Effectiveness of a combination of laccase and green coffee extract on oral malodor: a comparative, randomized, controlled, evaluator-blind, parallel-group trial.

Oral malodor negatively impacts a person's quality of life and may affect up to 50% of the population. The aim of this randomized, placebo and no-product controlled, evaluator-blind, proof-of-concept study was to evaluate the effectiveness and safety of the single use of two experimental lozenges containing the laccase enzyme and green coffee extract (with and without flavor) in reducing intrinsic oral malodor. Following 12-16 h of avoidance of oral hygiene,156 generally healthy subjects presented at screening and baseline visits with a mean organoleptic odor intensity (OI) score of ⩾2 and an OralChromareading of ⩾125 parts per billion (ppb) hydrogen sulfide (HS) gas and were randomly assigned to receive either one of the two experimental lozenges, a placebo lozenge, or no-product.

The Simultaneous Inhibition of Solute Carrier Family 6 Member 19 and Breast Cancer Resistance Protein Transporters Leads to an Increase of Indoxyl Sulfate (a Uremic Toxin) in Plasma and Kidney.

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.

Personalized interpretable prediction of perceived sleep quality: Models with meaningful cardiovascular and behavioral features.

Understanding a person's perceived quality of sleep is an important problem, but hard due to its poor definition and high intra- as well as inter-individual variation. In the short term, sleep quality has an established impact on cognitive function during the following day as well as on fatigue. In the long term, good quality sleep is essential for mental and physical health and contributes to quality of life.

Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause.

Objective: Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS.

Methods: The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance.

Modeling multiple sclerosis using mobile and wearable sensor data.

Multiple sclerosis (MS) is a neurological disease of the central nervous system that is the leading cause of non-traumatic disability in young adults. Clinical laboratory tests and neuroimaging studies are the standard methods to diagnose and monitor MS. However, due to infrequent clinic visits, it is fundamental to identify remote and frequent approaches for monitoring MS, which enable timely diagnosis, early access to treatment, and slowing down disease progression.

Comparing Synchronous and Asynchronous Task Delivery in Mixed Reality Environments.

Asynchronous digital communication is a widely applied and well-known form of information exchange. Most pieces of technology make use of some variation of asynchronous communication systems, be it messaging or email applications. This allows recipients to process digital messages immediately (synchronous) or whenever they have time (asynchronous), meaning that purely digital interruptions can be mitigated easily.

Video-based sympathetic arousal assessment via peripheral blood flow estimation.

Electrodermal activity (EDA) is considered a standard marker of sympathetic activity. However, traditional EDA measurement requires electrodes in steady contact with the skin. Can sympathetic arousal be measured using only an optical sensor, such as an RGB camera? This paper presents a novel approach to infer sympathetic arousal by measuring the peripheral blood flow on the face or hand optically.

Meaningful digital biomarkers derived from wearable sensors to predict daily fatigue in multiple sclerosis patients and healthy controls.

Fatigue is the most common symptom among multiple sclerosis (MS) patients and severely affects the quality of life. We investigate how perceived fatigue can be predicted using biomarkers collected from an arm-worn wearable sensor for MS patients (n = 51) and a healthy control group (n = 23) at an unprecedented time resolution of more than five times per day. On average, during our two-week study, participants reported their level of fatigue 51 times totaling more than 3,700 data points.

Controllers or Bare Hands? A Controlled Evaluation of Input Techniques on Interaction Performance and Exertion in Virtual Reality.

Virtual Reality (VR) systems have traditionally required users to operate the user interface with controllers in mid-air. More recent VR systems, however, integrate cameras to track the headset's position inside the environment as well as the user's hands when possible. This allows users to directly interact with virtual content in mid-air just by reaching out, thus discarding the need for hand-held physical controllers.

Noncanonical Activity of Tissue Inhibitor of Metalloproteinases 2 (TIMP2) Improves Cognition and Synapse Density in Aging.

Peripheral administration of tissue inhibitor of metalloproteinases 2 (TIMP2), a protein inhibitor of matrix metalloproteinases (MMPs), has previously been shown to have beneficial effects on cognition and neurons in aged mice. Here, to better understand the potential of recombinant TIMP2 proteins, an IgG4Fc fusion protein (TIMP2-hIgG4) was developed to extend the plasma half-life of TIMP2. Following one month of administration of TIMP2 or TIMP2-hIgG4 via intraperitoneal injections, 23-month-old male C57BL/6J mice showed improved hippocampal-dependent memory in a Y-maze, increased hippocampal gene expression, and increased excitatory synapse density in the CA1 and dentate gyrus (DG) of the hippocampus.

Combined BCL-2 and PI3K/AKT Pathway Inhibition in -Rearranged Acute B-Lymphoblastic Leukemia Cells.

Numerous hematologic neoplasms, including acute B-lymphoblastic leukemia (B-ALL), are characterized by overexpression of anti-apoptotic BCL-2 family proteins. Despite the high clinical efficacy of the specific BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), dose limitation and resistance argue for the early exploration of rational combination strategies. Recent data indicated that BCL-2 inhibition in B-ALL with rearrangements is a promising intervention option; however, combinatorial approaches have not been in focus so far.

Experiencing herd immunity in virtual reality increases COVID-19 vaccination intention: Evidence from a large-scale field intervention study.

This study investigates the impact of an immersive virtual reality (VR) simulation of herd immunity on vaccination intentions and its potential underlying mechanisms. In this preregistered field study,  = 654 participants were randomly assigned to one of the three VR conditions: (1) Gamified Herd Immunity; (2) Gamified Herd Immunity + Empathy (with additional narrative elements); (3) Control (gamified with no vaccination-related content). In the Gamified Herd Immunity simulation, participants embodied a vulnerable person and navigated a wedding venue trying to avoid getting infected.

Characterizing Physiological Responses to Fear, Frustration, and Insight in Virtual Reality.

Physiological sensing often complements studies of human behavior in virtual reality (VR) to detect users' affective and cognitive states. Some psychological states, such as fear and frustration, can be particularly hard to differentiate from a physiological perspective as they are close in the arousal and valence emotional space. Moreover, it is largely unclear how users' physiological reactions are expressed in response to transient psychological states such as fear, frustration, and insight-especially since these are rich indicators for characterizing users' responses to dynamic systems but are hard to capture in highly interactive settings.

Cognitive fatigability assessment test (cFAST): Development of a new instrument to assess cognitive fatigability and pilot study on its association to perceived fatigue in multiple sclerosis.

Background: Fatigue is a common symptom of many diseases, including multiple sclerosis. It manifests as a cognitive or physical condition. Fatigue is poorly understood, and effective therapies are missing.

Effective tumor cell abrogation via Venetoclax-mediated BCL-2 inhibition in KMT2A-rearranged acute B-lymphoblastic leukemia.

Dysregulation of the intrinsic BCL-2 pathway-mediated apoptosis cascade is a common feature of hematological malignancies including acute B-lymphoblastic leukemia (B-ALL). The KMT2A-rearranged high-risk cytogenetic subtype is characterized by high expression of antiapoptotic protein BCL-2, likely due to the direct activating binding of KMT2A fusion proteins to the BCL2 gene. The BCL-2 inhibitor venetoclax (VEN) has proven great clinical value in other blood cancers, however, data on B-ALL is sparse and past studies have not so far described the effects of VEN on gene and protein expression profiles.

Continuous monitoring with wearables in multiple sclerosis reveals an association of cardiac autonomic dysfunction with disease severity.

Background: Dysfunction of the autonomic nervous system is common in multiple sclerosis patients, and probably present years before diagnosis, but its role in the disease is poorly understood.

Objectives: To study the autonomic nervous system in patients with multiple sclerosis using cardiac autonomic regulation measured with a wearable.

Methods: In a two-week study, we present a method to standardize the measurement of heart rate variability using a wearable sensor that allows the investigation of circadian trends.

Virtual reality reduces COVID-19 vaccine hesitancy in the wild: a randomized trial.

Vaccine hesitancy poses one of the largest threats to global health. Informing people about the collective benefit of vaccination has great potential in increasing vaccination intentions. This research investigates the potential for engaging experiences in immersive virtual reality (VR) to strengthen participants' understanding of community immunity, and therefore, their intention to get vaccinated.

Evaluation of Real-Time Quaking-Induced Conversion, ELISA, and Immunohistochemistry for Chronic Wasting Disease Diagnosis.

Chronic wasting disease (CWD) is a transmissible prion disorder, primarily affecting free-ranging and captive cervids in North America (United States and Canada), South Korea, and Europe (Finland, Norway, and Sweden). Current diagnostic methods used in the United States for detection of CWD in hunter harvested deer involve demonstration of the causal misfolded prion protein (PrP) in the obex or retropharyngeal lymph nodes (RLNs) using an antigen detection ELISA as a screening tool, followed by a confirmation by the gold standard method, immunohistochemistry (IHC). Real-time quaking-induced conversion (RT-QuIC) assay is a newer approach that amplifies misfolded CWD prions and has facilitated CWD prion detection in a variety of tissues, body fluids, and excreta.

Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research.

Although exposure to ambient particulate matter (PM) is linked to asthma, the health effects of co-existing vapor-phase organic pollutants (vapor) and their combined effects with PM on this disease are poorly understood. We used a murine asthma model to test the hypothesis that exposure to vapor would enhance allergic sensitization and this effect would be further strengthened by co-existing PM. We found that vapor and PM each individually exerted adjuvant effects on OVA sensitization.

A self-administered virtual reality intervention increases COVID-19 vaccination intention.

Effective interventions for increasing people's intention to get vaccinated are crucial for global health, especially considering COVID-19. We devised a novel intervention using virtual reality (VR) consisting of a consultation with a general practitioner for communicating the benefits of COVID-19 vaccination and, in turn, increasing the intention to get vaccinated against COVID-19. We conducted a preregistered online experiment with a 2×2 between-participant design.

[Alcohol in social media: Where is the space for prevention?].

Background: Alcohol has an almost ubiquitous presence, both offline and online.

Research Aim: This paper therefore aims to describe the status quo of alcohol prevention on leading social media platforms in German-speaking countries.

Material And Methods: To this end, the international state of research on alcohol communication in social media is first summarized by means of a narrative review.

Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia.

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction.

Remedial capacity of diclosulam by cover plants in different edaphoclimatic conditions.

Pre-emergent herbicides have been developed for their long residual effect; however, they can make sensitive successor cultures unfeasible. Waste remediation techniques are needed for sustainable agricultural systems; for this, the edaphoclimatic asymmetries in the country must be considered. This study aimed to evaluate the remedial capacity of the herbicide diclosulam by covering crops under different edaphoclimatic conditions.