bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis
Authors: Lee Kyung-Ann , Kim Kyoung-Woon , Kim Bo-Mi , Won Ji-Yeon , Min Hong Ki , Lee Dhong Won , Kim Hae-Rim , Lee Sang-Heon 
Published: December 2019

Abstract
Background
The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA.

Methods
We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs.

Results
The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL.

Conclusions
IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.
Evaluation of serum iron overload, AST:ALT ratio and log10ferritin:AST ratio among schizophrenia patients in the Kumasi Metropolis, Ghana: a case–control study
Authors: Owiredu W. K. B. A. , Brenya Peter Kojo , Osei Yaw , Laing Edwin Ferguson , Okrah Clement Opoku , Obirikorang Christian , Anto Enoch Odame , Acheampong Emmanuel , Donkor Sampson 
Published: December 2019

Abstract
Objective
The association between unbalanced iron indices and the conditions of schizophrenia are not well understood. Liver dysfunction which has been linked to iron metabolism might be a contributing factor. This case–control study evaluated serum iron indices and liver function in treatment-naïve schizophrenia patients and those already on treatment at the Psychiatric Department of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana.

Results
The mean age of the respondents was 39.6 ± 0.8 years. Increased levels of serum iron, TS, AST, ALT and AST:ALT ratio and lower levels of UIBC, TIBC, Transferrin, and log Ferritin:AST ratio levels were observed among the treatment-naïve group compared to the control. The treatment-naïve and treatment groups showed significantly higher serum AST:ALT ratio, and lower log10ferrtin:AST ratio than the healthy controls. There was a significant correlation between log10ferritin and AST, and log10ferritin and GGT in both treatments (r = 0.343; p = 0.003, and r = 0.502; p = 0.001 respectively) and treatment-naïve groups (r = 0.348; p = 0.002, and r = 0.614; p < 0.001 respectively). Percentage transferrin saturation correlated significantly with GGT only, in the treatment-naïve group (r = 0.667; p < 0.001), and ALT and GGT in the treatment group (r = 0.252; p = 0.030 and r = 0.646; p = 0.014 respectively).
HHV-6A infection induces amyloid-beta expression and activation of microglial cells
Authors: Bortolotti Daria , Gentili Valentina , Rotola Antonella , Caselli Elisabetta , Rizzo Roberta 
Published: December 2019

Abstract
Background
The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression.

Methods
We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay.

Results
We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form.

Conclusions
In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection.
EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease
Authors: Poppe Lindsay , Rué Laura , Timmers Mieke , Lenaerts Annette , Storm Annet , Callaerts-Vegh Zsuzsanna , Courtand Gilles , de Boer Antina , Smolders Silke , Van Damme Philip , Van Den Bosch Ludo , D’Hooge Rudi , De Strooper Bart , Robberecht Wim , Lemmens Robin 
Published: December 2019

AbstractBackgroundEphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer’s disease (AD), characterized by synapse dysfunction and loss, and the progressive loss of memory and other cognitive functions. Reduced EphA4 signaling has been shown to rescue beta-amyloid-induced dendritic spine loss and long-term potentiation (LTP) deficits in cultured hippocampal slices and primary hippocampal cultures. In this study, we investigated whether EphA4 ablation might preserve synapse function and ameliorate cognitive performance in the APPPS1 transgenic mouse model of AD.MethodsA postnatal genetic ablation of EphA4 in the forebrain was established in the APPPS1 mouse model of AD, followed by a battery of cognitive tests at 9 months of age to investigate cognitive function upon EphA4 loss. A Golgi-Cox staining was used to explore alterations in dendritic spine density and morphology in the CA1 region of the hippocampus.ResultsUpon EphA4 loss in APPPS1 mice, we observed improved social memory in the preference for social novelty test without affecting other cognitive functions. Dendritic spine analysis revealed altered synapse morphology as characterized by increased dendritic spine length and head width. These modifications were independent of hippocampal plaque load and beta-amyloid peptide levels since these were similar in mice with normal versus reduced levels of EphA4.ConclusionLoss of EphA4 improved social memory in a mouse model of Alzheimer’s disease in association with alterations in spine morphology.
Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD)
Authors: Schmitt Lauren M. , Bojanek Erin , White Stormi P. , Ragozzino Michael E. , Cook Edwin H. , Sweeney John A. , Mosconi Matthew W. 
Published: December 2019

Abstract
Background
Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD.

Methods
We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+).

Results
Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP− parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively.

Conclusion
Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits.
Assessment of brain delivery of a model ABCB1/ABCG2 substrate in patients with non-contrast-enhancing brain tumors with positron emission tomography
Authors: Wulkersdorfer Beatrix , Bauer Martin , Karch Rudolf , Stefanits Harald , Philippe Cécile , Weber Maria , Czech Thomas , Menet Marie-Claude , Declèves Xavier , Hainfellner Johannes A. , Preusser Matthias , Hacker Marcus , Zeitlinger Markus , Müller Markus , Langer Oliver 
Published: December 2019

Abstract
Background
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood–brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood–brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors.

Materials and methods
We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [11C]tariquidar, a prototypical ABCB1/ABCG2 substrate, in seven patients with non-contrast -enhancing brain tumors (WHO grades I–III). In addition, ABCB1 and ABCG2 levels were determined in surgically resected tumor tissue of four patients using quantitative targeted absolute proteomics.

Results
Brain distribution of [11C]tariquidar was found to be very low across the whole brain and not significantly different between tumor and tumor-free brain tissue. Only one patient showed a small area of enhanced [11C]tariquidar uptake within the brain tumor. ABCG2/ABCB1 ratios in surgically resected tumor tissue (1.4 ± 0.2) were comparable to previously reported ABCG2/ABCB1 ratios in isolated human micro-vessels (1.3), which suggested that no overexpression of ABCB1 or ABCG2 occurred in the investigated tumors.

Conclusions
Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity.

Trial registration
European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.
Patient-reported data informing early benefit assessment of rare diseases in Germany: A systematic review
Authors: Babac Ana , Damm Kathrin , Graf von der Schulenburg J.-Matthias 
Published: December 2019

AbstractBackgroundSince the implementation of the Regulation on Patient Integration (2003), the Act on the Reorganization of the Pharmaceutical Market (2011), and the Patient Rights Law (2013), the inclusion of patient perspectives has been further anchored in the German early benefit assessment process. During the assessment of rare disease interventions, patient perspectives are particularly important, as clinical studies are often designed acknowledging small samples and patients suffering from severe symptoms and the chronic course of the disease. Therefore, our research question is whether patient perspectives are considered as part of early benefit assessments for rare diseases. We also strive to examine how patient perspectives are methodologically elicited and presented.MethodsOur empirical evidence comes from a systematic review of orphan drug value dossiers submitted to the German Federal Joint Committee as well as the corresponding evaluations conducted between January 1, 2011 and March 1, 2019 (n = 81). Data on patient perspective integration were extracted using the following patient-reported outcome subcategories: clinical patient-reported outcomes, health-related quality of life, patient preferences, and patient satisfaction.ResultsThe analysis demonstrates the specific relevance of patient-reported outcomes raised as part of the medical data set and presented during the early benefit assessment process. They are predominantly presented in the form of health-related quality of life data (n = 75%) and clinical outcomes (n = 49%). Preferences (n = 2%) and satisfaction (n = 1%) are still rarely presented, although the heated methodological discussion in Germany would suggest otherwise. While various methodologies for the integration of clinical outcomes and quality of life data were found, presenting data on satisfaction and preferences still lacks methodological rigor. The German Federal Joint Committee has not yet integrated these data in their decision text. Clinical outcomes and quality of life have been included in 46% and 73% of the cases, respectively.ConclusionsThe underlying analysis demonstrates that there is still a relative high potential for the regular and systematic inclusion of patient perspectives within the early benefit assessment process for rare diseases. In particular, patient preferences and patient satisfaction are still rarely included suggesting the need for a clear-cut methodological foundation and incentives.
Periodic solutions for second order damped boundary value problem with nonnegative Green’s functions
Authors: Jiang Yongxin 
Published: December 2019

AbstractIn this article, we study the existence of positive periodic solutions of second order damped boundary value problem$u'' + p(t)u'+q(t)u = g(t,u,u')$u″+p(t)u′+q(t)u=g(t,u,u′),$u(0) = u(T )$u(0)=u(T),$u'(0) = u'(T )$u′(0)=u′(T). The main tools are the nonlinear alternative principle of Leray–Schauder and Schauder’s fixed point theorem. We emphasize that the damped term and nonnegative Green’s functions are the key points. We also apply the results to examples for testing. Some recent results in the literature are improved and generalized.
A fourth order non-polynomial quintic spline collocation technique for solving time fractional superdiffusion equations
Authors: Amin Muhammad , Abbas Muhammad , Iqbal Muhammad Kashif , Ismail Ahmad Izani Md. , Baleanu Dumitru 
Published: December 2019

AbstractThe purpose of this article is to present a technique for the numerical solution of Caputo time fractional superdiffusion equation. The central difference approximation is used to discretize the time derivative, while non-polynomial quintic spline is employed as an interpolating function in the spatial direction. The proposed method is shown to be unconditionally stable and$O(h^{4}+\Delta t^{2})$O(h4+Δt2)accurate. In order to check the feasibility of the proposed technique, some test examples have been considered and the simulation results are compared with those available in the existing literature.
A discrete-time mathematical model of stage-structured mosquito populations
Authors: Xing Yanyuan , Liu Jian , Guo Zhiming 
Published: December 2019

AbstractThis paper proposes a system of difference equations to model mosquito population. In this study, we develop and analyze the stage-structured models which consist of four distinct mosquito metamorphic stages: eggs, larvae, pupae, and adults. First, a model with constant birth rate is studied, and the inherent net reproduction number $\Re _{0}$ℜ0 of the model is derived. If $\Re _{0}<1$ℜ0<1, the extinction equilibrium is globally asymptotically stable. If $\Re _{0}>1$ℜ0>1, there exists a unique positive equilibrium which is uniformly persistent. When breeding is seasonal for a special case, it indicates that a unique globally asymptotically stable periodic solution is admitted when the net reproductive number is larger than one. When this value is less than one, the mosquito population goes to extinction. Finally, numerical simulations to demonstrate our findings and brief discussion are also provided.
An adaptive moving mesh method for a time-fractional Black–Scholes equation
Authors: Huang Jian , Cen Zhongdi , Zhao Jialiang 
Published: December 2019

AbstractIn this paper we study the numerical method for a time-fractional Black–Scholes equation, which is used for option pricing. The solution of the fractional-order differential equation may be singular near certain domain boundaries, which leads to numerical difficulty. In order to capture the singular phenomena, a numerical method based on an adaptive moving mesh is developed. A finite difference method is used to discretize the time-fractional Black–Scholes equation and error analysis for the discretization scheme is derived. Then, an adaptive moving mesh based on an a priori error analysis is established by equidistributing monitor function. Numerical experiments support these theoretical results.
Coordinating across correctional, community, and VA systems: applying the Collaborative Chronic Care Model to post-incarceration healthcare and reentry support for veterans with mental health and substance use disorders
Authors: Kim Bo , Bolton Rendelle E. , Hyde Justeen , Fincke B. Graeme , Drainoni Mari-Lynn , Petrakis Beth Ann , Simmons Molly M. , McInnes D. Keith 
Published: December 2019

Abstract
Background
Between 12,000 and 16,000 veterans leave incarceration annually. As is known to be the case for justice-involved populations in general, mental health disorders (MHDs) and substance use disorders (SUDs) are highly prevalent among incarcerated veterans, and individuals with MHDs and SUDs reentering the community are at increased risk of deteriorating health and recidivism. We sought to identify opportunities to better coordinate care/services across correctional, community, and VA systems for reentry veterans with MHDs and SUDs.

Methods
We interviewed 16 veterans post-incarceration and 22 stakeholders from reentry-involved federal/state/community organizations. We performed a grounded thematic analysis, and recognizing consistencies between the emergent themes and the evidence-based Collaborative Chronic Care Model (CCM), we mapped findings to the CCM’s elements – work role redesign (WRR), patient self-management support (PSS), provider decision support (PDS), clinical information systems (CIS), linkages to community resources (LCR), and organizational/leadership support (OLS).

Results
Emergent themes included (i) WRR – coordination challenges among organizations involved in veterans’ reentry; (ii) PSS – veterans’ fear of reentering society; (iii) PDS – uneven knowledge by reentry support providers regarding available services when deciding which services to connect a reentry veteran to and whether he/she is ready and/or willing to receive services; (iv) CIS – lapses in MHD/SUD medications between release and a first scheduled health care appointment, as well as challenges in transfer of medical records; (v) LCR – inconsistent awareness of existing services and resources available across a disparate reentry system; and (vi) OLS – reentry plans designed to address only immediate transitional needs upon release, which do not always prioritize MHD/SUD needs.

Conclusions
Applying the CCM to coordinating cross-system health care and reentry support may contribute to reductions in mental health crises and overdoses in the precarious first weeks of the reentry period.
Challenges and responses to infant and young child feeding in rural Rwanda: a qualitative study
Authors: Ahishakiye Jeanine , Bouwman Laura , Brouwer Inge D. , Matsiko Eric , Armar-Klemesu Margaret , Koelen Maria 
Published: December 2019

AbstractBackgroundDespite different interventions to improve child nutrition conditions, chronic malnutrition is still a public health concern in Rwanda, with a high stunting prevalence of 38% among under 5-year-olds children. In Rwanda, only 18% of children aged 6–23 months are fed in accordance with the recommendations for infant and young child feeding practices. The aim of this study was to explore challenges to infant and young child feeding practices and the responses applied to overcome these challenges in Muhanga District, Southern province of Rwanda.MethodsSixteen (16) focus group discussions were held with mothers, fathers, grandmothers, and community health workers from 4 rural sectors of Muhanga District. The discussions were recorded, transcribed verbatim, and thematically analyzed using qualitative data analysis software, Atlas.ti.ResultsTwo main themes emerged from the data. Firstly, there was a discourse on optimal infant and young child feeding (IYCF) practices that reflects the knowledge and efforts to align with early initiation of breastfeeding, exclusive breastfeeding for the first 6 months, as well as initiation of complementary foods at 6 months recommendations. Secondly, challenging situations against optimal practices and coping responses applied were presented in a discourse on struggling with everyday reality. The challenging situations that emerged as impeding appropriate IYCF practices included perceived lack of breast milk, infant cues, women’s heavy workload, partner relations and living in poverty. Family and social support from community health workers and health facility staff, financial support through casual labor, and mothers saving and lending groups, as well as kitchen gardens, were used to cope with challenges.ConclusionFactors influencing IYCF practices are multifaceted. Hence, intervention strategies to improve child nutrition should acknowledge the socially embedded nature of IYCF and address economic and social environmental constraints and opportunities, in addition and above knowledge only.