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Recognition memory studies have shown that increased perceptual fluency results in more "old" responses and, presumably, increases familiarity. However, the exact neural mechanisms of these effects remain unresolved. We conducted two ERP experiments in which participants encoded words and performed a recognition test where fluency was manipulated by changing clarity of test words (half of them were clear or blurry). In the more demanding Experiment 1, we found a reversed effect of fluency on recognition (more hits for blurry words), which was accompanied by larger N400 and LPC old/new effects for blurry words. For high confidence responses, the topography of N400 shifted towards frontal electrodes (the FN400 for blurry words). In the less demanding Experiment 2, no behavioral differences between clear and blurry words were observed. However, there was a discrepancy in the ERP results, with the frontal FN400 for blurry words and the parietal N400 for clear words, suggesting that distinct neural pathways can support familiarity-based recognition for clear and blurry items. In both experiments, early perceptual fluency ERP effects were also observed. The results indicate that both semantic processing and familiarity can be enhanced by perceptual fluency and contribute to recognition judgments, depending on the interpretations of fluency. [ABSTRACT FROM AUTHOR]

Aim: Adolescent mental ill‐health is a common international challenge affecting both high‐ and lower‐middle‐income countries. The Republic of the Philippines enacted its first mental health law in 2019, underlining the importance of the promotion of adolescent mental health education in schools. In Japan, course instructions about mental ill‐health were formulated in a Course of Study that reflects governmental curriculum guidelines. Embedded since 2022, the Course of Study aimed to promote an understanding of current issues of adolescent health. The National Center for Global Health and Medicine in Japan has been sharing experience of promoting public health practices and advancing medical technology in low‐ and middle‐income countries, especially in the Western Pacific region. This paper describes the development process and content of these resources by an interdisciplinary team from Japan and the Philippines. Methods: The interdisciplinary team created an embedded mental health education programme using animated videos for the Philippine school curriculum to improve mental health literacy in adolescents. Results: Two six‐minute animated videos of age‐relevant stories were created. The animation scenarios illustrate: 1) mental health problems and recovery; and 2) major symptoms of mental illnesses, including depression, anxiety, and schizophrenia. Each animated video presents several items for discussion among students and/or teachers, both in class and online for students unable to attend school. Conclusion: Our efforts may provide good opportunities for enhancing adolescents' mental health activities in the Philippines. In the following steps, we should investigate the effectiveness of school‐based MHL using these animated videos with rigorous evaluation methods. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V. [ABSTRACT FROM AUTHOR]

[Display omitted] • A flexible anatomical digital Hyperpolarized C-13 brain phantom framework was developed. • The digital phantom data mimicked in vivo datasets well. • A U-Net was trained to estimate k PL maps for Hyperpolarized C-13 datasets. • The U-Net resulted in spatially-constrained and smoothed k PL maps. Fitting rate constants to Hyperpolarized [1-13C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting. In this work, we use a convolutional neural network, a U-Net, with convolutions across the 2D spatial dimensions to estimate pyruvate-to-lactate conversion rate, k PL , maps from dynamic HP C13 datasets. We designed a framework for creating simulated anatomically accurate brain data that matches typical HP C13 characteristics to provide large amounts of data for training with ground truth results. The U-Net is initially trained with the digital phantom data and then further trained with in vivo datasets for regularization. In simulation where ground-truth k PL maps are available, the U-Net outperforms voxel-wise fitting with and without spatiotemporal denoising, particularly for low SNR data. In vivo data was evaluated qualitatively, as no ground truth is available, and before regularization the U-Net predicted k PL maps appear oversmoothed. After further training with in vivo data, the resulting k PL maps appear more realistic. This study demonstrates how to use a U-Net to estimate rate constant maps for HP C13 data, including a comprehensive framework for generating a large amount of anatomically realistic simulated data and an approach for regularization. This simulation and architecture provide a foundation that can be built upon in the future for improved performance. [ABSTRACT FROM AUTHOR]

Recognition memory requires both retrieval processes and control processes such as criterion setting. Decision criteria were manipulated by offering different payoffs for correct "old" versus "new" responses. Criterion setting influenced the following late-occurring (1,000+ ms), conflict-sensitive event-related brain potential (ERP) components: the stimulus-locked late posterior negativity (LPN) and the response-locked error-related negativity (ERN). The LPN-ERN were most negative to hits under conservative payoff conditions involving conflict between the correct old response and the payoff for new responses. This same conservative-hit condition was most frequently associated with response reversals when fast initial judgments were followed by slowerjudgments. Postresponse ERP activity may index conflict-sensitive processes underlying postretrieval cognitive control mechanisms involved with assessing responses to current items and updating response criteria on later trials. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to orthographically similar words impairs the ability to complete word fragments (e.g., Smith and Tindell, 1997), providing evidence that retrieval has been blocked (the Memory Block Effect or MBE). Two studies measured event-related potentials (ERPs) to explore the neural correlates of priming and blocking. The behavioral data in both experiments revealed that exposure to blocking words decreased fragment completions, increased intrusions (i.e., attempts to complete fragments using a blocking word), and slowed response times relative to control fragments. The ERPs in Experiment 1 indicate that priming and blocking begin during the early stages of lexical processing because lexical-related ERP amplitudes (N200) were larger than the control condition. A negative, frontal ERP emerged approximately 500ms after fragment onset and was attenuated for blocking and primed fragments, which suggests that it reflects executive processes that govern solving fragments. Experiment 2 replicated these effects and revealed that both N200 and the late, negative ERP amplitudes varied according to whether or not the fragments were completed, which indicates that these ERPs reflect lexical activation and blocking processes. Collectively, the data suggest that blocking and priming begin to influence word fragment completion during early lexical processing and blocking impedes a normal memory search. [ABSTRACT FROM AUTHOR]

Background: Vasculopathy is a hallmark of systemic sclerosis (SSc) putting patients at an increased risk of cardiovascular disease. Approximately 20-25% of all SSc patients show prolonged elevated C-reactive protein (CRP) levels and thus signs of chronic low-grade inflammation. While CRP-positivity is an independent predictor of cardiovascular disease in non-SSc populations, the relationship between CRP-positivity and cardiovascular health/atherosclerosis in SSc patients is only incompletely understood. Here, we aimed to assess (1) which general, SSc disease-specific and cardiovascular parameters are associated with CRP-positivity in a cohort of SSc patients with prolonged CRP elevations (CRP+ SSc group) relative to SSc patients without CRP elevations (CRP- SSc group). In addition (2), we aimed to investigate whether prolonged CRP-positivity in SSc patients is associated with a higher cardiovascular risk and an increased atherosclerotic burden. We also aimed to (3) identify via random forest classification modeling which combined cardiovascular and/or SSc-specific parameters could differentiate best between SSc patients with elevated CRP levels (the so-called "inflammatory SSc subtype") and SSc patients without increased CRP levels., Methods: Sixty-five SSc patients were recruited and assigned to the CRP+ SSc group ( n  = 20) if their CRP levels were > 5 mg/L in at least three half-yearly visits within 2 years before enrolment or to the CRP- SSc group ( n  = 45), respectively. All patients underwent an anamnesis, physical examination, blood draw, and bilateral carotid ultrasound in order to assess arteriosclerotic burden including the presence, number and height of plaques, and carotid intima-media thickness (CIMT) as well as lipid profiles. 10-year ASCVD risk was estimated via the ASCVD risk estimator plus. Statistical evaluation included Spearman's correlations, logistic regression and random forest modeling under 5-fold cross-validation, and permutation testing to determine combinations of cardiovascular variables highly discriminatory for CRP-positivity., Results: SSc groups showed comparable mean age, height, and extent of SSc organ involvement. Regarding cardiovascular health, CRP+ SSc patients exhibited a significantly altered HDL-, LDL-, and triglyceride profile (0.001 ≤  p  ≤ 0.017) and a significantly higher 10-year ASCVD risk ( p  = 0.047), relative to CRP- SSc patients. Additionally, within the subgroup of CRP+ SSc patients, positive correlations between CRP levels and CIMT right ( ρ  = 0.657, p  = 0.002) and mean CIMT left and right (ρ = 0.497, p  = 0.026) were seen. Combined ROC models identified the four lipid components (HDL, LDL, total cholesterol, and triglycerides) or the SSc duration and ASCVD category to differentiate with high cross-validated ROC-AUCs (AUC: 0.83 ± 0.15, and AUC: 0.86 ± 0.09, p <  0.001) for prolonged CRP-positivity among SSc patients., Conclusion: Our data indicate that persistent CRP-positivity and thus chronic low-grade inflammation in SSc patients enhance the risk for arteriosclerotic-cardiovascular disease significantly beyond the ASCVD risk observed for our SSc patients without CRP elevations. It seems to be along with a disrupted lipid profile the hallmark of a distinct "inflammatory" subgroup of SSc patients. However, large population-based studies and clinical trials in patients with SSc are needed to validate our findings in a prospective or interventional setting., Competing Interests: UH has received grant support through the ECTS Academy personal research grant. FK was employed by the F. Hoffmann-La Roche. RV received honoraria as a speaker for Novartis, Roche, Janssen, Galapagos, Pfizer, Astra Zeneca, Böhringer-Ingelheim, as well as grant support from Novartis, Pfizer and BMS. RV also is a consultant for Novartis, Roche, Janssen, Galapagos, and Astra Zeneca. SF has received consulting/speaker’s fees from Abbvie, Alphasigma/Galapagos, AstraZeneca, Biotest, Celltrion, Janssen/J&J, Novartis, NovoNordisk and UCB, all unrelated to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Heilmeier, Feldmann, Leynes, Seng, Jandova, Keute, Kollert, Voll and Finzel.)

Background: In modern positron emission tomography (PET) with multi-modality imaging (e.g., PET/CT and PET/MR), the attenuation correction (AC) is the single largest correction factor for image reconstruction. One way to assess AC methods and other reconstruction parameters is to utilize software-based simulation tools, such as a lesion insertion tool. Extensive validation of these simulation tools is required to ensure results of the study are clinically meaningful., Purpose: To evaluate different PET AC methods using a synthetic lesion insertion tool that simulates lesions in a patient cohort that has both PET/MR and PET/CT images. To further demonstrate how lesion insertion tool may be used to extend knowledge of PET reconstruction parameters, including but not limited to AC., Methods: Lesion quantitation is compared using conventional Dixon-based MR-based AC (MRAC) to that of using CT-based AC (CTAC, a "ground truth"). First, the pre-existing lesions were simulated in a similar environment; a total of 71 lesions were identified in 18 pelvic PET/MR patient images acquired with a time-of-flight simultaneous PET/MR scanner, and matched lesions were inserted contralaterally on the same axial slice. Second, synthetic lesions were inserted into four anatomic target locations in a cohort of four patients who didn't have any observed clinical lesions in the pelvis., Results: The matched lesion insertions resulted in unity between the lesion error ratios (mean SUVs), demonstrating that the inserted lesions successfully simulated the original lesions. In the second study, the inserted lesions had distinct characteristics by target locations and demonstrated negative max-SUV%diff trends for bone-dominant sites across the patient cohort., Conclusions: The current work demonstrates that the applied lesion insertion tool can simulate uptake in pelvic lesions and their expected SUV values, and that the lesion insertion tool can be extended to evaluate further PET reconstruction corrections and algorithms and their impact on quantitation accuracy and precision., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)