Miracle-dz/UniFAR-FTUs huggingface dataset:
Tranexamic Acid in Craniosynostosis Surgery: A Systematic Review and Meta-Analysis

Supplemental Digital Content is available in the text Abstract Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A comprehensive systematic review and subsequent meta-analysis was undertaken, with the view to clarify the effectiveness of TXA in reducing blood loss and transfusion requirements in craniosynostosis surgery. Medline and PubMed databases were searched using the preferred reporting items for systematic reviews and meta-analyses technique, and 7003 articles were assessed based on predefined selection criteria. Seven trials were identified, of which 2 were randomized controlled trials and the remainder retrospective cohort studies. All trials were assessed using the Jadad and strengthening the reporting of observational studies in epidemiology scores. The meta-analysis found a clear statistical reduction in blood loss in those patients who received TXA perioperatively, with a combined blood loss reduction of 7.06 ml/kg (95% confidence interval −8.97 to −5.15, P < 0.00001). The blood loss reduction was found to extrapolate to a reduction in perioperative transfusion requirements by 8.47 ml/kg in this cohort (95% confidence interval −10.9 to −6.04, P < 00001). There were no TXA-related adverse outcomes recorded in the 258 patients who received TXA across all trials. The trials included in this meta-analysis were limited by underpowered population sizes and significant heterogeneity in blood loss recording techniques. Further, there was significant heterogeneity amongst operations performed. The current literature appears to support the use of TXA in craniosynostosis surgery, but further high quality randomized controlled trials are indicated, ideally including a subgroup analysis between the operations performed.
Characterization of Cytosolic Glutathione S-Transferases Involved in the Metabolism of the Aromatase Inhibitor, Exemestane

Exemestane (EXE) is a hormonal therapy used to treat estrogen receptor–positive breast cancer by inhibiting the final step of estrogen biosynthesis catalyzed by the enzyme aromatase. Cysteine conjugates of EXE and its active metabolite 17β-dihydro-EXE (DHE) are the major metabolites found in both the urine and plasma of patients taking EXE. The initial step in cysteine conjugate formation is glutathione conjugation catalyzed by the glutathione S-transferase (GST) family of enzymes. The goal of the present study was to identify cytosolic hepatic GSTs active in the GST-mediated metabolism of EXE and 17β-DHE. Twelve recombinant cytosolic hepatic GSTs were screened for their activity against EXE and 17β-DHE, and glutathionylated EXE and 17β-DHE conjugates were detected by ultra-performance liquid chromatography tandem mass spectrometry. GST α (GSTA) isoform 1, GST μ (GSTM) isoform 3 and isoform 1 were active against EXE, whereas only GSTA1 exhibited activity against 17β-DHE. GSTM1 exhibited the highest affinity against EXE with a Michaelis-Menten constant (KM) value that was 3.8- and 7.1-fold lower than that observed for GSTA1 and GSTM3, respectively. Of the three GSTs, GSTM3 exhibited the highest intrinsic clearance against EXE (intrinsic clearance = 0.14 nl·min−1·mg−1). The KM values observed for human liver cytosol against EXE (46 μM) and 17β-DHE (77 μM) were similar to those observed for recombinant GSTA1 (53 and 30 μM, respectively). Western blot analysis revealed that GSTA1 and GSTM1 composed 4.3% and 0.57%, respectively, of total protein in human liver cytosol; GSTM3 was not detected. These data suggest that GSTA1 is the major hepatic cytosolic enzyme involved in the clearance of EXE and its major active metabolite, 17β-DHE. SIGNIFICANCE STATEMENT Most previous studies related to the metabolism of the aromatase inhibitor exemestane (EXE) have focused mainly on phase I metabolic pathways and the glucuronidation phase II metabolic pathway. However, recent studies have indicated that glutathionylation is the major metabolic pathway for EXE. The present study is the first to characterize hepatic glutathione S-transferase (GST) activity against EXE and 17β-dihydro-EXE and to identify GST α 1 and GST μ 1 as the major cytosolic GSTs involved in the hepatic metabolism of EXE.
Modelling signalling pathways and cellular dynamics in vascular mechanobiology : a theoretical, experimental and computational study

Blood vessels are dynamic structures whose properties are continuously adapted by resident vascular cells. Existing mechanobiological models tend to ignore regulatory signalling and cell population dynamics, both key determinants of arterial growth and remodelling (G&R). In this D.Phil., a combined theoretical, experimental and computational approach is used to formulate, reﬁne and implement a novel model of the arterial wall that includes vascular mechanics, microstructure, biochemical metabolism and signalling, and cell phenotype and population dynamics. A mathematical chemo–mechano–biological (CMB) model is formulated by coupling a biomechanical model of the arterial wall as a cylindrical nonlinear elastic membrane to a system of biologically–informed evolution laws governing ﬁbroblast cell–mediated, transforming growth factor (TGF)-β–regulated collagen metabolism. Model simulation of inﬂammatory aneurysm development suggests that increasing TGF-β levels promotes a cell–driven proﬁbrotic response leading to aneurysm stabilisation, illustrating the model’s ability to couple chemo–biological processes to tissue–level mechanical evolution. To inform the theoretical framework experimentally, a recent mouse model of post–developmental disruption of medial smooth muscle TGF-β signalling is for the ﬁrst time subjected to hypertension, and characterised by biaxial mechanical testing and (immuno)histological staining. Increased adventitial TGF-β levels following perturbation are associated with strong proﬁbrotic responses (increased cellularity, collagen deposition, thicker walls) altering tissue mechanics (lower biaxial stress, higher structural stiffness). Simulation of realistic arterial geometries is enabled by coupling the 1D CMB model to a three–dimensional structural solver. Heterogeneous spatial distributions of mechanical, microstructural and chemo–biological variables determining the evolution of complex saccular aneurysm geometries can be simulated with this 3D implementation. A novel chemo–mechano–biological model of vascular cell dynamics and regulatory signalling governing arterial G&R is formulated, informed by speciﬁcally–generated experimental data, and implemented in an advanced 3D computational framework. This will allow for virtual investigation of therapies acting on chemo–biological agents of arterial G&R, with potential beneﬁts for vascular disease patients.
Downregulation of long non-coding RNA PVT1 enhances fracture healing via regulating microRNA-497-5p/HMGA2 axis

ABSTRACT Fragility fracture is a common and serious complication of osteoporosis. Abnormal expression of long non-coding RNAs is closely related to orthopedic diseases and bone metabolism. In the study, the role of lncRNA PVT1 during fracture healing, and the potential mechanism were explained. In the present study, 80 cases with fragility fracture were collected, serum samples were also collected at 7, 14, 21 days after standardized fixation therapy. qRT-PCR was applied for the measurement of mRNA levels. hFOB1.19 cells were recruited for the cell experiments, and the cell viability and apoptosis were detected. Luciferase reporter gene assay was performed for target gene confirmation. It was found that the level of PVT1 increased gradually, while miR-497-5p showed a downward trend over time in both intra-articular and hand fracture patients, and the changes reached a significant level at 21 day after treatment. In vitro experiments demonstrated that PVT1 knockdown promoted cell proliferation and inhibited cell apoptosis in HFOB1.19 cells. LncRNA PVT1 acts as a competing endogenous RNA (ceRNA) of miR-497-5p, and the influence of PVT1 knockdown on HFOB1.19 cell proliferation and apoptosis was reversed by miR-497-5p inhibition. HMGA2 is the target gene of miR-497-5p. It was concluded that LncRNA PVT1 silencing may enhance fracture healing via mediating miR-497-5p/HMGA2 axis.
Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study

Background: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. Objective: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. Methods: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. Results: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = −0.01; r = −0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test–Revised (BVMT-R; r = −0.14; r = −0.14) z-scores controlling for age, sex, and education. MVPA and SDMT (r = 0.05), CVLT-II (r = −0.07), and BVMT-R (r = 0.01) z-scores were not significantly correlated. Conclusion: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.
IRF3-mediated pathogenicity in a murine model of human hepatitis A

HAV-infected Ifnar1-/- mice recapitulate many of the cardinal features of hepatitis A in humans, including serum alanine aminotransferase (ALT) elevation, hepatocellular apoptosis, and liver inflammation. Previous studies implicate MAVS-IRF3 signaling in pathogenesis, but leave unresolved the role of IRF3-mediated transcription versus the non-transcriptional, pro-apoptotic activity of ubiquitylated IRF3. Here, we compare the intrahepatic transcriptomes of infected versus naïve Mavs-/- and Ifnar1-/- mice using high-throughput sequencing, and identify IRF3-mediated transcriptional responses associated with hepatocyte apoptosis and liver inflammation. Infection was transcriptionally silent in Mavs-/- mice, in which HAV replicates robustly within the liver without inducing inflammation or hepatocellular apoptosis. By contrast, infection resulted in the upregulation of hundreds of genes in Ifnar1-/- mice that develop acute hepatitis closely modeling human disease. Upregulated genes included pattern recognition receptors, interferons, chemokines, cytokines and other interferon-stimulated genes. Compared with Ifnar1-/- mice, HAV-induced inflammation was markedly attenuated and there were few apoptotic hepatocytes in livers of infected Irf3S1/S1Ifnar1-/- mice in which IRF3 is transcriptionally-inactive due to alanine substitutions at Ser-388 and Ser-390. Although transcriptome profiling revealed remarkably similar sets of genes induced in Irf3S1/S1Ifnar1-/- and Ifnar1-/- mice, a subset of genes was differentially expressed in relation to the severity of the liver injury. Prominent among these were both type 1 and type III interferons and interferon-responsive genes associated previously with apoptosis, including multiple members of the ISG12 and 2’-5’ oligoadenylate synthetase families. Ifnl3 and Ifnl2 transcript abundance correlated strongly with disease severity, but mice with dual type 1 and type III interferon receptor deficiency remained fully susceptible to liver injury. Collectively, our data show that IRF3-mediated transcription is required for HAV-induced liver injury in mice and identify key IRF3-responsive genes associated with pathogenicity, providing a clear distinction from the transcription-independent role of IRF3 in liver injury following binge exposure to alcohol.
100 years of inherited metabolic disorders in Austria—A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the “Registry for Inherited Metabolic Disorders” started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000‐113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months‐100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the “Registry for Inherited Metabolic Disorders” is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.
The visual arrays task: Visual storage capacity or attention control?

Extant literature suggests that performance on visual arrays tasks reflects limited-capacity storage of visual information. However, there is also evidence to suggest that visual arrays task performance reflects individual differences in controlled processing. The purpose of this study is to empirically evaluate the degree to which visual arrays tasks are more closely related to memory storage capacity or measures of attention control. To this end, we conducted new analyses on a series of large data sets that incorporate various versions of a visual arrays task. Based on these analyses, we suggest that the degree to which the visual arrays is related to memory storage ability or effortful attention control may be task-dependent. Specifically, when versions of the task require participants to ignore elements of the target display, individual differences in controlled attention reliably provide unique predictive value. Therefore, at least some versions of the visual arrays tasks can be used as valid indicators of individual differences in attention control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Investigation of Physicochemical and Textural Characteristics and Volatile Compounds of Kazakh Dry-cured Beef

College of Food and Wine, Yantai Research Institute of China Agricultural University, Yantai 264670, P.R. China College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, P.R. China Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing 100048, P.R. China Animal Science Academy of Xinjiang Uygur Autonomous Region, Urumqi 830000, P.R. China
Disrupted affective communication characterizes mothers of infants with disorganized but also ambivalent attachments: An Israeli study.

This study examined whether maternal disrupted communication, which is associated with disorganized infant attachment, also characterizes mothers of ambivalent infants. The study, conducted in Israel, included a Jewish sample (N = 163; 68 Girls) from diverse socioeconomic status, collected between 1991 and 1993 in an earlier study. The sample over-represented ambivalent and disorganized attachments. Attachment was assessed in the Strange Situation Procedure (SSP) at 12 months and disrupted communication was coded from the SSP using the Atypical Maternal Behavior Instrument for Assessment and Classification (AMBIANCE; Lyons-Ruth et al., 1999). Mothers of ambivalent infants showed higher disrupted communication than mothers of secure, avoidant, and disorganized infants. The findings shed further light on the correlates of ambivalent attachment and call for research regarding maternal and infant characteristics that differentiate ambivalent versus disorganized attachment.
Verrucoccum (Dothideomycetes, Dictyosporiaceae), a new genus of lichenicolous fungi on Lobaria s. lat. for the Dothidea hymeniicola species complex

ABSTRACT Two lichenicolous fungi, one growing on the thallus of Lobaria pulmonaria in the United Kingdom (Scotland) and the other in apothecia of Lobaria linita and L. oregana in northwestern North America (Alaska and British Columbia) and northeast Asia (Russian Far East, Khabarovsk Krai), show similarities to the species originally described as Dothidea hymeniicola (later transferred to Polycoccum s. lat and Endococcus) from a Lobaria s. lat. species in Central America. Critical morphological comparison showed that, despite the superficial resemblance between Alaskan, Canadian, Russian, and Scottish collections and the holotype of Dothidea hymeniicola, they can be distinguished by detailed microscopic analyses. Using three molecular markers, sequences of the nuc 18S, 28S, and internal transcribed spacer (ITS) rDNA regions of the recent Scottish and Alaskan collections were obtained. Phylogenetic analyses confirmed separation of the species and revealed them as a new lineage in Pleosporales, for which the new generic name Verrucoccum is introduced for the three species: V. coppinsii, sp. nov., V. hymeniicola, comb. nov. (syn. Dothidea hymeniicola), and V. spribillei, sp. nov.
Alpha Oscillations Shape Sensory Representation and Perceptual Sensitivity

Alpha activity (8–14 Hz) is the dominant rhythm in the awake brain and is thought to play an important role in setting the internal state of the brain. Previous work has associated states of decreased alpha power with enhanced neural excitability. However, evidence is mixed on whether and how such excitability enhancement modulates sensory signals of interest versus noise differently, and what, if any, are the consequences for subsequent perception. Here, human subjects (male and female) performed a visual detection task in which we manipulated their decision criteria in a blockwise manner. Although our manipulation led to substantial criterion shifts, these shifts were not reflected in prestimulus alpha band changes. Rather, lower prestimulus alpha power in occipital-parietal areas improved perceptual sensitivity and enhanced information content decodable from neural activity patterns. Additionally, oscillatory alpha phase immediately before stimulus presentation modulated accuracy. Together, our results suggest that alpha band dynamics modulate sensory signals of interest more strongly than noise. SIGNIFICANCE STATEMENT The internal state of our brain fluctuates, giving rise to variability in perception and action. Neural oscillations, most prominently in the alpha band, have been suggested to play a role in setting this internal state. Here, we show that ongoing alpha band activity in occipital-parietal regions predicts the quality of visual information decodable in neural activity patterns and subsequently the human observer's sensitivity in a visual detection task. Our results provide comprehensive evidence that visual representation is modulated by ongoing alpha band activity and advance our understanding on how, when faced with unchanging external stimuli, internal neural fluctuations influence perception and behavior.
Multi-scale noise transfer and feature frequency detection in SSVEP based on FitzHugh–Nagumo neuron system

Objective. The steady-state visual evoked potential (SSVEP) is one of the most commonly used control signals for brain–computer interfaces (BCIs) due to its excellent interactive potential, such as high tolerance to noises and robust performance across users. In addition, it has a stable cycle, obvious characteristics and minimal training requirements. However, the SSVEP is extremely weak and companied with strong and multi-scale noise, resulting in a poor signal-to-noise ratio in practice. Common algorithms for classification are based on the principle of template matching and spatial filtering, which cannot obtain satisfied performance of SSVEP detection under the multi-scale noise. Therefore, using linear methods to extract SSVEP with obvious nonlinear and non-stationary characteristics, the useful signal will be attenuated or lost. Approach. To address this issue, two novel frameworks based on a two-dimensional nonlinear FitzHugh–Nagumo (FHN) neuron system are proposed to extract feature frequency of SSVEP. Results. In order to evaluate the effectiveness of the proposed methods, this research recruit 22 subjects to participate the experiment. Experimental results show that nonlinear FHN neuron model can force the energy of noise to be transferred into SSVEP and hence amplifying the amplitude of the target frequency. Compared with the traditional methods, the FHN and FHNCCA methods can achieve higher classification accuracy and faster processing speed, which effectively improves the information transmission rate of SSVEP-based BCI.
Receiving Long‐Term Disability or Pursuing a Legal Claim May Prevent Recovery From Chronic Dizziness

Chronic dizziness (CD) and imbalance have multiple etiologies. CD is strongly linked with psychiatric and psychological comorbidities, thus an interdisciplinary approach, including psychopharmacological interventions, is recommended. Despite the use of this comprehensive treatment approach, the recovery of individuals with CD that pursue long‐term disability (LTD) insurance or legal claims (LC) appears hampered. As such, we aimed to compare symptom recovery from CD in an interdisciplinary setting between patients receiving LTD/LC versus those who were not, and to explore the factors that may contribute to changes in symptom severity.