Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.

We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency.

Mapping the Hydrogeological Structure of a Small Danish Island Using Transient Electromagnetic Methods.

Small island communities often rely on groundwater as their primary source of fresh water. However, the limited land area and high proportion of coastal zones pose unique challenges to groundwater management. A detailed understanding of the subsurface structure can provide valuable insights into aquifer structure, groundwater vulnerability, saltwater intrusion, and the location of water resources.

Chloroplast envelope K/H antiporters are involved in cytosol pH regulation.

Variations in light intensity induce cytosol pH changes in photosynthetic tissues, providing a possible signal to adjust a variety of biochemical, physiological and developmental processes to the energy status of the cells. It was shown that these pH changes are partially due to the transport of protons in or out of the thylakoid lumen. However, the ion transporters in the chloroplast that transmit these pH changes to the cytosol are not known.

A self-unfolding proximity enabling device for oral delivery of macromolecules.

Oral delivery of macromolecules remains highly challenging due to their rapid degradation in the gastrointestinal tract and poor absorption across the tight junctions of the epithelium. In the last decade, researchers have investigated several medical devices to overcome these challenges using various approaches, some of which involve piercing through the intestine using micro and macro needles. We have developed a new generation of medical devices called self-unfolding proximity enabling devices, which makes it possible to orally deliver macromolecules without perforating the intestine.

Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching.

Vacuolar-type adenosine triphosphatases (V-ATPases) are electrogenic rotary mechanoenzymes structurally related to F-type ATP synthases. They hydrolyse ATP to establish electrochemical proton gradients for a plethora of cellular processes. In neurons, the loading of all neurotransmitters into synaptic vesicles is energized by about one V-ATPase molecule per synaptic vesicle.

Increased Soluble PD-1 Predicts Response to Nivolumab plus Ipilimumab in Melanoma.

Background: Checkpoint inhibitors have revolutionized the treatment of metastatic melanoma, yielding long-term survival in a considerable proportion of the patients. Yet, 40-60% of patients do not achieve a long-term benefit from such therapy, emphasizing the urgent need to identify biomarkers that can predict response to immunotherapy and guide patients for the best possible treatment. Here, we exploited an unsupervised machine learning approach to identify potential inflammatory cytokine signatures from liquid biopsies, which could predict response to immunotherapy in melanoma.

Recreational screen media use among Danish children aged 6-11 years: influence of parental screen media habits and attitudes.

Aims: Little is known about the influence of parents' screen media habits and attitudes towards screen media on children's screen use. We investigated associations of parental screen use, their smartphone addiction and screen media attitudes, with children's recreational screen use.

Methods: This study was based on a population-based cross-sectional survey sent between May 2019 and November 2020 to a random sample of 6820 Danish parent-child dyads who answered questions regarding their screen media habits.

Effects of Limiting Recreational Screen Media Use on Physical Activity and Sleep in Families With Children: A Cluster Randomized Clinical Trial.

Importance: Children and adults spend large amounts of their leisure time using screen media, which may affect their health and behavior.

Objective: To investigate the effect of reducing household recreational screen media use on physical activity and sleep in children and adults.

Design, Setting, And Participants: This was a cluster randomized clinical trial with a 2-week follow-up.

TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS-CoV-2 infection.

Understanding the molecular pathways driving the acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments for severe COVID-19. Here, we find decreasing number of circulating plasmacytoid dendritic cells (pDCs) in COVID-19 patients early after symptom onset, correlating with disease severity. pDC depletion is transient and coincides with decreased expression of antiviral type I IFNα and of systemic inflammatory cytokines CXCL10 and IL-6.

Effects of limiting digital screen use on well-being, mood, and biomarkers of stress in adults.

Studies have linked higher digital screen use with poorer mental health. However, there is limited experimental evidence to suggest a causal relationship. In this trial, we aimed to investigate the effects of limiting recreational digital screen use on mental well-being, mood, and biomarkers of stress in healthy young and middle-aged adults.

Manual Annotation of Time in Bed Using Free-Living Recordings of Accelerometry Data.

With the emergence of machine learning for the classification of sleep and other human behaviors from accelerometer data, the need for correctly annotated data is higher than ever. We present and evaluate a novel method for the manual annotation of in-bed periods in accelerometer data using the open-source software Audacity, and we compare the method to the EEG-based sleep monitoring device Zmachine Insight+ and self-reported sleep diaries. For evaluating the manual annotation method, we calculated the inter- and intra-rater agreement and agreement with Zmachine and sleep diaries using interclass correlation coefficients and Bland-Altman analysis.

Recreational screen media use in Danish school-aged children and the role of parental education, family structures, and household screen media rules.

Screen media use is part of most children's everyday lives, but organisations have advised that use should be limited. The aims of this study were to describe 6-11-year-old Danish children's screen device ownership and screen media use (weekdays and weekends), including the role of parental education, family structure and household screen media rules. We conducted a cross-sectional study including 5274 Danish children aged 6-11-years sampled from ten Danish municipalities from May 2019 to November 2020.

Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C-C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status.

The chemokine receptor CCR5 is expressed on multiple cell types, including macrophages, dendritic cells, and T cells, and is the major co-receptor used during HIV transmission. Using a standard αCD3/CD28 stimulation protocol to render CD4+ T cells from PBMCs permissive to HIV infection, we discovered that the percentage of CCR5 T cells was significantly elevated in CD4+ T cells when stimulated in the presence of peripheral blood mononuclear cells (PBMCs) as compared to when stimulated as purified CD4+ T cells. This indicated that environmental factors unique to the T-PBMCs condition affect surface expression of CCR5 on CD4+ T cells.

Normal tissue complication probability models for prospectively scored late rectal and urinary morbidity after proton therapy of prostate cancer.

Background And Purpose: Photons and protons have fundamentally different properties, i.e. protons have a reduced dose bath but a higher relative biological effectiveness.

Feasibility of two screen media reduction interventions: Results from the SCREENS pilot trial.

Background: Advancements in screen media devices has transformed the way families engage with screen media. Although these modern devices offer many opportunities, e.g.

Feasibility of home-based sampling of salivary cortisol and cortisone in healthy adults.

Objective: Salivary cortisol and cortisone are used as biomarkers of physiological stress. Careful sampling of saliva for profiling of awakening response and the diurnal slope can be challenging in free-living environments, and validated sampling protocols are lacking. Therefore, we investigated (1) the level of compliance to a three-day home-based salivary sampling protocol, and (2) the within subject day-to-day variability of cortisol and cortisone outcomes and the required measuring days to obtain high reproducibility.

A Cognitive Functional Therapy+ Pathway Versus an Interdisciplinary Pain Management Pathway for Patients With Severe Chronic Low Back Pain (CONFeTTI Trial): Protocol for a Pragmatic Randomized Controlled Trial.

Objective: Chronic low back pain (cLBP) is the leading cause of disability. Interdisciplinary pain management is recommended for patients with severe/high-impact cLBP. Such programs are expensive, not easily accessible, and have limited effect; therefore, new cost-effective strategies are warranted.

A conserved, buried cysteine near the P-site is accessible to cysteine modifications and increases ROS stability in the P-type plasma membrane H+-ATPase.

Sulfur-containing amino acid residues function in antioxidative responses, which can be induced by the reactive oxygen species generated by excessive copper and hydrogen peroxide. In all Na+/K+, Ca2+, and H+ pumping P-type ATPases, a cysteine residue is present two residues upstream of the essential aspartate residue, which is obligatorily phosphorylated in each catalytic cycle. Despite its conservation, the function of this cysteine residue was hitherto unknown.

Multivariate normal tissue complication probability models for rectal and bladder morbidity in prostate cancer patients treated with proton therapy.

Background And Purpose: Normal tissue complication probability (NTCP) models applied for model-based patient selection to proton therapy (PT) have usually been derived using dose/volume histogram (DVH) parameters from photon-based radiotherapy. This study aimed to derive PT-specific multivariate NTCP models that also accounted for the spatial dose distribution (rectum only) as well as non-dose/volume related factors.

Materials And Methods: The study included rectum and bladder DVHs, 2D rectal dose maps and relevant patient/treatment characteristics from 1151 prostate cancer cases treated with PT.

Characterizing the diverse hydrogeology underlying rivers and estuaries using new floating transient electromagnetic methodology.

The hydrogeology below large surface water features such as rivers and estuaries is universally under-informed at the long reach to basin scales (tens of km+). This challenge inhibits the accurate modeling of fresh/saline groundwater interfaces and groundwater/surface water exchange patterns at management-relevant spatial extents. Here we introduce a towed, floating transient electromagnetic (TEM) system (i.

Channelrhodopsin-mediated optogenetics highlights a central role of depolarization-dependent plant proton pumps.

In plants, environmental stressors trigger plasma membrane depolarizations. Being electrically interconnected via plasmodesmata, proper functional dissection of electrical signaling by electrophysiology is basically impossible. The green alga evolved blue light-excited channelrhodopsins (ChR1, 2) to navigate.

Early initiated postoperative rehabilitation enhances quality of life in patients with operable lung cancer: Secondary outcomes from a randomized trial.

Introduction: Patients with lung cancer report a lower degree of Health Related Quality of Life (HRQoL) compared with other cancer patients. HRQoL reflects how patients experience the impact of their disease and its treatment on their quality of daily living. A widely used questionnaire in lung cancer patients is the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire.

Graph refinement based airway extraction using mean-field networks and graph neural networks.

Graph refinement, or the task of obtaining subgraphs of interest from over-complete graphs, can have many varied applications. In this work, we extract trees or collection of sub-trees from image data by, first deriving a graph-based representation of the volumetric data and then, posing the tree extraction as a graph refinement task. We present two methods to perform graph refinement.

Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors.

Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40-60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression in tumor cells is currently used as a predictive biomarker; however, it lacks specificity.

Plasma membrane H-ATPases sustain pollen tube growth and fertilization.

Pollen tubes are highly polarized tip-growing cells that depend on cytosolic pH gradients for signaling and growth. Autoinhibited plasma membrane proton (H) ATPases (AHAs) have been proposed to energize pollen tube growth and underlie cell polarity, however, mechanistic evidence for this is lacking. Here we report that the combined loss of AHA6, AHA8, and AHA9 in Arabidopsis thaliana delays pollen germination and causes pollen tube growth defects, leading to drastically reduced fertility.