bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Inference Accounting for Unobserved Confounding After Outcome Regression and Doubly Robust Estimation
Authors: Genbäck Minna , de Luna Xavier 
Published: November 2018

AbstractCausal inference with observational data can be performed under an assumption of no unobserved confounders (unconfoundedness assumption). There is, however, seldom clear subject-matter or empirical evidence for such an assumption. We therefore develop uncertainty intervals for average causal effects based on outcome regression estimators and doubly robust estimators, which provide inference taking into account both sampling variability and uncertainty due to unobserved confounders. In contrast with sampling variation, uncertainty due to unobserved confounding does not decrease with increasing sample size. The intervals introduced are obtained by modeling the treatment assignment mechanism and its correlation with the outcome given the observed confounders, allowing us to derive the bias of the estimators due to unobserved confounders. We are thus also able to contrast the size of the bias due to violation of the unconfoundedness assumption, with bias due to misspecification of the models used to explain potential outcomes. This is illustrated through numerical experiments where bias due to moderate unobserved confounding dominates misspecification bias for typical situations in terms of sample size and modeling assumptions. We also study the empirical coverage of the uncertainty intervals introduced and apply the results to a study of the effect of regular food intake on health. An R-package implementing the inference proposed is available.
Convex Clustering Analysis for Histogram-Valued Data
Authors: Park Cheolwoo , Choi Hosik , Delcher Chris , Wang Yanning , Yoon Young Joo 
Published: November 2018

Abstract
In recent years, there has been increased interest in symbolic data analysis, including for exploratory analysis, supervised and unsupervised learning, time series analysis, etc. Traditional statistical approaches that are designed to analyze single-valued data are not suitable because they cannot incorporate the additional information on data structure available in symbolic data, and thus new techniques have been proposed for symbolic data to bridge this gap. In this article, we develop a regularized convex clustering approach for grouping histogram-valued data. The convex clustering is a relaxation of hierarchical clustering methods, where prototypes are grouped by having exactly the same value in each group via penalization of parameters. We apply two different distance metrics to measure (dis)similarity between histograms. Various numerical examples confirm that the proposed method shows better performance than other competitors.
The efficacy of learning analytics interventions in higher education: A systematic review
Authors: Larrabee Sønderlund Anders , Hughes Emily , Smith Joanne 
Published: November 2018

AbstractEducational institutions are increasingly turning to learning analytics to identify and intervene with students at risk of underperformance or discontinuation. However, the extent to which the current evidence base supports this investment is currently unclear, and particularly so in relation to the effectiveness of interventions based on predictive models. The aim of the present paper was to conduct a systematic review and quality assessment of studies on the use of learning analytics in higher education, focusing specifically on intervention studies. Search terms identified 689 papers, but only 11 studies evaluated the effectiveness of interventions based on learning analytics. These studies highlighted the potential of such interventions, but the general quality of the research was moderate, and left several important questions unanswered. The key recommendation based on this review is that more research into the implementation and evaluation of scientifically driven learning analytics is needed to build a solid evidence base for the feasibility, effectiveness and generalizability of such interventions. This is particularly relevant when considering the increasing tendency of educational institutions around the world to implement learning analytics interventions with only little evidence of their effectiveness.
Practitioner NotesWhat is already known about this topic?

Drop‐out rates and underachivement is a significant issue at most Western universities.
Learning analytics have been shown to predict student performance and risk of dropping out.
Interventions based on learning analytics have emerged in recent years, some reportedly successful.
What this paper adds

The paper also reviews and synthesizes the evidence on the effectiveness of learning analytics interventions targeting student underperformance, experience and discontinuation.
The paper compares and contrasts past and current learning analytics methods and foci, and makes recommendations for the future research and practice.
It critically synthesizes the current evidence base on learning analytics interventions, which is a field that is in constant flux and development.
Implications for practice and/or policy

The paper focuses on an increasing part of higher education with the goal of validating learning analytics methods and usefulness.
The paper makes evidence‐based recommendations for institutions wishing to implement learning analytics programs and/or interventions.
The paper makes evidence‐based recommendations for instructors as well as researchers in the field.
Nuclear factor‐kappa B‐dependent X‐box binding protein 1 signalling promotes the proliferation of nucleus pulposus cells under tumour necrosis factor alpha stimulation
Authors: Chen Lu , Xie Zhi‐Yang , Liu Lei , Zhu Lei , Wang Feng , Fan Pan , Sinkemani Arjun , Zhang Cong , Hong Xin , Wu Xiao‐Tao 
Published: November 2018

AbstractObjectivesTumour necrosis factor alpha (TNF‐α) expressed by nucleus pulposus cells (NPCs) plays a critical role in intervertebral disc (IVD) degeneration. A key unfolded protein response (UPR) component, X‐box binding protein 1 (XBP1) and nuclear factor‐kappa B (NF‐κB) are essential for cell survival and proliferation. The aim of our study was to elucidate the roles of XBP1 and NF‐κB in IVD degeneration (IDD).Materials and methodsRat NPCs were cultured with TNF‐α in the presence or absence of XBP1 and NF‐κB‐p65 small interfering RNA. The associated genes and proteins were evaluated through quantitative real‐time PCR, Western blot analyses and immunofluorescence staining to monitor UPR and NF‐κB signalling and identify the regulatory mechanism of p65 by XBP1. Cell counting kit‐8 assay, cell cycle analysis and related gene and protein expression were performed to examine the proliferation of NPCs.ResultsThe acute exposure of TNF‐α accelerated the proliferation of rat NPCs by activating the UPR/XBP1 pathway. XBP1 signalling favoured the phosphorylation and nuclear translocation of p65 subunit of NF‐κB. The activation of NF‐κB in the later phase also enhanced NPC proliferation.ConclusionsUnfolded protein response reinforces the survival and proliferation of NPCs under TNF‐α stimulation by activating the XBP1 pathway, and NF‐κB serves as a vital mediator in these events. The XBP1 signalling of UPR can be a novel therapeutic target in IDD.
High concordance of BRAF mutational status in matched primary and metastatic melanoma
Authors: Cormican David , Kennedy Ciaran , Murphy Sandra , Werner Reiltin , Power Derek G. , Heffron Cynthia C. B. B. 
Published: November 2018

BackgroundTechniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites.MethodsBetween 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these cases, paired primary and metastatic specimens were available for polymerase chain reaction (PCR) and immunohistochemical evaluation.ResultsFifty‐two out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by immunohistochemistry (IHC). In one case, a metastasis and its matched primary were positive by IHC, but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary, and repeat PCR in the metastasis was positive, following macrodissection.ConclusionsOur results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, IHC provided strong evidence that initial PCR testing had provided a false‐negative result due to low tumor volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumor can be used with confidence.
Increased expression of PD1 and CD39 on CD3+CD4+ skin T cells in the elderly
Authors: Zuelgaray Elina , Boccara David , Ly Ka So Sophie , Boismal Françoise , Mimoun Maurice , Bagot Martine , Bensussan Armand , Bouaziz Jean‐David , Michel Laurence 
Published: November 2018

AbstractNormal ageing is associated with an impaired systemic immune response contributing to an increased susceptibility to infectious diseases. The aim of this study was to compare the lymphocyte phenotype in human skin from old and young healthy subjects. Skin samples from donors were used for explant cultures before flow cytometric analysis. Our results depicted a higher proportion of CD4+ and a lower proportion of CD8+ among CD3+ T cells, a decreased proportion of CD45RA+ naive T cells (3.5 ± 1.9% vs 22.9 ± 11.1%, P ≤ 0.007) and an upregulation of the expression of CD39 and PD1 on CD3+CD4+ T cells (25.1 ± 8.5% vs 12.5 ± 8.5%, P ≤ 0.003, 68.8 ± 11.6% vs 50.0 ± 11.3%, P ≤ 0.01, respectively) in the skin of old subjects. These findings could explain a reduced generation of long‐lived memory T cells and an impaired antitumoral response in the skin of the elderly.
Tacrolimus overexposure in kidney transplant recipients during the first post‐operative week: caution is required in older patients
Authors: Lemaitre Florian , Lorcy Nolwen , Tron Camille , Golbin Léonard , Petitcollin Antoine , Verdier Marie‐Clémence , Vigneau Cécile , Bellissant Eric 
Published: November 2018

AbstractIn liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post‐transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.
Phosphomimetic‐mediated in vitro rescue of hypertrophic cardiomyopathy linked to R58Q mutation in myosin regulatory light chain
Authors: Yadav Sunil , Kazmierczak Katarzyna , Liang Jingsheng , Sitbon Yoel H. , Szczesna‐Cordary Danuta 
Published: November 2018

Myosin regulatory light chain (RLC) phosphorylation is important for cardiac muscle mechanics/function as well as for the Ca2+‐troponin/tropomyosin regulation of muscle contraction. This study focuses on the arginine to glutamine (R58Q) substitution in the human ventricular RLC (MYL2 gene), linked to malignant hypertrophic cardiomyopathy in humans and causing severe functional abnormalities in transgenic (Tg) R58Q mice, including inhibition of cardiac RLC phosphorylation. Using a phosphomimic recombinant RLC variant where Ser‐15 at the phosphorylation site was substituted with aspartic acid (S15D) and placed in the background of R58Q, we aimed to assess whether we could rescue/mitigate R58Q‐induced structural/functional abnormalities in vitro. We show rescue of several R58Q‐exerted adverse phenotypes in S15D‐R58Q‐reconstituted porcine cardiac muscle preparations. A low level of maximal isometric force observed for R58Q‐ versus WT‐reconstituted fibers was restored by S15D‐R58Q. Significant beneficial effects were also observed on the Vmax of actin‐activated myosin ATPase activity in S15D‐R58Q versus R58Q‐reconstituted myosin, along with its binding to fluorescently labeled actin. We also report that R58Q promotes the OFF state of myosin, both in reconstituted porcine fibers and in Tg mouse papillary muscles, thereby stabilizing the super‐relaxed state (SRX) of myosin, characterized by a very low ATP turnover rate. Experiments in S15D‐R58Q‐reconstituted porcine fibers showed a mild destabilization of the SRX state, suggesting an S15D‐mediated shift in disordered‐relaxed (DRX)↔SRX equilibrium toward the DRX state of myosin. Our study shows that S15D‐phosphomimic can be used as a potential rescue strategy to abrogate/alleviate the RLC mutation‐induced phenotypes and is a likely candidate for therapeutic intervention in HCM patients.
An experimental investigation on the fatigue crack growth behaviour of AISI/SAE 1045 under load sequences containing underloads
Authors: Richter Hannes , Sander Manuela 
Published: November 2018

AbstractThe estimation of load interaction effects is essential for residual lifetime calculations of components with cracks. Whereas overloads are widely investigated, there is still no consensus about the effects and mechanisms of underloads. For this reason, load sequences containing underloads are experimentally examined within this paper. Because Kmax and R are not appropriate for describing the cyclic crack tip loading at tension/compression loading, the σtip concept is used to quantify the crack driving force at compressive loads. Among others, the tests also include load sequences that have not been reported in the literature yet like underloads that are applied at a certain distance after an overload. The influence of underloads on crack arrest is also investigated. The experimental tests are performed with the tool steel AISI/SAE 1045.
The spatial scale of homogenisation and differentiation in Chihuahuan Desert fish assemblages
Authors: Taylor Christopher M. , Miyazono Seiji , Cheek Christopher A. , Edwards Robert J. , Patiño Reynaldo 
Published: November 2018

Abstract

We examined riverine desert fish assemblages in the Chihuahuan Desert, U.S.A. at multiple spatial scales of similarity to assess long‐term changes to assemblage distinctiveness, identify individual species responsible for changes, and determine the importance of geographic context and species resolution in interpreting patterns of change.

We used a well‐documented historical data set on fish distribution and abundance, and recent collections of fishes that provided a paired analytical design across 36 localities spanning nearly 3 decades. Patterns of faunal homogenisation and differentiation were assessed at basin‐wide, sub‐basin and river‐reach scales with species occurrence and relative abundance data. Individual species responses were examined to identify the drivers of assemblage change across time.

Patterns of assemblage similarity varied across spatial scales and produced seemingly incongruous trends across time. Assemblage distinctiveness depended on the spatial extent of the analyses, the geographical structuring of the fish assemblages, and whether occurrence or relative abundance data were used. These dependencies led to interesting and conflicting patterns of homogenisation and differentiation. The Rio Grande sub‐basin showed strong homogenisation with convergence between upstream and downstream reaches that corresponded to declining water quality and quantity from the Rio Conchos in Mexico. In contrast, the Pecos River sub‐basin showed strong differentiation between upstream and downstream reaches that corresponded to the successful colonisation and spread of the non‐native gulf killifish (Fundulus grandis) in the upper reach, where water quantity and quality have declined. Spatial variability in fish assemblages and their degree of change from historical conditions were largely congruent with anthropogenic modifications to the flow regime and variability in the success of invasive gulf killifish in the basin.

The use of species occurrence as opposed to relative abundance data, and the spatial scale of analysis are crucial choices in studies of faunal homogenisation and differentiation, and we have demonstrated how these choices lead to variable results for our study system. Our multi‐scale approach and examination of individual species responses identified the ultimate drivers of these differences and illustrated the importance of scale‐dependent effects and geographical context on patterns of assemblage distinctiveness, especially with regard to species invasion, species loss and relative abundance shifts.
Organismal stoichiometry at the temporal scale: Seasonal variability shapes interspecific differences in fish
Authors: Mozsár Attila , Sály Péter , Antal László , Nagy Sándor Alex , Boros Gergely 
Published: November 2018

Abstract

Changes in organismal stoichiometry (OS) may be driven by seasonal changes in lipid reserves (i.e. energy) and gonadal development in fish. However, these relationships are understudied. Hence, we investigated how seasonal changes in body lipid content and gonadal development can drive the seasonal variability of OS traits at the example of three coexisting freshwater fish species. Furthermore, we aimed to assess the importance of seasonal OS alteration in comparison with interspecific differences.

Carbon (%C), nitrogen (%N) and phosphorus (%P) contents, and the molar ratios of these elements (C:N, C:P and N:P) were examined in rudd (Scardinius erythrophthalmus), pumpkinseed (Lepomis gibbosus) and Amur sleeper (Perccottus glenii). We consider the sex and seasonal changes in body size as a potential factor in shaping OS.

Substantial seasonal intraspecific variability occurred in all OS traits. Its extent exceeded interspecific differences in %C, %N and C:N, while %P and C:P, N:P were determined primarily by species identity. The effect of sex occurred sporadically and was considerable in some cases. Seasonal changes in total length did not contribute to intraspecific variability of OS. Intra‐annual changes in body lipid content affected seasonal variability of OS traits substantially, but the strength of this effect was species‐specific. The regulatory role of lipid reserve alterations worked only for those species that exhibited considerable seasonal variation in body fat content. Gonado‐somatic index proved to be marginal in shaping seasonal changes in OS, presumably because a substantial portion of the essential elemental demand for gonadal growth is supplied by rearrangements within the body, without notable changes in the entire elemental composition.

In the light of our findings, we suggest that more attention should be given to the influence of seasonal variability in OS traits, and sex should be considered as a taxon‐dependent effect. Ignoring this substantial degree of variability might lead to inaccuracies in assessing the extent of both intra‐ and interspecific OS differences. We conclude that seasonal OS variability might shape consumer‐driven nutrient dynamics.
Whole exome sequencing in the diagnostic workup of patients with a bleeding diathesis
Authors: Saes Joline L. , Simons Annet , de Munnik Sonja A. , Nijziel Marten R. , Blijlevens Nicole M. A. , Jongmans Marjolijn C. , van der Reijden Bert A. , Smit Yolba , Brons Paul P. , van Heerde Waander L. , Schols Saskia E. M. 
Published: November 2018

IntroductionBleeding assessment tools and laboratory phenotyping often remain inconclusive in patients with a haemorrhagic diathesis.AimTo describe the phenotype and genetic profile of patients with a bleeding tendency.MethodsWhole exome sequencing (WES) was incorporated in the routine diagnostic pathway of patients with thrombocytopenia (n = 17), platelet function disorders (n = 19) and an unexplained bleeding tendency (n = 51). The analysis of a panel of 126 OMIM (Online Mendelian Inheritance in Man) genes involved in thrombosis and haemostasis was conducted, and if negative, further exome‐wide analysis was performed if informed consent given.ResultsEighteen variants were detected in 15 patients from a total of 87 patients (17%). Causative variants were observed in MYH9 (two cases), SLFN14, P2RY12 and GP9. In addition, one case was considered solved due to combined carriership of F7 and F13A1 variants and one with combined carriership of F2, F8 and VWF, all variants related to secondary haemostasis protein aberrations. Two variants of uncertain significance (VUS) were found in two primary haemostasis genes: GFI1B and VWF. Eight patients were carriers of autosomal recessive disorders. Exome‐wide analysis was performed in 54 cases and identified three variants in candidate genes.ConclusionBased on our findings, we conclude that performing WES at the end of the diagnostic trajectory can be of additive value to explain the complete bleeding phenotype in patients without a definite diagnosis after conventional laboratory tests. Discovery of combinations of (novel) genes that predispose to bleeding will increase the diagnostic yield in patients with an unexplained bleeding diathesis.
Halitosis: Helicobacter pylori or oral factors
Authors: Anbari Fahimeh , Ashouri Moghaddam Anahita , Sabeti Elham , Khodabakhshi Azin 
Published: November 2018

AbstractIntroductionHalitosis is a common complaint among people which has various socioeconomic effects. The prevalence of halitosis includes a variety of 22% up to 50% in different societies. According to studies, there have been reports of remarkable improvements in halitosis after Helicobacter pylori eradication treatment. In studies on the relationship between H. Pylori and halitosis, the role of oral factors as the most important cause of halitosis has been neglected. This study was conducted with the aim of investigating the effect of oral factors on halitosis in patients with H. Pylori.Materials and MethodsA total of 100 dyspeptic patients who had H. pylori‐positive serologic test were examined by an organoleptic method for the presence of halitosis. DMFT index was used in order to record the dental status. Oral hygiene was evaluated using the simplified oral hygiene index (OHI‐S).ResultsThe mean DMFT index was 9.09 ± 3.97. The score of simplified oral hygiene index was 1.79 ± 0.949. There was a direct and significant relationship between halitosis with DMFT, OHI‐S (P < 0.01). There was no significant relationship between halitosis and coated tongue (P > 0.01).ConclusionsAccording to the results of this study, there is a relation between oral factors and halitosis in patients with positive H. pylori test. Due to the lower level of all these indices in patients with halitosis, we cannot attribute halitosis in patients with H. pylori infection to the presence of this microorganism with certainty.