bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haploinsufficiency of microglial MyD88 ameliorates Alzheimer's pathology and vascular disorders in APP/PS1‐transgenic mice
Authors: Quan Wenqiang , Luo Qinghua , Hao Wenlin , Tomic Inge , Furihata Tomomi , Schulz‐Schäffer Walter , Menger Michael D. , Fassbender Klaus , Liu Yang 
Published: May 2021

AbstractGrowing evidence indicates that innate immune molecules regulate microglial activation in Alzheimer's disease (AD); however, their effects on amyloid pathology and neurodegeneration remain inconclusive. Here, we conditionally deleted one allele of myd88 gene specifically in microglia in APP/PS1‐transgenic mice by 6 months and analyzed AD‐associated pathologies by 9 months. We observed that heterozygous deletion of myd88 gene in microglia decreased cerebral amyloid β (Aβ) load and improved cognitive function of AD mice, which was correlated with reduced number of microglia in the brain and inhibited transcription of inflammatory genes, for example, tnf‐α and il‐1β, in both brain tissues and individual microglia. To investigate mechanisms underlying the pathological improvement, we observed that haploinsufficiency of MyD88 increased microglial recruitment toward Aβ deposits, which might facilitate Aβ clearance. Microglia with haploinsufficient expression of MyD88 also increased vasculature in the brain of APP/PS1‐transgenic mice, which was associated with up‐regulated transcription of osteopontin and insulin‐like growth factor genes in microglia. Moreover, MyD88‐haploinsufficient microglia elevated protein levels of LRP1 in cerebral capillaries of APP/PS1‐transgenic mice. Cell culture experiments further showed that treatments with interleukin‐1β decreased LRP1 expression in pericytes. In summary, haploinsufficiency of MyD88 in microglia at a late disease stage attenuates pro‐inflammatory activation and amyloid pathology, prevents the impairment of microvasculature and perhaps also protects LRP1‐mediated Aβ clearance in the brain of APP/PS1‐transgenic mice, all of which improves neuronal function of AD mice.
Microglia‐mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke
Authors: Rudolph Max , Schmeer Christian W. , Günther Madlen , Woitke Florus , Kathner‐Schaffert Carolin , Karapetow Lina , Lindner Julia , Lehmann Thomas , Jirikowski Gustav , Witte Otto W. , Redecker Christoph , Keiner Silke 
Published: May 2021

AbstractFollowing stroke, neuronal death takes place both in the infarct region and in brain areas distal to the lesion site including the hippocampus. The hippocampus is critically involved in learning and memory processes and continuously generates new neurons. Dysregulation of adult neurogenesis may be associated with cognitive decline after a stroke lesion. In particular, proliferation of precursor cells and the formation of new neurons are increased after lesion. Within the first week, many new precursor cells die during development. How dying precursors are removed from the hippocampus and to what extent phagocytosis takes place after stroke is still not clear. Here, we evaluated the effect of a prefrontal stroke lesion on the phagocytic activity of microglia in the dentate gyrus (DG) of the hippocampus. Three‐months‐old C57BL/6J mice were injected once with the proliferation marker BrdU (250 mg/kg) 6 hr after a middle cerebral artery occlusion or sham surgery. The number of apoptotic cells and the phagocytic capacity of the microglia were evaluated by means of immunohistochemistry, confocal microscopy, and 3D‐reconstructions. We found a transient but significant increase in the number of apoptotic cells in the DG early after stroke, associated with impaired removal by microglia. Interestingly, phagocytosis of newly generated precursor cells was not affected. Our study shows that a prefrontal stroke lesion affects phagocytosis of apoptotic cells in the DG, a region distal to the lesion core. Whether disturbed phagocytosis might contribute to inflammatory‐ and maladaptive processes including cognitive impairment following stroke needs to be further investigated.
Bayesian estimation of maximum entropy model for individualized energy landscape analysis of brain state dynamics
Authors: Kang Jiyoung , Jeong Seok‐Oh , Pae Chongwon , Park Hae‐Jeong 
Published: May 2021

AbstractThe pairwise maximum entropy model (MEM) for resting state functional MRI (rsfMRI) has been used to generate energy landscape of brain states and to explore nonlinear brain state dynamics. Researches using MEM, however, has mostly been restricted to fixed‐effect group‐level analyses, using concatenated time series across individuals, due to the need for large samples in the parameter estimation of MEM. To mitigate the small sample problem in analyzing energy landscapes for individuals, we propose a Bayesian estimation of individual MEM using variational Bayes approximation (BMEM). We evaluated the performances of BMEM with respect to sample sizes and prior information using simulation. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data, particularly utilizing the empirical priors derived from group data. We then analyzed individual rsfMRI of the Human Connectome Project to show the usefulness of MEM in differentiating individuals and in exploring neural correlates for human behavior. MEM and its energy landscape properties showed high subject specificity comparable to that of functional connectivity. Canonical correlation analysis identified canonical variables for MEM highly associated with cognitive scores. Inter‐individual variations of cognitive scores were also reflected in energy landscape properties such as energies, occupation times, and basin sizes at local minima. We conclude that BMEM provides an efficient method to characterize dynamic properties of individuals using energy landscape analysis of individual brain states.
Neural representations of the amount and the delay time of reward in intertemporal decision making
Authors: Wang Qiang , Wang Yajie , Wang Pinchun , Peng Maomiao , Zhang Manman , Zhu Yuxuan , Wei Shiyu , Chen Chuansheng , Chen Xiongying , Luo Shan , Bai Xuejun 
Published: May 2021

AbstractNumerous studies have examined the neural substrates of intertemporal decision‐making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task‐based functional brain networks whose topological properties are related to impulsivity.
Effect of directly acting antivirals for hepatitis C virus infection on proprotein convertase subtilisin/kexin type 9 level
Authors: Torti Carlo , Scaglione Vincenzo , Cesana Bruno Mario , Costa Chiara , Marascio Nadia , Schiaroli Elisabetta , Busti Chiara , Bastianelli Sabrina , Mazzitelli Maria , Trecarichi Enrico Maria , Francisci Daniela 
Published: May 2021

AbstractBackground and aimsEradication of the hepatitis C virus (HCV) may affect proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and cardiovascular risk. However, information regarding PCSK9 level after HCV eradication is lacking. Hence, in this case‐control retrospective study, we aimed to evaluate PCSK9 level from pretherapy baseline up to sustained virological response (SVR).MethodsEighty‐four patients treated with directly acting antivirals (DAAs) between July 2015 and May 2018 were enrolled. Differences in baseline PCSK9 level due to absence/presence of recorded baseline characteristics (covariates) were evaluated. Changes in PCSK9 levels from pretherapy to SVR (ΔPCSK9) and their correlations with the covariates were assessed. The repeated measures analysis of variance was used to investigate the differences in PCSK9 level from the baseline to the achievement of SVR due to absence/presence of any covariate.ResultsThe mean age of the patients was 67.6 ± 11 years, and 53.6% were males. Baseline PCSK9 levels were statistically lower in patients using statins than in those not using statins (mean, 70.3 ± 43.1 ng/mL vs 271.8 ± 252.2 ng/mL; P = .017). PCSK9 level decreased significantly from baseline to the time of SVR (255 ± 248 ng/mL vs 169 ± 188 ng/mL; P < .001). PCSK9 levels were statistically higher in the HCV‐infected patients at baseline than in the control group (255 ± 248 vs 166.3 ± 120.2 ng/mL; P = .020); however, this difference was lost after achieving SVR (mean, 169 ± 188 vs 166.3 ± 120.2 ng/mL; P = .464). Changes in PCSK9 level was not statistically related to any of the recorded covariates. The PCSK9 mean level did not differ significantly with absence/presence of any covariate from pretherapy to SVR.ConclusionsThe reduction in mean PCSK9 level from baseline pretherapy to after HCV eradication was statistically significant. Whether PCSK9 is a new biomarker for cardiovascular risk in these patients remains to be ascertained.
Temporal dynamics of rotifers' feeding guilds shaped by chlorophyll‐a, nitrate, and environmental heterogeneity in subtropical floodplain lakes
Authors: Palazzo Fabiana , Bomfim Francieli F. , Dias Juliana D. , Simões Nadson R. , Lansac‐Tôha Fábio A. , Bonecker Claudia C. 
Published: May 2021

AbstractIn floodplains, rotifers are among the most abundant zooplankton organisms and play an important role in ecosystem functioning. Here, we evaluated the distribution of six feeding guilds of rotifers including filter C1 (body size: <200 µm), filter C2 (body size: >200 to <600 µm), filter C3 (body size: >600 to <1000 µm), filter C4 (body size: >1000 µm), suctor, and predator for 11 years. We also analyzed the relationship between guild distribution and environmental parameters (i.e., chlorophyll‐a, phosphate, nitrate, ammonia, and inorganic suspended matter). Finally, we investigated the relationship between feeding guilds heterogeneity (abundance inconsistency) and environmental heterogeneity. Sampling occurred every 3 months from 2000 to 2010 in six shallow lakes of the Upper Paraná River floodplains. Filters C1, Filter C2, and suctors were the dominant feeding guilds. Nitrate and chlorophyll‐a shaped the temporal distribution of the guilds. An intermediate value of environmental heterogeneity was correlated with greater feeding guilds heterogeneity, potentially indicating that intermediate disturbance in the environmental variables may allow for greater differences in abundance distribution between rotifer guilds in shallow floodplain lakes. Our study elucidated the role of rotifers in food resource consumption, energy transfer, and competitive relationships in response to temporal environmental heterogeneity in subtropical floodplains.
Flight polymorphism drives metacommunity structure of aquatic Heteroptera in tropical rock pools
Authors: Paripatyadar Shruti V. , Padhye Sameer M. , Padhye Anand D. 
Published: May 2021

AbstractRock pool metacommunities are shaped by the dispersal ability of organisms, which together with environmental heterogeneity, determine whether the metacommunity is structured more by environmental or spatial factors. To understand the effect of interspecific differences in dispersal capacity on beta diversity patterns and metacommunity structure, we studied aquatic Heteroptera (an actively dispersing insect group with species exhibiting flight polymorphism) in the rock pools on three outcrops in the Western Ghats, India. We used an abundance‐based gamma diversity partitioning framework to assess the percent contributions of similarity (S) and the decompositions of beta diversity‐abundance difference (D) and abundance replacement (R) to community structure for two mobility groups, that is, flying and flightless species. We compared the variation in beta diversity components “D” and “R” within and between outcrops for both mobility groups. We also studied the effects of the local environment on both mobility groups using redundancy analysis. Percent contributions of “S”, “D” and “R” changed according to the mobility group, with higher nestedness (S+D) in flying species (74.2%) and higher beta diversity (R+D) in flightless species (76.3%). There was a significant variation in overall beta diversity between outcrops for the respective mobility groups, caused by abundance difference for flying species (p = .003) and by abundance replacement for flightless species (p = .003). Flying and flightless species were not associated with different environmental variables. Our study demonstrates that dispersal capacity is responsible for structuring regional diversity, with distinct sources of dissimilarity being associated with each mobility group: Abundance replacements between assemblages imposed by dispersal limitation for flightless species and abundance differences in assemblages of flying species, which might reflect the carrying capacity of the habitats.
Joint time‐frequency analysis of visible laser reflections in a sheep heart
Authors: Stringer Bradley J. , Shumway Spencer B. , Willden Jeremy P. , Kuck Kai 
Published: May 2021

AbstractLimited methods exist to confirm the position of cardiovascular devices in the superior vena cava or right atrium of the heart. The aim of this study was to design, test and validate the feasibility of whether an optical fiber‐based instrument could accurately distinguish when a cardiovascular catheter was located in the superior vena cava vs in the right atrium. An optical fiber was placed in a cardiovascular catheter which was inserted into a living sheep and guided to the vicinity of the heart where diode laser‐based reflection intensity data were simultaneously gathered from two visible wavelengths of light reflected from the venous and atrial tissue surfaces near the cavoatrial junction. The time series data were postoperatively analyzed using methods of joint time‐frequency analysis and validated against catheter positions determined with fluoroscopy and ECG. The system was successful in distinguishing the location of the superior vena cava from the right atrium.
Effects of Osteoporosis on Bone Morphometry and Material Properties of Individual Human Trabeculae in the Femoral Head
Authors: Frank Martin , Reisinger Andreas G , Pahr Dieter H , Thurner Philipp J 
Published: May 2021

ABSTRACTOsteoporosis is the most common bone disease and is conventionally classified as a decrease of total bone mass. Current diagnosis of osteoporosis is based on clinical risk factors and dual energy X‐ray absorptiometry (DEXA) scans, but changes in bone quantity (bone mass) and quality (trabecular structure, material properties, and tissue composition) are not distinguished. Yet, osteoporosis is known to cause a deterioration of the trabecular network, which might be related to changes at the tissue scale—the material properties. The goal of the current study was to use a previously established test method to perform a thorough characterization of the material properties of individual human trabeculae from femoral heads in cyclic tensile tests in a close to physiologic, wet environment. A previously developed rheological model was used to extract elastic, viscous, and plastic aspects of material behavior. Bone morphometry and tissue mineralization were determined with a density calibrated micro‐computed tomography (μCT) set‐up. Osteoporotic trabeculae neither showed a significantly changed material or mechanical behavior nor changes in tissue mineralization, compared with age‐matched healthy controls. However, donors with osteopenia indicated significantly reduced apparent yield strain and elastic work with respect to osteoporosis, suggesting possible initial differences at disease onset. Bone morphometry indicated a lower bone volume to total volume for osteoporotic donors, caused by a smaller trabecular number and a larger trabecular separation. A correlation of age with tissue properties and bone morphometry revealed a similar behavior as in osteoporotic bone. In the range studied, age does affect morphometry but not material properties, except for moderately increased tissue strength in healthy donors and moderately increased hardening exponent in osteoporotic donors. Taken together, the distinct changes of trabecular bone quality in the femoral head caused by osteoporosis and aging could not be linked to suspected relevant changes in material properties or tissue mineralization. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis in Southern Han Chinese
Authors: Liu Juan , Deng Yanhan , Wang Zheng , Mo Biwen , Wei Jianghong , Cheng Zhenshun , Peng Qingzhen , Wei Guang , Li Jingping , Shu Ying , Yang Hua , Fang Shirong , Luo Guangwei , Yang Shuo , Wang Yingnan , Zhu Jing , Yang Jingping , Wu Ming , Xu Xuyan , Ge Renying , Zhang Xiaoju , Xiong Weining , Wang Xiaomei , Li Zongzhe 
Published: May 2021

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD‐ILD) has not been determined.MethodsA two‐stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD‐ILD cases, and 225 controls).ResultsWe identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212–4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376–4.128, p = 0.002 in stage two). However, we did not observe this association in CTD‐ILD (OR = 1.401, 95% CI = 0.790–2.485, p = 0.248).ConclusionOur findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD‐ILD.
Platelet‐Lymphocyte ratio is a predictor for the development of no‐reflow phenomenon in patients with ST‐segment elevation myocardial infarction after thrombus aspiration
Authors: ŞENÖZ Oktay , EMREN Sadık Volkan , ERSEÇGİN Ahmet , YAPAN EMREN Zeynep , GÜL İlker 
Published: May 2021

AbstractBackroundWe aimed to evaluate the utility of the preprocedural platelet–lymphocyte ratio (PLR) for predicting the no‐reflow phenomenon after thrombus aspiration during percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI).MethodWe retrospectively analyzed postprocedural thrombolysis in myocardial infarction (TIMI) flow grades and myocardial blush grades (MBG) of 247 patients who underwent a PCI procedure with thrombus aspiration.We divided these patients into two groups according to whether they had no‐reflow (TIMI < 3, MBG < 2) or not (TIMI 3, MBG ≥ 2).ResultsNo‐reflow developed in 43 (17%) patients.Preprocedural PLR was significantly higher in the no‐reflow group (183.76 ± 56.65 vs 118.32 ± 50.42 p < 0.001).Independent predictors of no‐reflow were as follows: higher preprocedural platelet‐lymphocyte ratio (PLR) (OR = 1.018; 95% CI = 1.004, 1.033; p = 0.013),mean corpuscular volume (MCV) (OR = 1.118; 95% CI = 1.024, 1.220; p = 0.012) and SYNTAX Score‐2 (OR = 1.073; 95% CI = 1.005, 1.146; p = 0.036). PLR of 144 had 79% sensitivity and 75% specificity for the prediction of no‐reflow.ConclusionPLR is a reliable predictor for no‐reflow in STEMI patients undergoing thrombus aspiration.
Social‐ecological theory, substance misuse, adverse childhood experiences, and adolescent suicidal ideation: Applications for community–academic partnerships
Authors: Aytur Semra A. , Carlino Sydney , Bernard Felicity , West Kelsi , Dobrzycki Victoria , Malik Riana 
Published: May 2021

AbstractSuicide is the second leading cause of death among youth in the United States. Data from the 2015 Youth Risk Behavior Survey of 9th–12th grade students in New Hampshire (N = 14,837) were utilized. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression models to evaluate associations between suicidal ideation, adverse childhood experiences (ACEs), and other risk factors including using opioids/drugs without a prescription and food insecurity. We also examined whether potentially protective behaviors may attenuate the relationship between ACEs and suicidal ideation. The prevalence of suicidal ideation was 15.4% (girls 20.15; boys 10.67). In unadjusted models, the crude odds ratio reflecting the relationship between suicidal ideation and higher ACE scores was 1.85 (95% CI 1.76–1.94). In adjusted models, suicidal ideation remained positively associated with higher ACE scores (aOR 1.61, 95% CI 1.52–1.70). Risk and protective behavioral factors identified in relation to suicidal ideation and ACEs are discussed within the context of community–academic partnerships and policy.
Defining severe and multiple disadvantage from the inside: Perspectives of young people and of their support workers
Authors: Sandu Rebeca D. 
Published: May 2021

AbstractThe aim of this study was to explore the way young people facing severe and multiple disadvantage and their support workers perceive the circumstances of the young person. The leaders of 11 U.K. and five U.S. support‐providing organisations identified 30 young people aged 16 to 25 who were in great need and 35 workers for this study. Thematic analysis of the semi‐structured interviews found that shame was a primary emotional reaction to severe and multiple disadvantage. A history of poor relationships led them to develop an acute assessment of others and a tendency to back away from help. Over time, they perceived themselves to be unworthy and unable. Findings underscored the young people's role in shaping their trajectories and shone light on the role of emotions in explaining disconnection from support.