bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Multiple Linear Regression Models for Predicting Chronic Iron Toxicity to Aquatic Organisms
Authors: Brix Kevin V. , Tear Lucinda , DeForest David K. , Adams William J. 
Published: March 2023

Abstract
We developed multiple linear regression (MLR) models for predicting iron (Fe) toxicity to aquatic organisms for use in deriving site-specific water quality guidelines (WQGs). The effects of dissolved organic carbon (DOC), hardness, and pH on Fe toxicity to three representative taxa (Ceriodaphnia dubia, Pimephales promelas, and Raphidocelis subcapitata) were evaluated. Both DOC and pH were identified as toxicity-modifying factors (TMFs) for P. promelas and R. subcapitata, whereas only DOC was a TMF for C. dubia. The MLR models based on effective concentration 10% and 20% values were developed and performed reasonably well, with adjusted R2 of 0.68–0.89 across all species and statistical endpoints. Differences among species in the MLR models precluded development of a pooled model. Instead, the species-specific models were assumed to be representative of invertebrates, fish, and algae and were applied accordingly to normalize toxicity data. The species sensitivity distribution (SSD) included standard laboratory toxicity data and effects data from mesocosm experiments on aquatic insects, with aquatic insects being the predominant taxa in the lowest quartile of the SSD. Using the European Union approach for deriving WQGs, application of MLR models to this SSD resulted in WQGs ranging from 114 to 765 μg l−1 Fe across the TMF conditions evaluated (DOC: 0.5–10 mg l−1; pH: 6.0–8.4), with slightly higher WQGs (199–910 μg l−1) derived using the US Environmental Protection Agency (USEPA) methodology. An important uncertainty in these derivations is the applicability of the C. dubia MLR model (no pH parameter) to aquatic insects, and understanding the pH sensitivity of aquatic insects to Fe toxicity is a research priority. An Excel-based tool for calculating Fe WQGs using both European Union and USEPA approaches across a range of TMF conditions is provided. Environ Toxicol Chem 2023;42:1386–1400. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Altered large‐scale dynamic connectivity patterns in Alzheimer's disease and mild cognitive impairment patients: A machine learning study
Authors: Jing Rixing , Chen Pindong , Wei Yongbin , Si Juanning , Zhou Yuying , Wang Dawei , Song Chengyuan , Yang Hongwei , Zhang Zengqiang , Yao Hongxiang , Kang Xiaopeng , Fan Lingzhong , Han Tong , Qin Wen , Zhou Bo , Jiang Tianzi , Lu Jie , Han Ying , Zhang Xi , Liu Bing , Yu Chunshui , Wang Pan , Liu Yong ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: March 2023

AbstractAlzheimer's disease (AD) is a common neurodegeneration disease associated with substantial disruptions in the brain network. However, most studies investigated static resting‐state functional connections, while the alteration of dynamic functional connectivity in AD remains largely unknown. This study used group independent component analysis and the sliding‐window method to estimate the subject‐specific dynamic connectivity states in 1704 individuals from three data sets. Informative inherent states were identified by the multivariate pattern classification method, and classifiers were built to distinguish ADs from normal controls (NCs) and to classify mild cognitive impairment (MCI) patients with informative inherent states similar to ADs or not. In addition, MCI subgroups with heterogeneous functional states were examined in the context of different cognition decline trajectories. Five informative states were identified by feature selection, mainly involving functional connectivity belonging to the default mode network and working memory network. The classifiers discriminating AD and NC achieved the mean area under the receiver operating characteristic curve of 0.87 with leave‐one‐site‐out cross‐validation. Alterations in connectivity strength, fluctuation, and inter‐synchronization were found in AD and MCIs. Moreover, individuals with MCI were clustered into two subgroups, which had different degrees of atrophy and different trajectories of cognition decline progression. The present study uncovered the alteration of dynamic functional connectivity in AD and highlighted that the dynamic states could be powerful features to discriminate patients from NCs. Furthermore, it demonstrated that these states help to identify MCIs with faster cognition decline and might contribute to the early prevention of AD.
Brain‐wide network analysis of resting‐state neuromagnetic data
Authors: Kida Tetsuo , Tanaka Emi , Kakigi Ryusuke , Inui Koji 
Published: March 2023

AbstractThe present study performed a brain‐wide network analysis of resting‐state magnetoencephalograms recorded from 53 healthy participants to visualize elaborate brain maps of phase‐ and amplitude‐derived graph‐theory metrics at different frequencies. To achieve this, we conducted a vertex‐wise computation of threshold‐independent graph metrics by combining proportional thresholding and a conjunction analysis and applied them to a correlation analysis of age and brain networks. Source power showed a frequency‐dependent cortical distribution. Threshold‐independent graph metrics derived from phase‐ and amplitude‐based connectivity showed similar or different distributions depending on frequency. Vertex‐wise age‐brain correlation maps revealed that source power at the beta band and the amplitude‐based degree at the alpha band changed with age in local regions. The present results indicate that a brain‐wide analysis of neuromagnetic data has the potential to reveal neurophysiological network features in the human brain in a resting state.
Evaluation of serum interleukin‐1 receptor antagonist levels in major depressive disorder: A case‐control study
Authors: Nahar Zabun , Monisha Shahrin Tasnim , Qusar MMA Shalahuddin , Islam Md. Rabiul 
Published: March 2023

AbstractBackground and AimsMajor depressive disorder (MDD) is characterized by the occurrence of one or more depressive episodes lasting a minimum of 2 weeks and is marked by a persistently low mood and a lack of enjoyment in daily activities. The diagnosis of MDD is not possible by a well‐established laboratory test or biomarker. A wide range of potential biomarkers for depression have been proposed by many studies, but none of them has adequately described the correlation between the biomarkers and depression. The purpose of this study was to evaluate serum interleukin‐1 receptor antagonist (IL‐1RA) levels as an early depression risk factor.MethodsThe present case‐control study included 88 participants. Among them, 44 MDD patients enrolled from the psychiatry department of a public hospital in Dhaka, Bangladesh, and 44 age‐ and sex‐matched healthy controls (HCs) from various sites in Dhaka city. A qualified psychiatrist evaluated the cases and HCs based on the fifth edition of the diagnostic and statistical manual of mental disorders (DSM‐5). The Hamilton depression (Ham‐D) rating scale was employed to evaluate the intensity of depression. An enzyme‐linked immunosorbent assay kit (Boster Bio, USA) was used to determine serum IL‐1RA concentrations.ResultsWe observed no marked alteration in the serum concentration of IL‐1RA in MDD patients in comparison to HCs (292.81 ± 24.81 and 288 ± 24.87 pg/mL; p > 0.05). Among MDD patients, we found no noteworthy association between the severity of depression and serum IL‐1RA levels.ConclusionThe findings of the present study imply that IL‐1RA may not be identified as a promising biomarker for risk assessment of depression. However, its neuroprotective role may be taken into consideration for the understanding of pathophysiology of MDD.
The other side of false belief: Constructing the objectivity of reality
Authors: Li Leon 
Published: March 2023

AbstractYoung children appear not to grasp the independence between objective reality and subjective beliefs, as evidenced by their errors on false belief tasks. Whereas decades of research have examined children's developing understanding of the subjectivity of beliefs, however, almost no research has examined the other side of the issue: How do humans come to understand the objectivity of reality, and why is this understanding important? To help address this gap, this article proposes an evolutionary‐developmental account of how the understanding that reality is objective may have emerged in human thinking. Three key steps are highlighted: (i) phylogenetic foundations in great ape competitive mindreading, (ii) ontogenetic foundations in preverbal infant joint attention, and (iii) key experiences of perspectival conflict in linguistic humans. Functionally, the concept of an objective reality facilitated collaborative reasoning and joint decision‐making. To arrive at good joint decisions, individuals needed to recognize that both their own beliefs and others' beliefs could be wrong—with respect to the objective reality.
Emergence of SARS‐CoV‐2 spike protein at the vaccination site
Authors: Beck Annika , Dietenberger Hanna , Kunz Sebastian N. , Mellert Kevin , Möller Peter 
Published: March 2023

AbstractBackgroundThe anti‐coronavirus disease 2019 (COVID‐19) vaccines are of paramount importance in the fight against the COVID‐19 pandemic. Both viral vector‐ and nucleic acid‐based vaccines are known to effectively induce protection against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus by generating high antibody titers and effective T‐cell responses to the spike protein they encode. Although these vaccines are being applied worldwide and have been extensively investigated, the immunomorphological events at the vaccination site with respect to SARS‐CoV‐2 spike protein expression have not yet been described.MethodsWe had the opportunity to examine the deltoid muscles of three men who died shortly after vaccination for unrelated reasons. We examined the vaccination sites histologically and immunohistochemically with various antibodies. Furthermore we incubated two different cell lines with one vaccine and examined the expression of the spike protein.ResultsThe vaccination sites show a dense lymphohistiocytic interstitial infiltrate which surrounds the small vessels and extends into the perimysium. The spike protein is expressed by histiocytic cells with a dendritic shape that are CD68‐positive and CD207‐negative, fibrocytes, and very rare S100‐positive cells. Interestingly, the skeletal muscle, being constitutively human leukocyte antigen (HLA)‐A,B,C‐negative, is induced at different levels in each specimen. In a cell culture experiment, we confirmed the ability of fibroblasts and interdigitating dendritic sarcoma cells to express spike protein in vitro after incubation with the Comirnaty vaccine.ConclusionsHistiocytic cells and fibrocytes are the heralds of spike protein synthesis at the vaccination site. The underlying cause of this apparent cell specifity is unknown. This needs to be investigated in future experiments, for example in an animal model.
Rapamycin treatment unmasks a sex‐specific pattern of scar expansion of the infarcted rat heart: The relationship between mTOR and KATP channel
Authors: Al‐Katat Aya , Bergeron Alexandre , Parent Lucie , Lorenzini Maxime , Fiset Celine , Calderone Angelino 
Published: March 2023

AbstractInhibition of the mammalian target of rapamycin (mTOR) with the macrolide rapamycin or pharmacological suppression of KATP channel opening translated to scar expansion of the myocardial infarcted (MI) adult female rodent heart. The present study tested the hypotheses that rapamycin‐mediated scar expansion was sex‐specific and that mTOR signaling directly influenced KATP channel subunit expression/activity. Scar size was significantly larger in post‐MI male rats as compared to the previous data reported in post‐MI female rats. The reported scar expansion of rapamycin‐treated post‐MI female rats was not observed following the administration of the macrolide to post‐MI male rats. Protein levels of the KATP channel subunits Kir6.2 and SUR2A and phosphorylation of the serine2448 residue of mTOR were similar in the normal heart of adult male and female rats. By contrast, greater tuberin inactivation characterized by the increased phosphorylation of the threonine1462 residue and reduced raptor protein levels were identified in the normal heart of adult female rats. Rapamycin pretreatment of phorbol 12,13‐dibutyrate (PDBu)‐treated neonatal rat ventricular cardiomyocytes (NNVMs) suppressed hypertrophy, inhibited p70S6K phosphorylation, and attenuated SUR2A protein upregulation. In the presence of low ATP levels, KATP channel activity detected in untreated NNVMs was significantly attenuated in PDBu‐induced hypertrophied NNVMs via a rapamycin‐independent pathway. Thus, rapamycin administration to post‐MI rats unmasked a sex‐specific pattern of scar expansion and mTOR signaling in PDBu‐induced hypertrophied NNVMs significantly increased SUR2A protein levels. However, the biological advantage associated with SUR2A protein upregulation was partially offset by an mTOR‐independent pathway that attenuated KATP channel activity in PDBu‐induced hypertrophied NNVMs.
Dendritic cell‐derived exosomal miR‐3064‐5p inhibits SIRT6/PCSK9 to protect the blood‐brain barrier after subarachnoid hemorrhage
Authors: Wang Yan , Zhang Long , Lv Li , Zhou Ziqi , Xi Haipeng 
Published: March 2023

AbstractThe protection of the blood‐brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR‐3064‐5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR‐3064‐5p in exosomes secreted by DCs (DCs‐exo). An SAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL‐IF staining. We found that overexpression of miR‐3064‐5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin‐3, ZO‐1), whereas knockdown of miR‐3064‐5p exerted the opposite effect. Dual‐LUC assay confirmed that miR‐3064‐5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL‐6, IL‐1β, IFN‐γ, and TGF‐β1) levels and apoptosis. The results of the co‐IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs‐exo reduced brain edema, upregulated miR‐3064‐5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs‐exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR‐3064‐5p enhanced the protective effect of DCs‐exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR‐3064‐5p to ameliorate BBB damage after SAH. Mechanistically, miR‐3064‐5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway.
Evaluation of cardiac chamber functions by speckle‐tracking echocardiography in the presence of coronary artery flow disturbances other than stenosis: A review
Authors: Khederlou Hamid , Hosseinsabet Ali 
Published: March 2023

AbstractConditions other than stenosis also disturb the coronary flow. Such conditions include the coronary slow flow phenomenon, coronary artery ectasia, and coronary artery tortuosity. Evidence exists regarding myocardial dysfunction in these conditions. In this review, we present studies that have used speckle‐tracking echocardiography to determine whether coronary flow disturbances are accompanied by myocardial dysfunction. Additionally, we seek to show the gaps in knowledge concerning this issue and the dimensions that future studies should consider.
Biphasic reinforcement of nascent adhesions by vinculin
Authors: Baumann Hella , Schwingel Melanie , Sestu Marcello , Burcza Anna , Marg Susanna , Ziegler Wolfgang , Taubenberger Anna V. , Muller Daniel J. , Bastmeyer Martin , Franz Clemens M. 
Published: March 2023

AbstractVinculin is an integral component of integrin adhesions, where it functions as a molecular clutch coupling intracellular contraction to the extracellular matrix. Quantitating its contribution to the reinforcement of newly forming adhesions, however, requires ultrasensitive cell force assays covering short time and low force ranges. Here, we have combined atomic force microscopy‐based single‐cell force spectroscopy (SCFS) and optical tweezers force spectroscopy to investigate the role of vinculin in reinforcement of individual nascent adhesions during the first 5 min of cell contact with fibronectin or vitronectin. At minimal adhesion times (5‐10 s), mouse embryonic fibroblast (MEF) wildtype (wt) and vinculin knock‐out (vin(−/−)) cells develop comparable adhesion forces on the scale of several individual integrin‐ligand bonds, confirming that vinculin is dispensable for adhesion initiation. In contrast, after 60 to 120 s, adhesion strength and traction reinforce quickly in wt cells, while remaining low in vin(−/−) cells. Re‐expression of full‐length vinculin or a constitutively active vinculin mutant (vinT12) in MEF vin(−/−) cells restored adhesion and traction with the same efficiency, while vinculin with a mutated talin‐binding head region (vinA50I) or missing the actin‐binding tail‐domain (vin880) was ineffective. Integrating total internal reflection fluorescence imaging into the SCFS setup furthermore enabled us to correlate vinculin‐green fluorescent protein (GFP) recruitment to nascent adhesion sites with the built‐up of vinculin‐dependent adhesion forces directly. Vinculin recruitment and cell adhesion reinforcement followed synchronous biphasic patterns, suggesting vinculin recruitment, but not activation, as the rate‐limiting step for adhesion reinforcement. Combining sensitive SCFS with fluorescence microscopy thus provides insight into the temporal sequence of vinculin‐dependent mechanical reinforcement in nascent integrin adhesions.
MRI of Peliosis Hepatis: A Case Series Presentation With a 2022 Systematic Literature Update
Authors: Calistri Linda , Nardi Cosimo , Rastrelli Vieri , Maraghelli Davide , Grazioli Luigi , Messerini Luca , Colagrande Stefano 
Published: March 2023

BackgroundPeliosis hepatis (PH) is a rare benign condition, characterized by hepatic sinusoidal dilatation and blood‐filled cystic cavities, often found incidentally, with still challenging diagnosis by imaging due to polymorphic appearance.PurposeBased on a retrospective analysis of our series (12 patients) and systematic literature review (1990–2022), to organize data about PH and identify features to improve characterization.Study TypeRetrospective case series and systematic review.PopulationTwelve patients (mean age 48 years, 55% female) with pathology‐proven PH and 49 patients (mean age 52 years, 67% female) identified in 33 studies from the literature (1990–2022).Field Strength/Sequence1,5‐T; T1‐weighted (T1W), T2‐weighted (T2W), diffusion‐weighted (DW), contrast‐enhanced (CE) T1W imaging.AssessmentWe compared our series and literature data in terms of demographic (gender/age/ethnicity), clinical characteristics (symptoms/physical examination/liver test), associated conditions (malignancies/infectious/hematologic/genetic or chronic disorders/drugs or toxic exposure) percentage. On magnetic resonance imaging lesion numbers/shape/mean maximum diameter/location/mass effect/signal intensity were compared. PH pathological type/proposed imaging diagnosis/patient follow‐up were also considered.Statistical TestsJoanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports/Series quality assessment. Intraclass correlation and Cohen's kappa coefficients for levels of inter/intrareader agreement in our experience.ResultsPatients were mainly asymptomatic (92% vs. 70% in our study and literature) with associated conditions (83% vs. 80%). Lesions showed homogeneous T1W‐hypointensity (58% vs. 65%) and T2W‐hyperintensity (58% vs. 66%). Heterogeneous nonspecific (25% vs. 51%), centrifugal (34% vs. 8%), or rim‐like centripetal (25% vs. 23%) patterns of enhancement were most frequent, with hypointensity on the hepatobiliary phase (HBP), without restricted diffusivity. Good inter‐ and intrareader agreement was observed in our experience. Concerning JBI Checklist, 19 out of 31 case reports met at least 7 out of 8 criteria, whereas 2 case series fulfilled 5 and 6 out of 10 items respectively.Data ConclusionA homogeneous, not well‐demarcated T1W‐hypointense and T2W‐hyperintense mass, with heterogeneous nonspecific or rim‐like centripetal or centrifugal pattern of enhancement, and hypointensity on HBP, may be helpful for PH diagnosis. Among associated conditions, malignancies and drug exposures were the most frequent.Level of Evidence4Technical EfficacyStage 2
Cardiac MRI‐Based Assessment of Myocardial Injury in Asymptomatic People Living With Human Immunodeficiency Virus: Correlation With nadir CD4 Count
Authors: Peng Xin , Ding Haibo , Huo Huaibi , Zheng Yue , Zhou Jie , Li Han , Hou Yang , Li Xiaolin , Geng Wenqing , Shang Hong , Liu Ting 
Published: March 2023

BackgroundThere are known cardiac manifestations of HIV, but the findings in asymptomatic subjects are still not fully explored.PurposeTo evaluate for the presence of subclinical myocardial injury in asymptomatic people living with human immunodeficiency virus (PLWH) by cardiac MRI and to explore the possible association between subclinical myocardial injury and HIV‐related clinical characteristics.Study TypeCross‐sectional.PopulationA total of 80 asymptomatic PLWH (age: 53 years [47–56 years]; 90% male) and 50 age‐ and sex‐matched healthy participants.Field Strength/SequenceA 3‐T, cine sequence, T1, T2, and T2* mapping.AssessmentFunction analysis was derived from short axis, two‐, three‐, and four‐chamber cine images by feature tracking. Regions of interest were manually selected in the midventricular septum T1, T2, and T2* mapping sequences. PLWH were evaluated for T1 increment (△T1 mapping = native T1 − cutoff values) and HIV‐related clinical characteristics, particularly the nadir CD4 count. And PLWH were stratified into two groups according to the cutoff value of native T1: elevated native T1 and normal.Statistical TestsT test, Wilcoxon rank‐sum test, Chi‐square test, Spearman rank correlation, and logistic regression. P <0.05 indicated statistical significance.ResultsAsymptomatic PLWH revealed significantly higher native myocardial T1 values (1241 ± 29 msec vs. 1189 ± 21 msec), T2 values (40.7 ± 1.5 msec vs. 37.9 ± 1.4 msec), and lower LVGRS (30.2% ± 6.2% vs. 35.8% ± 6.4%), LVGCS (−18.0% ± 2.5% vs. −19.5% ± 2.0%), and LVGLS (−16.0% ± 3.8% vs. −17.9% ± 2.6%) but showed no difference in T2* values (17.3 msec [16.3–19.1 msec] vs. 18.3 msec [16.5–19.3 msec], P = 0.201). A negative correlation between the native T1 increment in PLWH with subclinical myocardial injury and the nadir CD4 count (u = −0.316). Nadir CD4 count <500 cells/mm3 was associated with higher odds of elevated native T1 myocardial values (odds ratio, 6.12 [95% CI, 1.07–34.91]) in PLWH.Data ConclusionSubclinical myocardial inflammation and dysfunction were present in asymptomatic PLWH, and a lower nadir CD4 count may be a risk factor for subclinical myocardial injury.Evidence Level1.Technical EfficacyStage 2.