bluuebunny/crossref_metadata_2025_split huggingface dataset:
RANKL/RANK Pathway and Its Inhibitor RANK-Fc in Uterine Leiomyoma Growth
Authors: Ikhena Deborah E , Liu Shimeng , Kujawa Stacy , Esencan Ecem , Coon John S , Robins Jared , Bulun Serdar E , Yin Ping 
Published: March 2018

Abstract

Context
Uterine leiomyomas are the most common type of gynecologic tumor in women.

Objective
To determine the role of the cytokine receptor activator of nuclear factor κ-Β ligand (RANKL); its receptor, receptor activator of nuclear factor κ-Β (RANK); and the RANKL/RANK pathway inhibitor RANK-Fc in leiomyoma growth.

Design
Messenger RNA (mRNA) or protein levels of RANKL, RANK, and proliferation markers cyclin D1 and Ki67 were assessed in various leiomyoma tissues and cell populations. Human xenograft experiments were performed to determine the effects of RANK-Fc on leiomyoma growth in vivo.

Setting
Research laboratory.

Patients
Twenty-four regularly cycling premenopausal women (age 28 to 49 years) who were not receiving hormone therapy.

Interventions
None.

Main Outcome Measure
Tumor growth in a murine xenograft model following targeting of the RANKL/RANK pathway with RANK-Fc.

Results
RANKL mRNA levels in leiomyoma were significantly higher than those in myometrial tissues. The highest RANK levels were found in the leiomyoma stem cell population, which is deficient in progesterone receptor (PR). Conversely, the highest RANKL levels were found in the PR-rich leiomyoma intermediate cell (LIC) population. R5020, a PR agonist, specifically increased RANKL expression in LICs. RANK-Fc blocked RANKL-induced expression of the proliferative gene cyclin D1. Treatment with RANK-Fc also significantly decreased tumor growth in vivo and diminished the expression of proliferation marker Ki67 in tumors (P &lt; 0.01; n = 4).

Conclusions
Treatment with the RANKL/RANK pathway inhibitor RANK-Fc significantly decreased human leiomyoma cell proliferation and tumor growth. This suggests that the RANKL/RANK pathway could serve as a potential target for the prevention and treatment of uterine leiomyoma.
Identification of protective postexposure mycobacterial vaccine antigens using an immunosuppression-based reactivation model in the zebrafish
Authors: Myllymäki Henna , Niskanen Mirja , Luukinen Hanna , Parikka Mataleena , Rämet Mika 
Published: March 2018

ABSTRACT
Roughly one third of the human population carries a latent Mycobacterium tuberculosis infection, with a 5-10% lifetime risk of reactivation to active tuberculosis and further spreading the disease. The mechanisms leading to the reactivation of a latent Mycobacterium tuberculosis infection are insufficiently understood. Here, we used a natural fish pathogen, Mycobacterium marinum, to model the reactivation of a mycobacterial infection in the adult zebrafish (Danio rerio). A low-dose intraperitoneal injection (∼40 colony-forming units) led to a latent infection, with mycobacteria found in well-organized granulomas surrounded by a thick layer of fibrous tissue. A latent infection could be reactivated by oral dexamethasone treatment, which led to disruption of the granuloma structures and dissemination of bacteria. This was associated with the depletion of lymphocytes, especially CD4+ T cells. Using this model, we verified that ethambutol is effective against an active disease but not a latent infection. In addition, we screened 15 mycobacterial antigens as postexposure DNA vaccines, of which RpfB and MMAR_4207 reduced bacterial burdens upon reactivation, as did the Ag85-ESAT-6 combination. In conclusion, the adult zebrafish-M. marinum infection model provides a feasible tool for examining the mechanisms of reactivation in mycobacterial infections, and for screening vaccine and drug candidates.
This article has an associated First Person interview with the first author of the paper.
Loss of Zbtb32 in NOD mice does not significantly alter T cell responses.
Authors: Coley William D. , Zhao Yongge , Benck Charles J. , Liu Yi , Hotta-Iwamura Chie , Rahman M. Jubayer , Tarbell Kristin V 
Published: March 2018

Background:We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2+dendritic cells (DCs)in vivoinhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2+DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production.Methods:To further understand the role of Zbtb32 in T cell tolerance induction, we have now used CRISPR to target the Zbtb32 gene for deletion directly in NOD mice and characterized the mutant mice. We hypothesized that the systemic loss of Zbtb32 in NOD mice would lead to increased T cell activation and increased diabetes pathogenesis.Results:Although NOD.Zbtb32-/-male NOD mice showed a trend towards increased diabetes incidence compared to littermate controls, the difference was not significant. Furthermore, no significant alteration in lymphocyte number or function was observed. Importantly,in vitrostimulation of lymphocytes from NOD.Zbtb32-/-mice did not produce the expected hypersensitive phenotype observed in other genetic strains, potentially due to compensation by homologous genes.Conclusions:The loss of Zbtb32 in the NOD background does not result in the expected T cell activation phenotype.
Burden of neurodevelopmental disorders in low and middle-income countries: A systematic review and meta-analysis
Authors: Bitta Mary , Kariuki Symon M. , Abubakar Amina , Newton Charles R.J.C 
Published: March 2018

Background: Childhood mortality from infectious diseases has declined steadily in many low and middle-income (LAMIC) countries, with increased recognition of non-communicable diseases such as neurodevelopmental disorders (NDD). There is lack of data on the burden of NDD in LAMIC. Current global burden of these disorders are largely extrapolated from high-income countries. The main objective of the study was therefore to estimate the burden of NDD in LAMIC using meta-analytic techniques. Methods: We systematically searched online databases including Medline/PubMed, PsychoInfo, and Embase for studies that reported prevalence or incidence of NDD. Pooled prevalence, heterogeneity and risk factors for prevalence were determined using meta-analytic techniques. Results: We identified 4,802 records, but only 51 studies met the eligibility criteria. Most studies were from Asia-Pacific (52.2%) and most were on neurological disorders (63.1%). The median pooled prevalence per 1,000 for any NDD was 7.6 (95%CI 7.5-7.7), being 11.3 (11.7-12.0) for neurological disorders and 3.2 (95%CI 3.1-3.3) for mental conditions such as attention-deficit hyperactivity disorder (ADHD). The type of NDD was significantly associated with the greatest prevalence ratio in the multivariable model (PR=2.6(95%CI 0.6-11.6) (P>0.05). Incidence was only reported for epilepsy (mean of 447.7 (95%CI 415.3-481.9) per 100,000). Perinatal complications were the commonest risk factor for NDD. Conclusion: The burden of NDD in LAMIC is considerable. Epidemiological surveys on NDD should screen all types of NDD to provide reliable estimates.
The options for a tooth that requires root canal treatment
Authors: Eliyas Shiyana , Briggs Peter , Gallagher Jennifer E 
Published: March 2018

Abstract: There have been many advances in the replacement of teeth, especially using dental implants. There are a number of other options for when a tooth is lost; however, there is also value in maintaining a tooth with the provision of root canal treatment and a good coronal seal. This article summarizes the advantages and disadvantages of each option with supporting evidence from the literature.CPD/Clinical Relevance: This review article provides an updated practical perspective to decision-making when it comes to teeth requiring root canal treatment.
Post-operative sensitivity and posterior composite resin restorations: a review
Authors: Sabbagh Joseph , Fahd Jean Claude , McConnell Robert J 
Published: March 2018

Abstract: With an increasing use of posterior composite resin restorations, the incidence of post-operative sensitivity has become an everyday clinical problem. The aim of this paper is to identify the possible causes of post-operative sensitivity and explore how it can be avoided and treated. CPD/Clinical Relevance: This paper addresses the different causes responsible for post-operative sensitivity following composite placement. Also the management of this situation is discussed.
Understanding our patient base: an introduction to data analytics in dental practice
Authors: Pritchett Rosie , Coleman Shirley , Campbell James , Pabary Shiv 
Published: March 2018

Abstract: Dental practices are continually collecting patient data but it is often an underutilized resource. There is a growing trend towards use of data analytics within companies to guide business decisions. For dental practices which use digital systems, a large reserve of patient information is readily available. Simple data analytic techniques are presented which can be used to extract substantial insight into patient demographics, DNA (did not attend) rates and many other areas of practical relevance to clinical service delivery and business management. CPD/Clinical Relevance: Data analytics is well established in many industries and has the potential for encouraging colleagues to look at their data and understand their patient base and changes over time; practice owners can gain insight into patient demographics to guide business decisions and improve patient care.
Praca środkiem do ograniczenia wykluczenia społecznego, marginalizacji i ubóstwa
Authors: Heigelmann Małgorzata 
Published: March 2018

Wśród najbardziej palących problemów współczesności wymienić należy ubóstwo, będące efektem wykluczenia społecznego i marginalizacji. Różne mogą być przyczyny tego zjawiska (systemowe, strukturalne, kulturowe i indywidualne). Jednym z trudnych do przyjęcia skutków zjawiska globalizacji jest wzrost bezrobocia i wzrastające dysproporcje poziomu życia. Wpływa to również na ograniczenie możliwości wyrównania szans życiowych. Ojciec Święty Franciszek zdecydowanie przeciwstawia się ekonomii wykluczenia i nierówności społecznej, ponieważ godzi ona w podstawowe prawo do życia. „Ekonomia wykluczenia i nierówności społecznej” prowadzi do najbardziej nieludzkiego potraktowania drugiego człowieka i skazania go na całkowite odrzucenie. Troska o jego integralny rozwój, który może owocować wychodzeniem z tego zaklętego koła, powinna być pierwszorzędnym zadaniem każdego człowieka. Doktor Wanda Błeńska jest przykładem osoby, która inspiruje do poszukiwania sposobów pomocy najuboższym.
Assessing the usefulness of the photogrammetric method in the process of capturing data on parcel boundaries
Authors: Benduch Piotr , Pęska-Siwik Agnieszka 
Published: March 2018

Abstract
A parcel is the most important object of real estate cadastre. Its primary spatial attribute are boundaries, determining the extent of property rights. Capturing the data on boundaries should be performed in the way ensuring sufficiently high accuracy and reliability. In recent years, as part of the project “ZSIN – Construction of Integrated Real Estate Information System – Stage I”, in the territories of the participating districts, actions were taken aimed at the modernization of the register of land and buildings. In many cases, this process was carried out basing on photogrammetric materials. Applicable regulations allow such a possibility. This paper, basing on the documentation from the National Geodetic and Cartographic Documentation Center and on the authors’ own surveys attempts to assess the applicability of the photogrammetric method to capture data on the boundaries of cadastral parcels. The scope of the research, most importantly, included the problem of accuracy with which it was possible to determine the position of a boundary point using photogrammetric surveys carried out on the terrain model created from processed aerial photographs. The article demonstrates the manner of recording this information in the cadastral database, as well as the resulting legal consequences. Moreover, the level of reliability of the entered values of the selected attributes of boundary points was assessed.
Optimal Stratification and Allocation for the June Agricultural Survey
Authors: Lisic Jonathan , Sang Hejian , Zhu Zhengyuan , Zimmer Stephanie 
Published: March 2018

Abstract
A computational approach to optimal multivariate designs with respect to stratification and allocation is investigated under the assumptions of fixed total allocation, known number of strata, and the availability of administrative data correlated with thevariables of interest under coefficient-of-variation constraints. This approach uses a penalized objective function that is optimized by simulated annealing through exchanging sampling units and sample allocations among strata. Computational speed is improved through the use of a computationally efficient machine learning method such as K-means to create an initial stratification close to the optimal stratification. The numeric stability of the algorithm has been investigated and parallel processing has been employed where appropriate. Results are presented for both simulated data and USDA’s June Agricultural Survey. An R package has also been made available for evaluation.
Contrast relations in the early aber-clauses of German-speaking infants
Authors: Bartz Damaris , Bittner Dagmar 
Published: March 2018

Abstract
The paper focusses on the early production of aber- (‘but’-) clauses in German L1-acquisition. It aims to explain the delay in the realization of finite clause structure in aber-clauses reported in a previous study. Delayed realization of finite clause structure was also reported for clauses containing the additive particle auch (‘also/too’) by other researchers. It has been attributed to the information-structural properties of auch-clauses. Following this approach, we investigated the information-structural properties of the aber-clauses documented in the longitudinal data of five monolingual children (age range: 1;11–2;10) from the first documented aber-production to the emergence of finite clause structure in aber-clauses. Information-structural complexity is measured in terms of number and quality of the information-structural patterns of contrastive information in the aber-clause and the explicitness of the contrast realization. Analyses reveal a change in preference from topic-including contrasts to non-topic-including ones, that is, comment-located contrasts as well as a change from explicit to implicit contrast realization. We argue that the delayed realization of finite clause structure in aber-clauses is caused by an initial concentration on the complex content relations raised by the requirement of information-structural alignment of at least two different constituents as well as the anticipating of an implicit proposition.
Major Vault Protein, a Candidate Gene in 16p11.2 Microdeletion Syndrome, Is Required for the Homeostatic Regulation of Visual Cortical Plasticity
Authors: Ip Jacque P.K. , Nagakura Ikue , Petravicz Jeremy , Li Keji , Wiemer Erik A.C. , Sur Mriganka 
Published: March 2018

Microdeletion of a region in chromosome 16p11.2 increases susceptibility to autism. Although this region contains exons of 29 genes, disrupting only a small segment of the region, which spans five genes, is sufficient to cause autistic traits. One candidate gene in this critical segment isMVP, which encodes for the major vault protein (MVP) that has been implicated in regulation of cellular transport mechanisms. MVP expression levels inMVP+/−mice closely phenocopy those of 16p11.2 mutant mice, suggesting thatMVP+/−mice may serve as a model of MVP function in 16p11.2 microdeletion. Here we show that MVP regulates the homeostatic component of ocular dominance (OD) plasticity in primary visual cortex.MVP+/−mice of both sexes show impairment in strengthening of open-eye responses after several days of monocular deprivation (MD), whereas closed-eye responses are weakened as normal, resulting in reduced overall OD plasticity. The frequency of miniature EPSCs (mEPSCs) in pyramidal neurons is decreased inMVP+/−mice after extended MD, suggesting a reduction of functional synapses. Correspondingly, upregulation of surface GluA1 AMPA receptors is reduced inMVP+/−mice after extended MD, and is accompanied by altered expression of STAT1 and phosphorylated ERK, which have been previously implicated in OD plasticity. Normalization of STAT1 levels by introducing STAT1 shRNA rescues surface GluA1 and open-eye responses, implicating STAT1 as a downstream effector of MVP. These findings demonstrate a specific role for MVP as a key molecule influencing the homeostatic component of activity-dependent synaptic plasticity, and potentially the corresponding phenotypes of 16p11.2 microdeletion syndrome.SIGNIFICANCE STATEMENTMajor vault protein (MVP), a candidate gene in 16p11.2 microdeletion syndrome, has been implicated in the regulation of several cellular processes including transport mechanisms and scaffold signaling. However, its role in brain function and plasticity remains unknown. In this study, we identified MVP as an important regulator of the homeostatic component of experience-dependent plasticity, via regulation of STAT1 and ERK signaling. This study helps reveal a new mechanism for an autism-related gene in brain function, and suggests a broader role for neuro-immune interactions in circuit level plasticity. Importantly, our findings might explain specific components of the pathophysiology of 16p11.2 microdeletion syndrome.
The Role of the Mechanotransduction Ion Channel Candidate Nanchung-Inactive in Auditory Transduction in an Insect Ear
Authors: Warren Ben , Matheson Tom 
Published: March 2018

Insect auditory receivers provide an excellent comparative resource to understand general principles of auditory transduction, but analysis of the electrophysiological properties of the auditory neurons has been hampered by their tiny size and inaccessibility. Here we pioneer patch-clamp recordings from the auditory neurons of Müller's organ of the desert locustSchistocerca gregariato characterize dendritic spikes, axonal spikes, and the transduction current. We demonstrate that dendritic spikes, elicited by sound stimuli, trigger axonal spikes, and that both types are sodium and voltage dependent and blocked by TTX. Spontaneous discrete depolarizations summate upon acoustic stimulation to produce a graded transduction potential that in turn elicits the dendritic spikes. The transduction current of Group III neurons of Müller's organ, which are broadly tuned to 3 kHz, is blocked by three ion channel blockers (FM1-43, streptomycin, and 2-APB) that are known to block mechanotransduction channels. We investigated the contribution of the candidate mechanotransduction ion channel Nanchung-Inactive—which is expressed in Müller's organ—to the transduction current. A specific agonist of Nanchung-Inactive, pymetrozine, eliminates the sound-evoked transduction current while inducing a tonic depolarizing current of comparable amplitude. The Nanchung-Inactive ion channels, therefore, have the required conductance to carry the entire transduction current, and sound stimulation appears not to open any additional channels. The application of three mechanotransduction ion channel blockers prevented the pymetrozine-induced depolarizing current. This implies that either Nanchung-Inactive is, or forms part of, the mechanotransduction ion channel or it amplifies a relatively small current (<30 pA) produced by another mechanotransduction ion channel such as NompC.SIGNIFICANCE STATEMENTThe mechanically activated ion channel underpinning hearing is not known. We have pioneered intracellular patch-clamp recordings from locust auditory neurons to unravel the role of the candidate mechanotransduction ion channel Nanchung-Inactive in auditory transduction in insects.
METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes
Authors: Bello-Chavolla Omar Yaxmehen , Almeda-Valdes Paloma , Gomez-Velasco Donaji , Viveros-Ruiz Tannia , Cruz-Bautista Ivette , Romo-Romo Alonso , Sánchez-Lázaro Daniel , Meza-Oviedo Dushan , Vargas-Vázquez Arsenio , Campos Olimpia Arellano , Sevilla-González Magdalena del Rocío , Martagón Alexandro J , Hernández Liliana Muñoz , Mehta Roopa , Caballeros-Barragán César Rodolfo , Aguilar-Salinas Carlos A 
Published: March 2018

ObjectiveWe developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic–hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D).Design and methodsThe discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G0)+TG0)*BMI)/(Ln(HDL-c)) (G0: fasting glucose, TG0: fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects.ResultsMETS-IR demonstrated the better correlation with the MFFM (ρ = −0.622,P < 0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78–0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53–0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels (P < 0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile (>50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25–6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2,P < 0.001).ConclusionMETS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.