bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocyte–microglial association and matrix composition are common events in the natural history of primary familial brain calcification
Authors: Nahar Khayrun , Lebouvier Thibaud , Andaloussi Mäe Maarja , Konzer Anne , Bergquist Jonas , Zarb Yvette , Johansson Bengt , Betsholtz Christer , Vanlandewijck Michael 
Published: September 2019

AbstractPrimary familial brain calcification (PFBC) is an age‐dependent and rare neurodegenerative disorder characterized by microvascular calcium phosphate deposits in the deep brain regions. Known genetic causes of PFBC include loss‐of‐function mutations in genes involved in either of three processes—platelet‐derived growth factor (PDGF) signaling, phosphate homeostasis or protein glycosylation—with unclear molecular links. To provide insight into the pathogenesis of PFBC, we analyzed murine models of PFBC for the first two of these processes in Pdgfbret/ret and Slc20a2−/− mice with regard to the structure, molecular composition, development and distribution of perivascular calcified nodules. Analyses by transmission electron microscopy and immunofluorescence revealed that calcified nodules in both of these models have a multilayered ultrastructure and occur in direct contact with reactive astrocytes and microglia. However, whereas nodules in Pdgfbret/ret mice were large, solitary and smooth surfaced, the nodules in Slc20a2−/− mice were multi‐lobulated and occurred in clusters. The regional distribution of nodules also differed between the two models. Proteomic analysis and immunofluorescence stainings revealed a common molecular composition of the nodules in the two models, involving proteins implicated in bone homeostasis, but also proteins not previously linked to tissue mineralization. While the brain vasculature of Pdgfbret/ret mice has been reported to display reduced pericyte coverage and abnormal permeability, we found that Slc20a2−/− mice have a normal pericyte coverage and no overtly increased permeability. Thus, lack of pericytes and increase in permeability of the blood–brain barrier are likely not the causal triggers for PFBC pathogenesis. Instead, gene expression and spatial correlations suggest that astrocytes are intimately linked to the calcification process in PFBC.
Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network
Authors: Pouget Celso , Hergalant Sébastien , Lardenois Emilie , Lacomme Stéphanie , Houlgatte Rémi , Carpentier Catherine , Dehais Caroline , Rech Fabien , Taillandier Luc , Sanson Marc , Appay Romain , Colin Carole , Figarella‐Branger Dominique , Battaglia‐Hsu Shyue‐Fang , Gauchotte Guillaume 
Published: September 2019

AbstractAnaplastic oligodendroglioma (AO), IDH‐mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high‐grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki‐67, in a large series of IDHmut+/1p19qcodel AO included in the POLA (“Prise en charge des Oligodendrogliomes Anaplasiques”) French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labeling indices (LI) of MCM6 and Ki‐67 were obtained via computer‐assisted color image analyses on immunostained AO tissues of the cohort (n = 220). Furthermore, a subgroup of AO (n = 68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki‐67 (≥15%) correlated with shorter overall survival, both in univariate (P = 0.013 and P = 0.004, respectively) and multivariate analyses (P = 0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki‐67). MCM6 and Ki‐67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro‐neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta‐amyloid binding and postsynaptic specialization. In conclusion, the overexpression of MCM6 and/or Ki‐67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy‐to‐use and cost‐effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down‐regulated immune response and lower microglial cells activation, and bears pro‐neural phenotype.
Examining parent and child agreement in the diagnosis of adolescent depression
Authors: Orchard Faith , Pass Laura , Cocks Laura , Chessell Chloe , Reynolds Shirley 
Published: September 2019

BackgroundThe diagnosis of depression in adolescents relies on identifying the presence of specific core and additional symptoms. Symptoms can be identified using structured or unstructured interviews and a range of questionnaire measures, which are completed by the young person and by a parent or carer. The aim of this research was to examine the inter‐ and intra‐rater reliability of parent report and adolescent self‐report of depression symptoms.MethodIn a sample of parent–child dyads, where young people aged 13–17 were referred to a mental health service for depression, we examined adolescents’ (n = 46) and parents’ (n = 46) independent responses to the Schedule for Affective Disorders and Schizophrenia in School‐Age Children (Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1997, 980) and the Mood and Feelings Questionnaire (Journal of the American Academy of Child and Adolescent Psychiatry, 27, 1988, 726).ResultsIn the clinical interview, diagnostic criteria were more often met based on the adolescent's report, and adolescents endorsed more symptoms of depression than their parents. Tentative results also suggest that parent–child agreement about specific symptoms was low. Comparing different measures of depression revealed that adolescent report on the questionnaire and interview was significantly correlated. However, there was no significant correlation between parent questionnaire and interview report.ConclusionThese results suggest that relying solely on parents to identify depression in their children may result in young people with depression being missed and therefore untreated. Young people themselves should be encouraged and enabled to recognise the symptoms of depression and have an established pathway to services that offer assessment and treatment.
Key Practitioner Message

Diagnosis of depression in adolescents requires the identification of specific symptoms and can be identified using interviews or questionnaires.

Previous research has suggested that parents and young people provide differing reports regarding symptoms of adolescent depression.

Results indicated that diagnostic criteria were more often met based on young person report and that parents reported significantly less symptoms.

Parent–child agreement about specific symptoms was found to be low.

Assessment of adolescent depression should not rely solely on parental report.

Young people should be encouraged and enabled to recognise symptoms of depression and be able to access mental health services.
Genome‐wide DNA methylation and transcriptome and proteome changes in Mycobacterium tuberculosis with para‐aminosalicylic acid resistance
Authors: Li Hai‐cheng , Chen Tao , Yu Li , Guo Hui‐xin , Chen Liang , Chen Yu‐hui , Chen Mu , Zhao Jiao , Yan Hui‐min , Zhou Lin , Wang Wei 
Published: September 2019

AbstractPrevious studies have reported that genome‐wide DNA methylation and differentially expressed genes and proteins are closely associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis). However, no reports have explored such associations in para‐aminosalicylic acid (PAS)‐resistant M. tuberculosis H37Rv. Here, we investigated genome‐wide methylation and transcriptome and proteome changes to explore the associations between specific genes and PAS resistance in M. tuberculosis H37Rv. The results revealed that 1,388 differentially methylated (1,161 hypermethylated and 227 hypomethylated) genes, 214 significantly differentially expressed (103 up‐ and 111 down‐regulated) genes and 137 differentially expressed (48 up‐ and 89 down‐regulated) proteins were regulated by PAS in M. tuberculosis H37Rv. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways and ABC transporters were closely associated with differentially methylated and expressed genes, respectively. In addition, correlation analysis revealed that differentially methylated genes were negatively correlated with their transcriptional levels in PAS‐resistant M. tuberculosis H37Rv. Furthermore, the existence of five hypermethylated candidate genes (esxC, fabG3, fbpB, papA1 and pks2) in PAS‐resistant M. tuberculosis H37Rv was verified using protein–protein interaction analysis in the STRING database. The integrated DNA methylation and transcriptome and proteome analysis could provide valuable resources for epigenetics studies in PAS‐resistant M. tuberculosis H37Rv.
Indian = Hindu? The Development of Nationalist Attitudes Among Hindu and Muslim Children in India
Authors: Ellwood‐Lowe Monica E. , Berner Catherine , Dunham Yarrow , Srinivasan Mahesh 
Published: September 2019

Many political movements across the world today define citizenship in exclusionary ethnic or religious terms. This study extends research on ethnic–national associations in adults to children, adding to the relatively sparse literature on the development of national associations in children and in nonwestern contexts. Explicit and implicit religious–national associations were examined in a sample of 160 nine‐ to sixteen‐year‐olds (79 Hindu; 81 Muslim) in Gujarat, India. Results suggest that while Hindu children show a strong Indian = Hindu association by age 9, Muslim children appear to be buffered from this association. Furthermore, this association uniquely predicts variance in children’s attitudes about social policy and their concept of nationality, above and beyond their age, religion, and intergroup attitudes.
Is levator trauma an independent risk factor for anal incontinence?
Authors: Melendez‐Munoz J. , Subramanian N. , Friedman T. , Dietz H. P. 
Published: September 2019

AbstractAimTo determine the role of levator ani trauma in anal incontinence (AI), whilst controlling for anal sphincter injury.MethodsThe records of 1273 patients who had attended a tertiary urogynaecology unit between 1st of January to 31st December 2016 were reviewed. AI was assessed using St Mark's score and visual analogue scale (VAS). Levator muscle and anal sphincter trauma were examined by translabial ultrasound using tomographic imaging, with archived data sets investigated blinded against all clinical data. A complete avulsion was diagnosed if at least three central tomographic slices showed an abnormal muscle insertion, rated separately for each side. A significant anal sphincter defect was diagnosed if at least four out of six slices showed a defect of ≥ 30°.ResultsAvulsion was associated with St Mark's score (P = 0.005) and VAS bother of AI (P = 0.022) both on univariate analysis and when controlling for external anal sphincter (EAS) trauma on translabial imaging, forceps, body mass index (BMI) and age (P = 0.011 and P = 0.04, respectively). AI expressed as a binary variable was significantly associated with avulsion on univariate analysis (P = 0.011), although the association became nonsignificant after controlling for anal sphincter trauma, age, BMI and forceps delivery (P = 0.084).ConclusionIn this retrospective observational study, we found a weak association between levator ani avulsion and measures of AI, which largely remained significant when controlling for anal sphincter trauma. However, given the large data set, any clinical effect of levator trauma on AI is likely to be minor.
Children's (and Adults') Production Adjustments to Generic and Particular Listener Needs
Authors: Grigoroglou Myrto , Papafragou Anna 
Published: September 2019

AbstractAdults design utterances to match listeners' informational needs by making both “generic” adjustments (e.g., mentioning atypical more often than typical information) and “particular” adjustments tailored to their specific interlocutor (e.g., including things that their addressee cannot see). For children, however, relevant evidence is mixed. Three experiments investigated how generic and particular factors affect children's production. In Experiment 1, 4‐ to 5‐year‐old children and adults described typical and atypical instrument events to a silent listener who could either see or not see the events. In later extensions, participants described the same events to either a silent (Experiment 2) or an interactive (Experiment 3) addressee with a specific goal. Both adults and 4‐ to 5‐year‐olds performed generic adjustments but, unlike adults, children made listener‐particular adjustments inconsistently. These and prior findings can be explained by assuming that particular adjustments can be costlier for children to implement compared to generic adjustments.
Metformin‐sensitized NSCLC cells to osimertinib via AMPK‐dependent autophagy inhibition
Authors: Chen Hengyi , Lin Caiyu , Lu Conghua , Wang Yubo , Han Rui , Li Li , Hao Shuai , He Yong 
Published: September 2019

AbstractIntroductionThe third‐generation epidermal growth factor receptor (EGFR) inhibitor osimertinib is a promising therapeutic option for patients with advanced non‐small‐cell lung cancer (NSCLC) in second‐line or first‐line treatment because of its applications in selectively inhibiting EGFR T790M and EGFR‐tyrosine kinase inhibitor sensitizing mutations. However, the activation of autophagy associated with osimertinib treatment may play a protective role in NSCLC cells injury induced by osimertinib.ObjectivesThe aim of the present study was to study the effects of the osimertinib‐induced autophagy in NSCLC cells and whether metformin modulates the autophagy and enhances osimertinib sensitivity.MethodsThe effect of metformin on enhancing osimertinib sensitivity was examined in vitro and in vivo using MTT, BrdUrd incorporation assay, colony formation assay, invasion assay, flow cytometry analysis, western blot analysis and siRNA technique.ResultsIn the present study, we confirmed that osimertinib induced pro‐survival autophagy in H1975 and PC‐9GR cells, and metformin further sensitized H1975 and PC‐9GR cells to osimertinib via inhibiting autophagy. The potential mechanism was that the continual activation of AMPK induced by metformin could inhibit autophagy in a time‐dependent manner.ConclusionMetformin inhibited autophagy and enhanced osimertinib sensitivity via inducing AMPK activation in a time‐dependent manner.
Multidisciplinary long‐term care and modern surgical treatment of congenital melanocytic nevi – recommendations by the CMN surgery network
Authors: Ott Hagen , Krengel Sven , Beck Otfrid , Böhler Kornelia , Böttcher‐Haberzeth Sophie , Cangir Özlem , Fattouh Miriam , Häberle Beate , Hüging Martina , Königs Ingo , Kosch Ferdinand , Rok Kralj , Marathovouniotis Nicos , Meyer Lutz , Neuhaus Kathrin , Rothe Karin , Schiestl Clemens , Sinnig Mechthild , Theiler Martin , von der Heydt Susanne , Wälchli Regula , Weibel Lisa , Wendenburg Wera , Breuninger Helmut 
Published: September 2019

SummaryIn recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German‐speaking countries with extensive experience in long‐term care and surgical treatment of children and adults with CMN (CMN surgery network, “Netzwerk Nävuschirurgie”, NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi‐stage procedure. Today, the long‐term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of “removal at any cost” no longer holds. Potential treatment‐related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus‐based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.
Endoscopic ultrasound‐guided needle‐based confocal laser endomicroscopy in gastrointestinal subepithelial lesions: Feasibility study
Authors: Terada Tsuyoshi , Tahara Tomomitsu , Hashimoto Senju , Horiguchi Noriyuki , Funasaka Kohei , Nagasaka Mitsuo , Nakagawa Yoshihito , Shibata Tomoyuki , Yoshioka Kentaro , Tsukamoto Tetsuya , Kuroda Makoto , Ohmiya Naoki 
Published: September 2019

Background and AimNeedle‐based confocal laser endomicroscopy (nCLE) allows for real‐time optical biopsies during endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA). Little is known about nCLE imaging of gastrointestinal subepithelial lesions (GI‐SEL); therefore, we determined its feasibility.MethodsWe carried out EUS, nCLE, and finally FNA in 25 patients with GI‐SEL between November 2015 and December 2018. We retrospectively compared nCLE findings with pathological findings of EUS‐FNA or surgical specimens. For concordance analysis, two endoscopists independently validated representative nCLE images 5 months or more after examinations.ResultsAdequate sample acquisition rate of EUS‐FNA was 67% per needle pass and 96% per patient. EUS‐FNA was diagnostic in 80% (20/25), suspicious in 4% (1/25), and nondiagnostic in 16% (4/25). nCLE image acquisition rate was 100% and its concordance rate with final pathology was 88% (22/25), which was not significantly different from diagnostic and suspicious EUS‐FNA. nCLE could differentiate GI stromal tumors (GISTs) from leiomyoma, in that GISTs were characterized by contrast‐enhanced densely populated spindle cell tumors with unenhanced rod‐shaped nuclei in 93% of 14 patients, whereas leiomyomas were characterized by narrower spindle cell tumors with fewer and smaller unenhanced nuclei in 100% of three patients. In rectal metastasis from lung adenocarcinoma, some pleomorphic dark nests were observed. At concordance analysis between the two endoscopists’ validation results, κ value was 0.560 (P < 0.001), indicating moderate agreement. There were no adverse events associated with nCLE and EUS‐FNA.ConclusionNeedle‐based confocal laser endomicroscopy can be safe and useful for on‐site detection of abnormalities of GI‐SEL (UMIN 000013857).
Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy
Authors: Reilly F. , Sanchez‐Lechuga B. , Clinton S. , Crowe G. , Burke M. , Ng N. , Colclough K. , Byrne M. M. 
Published: September 2019

AbstractAimsTo examine the phenotypic features of people identified with ABCC8‐maturity‐onset diabetes of the young (MODY) who were included in the adult ‘Mater MODY’ cohort and to establish their response to sulfonylurea therapy.MethodsTen participants with activating ABCC8 mutations were phenotyped in detail. A 2‐hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C‐peptide measurements taken at baseline and 30‐min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8‐MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea.ResultsThe mean age at diagnosis of diabetes was 33.8 ± 11.1 years, with fasting glucose of 18.9 ± 11.5 mmol/l and a mean (range) HbA1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8‐MODY three out of four participants discontinued insulin (mean duration 10.6 ± 1.69 years) and started sulfonylurea treatment. The mean (range) HbA1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post‐treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants.ConclusionsLow‐dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.
Migration and household finances: How a different framing can improve thinking about migration
Authors: Clemens Michael A. , Ogden Timothy N. 
Published: September 2019

AbstractMotivationIt is time to reframe fundamentally the research agenda on migration, remittances, payments and development. Many policy‐makers in the developing world, and researchers, tend to view migrant remittances as windfall income, rather than as returns on investment, which is how families with migrants tend see remittances. Migration is thus, among other things, a strategy for financial management in poor households: location is an asset, migration an investment.PurposeWe propose that this shift of perspective on remittances—from windfall to return on investment—leads to more fruitful research questions.MethodsReviewing the literature, we summarize the research questions that have dominated the literature on migration and remittances and why, owing largely to unhelpful perspectives, they lead us to less informative answers.FindingsWe suggest 12 new and alternative research questions that have received relatively little attention in the literature on migration and remittances, to spur new, more productive research.Policy ImplicationsMigrant remittances are now several times larger than foreign aid. The effects of migration regulation and financial regulation on remittances have directly and significantly affect poverty and human security worldwide. But some of the most basic questions about remittances and their effects remain inadequately answered, in part because of a blinded research agenda. Asking better questions is a step toward better policies, programmes and regulations and, above all, to enable people on low incomes to improve their lives.