bluuebunny/crossref_metadata_2025 huggingface dataset:
Social risk management: structuring, validation, and testing of a survey in the mining industry
Authors: Maciel Ana Carolina de Moura , Pardini Daniel Jardim , Monteiro Plínio Rafael Reis
Published: January 2019

Purpose

This study aims to focus on the development and testing of a social risk management scale that could be applied to identify internal and external dimensions of strategic risks.

Design/methodology/approach

This study applied a quantitative approach for testing an theoretical model in the Brazilian mining sector, using partial least squares–structural equation modeling to assess reliability and validity of the dimensions and model.

Findings

Results points that internal and external risks have similar impact on general risk in the mining sector on the company studied. The research also identifies multidimensional scales consisting of internal (company policy, attitudes, loss of assets, human resources and operational) and external risks (market, strategic, social, credit, liquidity, loss of assets and technological). The results also points the relative importance of these dimensions and sub-dimensions on general business strategic risks.

Research limitations/implications

The scale was tested in just one company and, as a case study approach, the results are of limited generalization. Also, the scale was developed in the mining sector, so also the scale may require adaptation to applications in other contexts.

Practical implications

The multidimensional and hierarchical approach applied to modeling and scale development helps managers to understand the nature of risks and how to minimize them in business strategic settings.

Social implications

The study points out cues for managers to reconcile divergent sources of strategic risks that affect business, taking in to account the social dimension as a central element of risk management.

Originality/value

The study proposes and tests a scale with a multidimensional and hierarchical approach for social risk managing.
Incidence rate of cutaneous squamous cell carcinoma is rapidly increasing in Akita Prefecture: Urgent alert for super‐aged society
Authors: Umezono Yuko , Sato Yuriko , Noto Mai , Yamada Katsuhiro , Noguchi Natsuko , Hasunuma Naoko , Osada Shin‐Ichi , Manabe Motomu
Published: January 2019

Incidence rates of cutaneous squamous cell carcinoma (SCC) are increasing in many countries. To estimate detailed trends of SCC incidence rates in the population of Akita Prefecture as the forerunner of super‐aged societies, we conducted a retrospective analysis of patients diagnosed with SCC between 2007 and 2016 in Akita University Hospital. The crude SCC incidence rate increased rapidly between 2007 and 2016 from 2.5 to 10.0/100 000 people. Remarkably, the age‐specific incidence rate of people aged 80 years or over increased between 2007 and 2016 from 14.7 to 51.6/100 000 people, suggesting that SCC incidence rates increase possibly due to not only the increased number of aged people but also because of unidentified cancer‐prone environments. When the findings of the present study are generalized to other regions entering the era of super‐aging, it is clear that we need to prepare for the economic disease burden together with careful monitoring to confirm future trends for SCC.
Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta‐analysis
Authors: Yang Wenjia , Cai Xiaoling , Wu Haiya , Ji Linong
Published: January 2019

Background

Metformin is first‐line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta‐analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients.

Methods

PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes.

Results

Thirty‐one studies were included in the meta‐analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD −63.70; 95% CI −74.35, −53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD −14.68%; 95% CI −17.98%, −11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy.

Conclusions

Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.
Cue‐elicited craving–related lentiform activation during gaming deprivation is associated with the emergence of Internet gaming disorder
Authors: Dong Guangheng , Wang Min , Liu Xiaoyue , Liang Qianxin , Du Xiaoxia , Potenza Marc N.
Published: January 2019

Internet gaming disorder (IGD) is associated with negative health measures. However, little is known regarding the brain mechanisms or cognitive factors that may predict transitions from regular game use (RGU) to IGD. Such knowledge may help identify individuals who are particularly vulnerable to IGD and aid in prevention efforts. One hundred forty‐nine individuals with RGU were scanned when they were performing a cue‐elicited‐craving task before gaming and after gaming was suddenly ceased. One year later, 23 were found to have developed IGD (RGU_IGD). We compared the original data from these 23 RGU_IGD subjects and 23 one‐to‐one matched subjects still meeting criteria for RGU (RGU_RGU). RGU_IGD and RGU_RGU subjects showed similarities in the cue‐elicited‐craving task before gaming. Significant group‐by‐time interaction identified the bilateral lentiform nucleus. Post hoc analysis showed the interaction was related to increased activation in the RGU_IGD subjects following gaming. Significant correlations were observed between self‐reported cravings and lentiform activation in the RGU_IGD subjects. Among individuals with RGU, gaming‐cue‐induced lentiform activation following a session of gaming may predict subsequent development of IGD. The findings suggest a biological mechanism for emergence of IGD that may help inform prevention interventions.
Modelling continuous abstinence rates over time from clinical trials of pharmacological interventions for smoking cessation
Authors: Jackson Sarah E. , McGowan Jennifer A. , Ubhi Harveen Kaur , Proudfoot Hannah , Shahab Lion , Brown Jamie , West Robert
Published: January 2019

Background and aim

It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed to find the best‐fitting models of mean proportion abstinent with different smoking cessation pharmacotherapies up to 52 weeks from the quit date.

Methods

We searched the Cochrane Database of Systematic Reviews to identify randomized controlled trials (RCTs) of pharmacological treatments to aid smoking cessation. For comparability, we selected trials that provided 12 weeks of treatment. Continuous abstinence rates for each treatment at each follow‐up point in trials were extracted along with methodological details of the trial. Data points for each pharmacotherapy at each follow‐up point were aggregated where the total across contributing studies included at least 1000 participants per data point. Continuous abstinence curves were modelled using a range of different functions from the quit date to 52‐week follow‐up. Models were compared for fit using R2 and Bayesian information criterion (BIC).

Results

Studies meeting our selection criteria covered three pharmacotherapies [varenicline, nicotine replacement therapy (NRT) and bupropion] and placebo. Power functions provided the best fit (R2 > 0.99, BIC < 17.0) to continuous abstinence curves from the target quit date in all cases except for varenicline, where a logarithmic function described the curve best (R2 = 0.99, BIC = 21.2). At 52 weeks, abstinence rates were 22.5% (23.0% modelled) for varenicline, 16.7% (16.0% modelled) for bupropion, 13.0% (12.4% modelled) for NRT and 8.3% (8.9% modelled) for placebo. For varenicline, bupropion, NRT and placebo, respectively, 55.9, 65.0, 62.3 and 56.5% of participants who were abstinent at the end of treatment were still abstinent at 52 weeks.

Conclusions

Mean continuous abstinence rates up to 52 weeks from initiation of smoking cessation attempts in clinical trials can be modelled using simple power functions for placebo, nicotine replacement therapy and bupropion and a logarithmic function for varenicline. This allows accurate prediction of abstinence rates from any time point to any other time point up to 52 weeks.
Probing the provenance of archaeological glaze colorants: Polychrome faunal reliefs of the Ishtar Gate and the Processional Way of Babylon
Authors: Rodler A. S. , Klein S. , Artioli G. , Brøns C.
Published: January 2019

The polychrome glazes from the Processional Way and the Ishtar Gate of Babylon are among the best preserved from antiquity. Yet, little is known about the logistical choices involved in their production. Variations in isotope ratios can be useful for complementing an archaeological investigation of potential geological sources of raw materials. Consistent with archaeological evidence and ancient texts on trade in metals, Turkish ore deposits are thus tentatively proposed as possible sources of the metal oxide colorants used for the investigated polychrome glazes of three Neo‐Babylonian faunal reliefs that are now part of the collection of the Ny Carlsberg Glyptotek, Copenhagen.
Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes Treg development
Authors: Aqel S I , Kraus E E , Jena N , Kumari V , Granitto M C , Mao L , Farinas M F , Zhao E Y , Perottino G , Pei W , Lovett-Racke A E , Racke M K , Fuchs J R , Li C , Yang Y
Published: January 2019

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (Teff) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (Treg) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and Treg cells by promoting Th17 development and suppressing Treg development. Here we show that three novel small molecule IL-6 inhibitors, madindoline-5 (MDL-5), MDL-16 and MDL-101, significantly suppress IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner in vitro. MDL-101 showed superior potency in suppressing IL-17 production compared to MDL-5 and MDL-16. Treatment of myelin-specific CD4 T cells with MDL-101 in vitro reduced their encephalitogenic potential following their subsequent adoptive transfer. Furthermore, MDL-101 significantly suppressed proliferation and IL-17 production of anti-CD3-activated effector/memory CD45RO+CD4+ human CD4 T cells and promoted human Treg development. Together, these data demonstrate that these novel small molecule IL-6 inhibitors have the potential to shift the Teff : Treg balance, which may provide a novel therapeutic strategy for ameliorating disease progression in MS.
Adolescent use of combined hormonal contraception and peak bone mineral density accrual: A meta‐analysis of international prospective controlled studies
Authors: Goshtasebi Azita , Subotic Brajic Tatjana , Scholes Delia , Beres Lederer Goldberg Tamara , Berenson Abbey , Prior Jerilynn C.
Published: January 2019

Objective

Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC‐related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC.

Design/Participants

We performed literature searches for prospective published peer‐reviewed articles providing 12‐ to 24‐month BMD change in adolescent (12‐ to 19‐year‐old) women using CHC vs CHC‐unexposed control women.

Methods

Meta‐analyses used random‐effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers.

Results

Literature searches yielded 84 publications of which nine were eligible. Adolescent‐only data were sought from cohorts with wider age inclusions. The 12‐month LS meta‐analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of −0.02 (95% confidence interval [CI]: −0.05 to 0.00) g/cm2 in CHC‐exposed adolescents (P = 0.04). The 24‐month LS meta‐analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of −0.02 (95% CI: −0.03 to −0.01) g/cm2 in CHC‐exposed adolescents (P = 0.0006). Heterogeneities by I2 were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis.

Conclusion

Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.
Hautentzündungen mit Arthritis, Synovitis und Enthesitis. Teil 1: Psoriasisarthritis, SAPHO‐Syndrom, Morbus Still, Morbus Behçet
Authors: Huhn Christian K. , Schauer Franziska , Schempp Christoph M. , Venhoff Nils , Finzel Stephanie
Published: January 2019

Die Assoziation der Entzündung von Haut und Gelenken stellt Dermatologen und Rheumatologen oft vor diagnostische Herausforderungen. Um diese Krankheitsbilder adäquat managen zu können, benötigen beide Fachrichtungen solide Grundkenntnisse im jeweils anderen Fachgebiet. Bei Verdacht auf eine Gelenkbeteiligung kann die Kenntnis der zur Verfügung stehenden diagnostischen Möglichkeiten dem Dermatologen eine selektive und begründete konsiliarische Vorstellung bei einem Rheumatologen oder rheumatologischen Zentrum ermöglichen. Der vorliegende Beitrag vermittelt deshalb zunächst Grundkenntnisse der modernen rheumatologischen Stufendiagnostik. Diese umfasst neben labordiagnostischen Verfahren die Bildgebung wie den muskuloskelettalen Gelenkultraschall, Röntgen und Kernspintomografie. Anschließend werden Krankheitsbilder mit gleichzeitiger Entzündung von Haut und Gelenken besprochen: die Psoriasisarthritis und die autoinflammatorischen Syndrome SAPHO‐Syndrom, Morbus Still und Morbus Behçet. Bei jedem Krankheitsbild werden Epidemiologie, Ätiologie und Pathogenese, Klinik, Diagnostik und Grundzüge der Therapie besprochen.
Long‐term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104‐week VERTIS MET trial
Authors: Gallo Silvina , Charbonnel Bernard , Goldman Allison , Shi Harry , Huyck Susan , Darekar Amanda , Lauring Brett , Terra Steven G.
Published: January 2019

Aim

To evaluate the long‐term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin.

Materials and Methods

A 104‐week Phase III, randomized double‐blind study with a 26‐week placebo‐controlled period (Phase A) and a 78‐week period (Phase B) where blinded glimepiride was added to non‐rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported.

Results

Mean (standard error) change in HbA1c from baseline was −0.7% (0.07) and −1.0% (0.07) at week 52; −0.6% (0.08) and −0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) –0.50% (−0.95, −0.04) at week 52 and −0.84% (−1.44, −0.24) at week 104.

Conclusions

Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non‐clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.
IL‐17A synergistically enhances TLR3‐mediated IL‐36γ production by keratinocytes: A potential role in injury‐amplified psoriatic inflammation
Authors: Liu Shuangchun , Wu Fei , Wu Zongzhou , Li Ying , Zhang Shujie , Yu Ning
Published: January 2019

Skin injury can trigger formation of new lesions in psoriasis (Koebner phenomenon). The mechanisms through which injury exacerbates psoriasis are unclear. During wound repair, epidermal keratinocytes are activated and produce abundant IL‐36γ, further promoting the skin inflammation. IL‐17A is the cornerstone cytokine in the pathogenesis of psoriasis. We sought to investigate the effects of IL‐17A on injury‐induced keratinocyte activation and IL‐36γ production. Here, we demonstrated that dsRNA released from necrotic keratinocytes induced the expression of IL‐36γ. Silencing of TLR3 by siRNA decreased the IL‐36γ induction by necrotic keratinocyte supernatant. Co‐stimulation with dsRNA and IL‐17A synergistically increased the expression of IL‐36γ and other proinflammatory mediators (CCL20, CXCL8, DEFB4 and LCN2) in keratinocytes. The synergistic effects were not dependent on TLR3 upregulation, TNF receptor signalling and mRNA stabilization. Co‐stimulation with dsRNA and IL‐17A resulted in an accumulation of IκBζ. The synergistic upregulation of IL‐36γ and proinflammatory mediators were inhibited by IκBζ siRNA. Co‐stimulation with IL‐17A and poly(I:C) markedly activated the p38 MAPK and NF‐κB pathway, compared with poly(I:C). Blockade of p38 MAPK and NF‐κB suppressed dsRNA/IL‐17A–mediated IκBζ and IL‐36γ induction. These findings demonstrated that IL‐17A synergistically enhanced the dsRNA‐mediated IL‐36γ production through a p38 MAPK‐, NF‐κB–, and IκBζ‐dependent mechanism.
An adaptive clinical decision support system for serving the elderly with chronic diseases in healthcare industry
Authors: Tang Valerie , Siu Paul Kai Yuet , Choy King Lun , Lam Hoi Yan , Ho George To Sum , Lee Carman Ka Man , Tsang Yung Po
Published: January 2019

With the increasing ageing population worldwide, providing effective nursing care planning in nursing homes is important in meeting the expectations of elderly patients and in streamlining the healthcare information process, hence maintaining high‐quality services. Instead of the traditional manual nursing care planning formulation based on expert experience and subjective judgement, this paper describes an adaptive decision support system, namely, the cloud‐based nursing care planning system, to enable decision making in formulating nursing care strategies. By integrating cloud computing technology and the case‐based reasoning (CBR) technique, medical records and documents pertaining to the elderly can be captured in real time, whereas appropriate treatment plans based on past similar treatment records can be formulated. However, the current case adaptation processes in CBR rely on domain experts to modify retrieved cases, which may not satisfy the needs of the elderly. Therefore, text mining is integrated in the case adaptation process of CBR for extracting up‐to‐date medical information from the Internet so that its efficiency can be improved. By conducting a pilot study in a nursing home, it was shown that the time for formulating applicable treatment plans for elderly patients can be reduced, and the service satisfaction level can be enhanced.
A Multifaceted and Dyadic Examination of Intimate Relationship Quality during Pregnancy: Implications for Global Relationship Satisfaction
Authors: Ramsdell Erin L. , Franz Molly , Brock Rebecca L.
Published: January 2019

Understanding how couples navigate and negotiate the challenges and demands of pregnancy has important implications for family health. The aim of this study was to apply a multidimensional model of intimate relationship quality in a sample of 154 pregnant, cohabitating couples, to investigate the association between a range of intimate relationship processes (i.e., emotional intimacy, conflict management, sexual quality, received respect and acceptance, and received support) and the global relationship satisfaction of each partner. Semistructured clinical interviews were administered to each partner assessing multiple qualities of the relationship, and participants completed home surveys of global relationship satisfaction each day for 14 days. Results demonstrated that multiple dimensions of the intimate relationship were associated with greater relationship satisfaction. Some processes (e.g., degree of emotional intimacy and closeness, conflict management) had larger effects on relationship satisfaction than others (e.g., quality of the sexual relationship). Furthermore, some processes were more important for maternal than paternal satisfaction (e.g., emotional intimacy, support, respect). Finally, results varied, to some degree, as a function of whether parents were transitioning to parenthood for the first time. We discuss the implications of adopting a multidimensional approach to studying the specific relationship processes associated with global relationship satisfaction and present implications for clinicians working with couples navigating the transition into parenthood.
The Effect of Undetected Barriers on Groundwater Drawdown and Recovery
Authors: Marshall Sarah K. , Cook Peter G. , Miller Anthony D. , Simmons Craig T. , Dogramaci Shawan
Published: January 2019

In large‐scale pumping projects, such as mine dewatering, predictions are often made about the rate of groundwater level recovery after pumping has ceased. However, these predictions may be impacted by geological uncertainty—including the presence of undetected impermeable barriers. During pumping, an impermeable barrier may be undetected if it is located beyond the maximum extent of the cone of depression; yet it may still control drawdown during the recovery phase. This has implications for regional‐scale modeling and monitoring of groundwater level recovery. In this article, non‐dimensional solutions are developed to show the conditions under which a barrier may be undetected during pumping but still significantly impact groundwater level recovery. The magnitude of the impact from an undetected barrier will increase as the ratio of pumping rate to aquifer transmissivity increases. The results are exemplified for a hypothetical aquifer with an unknown barrier 3 km from a pumping well. The difference in drawdown between a model with and without a barrier may be <1 m in the 10 years while pumping is occurring, but up to 50 m after pumping has ceased.
Leaky Aquifer Models to Simulate the Well Flow in Fractured Aquifers with Linear Interporosity Flow
Authors: Székely Ferenc , Szűcs Péter , Zákányi Balázs
Published: January 2019

Following Hemker and Maas (1987) the models of two or three leaky aquifers are applied to simulate the flow to vertical wells operating in the fractured or dual porosity aquifers. The software WellTest (WT) (Székely 2015) is used for calculating the drawdown and discharge rate variation. The comparative analysis with the independent analytical solutions by Boulton and Streltsova‐Adams (1978), Warren and Root (1963), Kazemi et al. (1969) concluded with acceptable agreement between the WT simulation and the alternate calculation methods. The selected field tests have been conducted in fractured limestone aquifers. The pumping test west of Copenhagen shows an example of fractured aquifer with considerable negative skin effect at the well face. The flowing well Wafra W1 in Kuwait operates in the two‐zone aquifer exhibiting sufficient vertical recharge via leakage beyond a circular domain of estimated radius of 2460 m.
Netrin‐1 alleviates subarachnoid haemorrhage‐induced brain injury via the PPARγ/NF‐KB signalling pathway
Authors: Chen Junhui , Xuan Yong , Chen Yan , Wu Ting , Chen Lei , Guan Haoxiang , Yang Shuo , He Jianqing , Shi Dongliang , Wang Yuhai
Published: January 2019

Netrin‐1 (NTN‐1) is a novel drug to alleviate early brain injury following subarachnoid haemorrhage (SAH). However the molecular mechanism of NTN‐1‐mediated protection against early brain injury following SAH remains largely elusive. This study aims to evaluate the effects and mechanisms of NTN‐1 in protecting SAH‐induced early brain injury. The endovascular perforation SAH model was constructed using male C57BL/6J mice, and recombinant NTN‐1 was administrated intravenously. Mortality rates, SAH grade, brain water content, neurological score and neuronal apoptosis were evaluated. The expression of PPARγ, Bcl‐2, Bax and nuclear factor‐kappa B (NF‐κB) were detected by Western blot. Small interfering RNA specific to NTN‐1 receptor, UNC5B, and a selective PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), were applied in combination with NTN‐1. The results suggested that NTN‐1 improved the neurological deficits, reduced the brain water content and alleviated neuronal apoptosis. In addition, NTN‐1 enhanced PPARγ and Bcl‐2 expression and decreased the levels of Bax and NF‐κB. However, the neuroprotection of NTN‐1 was abolished by UNC5B and BADGE. In conclusion, our results demonstrated that NTN‐1 attenuates early brain injury following SAH via the UNC5B PPARγ/NF‐κB signalling pathway.
Histone demethylase KDM7A reciprocally regulates adipogenic and osteogenic differentiation via regulation of C/EBPα and canonical Wnt signalling
Authors: Yang Xiaoyue , Wang Guannan , Wang Yi , Zhou Jie , Yuan Hairui , Li Xiaoxia , Liu Ying , Wang Baoli
Published: January 2019

Recent emerging evidences revealed that epigenetic methylation of histone and DNA regulates the lineage commitment of mesenchymal progenitor cells. This study was undertaken to delineate the actions of histone lysine demethylase 7A (KDM7A) on osteogenic and adipogenic differentiation. Kdm7a expression was up‐regulated in primary marrow stromal cells and established stromal ST2 line after adipogenic and osteogenic treatment. Silencing of endogenous Kdm7a in the cells blocked adipogenic differentiation whereas promoted osteogenic differentiation. Conversely, overexpression of wild‐type Kdm7a in the progenitor cells enhanced adipogenic differentiation whereas inhibited osteogenic differentiation. However, the effect of KDM7A on cell differentiation was largely attenuated when the point mutation was made that abolishes enzymatic activity of KDM7A. Mechanism investigations revealed that silencing of Kdm7a down‐regulated the expression of the CCAAT/enhancer binding protein α (C/EBPα) and secreted frizzled‐related protein 1 (Sfrp1). Chromatin immunoprecipitation (ChIP) assay revealed that KDM7A directly binds to the promoters of C/EBPα and Sfrp1 and removes the histone methylation marks H3K9me2 and H3K27me2. Furthermore, silencing of Kdm7a activated canonical Wnt signalling. Thereafter, activation of canonical Wnt signalling through silencing of Sfrp1 in ST2 attenuated the stimulation of adipogenic differentiation and inhibition of osteogenic differentiation by KDM7A. Our study suggests that KDM7A balances adipogenic and osteogenic differentiation from progenitor cells through epigenetic control of C/EBPα and canonical Wnt signalling and implicates that control of KDM7A action has an epigenetic perspective of curtailing metabolic disorders like osteoporosis.
Insights into paediatric non‐alcoholic fatty liver disease from genetic variants
Authors: Dong Jiawen , Im Yu Ri , Mann Jake P.
Published: January 2019

See Article on Page 540
Genetic association with high‐resolution climate data reveals selection footprints in the genomes of barley landraces across the Iberian Peninsula
Authors: Contreras‐Moreira Bruno , Serrano‐Notivoli Roberto , Mohammed Naheif E. , Cantalapiedra Carlos P. , Beguería Santiago , Casas Ana M. , Igartua Ernesto
Published: January 2019

Landraces are local populations of crop plants adapted to a particular environment. Extant landraces are surviving genetic archives, keeping signatures of the selection processes experienced by them until settling in their current niches. This study intends to establish relationships between genetic diversity of barley (Hordeum vulgare L.) landraces collected in Spain and the climate of their collection sites. A high‐resolution climatic data set (5 × 5 km spatial, 1‐day temporal grid) was computed from over 2,000 temperature and 7,000 precipitation stations across peninsular Spain. This data set, spanning the period 1981–2010, was used to derive agroclimatic variables meaningful for cereal production at the collection sites of 135 barley landraces. Variables summarize temperature, precipitation, evapotranspiration, potential vernalization and frost probability at different times of the year and time scales (season and month). SNP genotyping of the landraces was carried out combining Illumina Infinium assays and genotyping‐by‐sequencing, yielding 9,920 biallelic markers (7,479 with position on the barley reference genome). The association of these SNPs with agroclimatic variables was analysed at two levels of genetic diversity, with and without taking into account population structure. The whole data sets and analysis pipelines are documented and available at https://eead-csic-compbio.github.io/barley-agroclimatic-association. We found differential adaptation of the germplasm groups identified to be dominated by reactions to cold temperature and late‐season frost occurrence, as well as to water availability. Several significant associations pointing at specific adaptations to agroclimatic features related to temperature and water availability were observed, and candidate genes underlying some of the main regions are proposed.
Understanding the pathophysiology behind chairside diagnostics and genetic testing for IL‐1 and IL‐6
Authors: Rudick Courtney P. , Lang Melissa S. , Miyamoto Takanari
Published: January 2019

In order for chairside diagnostic testing to make an impact on dental therapy, practitioners require a better understanding of genetic mutations contributing to the pathophysiology of periodontal disease. Commensal and pathogenic bacterial colonization in oral cavity tissues produces a cascade of proinflammatory signaling pathways ultimately detrimental to host tissues. Resolving inflammation is a multifactorial process involving the downregulation of proinflammatory cytokines while allowing commensal bacterial levels to return to normal. Because of the complicated nature of commensal bacteria and oral health homeostasis, the emphasis of dental therapy should place renewed focus on limiting destructive inflammation rather than solely eliminating bacteria. Salivary diagnostics are an easy, non‐invasive way to assess inflammatory markers. Inflammatory cytokine levels can help determine the subclinical health of a patient, showing the transition from health to gingivitis, or periodontitis, prior to clinical presentation. Single nucleotide polymorphism mutations can aid in determining increased risk of developing periodontitis. Taken together, and alongside regular clinical evaluations, chairside diagnostics help individualize treatment plans to slow, or halt, the progression of disease—before tissue destruction can take place. While more studies are needed analyzing specific mutations across periodontal categories, chairside diagnostics present an exciting adjunct to improve patient care.
Curcumin, a turmeric extract, for oral lichen planus: A systematic review
Authors: White C. Michael , Chamberlin Kevin , Eisenberg Ellen
Published: January 2019

Objective

Conduct a PROSPERO registered (CRD42018105227) systematic review of the efficacy of curcumin in the treatment of oral lichen planus (OLP).

Data sources

Medline from the earliest possible date to the present (December 18, 2018) using the terms “turmeric” OR “curcumin” OR “curcuma“ AND “oral lichen planus“.

Study selection and data extraction

Studies assessing patient outcomes in OLP. There were four trials assessing the comparative efficacy of topical curcumin vs. topical corticosteroids and three trials assessing the efficacy of oral curcumin vs. placebo.

Data synthesis

Clinical and methodological heterogeneity precluded statistical pooling. There were many limitations in the literature weakening the strength and applicability of evidence. Topical curcumin provided reductions in pain, burning, and clinical manifestations of OLP versus baseline, effects similar or inferior to topical corticosteroids. In oral curcumin trials, there were no significant benefits of curcumin therapy versus placebo but there were some potential benefits and reasonable safety in an observational extension study.

Conclusions

It is difficult to determine whether topical or oral curcumin is a viable therapy for oral lichen planus. Topically applied curcumin in particular shows promising preliminary data but would likely not supplant topical corticosteroids as the modality of choice for most patients.
Proximal remote sensing to differentiate nonviruliferous and viruliferous insect vectors – proof of concept and importance of input data robustness
Authors: Nansen C. , Stewart A. N. , Gutierrez T. A. M. , Wintermantel W. M. , McRoberts N. , Gilbertson R. L.
Published: January 2019

Proximal remote sensing is being widely studied as a noninvasive method to partially automate diagnostics of plants and insects. The hypothesis that proximal remote sensing can be used to differentiate specimens of adult beet leafhoppers (Circulifer tenellus) that were nonviruliferous or viruliferous for beet curly top virus (BCTV) was tested. A key aspect of applications of proximal remote sensing is the ‘robustness’ or repeatability of input reflectance data. Many factors may contribute to low input reflectance data robustness; these include: (i) issues related to the consistency of proximal remote sensing conditions (light intensity and spectral composition, ambient temperature), (ii) insect specimen preparation (projection angle, storage and handling), and (iii) insect specimen characteristics (age, growing conditions, variety/biotype, host plant). This study demonstrates that nonviruliferous and viruliferous specimens of adult beet leafhoppers possess unique body reflectance features and, therefore, can be differentiated. However, insect specimen preparation (removal of wings and placement) markedly affected the classification accuracy. Addition of experimental noise to input reflectance data was conducted to simulate varying degrees of input reflectance data robustness. The potential of developing reflectance‐based diagnostic tools for detection of plant pathogenic viruses in insects is discussed, with an emphasis on input data robustness.
Follicular dynamics and colour Doppler vascularity evaluations of follicles and corpus luteum in relation to plasma progesterone during the oestrous cycle of Surti buffaloes
Authors: Gaur Mitesh , Purohit Govind Narayan
Published: January 2019

Contents

With an objective to evaluate the follicular dynamics and vascularity changes in follicles and corpus luteum, the ovaries of cyclic Surti buffaloes (n = 9) were examined daily sequentially by transrectal B‐mode and colour flow mode (CFM) ultrasonography starting from the day of oestrus till the onset of next oestrus. Higher proportion of buffaloes evidenced one‐wave cycle (66.66%) compared to two‐wave cycle (33.34%) with none showing a three‐wave cycle. The dominant follicle of the first follicular wave was the ovulatory follicle and persisted for 19.70 ± 0.50 days compared to its persistence for 16.5 ± 1.45 days in a two‐wave cycle. The maximum diameter of the ovulatory follicle in a one‐wave and two‐wave cycle did not differ yet their linear growth rates were significantly lower (p < 0.01) in a one‐wave cycle. Colour flow mode examination of follicles revealed that the percentage of follicles with detectable blood flow in the subsequently determined largest follicle (dominant follicle) was not different from that in the second largest follicle before follicle deviation. The blood flow in the dominant follicle increased significantly on the day of oestrus. The mean diameter and blood flow to the corpus luteum (CL) increased linearly and significantly from Day 5 of oestrus till Day 13 after which both parameters started declining. At or around Day 16, there was precipitous fall in the blood supply to the CL and CL diameter that continued declining thereafter to reach the lowest around Day 20 of the oestrous cycle. Rise in plasma progesterone concentrations was synchronous to CL diameter and vascularity and showed significant and positive correlations. It was concluded that Surti buffaloes evidence a preponderance of one‐wave follicular growth pattern with a significant increase in the vascularity of ovulatory follicle on the day of oestrus and corpus luteum on Day 13 of the oestrous cycle.
Impact of TBX21, GATA3, and FOXP3 gene polymorphisms on acute cellular rejection after liver transplantation
Authors: Thude Hansjörg , Tiede Petra , Sterneck Martina , Nashan Björn , Koch Martina
Published: January 2019

The single nucleotide polymorphisms (SNPs) rs4794067, rs2275806, rs2232365, and rs3761548 map in the genes of TBX21, GATA3, and FOXP3 involved in mediating acute cellular rejection. We investigated whether these SNPs are associated with acute cellular liver transplant rejection. The SNPs were analyzed in recipients with early acute cellular rejection (n = 97), recipients with late acute cellular rejection (n = 49), and recipients without rejection (n = 149). There was no association between acute cellular rejection and SNPs rs4794067, rs2275806, and rs2232365. In contrast, the allele −3279A of FOXP3 SNP rs3761548 exhibited a higher frequency in recipients with late acute cellular rejection as compared with recipients without rejection. This result indicates that the allele −3279A of the SNP rs3761548 may predispose to the development of late acute cellular rejection.
Computational multivariate modelling of electrical activity of the porcine uterus during spontaneous and hormone‐induced oestrus
Authors: Domino Malgorzata , Domino Krzysztof , Pawlinski Bartosz , Sady Maria , Gajewska Magdalena , Gajewski Zdzislaw
Published: January 2019

New Findings

What is the central question of this study?

Does oestrous cycle synchronization influence myoelectrical activity of porcine myometrium?

What is the main finding and its importance?

Exogenous hormones used to synchronize oestrus in pigs altered myoelectrical activity, which was effectively modelled. Higher‐order multivariate statistic modelling provided evidence of similar activity in both types of oestrus, but a larger order of EMG signals during induced oestrus. Higher‐order statistical analysis of the probabilistic model suggests the beginning of the early follicular phase and the mid‐luteal phase to be most important in evaluation of the natural patterns of myoelectrical activity. Higher‐order multivariate cumulants are more informative than classical statistics in characterization of myoelectrical activity changes in porcine myometrium.

In pig production units, control of the oestrous cycle and synchronization of ovulation have become routine herd management procedures. During the oestrous cycle, in both induced and spontaneous conditions, the ovaries and the uterus undergo hormone‐dominated physiological changes, which are consistent with the hypothesis that there is a functional role of uterine contractions in promoting fertilization. We have used electromyography to determine whether the use of exogenous hormones, such as equine chorionic gonadotrophin and human chorionic gonadotrophin, which have the potential to control the timing of ovulation in female pigs, changes the multivariate relationships between parameters of electrical bursts and modulates the patterns of myoelectrical activity. We used the mathematical approach of higher‐order multivariate cumulants in complex modelling of the myometrial electrical activity. The experiment was conducted on 12 mature Polish Landrace sows, and uterine activity was recorded during both spontaneous and induced oestrous cycles. The burst parameters were determined using six features in the time domain and, after Fast Fourier transformation, in the frequency domain. Evaluation of myoelectrical activity patterns was conducted based on classical univariate statistical methods and multivariate probabilistic modelling. The classical statistical approach indicated weaker myoelectrical activity after hormonal stimulation, whereas the higher‐order multivariate statistical model showed evidence of similar status of activity and a larger order of signals during induced oestrus. Routine oestrous cycle synchronization affects the multivariate probabilistic model of myometrial electrical activity.
Gelation and long-time relaxation of aqueous solutions of Pluronic F127
Authors: Hopkins Cameron C. , de Bruyn John R.
Published: January 2019

We have studied the gelation dynamics of solutions of Pluronic F127, a triblock copolymer, using oscillatory rheometry. As the solutions are slowly heated from 10 to 85°C, they undergo a transition from sol to gel around room temperature, followed by a gel-sol transition at a higher temperature. The sol-gel transition temperature decreases and the width in the temperature of the gel phase broadens with increasing concentration. The reverse transitions occur on cooling. Both transitions are hysteretic, and the temperature range over which the transitions occur is different on cooling than on heating. Near the phase transitions, the rheological relaxation time becomes very long, up to of order τs∼104s. Gelation in Pluronic solutions is due to the arrangement of micelles into an organized large-scale structure, and our results suggest that the rearrangement of micelles into or out of the gel structure is a slow process at temperatures within the phase transitions.
Evolution of Daptomycin Resistance in Coagulase-Negative Staphylococci Involves Mutations of the Essential Two-Component Regulator WalKR
Authors: Jiang Jhih-Hang , Dexter Carina , Cameron David R. , Monk Ian R. , Baines Sarah L. , Abbott Iain J. , Spelman Denis W. , Kostoulias Xenia , Nethercott Cara , Howden Benjamin P. , Peleg Anton Y.
Published: January 2019

Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS.
Orphan Hybrid Histidine Protein Kinase SinK Acts as a Signal Integrator To Fine-Tune Multicellular Behavior in
Myxococcus xanthus
Authors: Glaser Maike M. , Higgs Penelope I.
Published: January 2019

Biofilms are multicellular communities of microorganisms that play important roles in host disease or environmental biofouling. Design of preventative strategies to block biofilms depends on understanding the molecular mechanisms used by microorganisms to build them. The production of biofilms in bacteria often involves two-component signal transduction systems in which one protein component (a kinase) detects an environmental signal and, through phosphotransfer, activates a second protein component (a response regulator) to change the transcription of genes necessary to produce a biofilm. We show that an atypical kinase, SinK, modulates several distinct stages of specialized biofilm produced by the environmental bacterium
Myxococcus xanthus
. SinK likely integrates multiple signals to fine-tune biofilm formation in response to distinct environmental conditions.
Cross-Domain and Viral Interactions in the Microbiome
Authors: Rowan-Nash Aislinn D. , Korry Benjamin J. , Mylonakis Eleftherios , Belenky Peter
Published: January 2019

The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract.
Decreased Snow Cover Stimulates Under-Ice Primary Producers but Impairs Methanotrophic Capacity
Authors: Garcia Sarahi L. , Szekely Anna J. , Bergvall Christoffer , Schattenhofer Martha , Peura Sari
Published: January 2019

Small lakes are an important source of greenhouse gases in the boreal zone. These lakes are severely impacted by the winter season, when ice and snow cover obstruct gas exchange between the lake and the atmosphere and diminish light availability in the water column. Currently, climate change is resulting in reduced spring snow cover. A short-term removal of the snow from the ice stimulated algal primary producers and subsequently heterotrophic bacteria. Concurrently, the relative abundance of methanotrophic bacteria decreased and methane concentrations increased. Our results increase the general knowledge of microbial life under ice and, specifically, the understanding of the potential impact of climate change on boreal lakes.
Fifteen-minute consultation: Why and how do children get urinary tract infections?
Authors: Tullus Kjell
Published: January 2019

This paper describes urinary tract infections (UTI) from the perspective of a disturbed balance between bacterial virulence and host defence. In some children, a UTI is caused by a virulent Escherichia coli, while in other cases children with abnormal renal tracts can get infected by almost any bacteria. Such knowledge can help in guiding treatment, investigations and follow-up of a child with a UTI.