistance to stem cells. The clinical correlates of these findings will be discussed, as will their therapeutic implications.
Tooth microwear and occlusal modes of euharamiyidans from the Jurassic Yanliao Biota reveal mosaic tooth evolution in Mesozoic allotherian mammals
Authors: Mao Fangyuan , Meng Jin
Published: February 2019

‘Haramiyidans’ are extinct mammaliaforms often clustered with Multituberculata as Allotheria, and with a fossil record extending from the Upper Triassic to possibly the Upper Cretaceous. For many decades, ‘haramiyidans’ were known only from isolated teeth, and their relationships to other mammaliaforms remain unclear. With the discovery of several euharamiyidans represented by skeletal specimens from the Jurassic Yanliao Biota, north‐western China, our knowledge of this group has significantly advanced. Nonetheless, much morphology, including dentition and occlusal patterns, has only been briefly described for most taxa, and phylogenetic reconstruction and interpretation of the biology of the group still remain unclear or controversial. Here we provide systematic descriptions of the dental wear of shenshouids (Qishou and Shenshou) from the Yanliao Biota. We reconstruct the occlusal mode of shenshouids and compare it with those of other taxa based on our observation of specimens of most known ‘haramiyidan’ taxa. Several occlusal patterns are recognized. In particular, that of Thomasia, Haramiyavia and Maiopatagium is similar to the multituberculate M1/m1 occlusal relationship and probably represents the primitive occlusal condition in ‘haramiyidans’. The occlusal mode of shenshouids resembles the multituberculate M2/m2 occlusion. The double‐engaged mode in Arboroharamiya and Vilevolodon, as well as that of Eleutherodon, represents a more advanced occlusal pattern. The diverse dental occlusions suggest diverse diet adaptations and resource partitioning from co‐existing taxa in the Jurassic forests; they also reflect mosaic evolutionary transformations and complicated phylogenetic relationships within the group. Some aspects of the dental evolution remain challenging and require further vigorous testing.
Urine metabolic profiles in paediatric asthma
Authors: Tao Jia‐Lei , Chen Yan‐Zhen , Dai Qi‐Gang , Tian Man , Wang Shou‐Chuan , Shan Jin‐Jun , Ji Jian‐Jian , Lin Li‐Li , Li Wei‐Wei , Yuan Bin
Published: February 2019

Background and objective

Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology.

Methods

Children (aged 6–11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography–mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma‐related genes.

Results

We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold‐change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor‐controlled or well‐controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress‐related biological progression of paediatric asthma.

Conclusion

Metabolomic analysis of patient urine combined with network‐biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.
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

Sociologists 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

Objective

Maternal 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.

Methods

In 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.

Results

Mean 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.

Conclusions

Mid‐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

Purpose

The 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.

Methods

Retrospective 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.

Results

Fourteen 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.

Conclusions

Results 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.
Examining the STEM Awareness and Entrepreneurship Levels of Pre-Service Science Teachers
Authors: Ergün Selcen Süheyla
Published: February 2019

The scientific and technological developments in today's world require countries to raise entrepreneurial, productive, critical, problem-solving, and entrepreneurial individuals. Therefore, STEM (Science, Technology, Engineering, and Mathematics) education has gained importance today. STEM education is defined as an approach that takes an interdisciplinary relationship and takes a holistic approach to science, technology, engineering, and mathematics. STEM education includes the activities that will increase the students' interest and orientations towards science, technology, engineering, and mathematics fields using the skills that should be possessed today. The aim of this study was to examine the STEM awareness and entrepreneurship levels of pre-service science teachers. The sample of the study consisted of 93 female and 20 male students studying in the Science Education Department at Afyon Kocatepe University. As a quantitative research type, survey method was used in this study. “STEM Awareness Scale” (SAS) developed by Buyruk and Korkmaz (2016) and “Entrepreneurship Scale for Teacher Candidates” developed by Deveci and Cepni (2015) were used as data collection tools. As a result of analyses, it was seen that science teachers' attitudes towards STEM education were positive. Females’ STEM awareness was significantly higher than males’ in both positive and negative sub-factors. STEM awareness of the first grade students was significantly lower than the other classes in the positive sub-factor, and significant differences were found between the first grade and second grade, and the second grade and the fourth grade in the negative sub-factor. There were no significant differences of entrepreneurship levels in terms of gender. Also, the entrepreneurship characteristics of the second grade were significantly higher than the other grade levels.
Modeling low-frequency vibration in light-weight timber floor/ceiling systems
Authors: Fox Colin , Chung Hyuck
Published: February 2019

Producing practical designs for light-weight timber-framed structures that achieve high sound isolation remains a challenging task, in part because of the lack of models that can accurately predict the sound transmission through proposed designs. This work develops detailed modeling of structural vibration in timber floor/ceiling systems, from which sound transmission in the low-frequency regime (10–150 Hz) can be computed, as a design tool for producing practical timber floor/ceiling details that achieve high isolation for low-frequency sound. The mathematical model uses a variational formulation that enables straightforward modeling of complex composite structures, and introduces the notion of coupling layers to model the movement between joined materials that occurs with practical bonding methods, thereby improving on existing models that assume either perfectly bonded or perfectly slipping interfaces. The composite model structure is assembled only at the computational step, giving an efficient computational scheme that also fits well into the design-development cycle. Results from a parallel experimental program are used to validate the model and to determine effective coupling and damping parameters. The influence of coupling parameters is shown for an example floor, demonstrating that finite slippage at joints is required for the model to predict low-frequency vibration in practical constructions.
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.
Effect of Rail Irregularities on Ride Comfort of Train Moving Over Ballast-Less Tracks
Authors: Sadeghi Javad , Rabiee Siamak , Khajehdezfuly Amin
Published: February 2019

Rail irregularities are the main factors influencing the ride comfort of trains moving over tracks. Despite various investigations made in this regard for the ballasted tracks, there is a lack of studies for the ballast-less tracks. This limitation is addressed in this study. To this end, a vehicle/slab-track interaction numerical model was developed, which was validated by comparison of the results obtained herein with those of the field tests carried out in this study. The effects of rail irregularities with various amplitudes and wavelengths on the ride comfort were studied by a comprehensive parametric analysis. Particularly, the effects of the wavelengths and amplitudes of rail irregularity on the ride comfort were investigated. Contrary to the current understanding, it was shown that rail irregularities with short wavelength have considerable effects on the ride comfort for the slab-tracks. In addition, the ride comfort decreases significantly when the wavelengths of rail irregularity become less than 0.75[Formula: see text]m in the metro lines. The critical speed of the train (at which the lowest ride comfort is obtained) was derived as a function of rail irregularity. The results obtained indicate that the amplitude of rail irregularity has negligible influence on the critical speed of the train.
Axial coordination reactions with nitrogenous bases and determination of equilibrium constants for zinc tetraarylporphyrins containing four β,β′-fused butano and benzo groups in nonaqueous media
Authors: Ye Lina , Fang Yuanyuan , Ou Zhongping , Wang Liping , Xue Songlin , Lu Yang , Kadish Karl M.
Published: February 2019

The axial coordination properties of six zinc tetraarylporphyrins with seven different nitrogenous bases were examined in CH2Cl2 for derivatives containing four [Formula: see text],[Formula: see text]-fused butano or benzo groups and the equilibrium constants (log[Formula: see text] determined using spectral titration methods. The examined compounds are represented as butano(YPh)4PorZn and benzo(YPh)4PorZn, where Por is the porphyrin dianion and Y is a CH3, H or Cl substituent on the para-position of each meso-phenyl ring of the macrocycle. The initial four-coordinate butano- and benzoporphyrins will axially bind one nitrogenous base to form five-coordinate derivatives in CH2Cl2 and this leads to a 4–22 nm red-shift of the Soret and Q bands. The log[Formula: see text] values range from 1.98 to 4.69 for butano(YPh)4PorZn and from 3.42 to 5.36 for benzo(YPh)4PorZn, with the exact value depending upon the meso and [Formula: see text]-substituents of the porphyrin and the conjugate acid dissociation constants (p[Formula: see text] of the nitrogenous base.
Soapstone in
Jugend
(Art Nouveau) architecture of northern European cities (1890s–1910s)
Authors: Bulakh Andrey , Selonen Olavi , Pirinen Heikki
Published: February 2019

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.
Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either
Authors: Hartmann Phillipp , Chu Huikuan , Duan Yi , Schnabl Bernd
Published: February 2019

The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on their host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis and hepatic tumors induced by chemicals, or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis. In alcoholic liver disease, nonalcoholic fatty liver disease, and autoimmune cholangiopathies, germ-free status can be associated with worsened or improved hepatic phenotype depending on the experimental model and type of rodent. Some of the unexpected outcomes can be explained by the limitations of rodents raised in a germ-free environment including a deficient immune system and an altered metabolism of lipids, cholesterol, xenobiotics/toxins, and bile acids. Given these limitations and to advance understanding of the interactions between host and intestinal microbiota, simplified model systems such as humanized gnotobiotic mice, or gnotobiotic mice monoassociated with a single bacterial strain or colonized with a defined set of microbes, are unique and useful models for investigation of liver disease in a complex ecosystem.
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

Costimulation 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 (>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

[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