acerbated by concomitant use of statins.
A consistent finding in the literature is the decline in physical activity during adolescence, resulting in activity levels below the recommended guidelines. Therefore, promotion of physical activity is recommended specifically for prevocational students.

This protocol paper describes the background and design of a physical activity promotion intervention study in which prevocational students are invited to participate in the design and implementation of an intervention mix. The intervention is expected to prevent a decline in physical activity in the target group.

The effectiveness of the intervention was evaluated in a two-group cluster randomized controlled trial with assessments at baseline and 2-year follow-up. A simple randomization was applied, allocating 11 schools to the intervention group and 11 schools to the control group, which followed the regular school curriculum. The research population consisted of 3003 prevocational students, aged 13-15 years. The primary outcome measures were self-rerovide structured health promotion for future public health.

ISRCTN Registry ISRCTN35992636; http//www.isrctn.com/ISRCTN35992636.

DERR1-10.2196/28273.
DERR1-10.2196/28273.
Adherence to treatment is critical for successful treatment outcomes. Although factors influencing antiretroviral therapy (ART) adherence vary, young adults are less likely to adhere owing to psychosocial issues such as stigma, ART-related side effects, and a lack of access to treatment. The Call for Life Uganda (CFLU) mobile health (mHealth) tool is a mobile phone-based technology that provides text messages or interactive voice response functionalities through a web interface and offers 4 modules of support.

This study aims to describe the acceptability and feasibility of a mobile phone support tool to promote adherence to ART among young adults in a randomized controlled trial.

An exploratory qualitative design with a phenomenological approach at 2 study sites was used. A total of 17 purposively selected young adults with HIV infection who had used the mHealth tool CFLU from 2 clinics were included. In total, 11 in-depth interviews and 1 focus group discussion were conducted to examine the following he problems of forgetfulness and stigma-related issues. HIV-related stigma was reported by a few young people. Participants requested extra support for scaling up CFLU to make it more youth friendly. Improving the tool to reduce technical issues, including network outages and a period of software failure, was suggested. They suggested that in addition to digital solutions, other support, including the promotion of peer support meetings and the establishment of a designated space and staff members for youth, was also important.

This mHealth tool was an acceptable and feasible strategy for improving ART adherence and retention among young adults in resource-limited settings.

ClinicalTrials.gov NCT02953080; https//clinicaltrials.gov/ct2/show/NCT02953080.
ClinicalTrials.gov NCT02953080; https//clinicaltrials.gov/ct2/show/NCT02953080.
Patients on hemodialysis receive dialysis thrice weekly for about 4 hours per session. Intradialytic hypotension (IDH)-low blood pressure during hemodialysis-is a serious but common complication of hemodialysis. Although patients on dialysis already participate in their care, activating patients toward IDH prevention may reduce their risk of IDH. Interactive, technology-based interventions hold promise as a platform for patient activation. However, little is known about the usability challenges that patients undergoing hemodialysis may face when using tablet-based informatics interventions, especially while dialyzing.

This study aims to test the usability of a patient-facing, tablet-based intervention that includes theory-informed educational modules and motivational interviewing-based mentoring from patient peers via videoconferencing.

We conducted a cross-sectional, mixed methods usability evaluation of the tablet-based intervention by using think-aloud methods, field notes, and structured observationnext version of this intervention. We frame these implications first through the context of the role the patients' physical body plays when interacting with the intervention and then through the digital considerations for software and interface interaction.
In this paper, we present implications for designing informatics interventions for patients on dialysis and detail resulting changes to be implemented in the next version of this intervention. We frame these implications first through the context of the role the patients' physical body plays when interacting with the intervention and then through the digital considerations for software and interface interaction.Locomotion generates adventitious sounds which enable detection and localization of predators and prey. Such sounds contain brisk changes or transients in amplitude. We investigated the hypothesis that ill-understood temporal specializations in binaural circuits subserve lateralization of such sound transients, based on different time of arrival at the ears (interaural time differences, ITDs). We find that Lateral Superior Olive (LSO) neurons show exquisite ITD-sensitivity, reflecting extreme precision and reliability of excitatory and inhibitory postsynaptic potentials, in contrast to Medial Superior Olive neurons, traditionally viewed as the ultimate ITD-detectors. In vivo, inhibition blocks LSO excitation over an extremely short window, which, in vitro, required synaptically evoked inhibition. Light and electron microscopy revealed inhibitory synapses on the axon initial segment as the structural basis of this observation. These results reveal a neural vetoing mechanism with extreme temporal and spatial precision and establish the LSO as the primary nucleus for binaural processing of sound transients.Horizontal gene transfer (HGT) is an essential force in microbial evolution. Despite detailed studies on a variety of systems, a global picture of HGT in the microbial world is still missing. Here, we exploit that HGT creates long identical DNA sequences in the genomes of distant species, which can be found efficiently using alignment-free methods. Our pairwise analysis of 93,481 bacterial genomes identified 138,273 HGT events. We developed a model to explain their statistical properties as well as estimate the transfer rate between pairs of taxa. This reveals that long-distance HGT is frequent our results indicate that HGT between species from different phyla has occurred in at least 8% of the species. Finally, our results confirm that the function of sequences strongly impacts their transfer rate, which varies by more than three orders of magnitude between different functional categories. Overall, we provide a comprehensive view of HGT, illuminating a fundamental process driving bacterial evolution.Time-resolved X-ray diffraction of isolated fast-twitch muscles of mice was used to show how structural changes in the myosin-containing thick filaments contribute to the regulation of muscle contraction, extending the previous focus on regulation by the actin-containing thin filaments. This study shows that muscle activation involves the following sequence of structural changes thin filament activation, disruption of the helical array of myosin motors characteristic of resting muscle, release of myosin motor domains from the folded conformation on the filament backbone, and actin attachment. Physiological force generation in the 'twitch' response of skeletal muscle to single action potential stimulation is limited by incomplete activation of the thick filament and the rapid inactivation of both filaments. Muscle relaxation after repetitive stimulation is accompanied by a complete recovery of the folded motor conformation on the filament backbone but by incomplete reformation of the helical array, revealing a structural basis for post-tetanic potentiation in isolated muscles.Lineage transformation between lung cancer subtypes is a poorly understood phenomenon associated with resistance to treatment and poor patient outcomes. Here, we aimed to model this transition to define underlying biological mechanisms and identify potential avenues for therapeutic intervention. Small cell lung cancer (SCLC) is neuroendocrine in identity and, in contrast to non-SCLC (NSCLC), rarely contains mutations that drive the MAPK pathway. Likewise, NSCLCs that transform to SCLC concomitantly with development of therapy resistance downregulate MAPK signaling, suggesting an inverse relationship between pathway activation and lineage state. To test this, we activated MAPK in SCLC through conditional expression of mutant KRAS or EGFR, which revealed suppression of the neuroendocrine differentiation program via ERK. We found that ERK induces the expression of ETS factors that mediate transformation into a NSCLC-like state. ATAC-seq demonstrated ERK-driven changes in chromatin accessibility at putative regulatory regions and global chromatin rewiring at neuroendocrine and ETS transcriptional targets. Further, ERK-mediated induction of ETS factors as well as suppression of neuroendocrine differentiation were dependent on histone acetyltransferase activities of CBP/p300. Overall, we describe how the ERK-CBP/p300-ETS axis promotes a lineage shift between neuroendocrine and non-neuroendocrine lung cancer phenotypes and provide rationale for the disruption of this program during transformation-driven resistance to targeted therapy.Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. LAIR-2 is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 expressed on immune cells, and that LAIR-2 releases LAIR-1-mediated immune suppression. Analysis of public human datasets shows that collagens, LAIR-1 and LAIR-2 have unique and overlapping associations with survival in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 increases human T cell expansion and effector function in vivo in a mouse xenogeneic-graft versus-host disease model. In humanized mouse tumor models, NC410 reduces tumor growth that is dependent on T cells. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1+ immune cells are localized. https://www.selleckchem.com/products/dx600.html Our findings show that NC410 might be a novel strategy for cancer immunotherapy for immune-excluded tumors.Conflict detection in sensory input is central to adaptive human behavior. Perhaps unsurprisingly, past research has shown that conflict may even be detected in the absence of conflict awareness, suggesting that conflict detection is an automatic process that does not require attention. To test the possibility of conflict processing in the absence of attention, we manipulated task relevance and response overlap of potentially conflicting stimulus features across six behavioral tasks. Multivariate analyses on human electroencephalographic data revealed neural signatures of conflict only when at least one feature of a conflicting stimulus was attended, regardless of whether that feature was part of the conflict, or overlaps with the response. In contrast, neural signatures of basic sensory processes were present even when a stimulus was completely unattended. These data reveal an attentional bottleneck at the level of objects, suggesting that object-based attention is a prerequisite for cognitive control operations involved in conflict detection.