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Learning to read depends on the ability to extract precise details of letter combinations, which convey critical information that distinguishes tens of thousands of visual word forms. To support fluent reading skill, one crucial neural developmental process is one's brain sensitivity to statistical constraints inherent in combining letters into visual word forms. To test this idea in early readers, we tracked the impact of two years of schooling on within-subject longitudinal changes in cortical responses to three different properties of words: coarse tuning for print, and fine tuning to either familiar letter combinations within visual word forms or whole word representations. We then examined how each related to growth in reading skill. Three stimulus contrasts--words versus pseudofonts, words versus pseudowords, pseudowords versus nonwords--were presented while high-density EEG Steady-State Visual Evoked Potentials (SSVEPs, n = 31) were recorded. Internalization of abstract visual word form structures over two years of reading experience resulted in a near doubling of SSVEP amplitude, with increasing left lateralization. Longitudinal changes (decreases) in brain responses to such word form structural information were linked to the growth in reading skills, especially in rapid automatic naming of letters. No such changes were observed for whole word representation processing and coarse tuning for print. Collectively, these findings indicate that sensitivity to visual word form structure develops rapidly through exposure to print and is linked to growth in reading skill.

There are multiple levels of processing relevant to reading that vary in their visual, sublexical, and lexical orthographic processing demands. Segregating distinct cortical sources for each of these levels has been challenging in EEG studies of early readers. To address this challenge, we applied recent advances in analyzing high-density EEG using Steady-State Visual Evoked Potentials (SSVEPs) via data-driven Reliable Components Analysis (RCA) in a group of early readers spanning from kindergarten to second grade. Three controlled stimulus contrasts--familiar words versus unfamiliar pseudofonts, familiar words versus pseudowords, and pseudowords versus nonwords--were used to isolate coarse print tuning, lexical processing, and sublexical orthography-related processing, respectively. First, three overlapping yet distinct neural sources--left vOT, dorsal parietal, and primary visual cortex were revealed underlying coarse print tuning. Second, we segregated distinct cortical sources for the other two levels of processing: lexical fine tuning over occipito-temporal/parietal regions; sublexical orthographic fine tuning over left occipital regions. Finally, exploratory group analyses based on children's reading fluency suggested that coarse print tuning emerges early even in children with limited reading knowledge, while sublexical and higher-level lexical processing emerge only in children with sufficient reading knowledge.

Abstract Background Patients with suspected prostate cancer usually undergo transrectal ultrasound‐guided (TRUS) systematic biopsy, which can miss relevant prostate cancers and lead to overtreatment. Aims The aim of this study was to evaluate the detection rate for prostate cancer in MR‐guided targeted biopsy (TB) and systematic biopsy (SB) in comparison with mpMRI of the prostate. Methods and results Three hundred and eight men who underwent mpMRI due to elevated PSA values between 2015 and 2020 were studied at university hospital Aachen, Germany. MRI‐images were divided into cohorts with suspicious findings (PI‐RADS ≥ 3) and negative findings (PI‐RADS

BackgroundGlioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).MethodsCaregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.ResultsThe final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.ConclusionThis study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

African swine fever virus (ASFV) is circulating in many swine-producing countries, causing significant economic losses. It is observed that pigs experimentally vaccinated with a live-attenuated virus (LAV) but not a killed virus (KV) vaccine develop solid homologous protective immunity. The objective of this study was to comparatively analyze antibody profiles between pigs vaccinated with an LAV vaccine and those vaccinated with a KV vaccine to identify potential markers of vaccine-induced protection. Thirty ASFV seronegative pigs were divided into three groups: Group 1 received a single dose of an experimental LAV, Group 2 received two doses of an experimental KV vaccine, and Group 3 was kept as a non-vaccinated (NV) control. At 42 days post-vaccination, all pigs were challenged with the parental virulent ASFV strain and monitored for 21 days. All pigs vaccinated with the LAV vaccine survived the challenge. In contrast, eight pigs from the KV group and seven pigs from the NV group died within 14 days post-challenge. Serum samples collected on 41 days post-vaccination were analyzed for their reactivity against a panel of 29 viral structural proteins. The sera of pigs from the LAV group exhibited a strong antibody reactivity against various viral structural proteins, while the sera of pigs in the KV group only displayed weak antibody reactivity against the inner envelope (p32, p54, p12). There was a negative correlation between the intensity of antibody reactivity against five ASFV antigens, namely p12, p14, p15, p32, and pD205R, and the viral DNA titers in the blood of animals after the challenge infection. Thus, antibody reactivities against these five antigens warrant further evaluation as potential indicators of vaccine-induced protection.

Viola dalatensis, belonging to the Violaceae family, is an endemic species to Vietnam. The present study aimed to determine phenolic compounds in extracts from aerial parts of the plant species using high performance liquid chromatography with diode-array detection (HPLC-DAD). In addition, free radical scavenging and bovine albumin denaturation inhibition assays were performed to evaluate the antioxidant and in vitro anti-inflammatory activities of the extracts. Most of the phenolic compounds in the methanolic extract were detected at the greatest concentrations compared to the other extracts, which was also supported by the highest total phenolic content (26.70 ± 0.1059 mg GAE/g). In general, the antioxidant activities of the methanolic and ethanolic extracts were found to be stronger than those of the other extracts. The aqueous extract exhibited the most potent inhibitory effect on albumin denaturation (IC50 = 90.39 ± 8.415 µg/mL), comparable with that of diclofenac. Through principal component analysis, 88.60% of the total variance in the phenolic dataset was explained. The correlation analysis showed that chlorogenic acid, ferulic acid, epigallocatechin gallate, rutin, and kaempferol may play important roles in antioxidant activity while gallic acid could contribute to in vitro anti-inflammatory activity of the extracts. The findings of this study provide the first evidence of the bioactive compounds present in V. dalatensis and shed light on the potential health-promoting properties linked to its aerial parts. [ABSTRACT FROM AUTHOR]

Abstract Monomeric autotransporters have been used extensively to transport recombinant proteins or protein domains to the cell surface of Gram-negative bacteria amongst others for antigen display. Genetic fusion of such antigens into autotransporters has yielded chimeras that can be used for vaccination purposes. However, not every fusion construct is transported efficiently across the cell envelope. Problems occur in particular when the fused antigen attains a relatively complex structure in the periplasm, prior to its translocation across the outer membrane. The latter step requires the interaction with periplasmic chaperones and the BAM (β-barrel assembly machinery) complex in the outer membrane. This complex catalyzes insertion and folding of β-barrel outer membrane proteins, including the β-barrel domain of autotransporters. Here, we investigated whether the availability of periplasmic chaperones or the BAM complex is a limiting factor for the surface localization of difficult-to-secrete chimeric autotransporter constructs. Indeed, we found that overproduction of in particular the BAM complex, increases surface display of difficult-to-secrete chimeras. Importantly, this beneficial effect appeared to be generic not only for a number of monomeric autotransporter fusions but also for fusions to trimeric autotransporters. Therefore, overproduction of BAM might be an attractive strategy to improve the production of recombinant autotransporter constructs.

Abstract EEG has been central to investigations of the time course of various neural functions underpinning visual word recognition. Recently the steady-state visual evoked potential (SSVEP) paradigm has been increasingly adopted for word recognition studies due to its high signal-to-noise ratio. Such studies, however, have been typically framed around a single source in the left ventral occipitotemporal cortex (vOT). Here, we combine SSVEP recorded from 16 adult native English speakers with a data-driven spatial filtering approach—Reliable Components Analysis (RCA)—to elucidate distinct functional sources with overlapping yet separable time courses and topographies that emerge when contrasting words with pseudofont visual controls. The first component topography was maximal over left vOT regions with a shorter latency (approximately 180 ms). A second component was maximal over more dorsal parietal regions with a longer latency (approximately 260 ms). Both components consistently emerged across a range of parameter manipulations including changes in the spatial overlap between successive stimuli, and changes in both base and deviation frequency. We then contrasted word-in-nonword and word-in-pseudoword to test the hierarchical processing mechanisms underlying visual word recognition. Results suggest that these hierarchical contrasts fail to evoke a unitary component that might be reasonably associated with lexical access.

Many questions surround the underlying mechanism for the differential metabolic processing observed for the prion protein (PrP) in healthy and prion-infected mammals. Foremost, the physiological α-cleavage of PrP interrupts a region critical for both toxicity and conversion of cellular PrP (PrPC) into its misfolded pathogenic isoform (PrPSc) by generating a glycosylphosphatidylinositol (GPI)-anchored C1 fragment. During prion diseases, alternative β-cleavage of PrP becomes prominent, producing a GPI-anchored C2 fragment with this particular region intact. It remains unexplored whether physical up-regulation of α-cleavage can inhibit disease progression. Furthermore, several pieces of evidence indicate that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 play a much smaller role in the α-cleavage of PrPC than originally believed, thus presenting the need to identify the primary protease(s) responsible. For this purpose, we characterized the ability of plasmin to perform PrP α-cleavage. Then, we conducted functional assays using protein misfolding cyclic amplification (PMCA) and prion-infected cell lines to clarify the role of plasmin-mediated α-cleavage during prion propagation. Here, we demonstrated an inhibitory role of plasmin for PrPSc formation through PrP α-cleavage that increased C1 fragments resulting in reduced prion conversion compared with non-treated PMCA and cell cultures. The reduction of prion infectious titer in the bioassay of plasmin-treated PMCA material also supported the inhibitory role of plasmin on PrPSc replication. Our results suggest that plasmin-mediated endoproteolytic cleavage of PrP may be an important event to prevent prion propagation.

Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates the magnitude of cellular responses to ligands perceived by interleukin-1 receptors (IL-1Rs) and Toll-like receptors (TLRs), leading to decreases in pro-inflammatory cytokines and suppressed inflammation. The molecular mechanism of IRAK3’s action remains unknown. IRAK3 functions as a guanylate cyclase, and its cGMP product suppresses lipopolysaccharide (LPS)-induced nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activity. To understand the implications of this phenomenon, we expanded the structure–function analyses of IRAK3 through site-directed mutagenesis of amino acids known or predicted to impact different activities of IRAK3. We verified the capacity of the mutated IRAK3 variants to generate cGMP in vitro and revealed residues in and in the vicinity of its GC catalytic center that impact the LPS-induced NFκB activity in immortalized cell lines in the absence or presence of an exogenous membrane-permeable cGMP analog. Mutant IRAK3 variants with reduced cGMP generating capacity and differential regulation of NFκB activity influence subcellular localization of IRAK3 in HEK293T cells and fail to rescue IRAK3 function in IRAK3 knock-out THP-1 monocytes stimulated with LPS unless the cGMP analog is present. Together, our results shed new light on the mechanism by which IRAK3 and its enzymatic product control the downstream signaling, affecting inflammatory responses in immortalized cell lines.

Spent coffee ground (SCG) is a residue released during coffee brewing. Disposal of SCG is able to lead to a loss of bioactive constituents and have a negative impact upon the environment. This study aimed to explore fatty acids, bioactive phenolics, antioxidant and anti-aging potentials of SCG samples obtained from coffee shops in Ho Chi Minh city, Vietnam. The oil content of the SCG samples ranged from 6.3 to 10.5%, and linoleic (43%), palmitic (33.4%) and oleic (11%) acids were identified as major constituents of the oil. Chlorogenic acid was the most abundant phenolic acid examined (832.9–7657.7 μg/g of dry weight), followed by ferulic acid (40.5–1041.7 μg/g). Through anti-collagenase and anti-elastase assays, SCG showed a promising anti-aging activity, with IC50 values comparable with those of epigallocatechin gallate. The correlation analysis revealed gallic acid positively correlated with the free radical scavenging potential evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and the inhibitory effect on elastase. The results demonstrated that utilization of SCG prepared from Vietnamese coffee could open new avenues for food and cosmeceutical industry.

Symplocos cochinchinensis (Lour.) Moore ssp. laurina (Retz) Noot. has been commonly used in traditional medicine to treat different ailments in many Asian countries. This study aimed to compare phenolics, antioxidant activity, and inhibitory effects on α-amylase, α-glucosidase, and albumin denaturation of S. cochinchinensis leaf extracts obtained by different extraction methods. 9 phenolics in the extracts were quantified and the results showed the 50% methanol extract contained the greatest sum of phenolics (193.72 mg/g) compared to the others. The 50% acetone extract exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (IC50= 183.88 μg/mL) while the 50% ethanol extract showed the most potent activity predicted by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) assay (IC50= 365.05 αg/mL). In general, all the S. cochinchinensis leaf extracts had comparatively low inhibitory effects on α-amylase and α-glucosidase compared to acarbose used as a reference standard. The ethanol extract presented the lowest IC50 values (184.49 μg/mL), indicating the strongest protection of albumin from denaturation. The results also the applications of enzyme and ultrasound to extraction of S. cochinchinensis leaves proved effective in extracting phenolics. The findings of the study provide a better understanding of phytochemicals and potential health benefits of S. cochinchinensis leaves, which is useful for development of new naturally occurring agents for disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Format changes in U.S. schooling in response to the COVID-19 pandemic varied by month and by school district, ranging from exclusively home-based to full in-person learning. The impact of these changes on adolescent schooling experiences, and the factors that mitigate such impact, have been challenging to quantify. To address these challenges we employed bi-monthly repeated surveys of youths (N = 6, 546, aged 13–14 years) in a longitudinal study, starting before the pandemic peak (October 2020) and continuing through one year after the pandemic was declared (March 2021). We investigated how school format (in-person vs. remote) impacted objective time spent on academic activities and the subjective experience of school, and how these were influenced by parental engagement. Periods of exclusive at-home remote schooling were pervasive—reported by more than 60% of youths—and linked to a reduction in school enjoyment and time spent on reading, math, and science. In contrast, such periods were linked to more time with parents or guardians helping with school activities, and the frequency of such parental involvement was associated with reductions in negative feelings about school. Results point to potential pathways to mitigate the negative consequences of future school disruptions.

Background Interleukin-1 receptor associated kinase 3 (IRAK3) is a critical modulator of inflammation and is associated with endotoxin tolerance and sepsis. Although IRAK3 is known as a negative regulator of inflammation, several studies have reported opposing functions, and the temporal actions of IRAK3 on inflammation remain unclear. A systematic review and meta-analyses were performed to investigate IRAK3 expression and its effects on inflammatory markers (TNF-α and IL-6) after one- or two-challenge interventions, which mimic the hyperinflammatory and immunosuppression phases of sepsis, respectively, using human or animal in vivo models. Methods This systematic review and meta-analyses has been registered in the Open Science Framework (OSF) (Registration DOI: 10.17605/OSF.IO/V39UR). A systematic search was performed to identify in vivo studies reporting outcome measures of expression of IRAK3 and inflammatory markers. Meta-analyses were performed where sufficient data was available. Results The search identified 7778 studies for screening. After screening titles, abstracts and full texts, a total of 49 studies were included in the systematic review. The review identified significant increase of IRAK3 mRNA and protein expression at different times in humans compared to rodents following one-challenge, whereas the increases of IL-6 and TNF-α protein expression in humans were similar to rodent in vivo models. Meta-analyses confirmed the inhibitory effect of IRAK3 on TNF-α mRNA and protein expression after two challenges. Conclusions A negative correlation between IRAK3 and TNF-α expression in rodents following two challenges demonstrates the association of IRAK3 in the immunosuppression phase of sepsis. Species differences in underlying biology affect the translatability of immune responses of animal models to human, as shown by the dissimilarity in patterns of IRAK3 mRNA and protein expression between humans and rodents following one challenge that are further influenced by variations in experimental procedures.

Skinfold thickness is an indicator of body fat, allowing a more detailed description of obesity. In Vietnam, there are no published percentile values for triceps and subscapular skinfold measurements from population-based studies of adolescents. This study aims to establish percentile tables for triceps, subscapular, and triceps + subscapular skinfolds (TSF + SSSF) sum. We used data from a cross-sectional survey conducted in Ho Chi Minh City. BMI, triceps and subscapular skinfold measurements of 2660 students were obtained. The L (Box-Cox transformation), M (median), and S (coefficient of variation) parameters were used to generate exact percentiles. The proportion of overweight was higher in boys (18.4% vs. 8.2%, p < 0.0001). Triceps, subscapular skinfolds, and TSF + SSSF were significantly higher in girls than in boys (p < 0.001). Our results provide sex- and age-specific reference values for skinfold thickness that can be applied as a new complimentary assessment tool for Vietnamese adolescents., Author(s): Hong K. Tang [sup.1], Steven J. Bowe [sup.2], Trang H. H. D. Nguyen [sup.1], Michael J. Dibley [sup.3] Author Affiliations: (1) Department of Epidemiology, Faculty of Public Health, Pham [...]