bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial﻿ signalling pathway deficits associated with the patient derived R47H TREM2 variants linked to AD indicate inability to activate inflammasome
Authors: Cosker Katharina , Mallach Anna , Limaye Janhavi , Piers Thomas M. , Staddon James , Neame Stephen J. , Hardy John , Pocock Jennifer M. 
Published: June 2021

AbstractThe R47H variant of the microglial membrane receptor TREM2 is linked to increased risk of late onset Alzheimer’s disease. Human induced pluripotent stem cell derived microglia (iPS-Mg) from patient iPSC lines expressing the AD-linked R47Hhet TREM2 variant, common variant (Cv) or an R47Hhom CRISPR edited line and its isogeneic control, demonstrated that R47H-expressing iPS-Mg expressed a deficit in signal transduction in response to the TREM2 endogenous ligand phosphatidylserine with reduced pSYK-pERK1/2 signalling and a reduced NLRP3 inflammasome response, (including ASC speck formation, Caspase-1 activation and IL-1beta secretion). Apoptotic cell phagocytosis and soluble TREM2 shedding were unaltered, suggesting a disjoint between these pathways and the signalling cascades downstream of TREM2 in R47H-expressing iPS-Mg, whilst metabolic deficits in glycolytic capacity and maximum respiration were reversed when R47H expressing iPS-Mg were exposed to PS+ expressing cells. These findings suggest that R47H-expressing microglia are unable to respond fully to cell damage signals such as phosphatidylserine, which may contribute to the progression of neurodegeneration in late-onset AD.
Inter-provincial disparity of COVID-19 transmission and control in Nepal
Authors: Pantha Buddhi , Acharya Subas , Joshi Hem Raj , Vaidya Naveen K. 
Published: June 2021

AbstractDespite the global efforts to mitigate the ongoing COVID-19 pandemic, the disease transmission and the effective controls still remain uncertain as the outcome of the epidemic varies from place to place. In this regard, the province-wise data from Nepal provides a unique opportunity to study the effective control strategies. This is because (a) some provinces of Nepal share an open-border with India, resulting in a significantly high inflow of COVID-19 cases from India; (b) despite the inflow of a considerable number of cases, the local spread was quite controlled until mid-June of 2020, presumably due to control policies implemented; and (c) the relaxation of policies caused a rapid surge of the COVID-19 cases, providing a multi-phasic trend of disease dynamics. In this study, we used this unique data set to explore the inter-provincial disparities of the important indicators, such as epidemic trend, epidemic growth rate, and reproduction numbers. Furthermore, we extended our analysis to identify prevention and control policies that are effective in altering these indicators. Our analysis identified a noticeable inter-province variation in the epidemic trend (3 per day to 104 per day linear increase during third surge period), the median daily growth rate (1 to 4% per day exponential growth), the basic reproduction number (0.71 to 1.21), and the effective reproduction number (maximum values ranging from 1.20 to 2.86). Importantly, results from our modeling show that the type and number of control strategies that are effective in altering the indicators vary among provinces, underscoring the need for province-focused strategies along with the national-level strategy in order to ensure the control of a local spread.
Solid fuels use for cooking and sleep health in adults aged 45 years and older in China
Authors: Yu Haiqing , Luo Jiajun , Chen Kai , Pollitt Krystal J. Godri , Liew Zeyan 
Published: June 2021

AbstractOutdoor air pollution has been linked to poor sleep health, but limited studies have investigated the relationship between solid cooking fuels and sleep health in adults. Therefore, we analyzed data from the China Health and Retirement Survey (CHARLS), a national survey of about 17,000 residents aged over 45. Participants were restricted to those who participated in CHARLS 2011, 2013 and 2015 (n = 8,668). Sleep health was indicated by self-reported average sleep hours at night and the numbers of unrested days/week in CHARLS 2015. We analyzed cooking fuel types reported and assessed the duration of solid fuels usage as consistent (indicated use in all three surveys or 6 + years) or inconsistent use (indicated use in one or two surveys or 1–4 years). We found consistent use of solid fuels was associated with a shorter sleep duration (OR = 1.17 95% CI 1.01, 1.35 for ≤ 6 h vs. 7–9 h/day) and higher frequencies of feeling unrested (OR = 1.32 95% CI 1.12, 1.55 for ≥ 5 days/week vs. none) compared with cleaner fuels use. The associations for inconsistent solid fuels use and sleep health were in the similar direction but smaller in magnitude. Further research is needed to confirm our findings and evaluate the exposure impact of specific fuel types to inform intervention strategies.
A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression
Authors: Lu Furong , Chen Hongpeng , Hong Yuan , Lin Yao , Liu Lizhen , Wei Ning , Wu Qinyan , Liao Shuanglin , Yang Shuai , He Junbing , Shao Yiming 
Published: June 2021

AbstractNucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3′-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3′-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.
Seasonal influence on the bathymetric distribution of an endangered fish within a marine protected area
Authors: Brazo A. , Marques R. , Zimmermann M. , Aspillaga E. , Hereu B. , Saragoni G. , Mercière A. , Crec’Hriou R. , Mercader M. , Verdoit-Jarraya M. , Cadène F. , Lenfant P. 
Published: June 2021

AbstractThe spatio-temporal variability of fish distribution is important to better manage and protect the populations of endangered species. In this sense, the vertical movements of a vulnerable and protected species,Sciaena umbra, were assessed in a marine protected area (theRéserve Naturelle Marine de Cerbère-Banyuls, south of France) to study the variability of their bathymetric distribution at different time scales. Twenty adults were marked with acoustic transmitters and acoustically monitored over 2.5 years. This revealed that some individuals remained at shallow waters (< 8 m) all year round, while others presented vertical segregation at deeper waters during the cold months (mean depth of 22.5 ± 0.04 m) and all aggregated in shallow waters during the warm months. The brown meagre was more active during the night, except in June and July when peaks of activity were observed at dusk. These patterns are likely associated with foraging and reproductive behavior during the cold and warm periods, respectively, and likely regulated by water temperature and the depth of the thermocline. Here, we provide valuable information on when and where in the water column critical periods ofS. umbralife cycle are expected to occur, which should be considered in management and protection plans.
The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis
Authors: Arai Momoko , Mii Akiko , Kashiwagi Tetsuya , Shimizu Akira , Sakai Yukinao 
Published: June 2021

AbstractEndocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch–Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.
Exposures associated with the onset of Kawasaki disease in infancy from the Japan Environment and Children’s Study
Authors: Fukuda Sayaka , Tanaka Shiro , Kawakami Chihiro , Kobayashi Tohru , Ito Shuichi ,   the Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko 
Published: June 2021

AbstractKawasaki disease (KD) is an acute systemic vasculitis that mainly affects infants and young children. The etiology of KD has been discussed for several decades; however, no reproducible risk factors have yet been proven. We used the Japan Environment and Children’s Study data to explore the association between the causal effects of exposure during the fetal and neonatal periods and KD onset. The Japan Environment and Children’s Study, a nationwide birth cohort study, has followed approximately 100,000 children since 2011. We obtained data on exposures and outcomes from the first trimester to 12 months after birth. Finally, we included 90,486 children who were followed for 12 months. Among them, 343 children developed KD. Multivariate logistic regression revealed that insufficient intake of folic acid during pregnancy (odds ratio [OR], 1.37; 95% CI 1.08–1.74), maternal thyroid disease during pregnancy (OR, 2.03; 95% CI 1.04–3.94), and presence of siblings (OR, 1.33; 95% CI 1.06–1.67) were associated with KD onset in infancy. In this study, we identified three exposures as risk factors for KD. Further well-designed studies are needed to confirm a causal relationship between these exposures and KD onset.
Scale free is not rare in international trade networks
Authors: Liu Linqing , Shen Mengyun , Tan Chang 
Published: June 2021

AbstractFailing to consider the strong correlations between weights and topological properties in capacity-weighted networks renders test results on the scale-free property unreliable. According to the preferential attachment mechanism, existing high-degree nodes normally attract new nodes. However, in capacity-weighted networks, the weights of existing edges increase as the network grows. We propose an optimized simplification method and apply it to international trade networks. Our study covers more than 1200 product categories annually from 1995 to 2018. We find that, on average, 38%, 38% and 69% of product networks in export, import and total trade are scale-free. Furthermore, the scale-free characteristics differ depending on the technology. Counter to expectations, the exports of high-technology products are distributed worldwide rather than concentrated in a few developed countries. Our research extends the scale-free exploration of capacity-weighted networks and demonstrates that choosing appropriate filtering methods can clarify the properties of complex networks.
MCT4 is induced by metastasis-enhancing pathogenic mitochondrial NADH dehydrogenase gene mutations and can be a therapeutic target
Authors: Takenaga Keizo , Koshikawa Nobuko , Akimoto Miho , Tatsumi Yasutoshi , Lin Jason , Itami Makiko , Nagase Hiroki 
Published: June 2021

AbstractPathogenic mitochondrial NADH dehydrogenase (ND) gene mutations enhance the invasion and metastasis of various cancer cells, and they are associated with metastasis in human non-small cell lung cancer (NSCLC). Moreover, monocarboxylate transporter 4 (MCT4) is overexpressed in solid cancers and plays a role in cancer cell proliferation and survival. Here, we report that MCT4 is exclusively expressed in mouse transmitochondrial cybrids with metastasis-enhancing pathogenic ND6 mutations. A high level of MCT4 is also detected in human NSCLC cell lines and tissues predicted to carry pathogenic ND mutations and is associated with poor prognosis in NSCLC patients. MCT4 expression in the cell lines is suppressed by N-acetyl-L-cysteine. Phosphatidylinositol-3 kinase (PI3K), AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) are involved in the regulation of MCT4 expression in the transmitochondrial cybrid cells. An MCT1/4 inhibitor effectively kills NSCLC cells with predicted pathogenic ND mutations, but an MCT1/2 inhibitor does not have the same effect. Thus, MCT4 expression is augmented by pathogenic ND mutations and could be a biomarker and a therapeutic target in pathogenic ND mutation-harbouring metastatic tumours.
Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer
Authors: Lacombe Valentin , Chabrun Floris , Lacout Carole , Ghali Alaa , Capitain Olivier , Patsouris Anne , Lavigne Christian , Urbanski Geoffrey 
Published: June 2021

AbstractElevated plasma vitamin B12 has been associated with solid cancers, based on a single B12 measurement. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. Patients with elevated plasma B12 (≥ 1000 ng/L) at first measurement (n = 344) were matched for age and sex with patients having 2 normal B12 measurements (< 1000 ng/L) (NN group, n = 344). The patients with elevated plasma B12 at first measurement were split into 2 groups, according to the presence (EE group, n = 144) or the absence (EN group, n = 200) of persistent elevated plasma B12 at second measurement. We compared the cancer-free survival during 60 months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Compared to the NN group, a persistent elevated plasma B12 ≥ 1000 ng/mL was strongly associated with the occurrence of solid cancer (HR 5.90 [95% CI 2.79–12.45], p < 0.001), contrary to non-persistent plasma B12 elevation (p = 0.29). These results could help to select patients in whom the screening for solid cancers would be of interest.
Crystal phases of charged interlayer excitons in van der Waals heterostructures
Authors: Bondarev Igor V. , Berman Oleg L. , Kezerashvili Roman Ya. , Lozovik Yurii E. 
Published: June 2021

AbstractThroughout the years, strongly correlated coherent states of excitons have been the subject of intense theoretical and experimental studies. This topic has recently boomed due to new emerging quantum materials such as van der Waals (vdW) bound atomically thin layers of transition metal dichalcogenides (TMDs). We analyze the collective properties of charged interlayer excitons observed recently in bilayer TMD heterostructures. We predict strongly correlated phases—crystal and Wigner crystal—that can be selectively realized with TMD bilayers of properly chosen electron-hole effective masses by just varying their interlayer separation distance. Our results can be used for nonlinear coherent control, charge transport and spinoptronics application development with quantum vdW heterostuctures.
Die deutsche Version des Brunel Balance Assessments zur Erfassung der Gleichgewichtsfähigkeit bei Menschen nach einem Schlaganfall: kulturelle Adaptation und erste psychometrische Evaluation
Authors: Wischke-Baltes Agnes , Tyson Sarah F , Braun Tobias 
Published: June 2021

ZusammenfassungHintergrund Das Brunel Balance Assessments (BBA) ist ein klinisches Messinstrument zur Erfassung der Gleichgewichtsfähigkeit von Menschen nach Schlaganfall. Die englischsprachige Originalversion des Assessments weist gute Gütekriterien auf.Ziel Übersetzung und kulturelle Adaptation des BBA für den deutschsprachigen Raum sowie erste Einschätzung der Praktikabilität und Konstruktvalidität.Methode Das BBA wurde konform einer etablierten Leitlinie ins Deutsche übersetzt. Als Teil dieses Prozesses wurde eine präfinale deutsche Version des Assessments über einen Zeitraum von 10 Wochen in einem ambulanten Rehabilitationszentrum von Physiotherapeut*innen klinisch angewendet. Die anschließende Überarbeitung des Assessments basierte auf den Erfahrungen der Anwender*innen. Eine erste Analyse der Konstruktvalidität folgte dem Ansatz des Hypothesentestens. Es wurde angenommen, dass das BBA stark mit Testwerten anderer Assessments des funktionellen Gleichgewichts und der Gehfähigkeit korreliert. Als Indikator der Praktikabilität wurde die Durchführungszeit des BBA erfasst.Ergebnisse Die präfinale deutsche Version wurde von 10 Therapeut*innen mit 25 Patient*innen nach Schlaganfall klinisch angewendet. Durch geringfügige Anpassungen wurde eine finale deutsche Version des BBA erstellt. BBA-Testwerte korrelierten moderat mit Testwerten des TUG und Testwerten der FAC. Die durchschnittliche Durchführungszeit des BBA betrug 17 ± 4 Minuten.Schlussfolgerung Das BBA wurde übersetzt, kulturell für den deutschsprachigen Raum adaptiert und steht nun für die klinische Anwendung zur Verfügung. Vorläufige Analysen weisen auf eine moderate Konstruktvalidität bei Patient*innen nach einem Schlaganfall im ambulanten Setting hin. Eine ausführliche Überprüfung der Gütekriterien steht aus.
Ein neurophysiologischer Ansatz in der Physiotherapie zur Behandlung von Developmental Coordination Disorder (DCD) – Ergebnisse einer retrospektiven Studie
Authors: Seeländer Johanna , Fricke Oliver 
Published: June 2021

ZusammenfassungHintergrund Untersuchung der Veränderung motorischer Funktionen von Kindern mit Developmental Coordination Disorder (DCD) bzw. Umschriebener Entwicklungsstörung motorischer Funktion (UEMF) nach 24 Einheiten Physiotherapie auf neurophysiologischer Grundlage oder spezifiziert als neurophysiologische Entwicklungstherapie (NET).Ziel Die nicht kontrollierte Pilotstudie untersuchte, ob die NET mit einem positiven und langanhaltenden Effekt auf Koordinationsstörungen bei Kindern mit DCD assoziiert ist.Methode 10 Kinder (4 Mädchen, 6 Jungen, Alter: 6,42 (3,02) Jahre) mit einer DCD-Diagnose wurden mit 24 1:1-Einheiten NET (eine oder 2 Einheiten pro Woche) behandelt. Die motorischen Fähigkeiten wurden dreimal anhand des M-ABC 2 beurteilt: direkt vor, direkt nach und 12 Wochen nach dem Ende der Behandlung.Ergebnisse Erhebliche Verbesserungen der Ballfertigkeiten (Perzentilrang (PR) 5→75), des Gleichgewichts (PR 91→99,9), der allgemeinen motorischen Fähigkeiten (PR 50→99) und der individuell schwierigsten Teilaufgabe des M-ABC 2 (PR 1→50) von vor bis nach Behandlung. Diese Verbesserungen blieben über die nächsten 12 Wochen stabil und waren unabhängig vom Alter und BMI des Kindes.Schlussfolgerung Die Ergebnisse vermitteln einen positiven ersten Eindruck über den Nutzen der NET auf die motorischen Fähigkeiten bei Kindern mit DCD.
Value of [11C]-Methionine PET/CT in Preoperative Localization of Parathyroid Adenomas
Authors: Saerens Julie , Velkeniers Brigitte , Keyaerts Marleen , Raeymaeckers Steven , Vanhoeij Marian , Blotwijk Susanne , Bravenboer Bert 
Published: June 2021

AbstractThere are multiple imaging modalities in primary hyperparathyroidism. Ultrasound examination and subtraction scintigraphy are usually the first-line imaging techniques. When these results are negative or inconsistent, additional [11C]-methionine PET/CT (MET-PET/CT) or 4-dimensional computed tomography can be performed. ​This study aims to evaluate MET-PET/CT in comparison with other imaging techniques in primary hyperparathyroidism. This is a retrospective cohort study. Eighty-four patients with primary hyperparathyroidism, who underwent parathyroid surgery, were included. ​Imaging results have been correlated to the perioperative drop in parathyroid hormone level and to the pathological analysis. ​Descriptive statistics are used, supplemented with 95% Clopper–Pearson confidence intervals for sensitivity and specificity and a sub-analysis with the McNemar test on paired data only. The per-lesion sensitivity of MET-PET/CT seems higher than that of [99mTc]-sestamibi or [99mTc]-tetrofosmin and [99mTc]-pertechnetate subtraction scintigraphy. The McNemar test, on paired data only, shows significantly higher sensitivity of MET-PET/CT compared to ultrasound (p=0.039) and significantly higher specificity of ultrasound compared to subtraction scintigraphy (p=0.035).​ MET-PET/CT after inconclusive or negative ultrasound and/or subtraction scintigraphy has an additional value in 70% of the cases.​ Preoperative parathyroid hormone levels were higher in patients in whom MET-PET/CT correctly predicted the pathological parathyroid glands, compared to those where MET-PET/CT missed at least one adenoma. The same trend was seen for 4-dimensional computed tomography. In conclusion, MET-PET/CT seems a valuable imaging modality in primary hyperparathyroidism, at least as second line imaging approach, with a higher per-lesion sensitivity than ultrasound in such setting. Especially when ultrasound and/or subtraction scintigraphy are inconclusive or negative, MET-PET/CT directs the surgeon to the correct localization of the parathyroid adenoma.