bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐32γ: Possible association with the activity and development of nephritis in patients with systemic lupus erythematosus
Authors: Kwon Oh Chan , Ghang Byeongzu , Lee Eun‐Ju , Hong Seokchan , Lee Chang‐Keun , Yoo Bin , Kim Soohyun , Kim Yong‐Gil 
Published: April 2019

AbstractAimGrowing evidence suggests that interleukin (IL)‐32 is a cytokine involved in various autoimmune diseases. We aimed to investigate whether IL‐32γ is involved in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis (LN).MethodSera from SLE patients without LN (n = 47), LN patients (n = 19) and healthy controls (n = 10) were collected. The serum concentrations of inflammatory cytokines, including tumor necrosis factor‐α, interferon‐γ, IL‐6, IL‐18, and IL‐32γ, were measured using enzyme‐linked immunosorbent assay. Clinical parameters at the time of sampling were obtained from medical records, and correlations between IL‐32γ and clinical parameters were analyzed by Spearman correlation analysis. Immunohistochemistry evaluating IL‐32 expression was performed in renal tissues of LN patients and healthy controls.ResultsAmong the cytokines measured in sera, the level of IL‐32γ was higher in LN patients than in SLE patients without LN and in healthy controls. Among clinical parameters, concentrations of C3/C4 were lower and erythrocyte sedimentation rate, C‐reactive protein, anti‐double‐stranded DNA (anti‐dsDNA) antibodies, and SLE Disease Activity Index‐2000 (SLEDAI‐2K) were higher in LN patients than in SLE patients without LN. IL‐32γ level was negatively correlated with C3/C4 and positively correlated with anti‐dsDNA antibodies and the renal component of SLEDAI‐2K. In LN patients, IL‐32γ level was positively correlated with the activity and chronicity indices. IL‐32 expression was significantly higher in renal tissues of LN patients than in healthy controls.ConclusionIL‐32γ could be associated with the activity and development of LN in SLE.
Peptides stimulating synthesis of extracellular matrix used in anti‐ageing cosmetics: Are they clinically tested? A systematic review of the literature
Authors: Michalek Irmina Maria , Lelen‐Kaminska Karolina , Caetano dos Santos Florentino Luciano 
Published: April 2019

AbstractPeptides stimulating synthesis of extracellular matrix are now commonly used in the production of anti‐ageing cosmetics. However, much uncertainty still exists about the methodology of their clinical assessment. The aim of the study was to review the literature for clinical study designs assessing the efficacy of these peptides. The authors searched systematically publications indexed in PubMed, Scope and Web of Science, according to the PRISMA protocol. Altogether 12 scientific papers, reporting results of 15 independent studies were identified. Out of these 15 studies, only six used a placebo control. Double‐blinding was applied in five out of 15 studies. Nine studies were based on female‐only populations. For the product performance evaluation, most of the studies (10 out of the 15) used image‐based methods. The literature on the topic is sparse. The studies carried out so far have many methodological limitations. Most of the clinical experiments hitherto conducted were non‐double‐blind and used no placebo control. There is a need for better planned and controlled clinical trials in this area.
Great minds think different: Preserving cognitive diversity in an age of gene editing
Authors: Anomaly Jonathan , Gyngell Christopher , Savulescu Julian 
Published: April 2019

AbstractIt is likely that gene editing technologies will become viable in the current century. As scientists uncover the genetic contribution to personality traits and cognitive styles, parents will face hard choices. Some of these choices will involve trade‐offs from the standpoint of the individual's welfare, while others will involve trade‐offs between what is best for each and what is good for all. Although we think we should generally defer to the informed choices of parents about what kinds of children to create, we argue that decisions to manipulate polygenic psychological traits will be much more ethically complicated than choosing Mendelian traits like blood type. We end by defending the principle of regulatory parsimony, which holds that when legislation is necessary to prevent serious harms, we should aim for simple rules that apply to all, rather than micro‐managing parental choices that shape the traits of their children. While we focus on embryo selection and gene editing, our arguments apply to all powerful technologies which influence the development of children.
Fertility desires and reproductive needs of transgender people: Challenges and considerations for clinical practice
Authors: Feigerlová Eva , Pascal Véronique , Ganne‐Devonec Marie‐Odile , Klein Marc , Guerci Bruno 
Published: April 2019

AbstractThe majority of transgender and gender nonconforming persons seeking medical care are of reproductive age. Hormonal treatment and sex reassignment surgery, which are used in the management of gender dysphoria, compromise fertility potential. Children and adolescents with gender dysphoria have specific treatment regimens starting with puberty‐blocking medications. According to international guidelines, fertility preservation should be discussed before any hormonal treatment, although our knowledge on the reproductive needs of transgender and gender nonconforming persons is limited. Recently, some data have emerged on fertility management in some centres for the adult population with gender dysphoria. The goal of this review was to summarize the available evidence on the fertility desires and parental roles of transgender and gender nonconforming people. In light of newly emerging societal challenges, we aim to provide some considerations for clinical practice and suggest further areas of research.
Relating characteristics of global biodiversity targets to reported progress
Authors: Green Elizabeth J. , Buchanan Graeme M. , Butchart Stuart H. M. , Chandler Georgina M. , Burgess Neil D. , Hill Samantha L. L. , Gregory Richard D. 
Published: April 2019

AbstractTo inform governmental discussions on the nature of a revised Strategic Plan for Biodiversity of the Convention on Biological Diversity (CBD), we reviewed the relevant literature and assessed the framing of the 20 Aichi Biodiversity Targets in the current strategic plan. We asked international experts from nongovernmental organizations, academia, government agencies, international organizations, research institutes, and the CBD to score the Aichi Targets and their constituent elements against a set of specific, measurable, ambitious, realistic, unambiguous, scalable, and comprehensive criteria (SMART based, excluding time bound because all targets are bound to 2015 or 2020). We then investigated the relationship between these expert scores and reported progress toward the target elements by using the findings from 2 global progress assessments (Global Biodiversity Outlook and the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services). We analyzed the data with ordinal logistic regressions. We found significant positive relationships (p < 0.05) between progress and the extent to which the target elements were perceived to be measurable, realistic, unambiguous, and scalable. There was some evidence of a relationship between progress and specificity of the target elements, but no relationship between progress and ambition. We are the first to show associations between progress and the extent to which the Aichi Targets meet certain SMART criteria. As negotiations around the post‐2020 biodiversity framework proceed, decision makers should strive to ensure that new or revised targets are effectively structured and clearly worded to allow the translation of targets into actionable policies that can be successfully implemented nationally, regionally, and globally.
Motor function in children with congenital Zika syndrome
Authors: Melo Adriana , Gama Gabriela L , Da Silva Júnior Renan A , De Assunção Paula L , Tavares Jousilene S , Da Silva Mariana B , Costa Kamila N F S , Vânia Mell L , Evangelista Morgana A , De Amorim Melania M R 
Published: April 2019

AimTo evaluate gross motor function and associated factors in children with congenital Zika syndrome (CZS).MethodFifty‐nine children (30 males, 29 females) with CZS at a mean (SD) age of 14.7 (3.9), months (range 5–29mo) were evaluated using the Gross Motor Function Measure (GMFM) and classified according to the Gross Motor Function Classification System (GMFCS). Neurological damage was evaluated by neuroimaging. The mothers’ sociodemographic characteristics and general data on the children were obtained from interviews with the mothers and from the children's medical records. Correlational and multiple regression analyses were performed to identify factors associated with these children's motor function.ResultsIn 81% of the children, motor function impairment was severe, classified as GMFCS level V. The overall GMFM score ranged from 5 to 210 (median 18; interquartile range 11), with only four children receiving scores in the D and E dimensions. The factors found to affect motor function were the presence of severe malformations of cortical development and small head circumference at birth.InterpretationAlthough motor impairment may be mild in some children, it is generally severe. Severe malformations of cortical development and small head circumference at birth were factors associated with poorer motor function, reflecting the greater severity of brain damage.What this paper adds

Motor impairment is severe in most children with congenital Zika syndrome (CZS).

Motor skills are adequate or close to adequate for age in 7% of children with CZS.

Severe malformations of cortical development are associated with poor motor control.

Small head circumference at birth is also associated with poor motor control.
No beneficial effects of aspirin on secondary cardiovascular prevention in patients with type 2 diabetes using non‐steroidal anti‐inflammatory drugs
Authors: Tsujimoto Tetsuro , Kajio Hiroshi 
Published: April 2019

AbstractThere is little evidence on whether non‐steroidal anti‐inflammatory drugs (NSAIDs) and aspirin interact in secondary cardiovascular prevention in type 2 diabetic patients. This is an observational study using data from the Action to Control Cardiovascular Risk in Diabetes and Follow‐on studies. Hazard ratios (HRs) for mortality with 95% confidence intervals (95% CIs) were calculated using Cox proportional hazard models to compare time to death in patients using and not using aspirin who were simultaneously using or not using NSAIDs. A total of 3600 type 2 diabetic patients with cardiovascular disease were included. During a mean follow‐up period of 8.8 years, 948 patients died. After adjustments, the risk of all‐cause mortality in patients not using NSAIDs was significantly lower in those using aspirin than in those not using aspirin (HR, 0.81; 95% CI, 0.70‐0.93; P = 0.004). The risk in patients using NSAIDs did not differ significantly between the two groups. There was a significant interaction between aspirin use and NSAIDs use. In type 2 diabetic patients with cardiovascular disease, aspirin use was not beneficial for those using NSAIDs.
Loss of striatal tyrosine‐hydroxylase interneurons impairs instrumental goal‐directed behavior
Authors: Kaminer Jaime , Espinoza Diego , Bhimani Shaznaan , Tepper James M. , Koos Tibor , Shiflett Michael W. 
Published: April 2019

AbstractThe striatum mediates a broad range of cognitive and motor functions. Within the striatum, recently discovered tyrosine hydroxylase expressing interneurons (THINs) provide a source of intrastriatal synaptic connectivity that is critical for regulating striatal activity, yet the role of THIN's in behavior remains unknown. Given the important role of the striatum in reward‐based behaviors, we investigated whether loss of striatal THINs would impact instrumental behavior in mice. We selectively ablated striatal THINs in TH‐Cre mice using chemogenetic techniques, and then tested THIN‐lesioned or control mice on three reward‐based striatal‐dependent instrumental tests: (a) progressive ratio test; (b) choice test following selective‐satiety induced outcome devaluation; (c) outcome reinstatement test. Both striatal‐THIN‐lesioned and control mice acquired an instrumental response for flavored food pellets, and their behavior did not differ in the progressive ratio test, suggesting intact effort to obtain rewards. However, striatal THIN lesions markedly impaired choice performance following selective‐satiety induced outcome devaluation. Unlike control mice, THIN‐lesioned mice did not adjust their choice of actions following a change in outcome value. In the outcome reinstatement test THIN‐lesioned and control mice showed response invigoration by outcome presentation, suggesting the incentive properties of outcomes were not disrupted by THIN lesions. Overall, we found that striatal THIN lesions selectively impaired goal‐directed behavior, while preserving motoric and appetitive behaviors. These findings are the first to describe a function of striatal THINs in reward‐based behavior, and further illustrate the important role for intrastriatal interneuronal connectivity in behavioral functions ascribed to the striatum more generally.
The puzzle of philosophical testimony
Authors: Ranalli Chris 
Published: April 2019

AbstractAn epistemologist tells you that knowledge is more than justified true belief. You trust them and thus come to believe this on the basis of their testimony. Did you thereby come to know that this view is correct? Intuitively, there is something intellectually wrong with forming philosophical beliefs on the basis of testimony, and yet it's hard to see why philosophy should be significantly epistemically different from other areas of inquiry in a way that would fully prohibit belief by testimony. This, I argue, is the puzzle of philosophical testimony. In this paper, I explore the puzzle of philosophical testimony and its ramifications. In particular, I examine the case for pessimism about philosophical testimony—the thesis that philosophical belief on the basis of testimony is impossible or is in some way illegitimate—and I argue that it lacks adequate support. I then consider whether the source of the apparent intellectual wrongness of testimonial‐based philosophical belief is grounded in non‐epistemic norms and goals of philosophical practice itself and argue that such norms are implausible, don't conflict with testimonial‐based philosophical belief, or else are mere disciplinary norms, lacking substantial normative force that would make it wrong to form testimonial‐based philosophical belief.
CFP‐1 interacts with HDAC1/2 complexes in C. elegans development
Authors: Pokhrel Bharat , Chen Yannic , Biro Jonathan Joseph 
Published: April 2019

CXXC finger binding protein 1 (CFP‐1) is an evolutionarily conserved protein that binds to non‐methylated CpG‐rich promoters in mammals and Caenorhabditis elegans. This conserved epigenetic regulator is part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET‐2 in C. elegans. Previous studies have indicated the importance of CFP1 in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action of CFP1 is well understood at the organismal level. Here, we have used cfp‐1(tm6369) and set‐2(bn129) C. elegans mutants to investigate the function of CFP‐1 in gene induction and development. We have characterised C. elegansCOMPASS mutants cfp‐1(tm6369) and set‐2(bn129) and found that both cfp‐1 and set‐2 play an important role in the regulation of fertility and development of the organism. Furthermore, we found that both cfp‐1 and set‐2 are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt‐inducible genes. Interestingly, we found that cfp‐1 but not set‐2 genetically interacts with histone deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP‐1 outside of the COMPASS complex. Additionally, we found that cfp‐1 and set‐2 independently regulate fertility and development of the organism. Our results suggest that CFP‐1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within the COMPASS complex. We propose that CFP‐1 could cooperate with the COMPASS complex and/or HDAC1/2 in a context‐dependent manner.
Crystal structure and activation mechanism of DR3 death domain
Authors: Yin Xueying , Li Wenqian , Ma Huan , Zeng Weihong , Peng Chao , Li Yajuan , Liu Muziying , Chen Quan , Zhou Rongbin , Jin Tengchuan 
Published: April 2019

Death receptor 3 (DR3) (a.k.a. tumor necrosis factor receptor superfamily 25) plays a key role in the immune system by activating nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling pathway. Here we present the crystal structures of human and mouse DR3 intracellular death domain (DD) at 2.7 and 2.5 Å resolutions, respectively. The mouse DR3 DD adopts a classical six‐helix bundle structure while human DR3 DD displays an extended fold. Though there is one‐amino‐acid difference in the linker between maltose‐binding protein (MBP) tag and DR3 DD, according to our self‐interaction analysis, the hydrophobic interface discovered in MBP–hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. Furthermore, our biochemical analysis indicates that the sequence variation between human and mouse DR3 DD does not affect its structure and function. Small‐angle X‐ray scattering analysis shows the averaged solution structures of both human and mouse MBP‐DR3 DD are the combination of different conformations with different proportion. Through switching to the open conformation, DR3 DD could improve the interaction with downstream element TNFR‐associated death domain (TRADD). Here we propose an activation‐dependent structural rearrangement model: the DD region is folded as the six‐helix bundles in the resting state, while upon extracellular ligand engagement, it switches to the open conformation, which facilitates its self‐association and the recruitment of TRADD. Our results provide detailed insights into the architecture of DR3 DD and the molecular mechanism of activation.DatabasesAll refined structure coordinates as well as the corresponding structure factors have been deposited in the PDB under the accession codes 5YGS, 5YEV, 5YGP, 5ZNY, 5ZNZ.
Mucocutaneous manifestations in systemic amyloidosis A retrospective analytical study in a tertiary care center
Authors: Flores‐Bozo Luis‐Rodrigo , Echevarría‐Keel Josune , Domínguez‐Cherit Judith , Esquivel‐Pedraza Lilly , Méndez‐Flores Silvia 
Published: April 2019

AbstractBackgroundThe mucocutaneous clinical profile of patients with amyloidosis in Latin America has been scarcely reported.ObjectiveTo describe clinical characteristics of skin and mucosal manifestations in systemic amyloidosis in a tertiary care center in Mexico City.MethodsA cross sectional, retrospective analytical study was performed in patients with systemic amyloidosis over a 15‐year period. Statistical analysis was done.ResultsA total of 98 patients were included (53 [54%] men; overall median age = 49 years old). Acquired systemic immunoglobulin light chain amyloidosis (AL) was the most common (49%) type, followed by (24.5%) wild‐type transthyretin amyloidosis (H‐TTR) (24.5%), undetermined cases (21%), and reactive systemic amyloidosis (AA) (6.1%). There were mucocutaneous manifestations in 34.7% of cases, mostly multiple myeloma‐related AL (ALMM). Head and neck was the most often affected site (38.2%), and purpuric macules were the most common morphology (44.1%). Mucocutaneous affectation was predominantly observed in AL (50.0%) compared to other types (20.0%) of amyloidosis (P = 0.01). Likewise, involvement of organs was also significantly different among the diverse amyloidosis types (P < 0.05). The most frequent comorbidities were hypertension (18.3%) and hypothyroidism (18.3%).ConclusionThe clinical spectrum of manifestations in amyloidosis is wide. Involvement of skin and mucosa in amyloidosis is common; significant differences were observed concerning distribution of mucocutaneous amyloid manifestations among the different types of amyloidosis.
Borderline high serum calcium levels are associated with arterial stiffness and 10‐year cardiovascular disease risk determined by Framingham risk score
Authors: Park Byoungjin , Lee Yong‐Jae 
Published: April 2019

AbstractRecent epidemiological data indicate that the concentration of circulating calcium is related to cardiovascular disease (CVD) mortality. We determined whether serum calcium level is related to arterial stiffness and 10‐year CVD risk calculated by Framingham risk score (FRS). We examined the association of normal‐range serum calcium level with arterial stiffness and FRS in 565 Korean adults participating at the Health Promotion Center of Gangnam Severance Hospital between March 2016 and May 2017. High brachial‐ankle pulse wave velocity (baPWV) was defined as >1460 cm/s, and high FRS was defined as ≥10 percent for 10‐year CVD risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for high baPWV and high FRS were calculated using multiple logistic regression analysis after adjusting for confounding variables. The OR (95% CI) for high baPWV was 3.91 (1.15‐7.36) per 1 mg/dL increment of serum calcium after adjusting for age, sex, body mass index, smoking status, exercise regularity, alcohol consumption, mean blood pressure, fasting plasma glucose, triglyceride, HDL‐cholesterol, C‐reactive protein, γ‐glutamyltransferase, uric acid level, phosphate level, potassium level, and presence of hypertension, diabetes and dyslipidemia medications (P = 0.024). A positive association between serum calcium level and high FRS was also observed after adjusting for the same covariables (OR, 3.54 [95% CI, 1.01‐12.44],P = 0.048). Serum calcium level was independently and positively associated with baPWV and 10‐year CVD risk estimates. Early detection of higher serum calcium level may be important for the assessment of arterial stiffness and future risk of a cardiovascular event.