Waxy- or Putty-Like Materials as a Novel Drug Preparation for Synthetic Cannabinoid Receptor Agonists: Detection in Prisons and In Vitro Cannabinoid Receptor Activity.

After the Scottish Prison Service (SPS) introduced mail photocopying procedures in December 2021, a shift in smuggling methods was observed for synthetic cannabinoid receptor agonists (SCRAs) and other new psychoactive substances (NPS) from drug-infused papers back to traditional sample matrices (e.g., tablets and powders), although new matrices also emerged.

A functional contextual, observer-centric, quantum mechanical, and neuro-symbolic approach to solving the alignment problem of artificial general intelligence: safe AI through intersecting computational psychological neuroscience and LLM architecture for emergent theory of mind.

There have been impressive advancements in the field of natural language processing (NLP) in recent years, largely driven by innovations in the development of transformer-based large language models (LLM) that utilize "attention." This approach employs masked self-attention to establish (via similarly) different positions of tokens (words) within an inputted sequence of tokens to compute the most appropriate response based on its training corpus. However, there is speculation as to whether this approach alone can be scaled up to develop emergent artificial general intelligence (AGI), and whether it can address the alignment of AGI values with human values (called the alignment problem).

PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia.

The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi.

Mixed-methods feasibility outcomes for a novel ACT-based video game 'ACTing Minds' to support mental health.

Objectives: To determine the feasibility and acceptability of 'ACTing Minds', a novel single-player adventure video game based on acceptance and commitment therapy (ACT).

Design: A single-arm, mixed-methods repeated measures feasibility study.

Setting: Intervention and questionnaires were completed at home by participants.

Susceptibility of pediatric acute lymphoblastic leukemia to STAT3 inhibition depends on p53 induction.

Advances in the clinical management of pediatric B-cell acute lymphoblastic leukemia (B-ALL) have dramatically improved outcomes for this disease. However, relapsed and high-risk disease still contribute to significant numbers of treatment failures. Development of new, broad range therapies is urgently needed for these cases.

Structure-Guided Design and Synthesis of a Pyridazinone Series of Proteasome Inhibitors.

There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the proteasome. A related analogue, active against , showed suboptimal efficacy in an animal model of Chagas disease, so alternative proteasome inhibitors were investigated.

Applying an osteopathic intervention to improve mild to moderate mental health symptoms: a mixed-methods feasibility study protocol.

Introduction: Mental health services are stretched in the UK and are in need of support. One approach that could improve mental health symptoms is osteopathy. Research suggests that osteopathy influences psychophysiological factors, which could lead to improvements in mental health.

Functional contextual implementation of an evolutionary, entropy-based, and embodied free energy framework: Utilizing Lagrangian mechanics and evolutionary game theory's truth vs. fitness test of the veridicality of phenomenological experience.

The Bayesian approach of cognitive science largely takes the position that evolution drives perception to produce precepts that are veridical. However, some efforts utilizing evolutionary game theory simulations have shown that perception is more likely based on a fitness function, which promotes survival rather than promoting perceptual truth about the environment. Although these findings do not correspond well with the standard Bayesian approach to cognition, they may correspond with a behavioral functional contextual approach that is ontologically neutral (a-ontological).

Going beyond the DSM in predicting, diagnosing, and treating autism spectrum disorder with covarying alexithymia and OCD: A structural equation model and process-based predictive coding account.

Background: There is much overlap among the symptomology of autistic spectrum disorders (ASDs), obsessive compulsive disorders (OCDs), and alexithymia, which all typically involve impaired social interactions, repetitive impulsive behaviors, problems with communication, and mental health.

Aim: This study aimed to identify direct and indirect associations among alexithymia, OCD, cardiac interoception, psychological inflexibility, and self-as-context, with the DV ASD and depression, while controlling for vagal related aging.

Methodology: The data involved electrocardiogram (ECG) heart rate variability (HRV) and questionnaire data.

High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria.

Artemisinin-based combination therapies have been crucial in driving down the global burden of malaria, the world's largest parasitic killer. However, their efficacy is now threatened by the emergence of resistance in Southeast Asia and sub-Saharan Africa. Thus, there is a pressing need to develop new antimalarials with diverse mechanisms of action.

A Functional Contextual Account of Background Knowledge in Categorization: Implications for Artificial General Intelligence and Cognitive Accounts of General Knowledge.

Psychology has benefited from an enormous wealth of knowledge about processes of cognition in relation to how the brain organizes information. Within the categorization literature, this behavior is often explained through theories of memory construction called exemplar theory and prototype theory which are typically based on similarity or rule functions as explanations of how categories emerge. Although these theories work well at modeling highly controlled stimuli in laboratory settings, they often perform less well outside of these settings, such as explaining the emergence of background knowledge processes.

High-throughput sequencing of peripheral blood for minimal residual disease monitoring in childhood precursor B-cell acute lymphoblastic leukemia: A prospective feasibility study.

Background: Minimal residual disease (MRD) measured on end-of-induction bone marrow (BM) is the most important biomarker for guiding therapy in pediatric acute lymphoblastic leukemia (ALL). Due to limited sensitivity of current approaches, peripheral blood (PB) is not a reliable source for identifying patients needing treatment changes. We sought to determine if high-throughput sequencing (HTS) (next-generation sequencing) of rearranged immunoglobulin and T-cell receptor genes can overcome this and be used to measure MRD in PB.

The metabolism of the synthetic cannabinoids ADB-BUTINACA and ADB-4en-PINACA and their detection in forensic toxicology casework and infused papers seized in prisons.

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after.

Ensuring Effective Public Health Communication: Insights and Modeling Efforts From Theories of Behavioral Economics, Heuristics, and Behavioral Analysis for Decision Making Under Risk.

Public health (PH) messaging can have an enormous impact on shaping how individuals within society behave, and can ensure it is in a safe and responsible way, consistent with up-to-date evidence-based PH guidelines. If done effectively, messaging can save lives and improve the health of those within society. However, unfortunately, those within Government PH bodies typically have little training about how to effectively represent PH messages in a way that is consistent with psychological theories of cognitive bias, in order to avoid cognitively biasing the public through their messages.

Associations Between Mental Health, Interoception, Psychological Flexibility, and Self-as-Context, as Predictors for Alexithymia: A Deep Artificial Neural Network Approach.

Alexithymia is a personality trait which is characterized by an inability to identify and describe conscious emotions of oneself and others. The present study aimed to determine whether various measures of mental health, interoception, psychological flexibility, and self-as-context, predicted through linear associations alexithymia as an outcome. This also included relevant mediators and non-linear predictors identified for particular sub-groups of participants through cluster analyses of an Artificial Neural Network (ANN) output.

A novel ACT-based video game to support mental health through embedded learning: a mixed-methods feasibility study protocol.

Introduction: In recent years, serious video games have been used to promote emotional regulation in individuals with mental health issues. Although these therapeutic strategies are innovative, they are limited with respect to scope of treatment, often focusing on specific cognitive skills, to help remediate a specific mental health disorder.

Objective: Here, we propose a protocol for assessing the feasibility of a novel acceptance and commitment therapy (ACT)-based video game for young adults.

Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs.

Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually.

A Systematic Review of Associations Between Interoception, Vagal Tone, and Emotional Regulation: Potential Applications for Mental Health, Wellbeing, Psychological Flexibility, and Chronic Conditions.

Interoception and heart rate variability have been found to predict outcomes of mental health and well-being. However, these have usually been investigated independently of one another. This systematic review aimed to explore a key gap in the current literature, that being, identifying whether HRV and interoception predict emotional regulation outcomes and strategies.

Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial.

Background: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers.

Methods: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation).

Corrigendum: The Immediate Effect of Therapeutic Touch and Deep Touch Pressure on Range of Motion, Interoceptive Accuracy and Heart Rate Variability: A Randomized Controlled Trial With Moderation Analysis.

[This corrects the article DOI: 10.3389/fnint.2018.

Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase.

Methionyl-tRNA synthetase (MetRS) is a chemically validated drug target in kinetoplastid parasites and . To date, all kinetoplastid MetRS inhibitors described bind in a similar way to an expanded methionine pocket and an adjacent, auxiliary pocket. In the current study, we have identified a structurally novel class of inhibitors containing a 4,6-diamino-substituted pyrazolopyrimidine core (the MetRS02 series).

Immediate effects and associations between interoceptive accuracy and range of motion after a HVLA thrust on the thoracolumbar junction: A randomised controlled trial.

Background: There is paucity in the literature regarding the role of interoceptive accuracy (IAc) at predicting the effectiveness of osteopathic techniques which increase spinal mobility when directed specifically at the thoracolumbar junction (TLJ).

Aims: The study aimed to explore whether a high velocity, low amplitude (HVLA) thrust of the TLJ would increase spinal mobility (measured through Range of Motion; ROM) and change IAc. Also, whether baseline IAc correlated with the post-ROM measures and change in ROM.