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A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV), mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln) amidotransferase complex], histone methylation (Set1C–COMPASS), lysosome biogenesis (AP-3 adapter complex), and mRNA processing and P-body formation (PAN complex). We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial respiratory chain complexes required for their proliferation.

Abstract Kinematic data is a valuable source of movement information that provides insights into the health status, mental state, and motor skills of individuals. Additionally, kinematic data can serve as biometric data, enabling the identification of personal characteristics such as height, weight, and sex. In CeTI-Locomotion, four types of walking tasks and the 5 times sit-to-stand test (5RSTST) were recorded from 50 young adults wearing motion capture (mocap) suits equipped with Inertia-Measurement-Units (IMU). Our dataset is unique in that it allows the study of both intra- and inter-participant variability with high quality kinematic motion data for different motion tasks. Along with the raw kinematic data, we provide the source code for phase segmentation and the processed data, which has been segmented into a total of 4672 individual motion repetitions. To validate the data, we conducted visual inspection as well as machine-learning based identity and action recognition tests, achieving 97% and 84% accuracy, respectively. The data can serve as a normative reference of gait and sit-to-stand movements in healthy young adults and as training data for biometric recognition.

Abstract Digital technologies, such as virtual or augmented reality, can potentially support neurocognitive functions of the aging populations worldwide and complement existing intervention methods. However, aging-related declines in the frontal-parietal network and dopaminergic modulation which progress gradually across the later periods of the adult lifespan may affect the processing of multisensory congruence and expectancy based contextual plausibility. We assessed hemodynamic brain responses while middle-aged and old adults experienced car-riding virtual-reality scenarios where the plausibility of vibrotactile stimulations was manipulated by delivering stimulus intensities that were either congruent or incongruent with the digitalized audio-visual contexts of the respective scenarios. Relative to previous findings observed in young adults, although highly plausible vibrotactile stimulations confirming with contextual expectations also elicited higher brain hemodynamic responses in middle-aged and old adults, this effect was limited to virtual scenarios with extreme expectancy violations. Moreover, individual differences in plausibility-related frontal activity did not correlate with plausibility violation costs in the sensorimotor cortex, indicating less systematic frontal context-based sensory filtering in older ages. These findings have practical implications for advancing digital technologies to support aging societies.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Abstract Background Repeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks. Methods In our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60–80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample. Results For the primary outcome, no difference was observed in the ITT (β = 0.1, 95%-CI [− 1.2, 1.3, p = 0.93] or PP sample (β = − 0.2, 95%-CI [− 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, β = 5.0, 95%-CI [− 0.1, 10.2], p = 0.06, d-prime β = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, β = 3.0, 95%-CI [− 3.9, 9.9], p = 0.39, d-prime β = 0.1, 95%-CI [− 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (p FDR

Abstract The Tactile Internet aims to advance human-human and human-machine interactions that also utilize hand movements in real, digitized, and remote environments. Attention to elderly generations is necessary to make the Tactile Internet age inclusive. We present the first age-representative kinematic database consisting of various hand gesturing and grasping movements at individualized paces, thus capturing naturalistic movements. We make this comprehensive database of kinematic hand movements across the adult lifespan (CeTI-Age-Kinematic-Hand) publicly available to facilitate a deeper understanding of intra-individual–focusing especially on age-related differences–and inter-individual variability in hand kinematics. The core of the database contains participants’ hand kinematics recorded with wearable resistive bend sensors, individual static 3D hand models, and all instructional videos used during the data acquisition. Sixty-three participants ranging from age 20 to 80 years performed six repetitions of 40 different naturalistic hand movements at individual paces. This unique database with data recorded from an adult lifespan sample can be used to advance machine-learning approaches in hand kinematic modeling and movement prediction for age-inclusive applications.

Older adults demonstrate difficulties in sequential decision-making, which is partly attributed to under-recruitment of prefrontal networks. It is, therefore, important to understand the mechanisms that may improve this ability. This study investigated the effectiveness of an 18-sessions, home-based cognitive intervention and the neural mechanisms that underpin individual differences in intervention effects. Participants were required to learn sequential choices in a 3-stage Markov decision-making task that would yield the most rewards. Participants were assigned to better or worse responders group based on their performance at the last intervention session (T18). Better responders improved significantly starting from the fifth intervention session while worse responders did not improve across all training sessions. At post-intervention, only better responders showed condition-dependent modulation of the dorsolateral prefrontal cortex (DLPFC) as measured by fNIRS, with higher DLPFC activity in the delayed condition. Despite large individual differences, our data showed that value-based sequential-decision-making and its corresponding neural mechanisms can be remediated via home-based cognitive intervention in some older adults; moreover, individual differences in recruiting prefrontal activities after the intervention are associated with variations in intervention outcomes. Intervention-related gains were also maintained at three months after post-intervention. However, future studies should investigate the potential of combining other intervention methods such as non-invasive brain stimulation with cognitive intervention for older adults who do not respond to the intervention, thus emphasizing the importance of developing individualized intervention programs for older adults.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCSfMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future. [ABSTRACT FROM AUTHOR]

Numerous technological solutions have been proposed to promote piano learning and teaching, but very few with market success. We are convinced that users’ needs should be the starting point for an effective and transdisciplinary development process of piano-related Tactile Internet with Human-in-the-Loop (TaHIL) applications. Thus, we propose to include end users in the initial stage of technology development. We gathered insights from adult piano teachers and students through an online survey and digital interviews. Three potential literature-based solutions have been visualized as scenarios to inspire participants throughout the interviews. Our main findings indicate that potential end users consider posture and body movements, teacher–student communication, and self-practice as crucial aspects of piano education. Further insights resulted in so-called acceptance requirements for each scenario, such as enabling meaningful communication in distance teaching, providing advanced data on a performer’s body movement for increased well-being, and improving students’ motivation for self-practice, all while allowing or even promoting artistic freedom of expression and having an assisting instead of judging character. By putting the users in the center of the fuzzy front end of technology development, we have gone a step further toward concretizing TaHIL applications that may contribute to the routines of piano teaching and learning.