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Introduction: Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, pre- and post language-learning intervention., Methods: A group of 41 participants (age:60-80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period., Results: We found that performance on the Stroop task, as evidenced by accuracy and reaction time, improved following the language learning intervention. With the neuroimaging data, we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex. These results are consistent with previous reports using the Stroop paradigm. We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas. Specifically, we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before., Discussion: Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations., Competing Interests: The 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., (Copyright © 2024 Schultz, Gansemer, Allgood, Gentz, Secilmis, Deldar, Savage and Ghazi Saidi.)

Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity. Pep 14 functions via modulation of PP2A, an understudied holoenzyme that promotes genomic stability and is involved in DNA repair and senescence pathways. At the single-cell level, Pep 14 modulates genes that prevent senescence progression by arresting the cell cycle and enhancing DNA repair, which consequently reduce the number of cells progressing to late senescence. When applied on aged ex vivo skin, Pep 14 promoted a healthy skin phenotype with structural and molecular resemblance to young ex vivo skin, decreased the expression of senescence markers, including SASP, and reduced the DNA methylation age. In summary, this work shows the safe reduction of the biological age of ex vivo human skins by a senomorphic peptide., (© 2023. The Author(s).)

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, and archival patient samples exhibited large populations in vivo of hybrid E/M cells that lead invasion ex vivo while expressing both epithelial and mesenchymal characteristics. The mesenchymal marker vimentin promoted invasion and repressed metastatic outgrowth. We next tested the requirement for five EMT transcription factors and observed distinct patterns of utilization during invasion and colony formation. These differences suggested a sequential activation of multiple EMT molecular programs during the metastatic cascade. Consistent with this model, our longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns. We observed cancer cells progressing from epithelial to hybrid E/M and strongly mesenchymal patterns during invasion and from epithelial to a hybrid E/M pattern during colony formation. We next investigated the relative epithelial versus mesenchymal state of cancer cells in both GEMM and patient metastases. In both contexts, we observed heterogeneity between and within metastases in the same individual. We observed a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases, suggesting that there are multiple successful molecular strategies for distant organ colonization. Together, our results demonstrate an important and complex role for EMT programs during TNBC metastasis.

Background: Since facial paralysis is a dynamic condition, the analysis of still photographs is not sufficient for measurement of facial reanimation outcomes. This study aimed at evaluating an artificial intelligence (AI)-driven software as a novel video assessment tool for smile reanimation surgery and at comparing it with the Terzis score. Methods: Patients with facial paralysis undergoing smile reanimation surgery between January 2008 and April 2020 were eligible for this retrospective study. Inclusion criteria were at least 6 months of follow-up and availability of both pre- and post-operative video documentation. The software output was given as intensity score (IS) values between 0 and 1, representing emotions/action units (AUs) that are absent or fully present, respectively. Results: During the study period, 240 patients underwent facial reanimation surgery, of whom 63 patients met the inclusion criteria. Postoperatively, the median IS of the happiness emotion and lip corner puller AU increased significantly ( p  < 0.001). There was a positive correlation of Terzis score with the IS of happiness emotion ( r  = 0.8) and lip corner puller AU ( r  = 0.74). Conclusions: The novel AI-driven video analysis is strongly correlated with the Terzis score and shows promise for objective functional outcome evaluation after smile reanimation surgery.

The identification of social interactions is of fundamental importance for animal behavioral studies, addressing numerous problems like investigating the influence of social hierarchical structures or the drivers of agonistic behavioral disorders. However, the majority of previous studies often rely on manual determination of the number and types of social encounters by direct observation which requires a large amount of personnel and economical efforts. To overcome this limitation and increase research efficiency and, thus, contribute to animal welfare in the long term, we propose in this study a framework for the automated identification of social contacts. In this framework, we apply a convolutional neural network (CNN) to detect the location and orientation of pigs within a video and track their movement trajectories over a period of time using a Kalman filter (KF) algorithm. Based on the tracking information, we automatically identify social contacts in the form of head-head and head-tail contacts. Moreover, by using the individual animal IDs, we construct a network of social contacts as the final output. We evaluated the performance of our framework based on two distinct test sets for pig detection and tracking. Consequently, we achieved a Sensitivity, Precision, and F1-score of 94.2%, 95.4%, and 95.1%, respectively, and a MOTA score of 94.4%. The findings of this study demonstrate the effectiveness of our keypoint-based tracking-by-detection strategy and can be applied to enhance animal monitoring systems.

Background: The number of people with intellectual disabilities reaching retirement age has risen by more than two thirds in the last decade., Objective: Due to the high number of retirements in this group of persons, the facilities for integration assistance are required to provide appropriate offers, both in terms of the transition to retirement and the course of retirement., Methods: Interviews on retirement planning were conducted with aspiring pensioners from several workshops for disabled people, which were mostly located in urban areas., Results: These interviews showed that people with intellectual and mental disabilities wanted a balance between structured group offers and individual privacy. Sporting and creative offers were perceived as positive. Maintaining interpersonal contact is very important for the respondents. The upcoming retirement was seen as positive by the majority of the respondents because of the associated "new freedom". Only a few worried about the financial situation in old age., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses. The identification of the genetic causes of these diseases therefore has critical clinical implications. We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32, which encodes glycoprotein A repetitions predominant (GARP). These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells (Tregs). Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function. In a model of conditional Garp deficiency in mice, we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased. Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability. Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.

Behavioural research of pigs can be greatly simplified if automatic recognition systems are used. Systems based on computer vision in particular have the advantage that they allow an evaluation without affecting the normal behaviour of the animals. In recent years, methods based on deep learning have been introduced and have shown excellent results. Object and keypoint detector have frequently been used to detect individual animals. Despite promising results, bounding boxes and sparse keypoints do not trace the contours of the animals, resulting in a lot of information being lost. Therefore, this paper follows the relatively new approach of panoptic segmentation and aims at the pixel accurate segmentation of individual pigs. A framework consisting of a neural network for semantic segmentation as well as different network heads and postprocessing methods will be discussed. The method was tested on a data set of 1000 hand-labeled images created specifically for this experiment and achieves detection rates of around 95% (F1 score) despite disturbances such as occlusions and dirty lenses.

The aim of the present study was to classify and characterise pigs with tail lesions using a combined parameter based on the frequency and duration of tail lesions and to find out whether biologically relevant groups could be separated by cluster analysis. Pigs (n = 677, 50% docked, 50% undocked) from three farrowing systems, as follows: (1) Conventional farrowing crate (FC), (2) free farrowing (FF), and (3) a group housing lactating sows (GH), were divided into two rearing systems as follows: (1) A conventional system (CONV) and (2) a wean-to-finish (W-F) system. Within 18 assessment weeks, starting after weaning, animal tail lesions were recorded individually. The animals were characterised into five lesion groups, as follows: (I) No lesions to (V) many long lasting lesions. The separability of the predefined lesion groups was checked by an animal individual lesion parameter. By using a k-means cluster analysis, it was shown that the docking status was the mainly affected parameter on the tail lesions. The separation of the groups only succeeded for the most distinct groups, I and V. The high impact of the docking status and the reduction of tail lesions by more space allowance was shown. More characterising information for the individual pigs would improve the separability of the lesion groups.

Consumer perspectives of beef quality are complex, leading to a market that is increasingly differentiating. Thus, ongoing monitoring and assessment of changes in consumer perspectives is essential to identify changing market conditions. Often only credence and search characteristics are evaluated in consumer studies; therefore the object of the present study is to examine consumer preferences and perceptions towards beef steaks, also including experience characteristics, using a mixed methods approach. For this reason, 55 consumers participated in an experiment in Germany, including a sensory acceptance test, stated willingness to pay, and choice-based conjoint analysis (CBCA). Different quality characteristics were included, but a focus on the quality labels of 'dry aged beef', 'Block House beef', and 'Angus beef' was predominant throughout the experiment with the results showing that quality labels significantly increased overall liking as well as the stated willingness to pay. Quality labels were also the one of the most important characteristics in the conjoint analysis, after origin and price. The results of all applied methods are comparable for the characteristic quality label. The combination of sensory acceptance test and CBCA were additionally able to evaluate all three kinds of beef quality characteristics, which could not be evaluated together only using a single method. This suggests that a mixture of methods should be used to gain better knowledge on the true behavior of beef consumers. Experience and credence characteristics, including beef quality labels, present opportunities for future research as well as the potential for determining product and market differentiation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Antiretroviral resistance in treatment-naïve patients with HIV-1 infection is on the rise in both resource-rich and resource-poor countries. We report a case of three-class primary antiretroviral resistance detected by a genotypic assay in a 19-year-old woman with acute HIV-1 infection. Her risk factor for HIV acquisition was unprotected sexual intercourse with a HIV-positive man. At diagnosis, her HIV-1 RNA level was 730,376 copies per milliliter, and 2 weeks later her CD4+ cell count was 465 cells/mm(3). The patient's antiretroviral therapy was chosen based on the genotype of the source patient. Subsequent analysis of our patient's virus revealed an identical genotype to that of the source patient. The patient tolerated therapy well and continues to be virologically suppressed after 1 year of therapy. Her current CD4+ cell count is 537 cells/mm(3) and HIV-1 RNA is less than 400 copies per milliliter. This case supports the current recommendations from several HIV therapy guidelines to perform resistance testing in patients with acute HIV-1 infection.