Molecular recognition of peptides and proteins by cucurbit[]urils: systems and applications.

The development of methodology for attaching ligand binding sites to proteins of interest has accelerated biomedical science. Such protein tags have widespread applications as well as properties that significantly limit their utility. This review describes the mechanisms and applications of supramolecular systems comprising the synthetic receptors cucurbit[7]uril (Q7) or cucurbit[8]uril (Q8) and their polypeptide ligands.

PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells.

Emotion Regulation Self-Efficacy as a Mechanism of Alliance and Outcomes in a Brief, Transdiagnostic Digital Mental Health Intervention: L'auto-efficacité de la régulation des émotions en tant que mécanisme d'alliance et de résultats dans une brève intervention transdiagnostique numérique en santé mentale.

Objectives: Digital mental health interventions have shown promise for alleviating various forms of psychopathology, including depression and anxiety. However, the mechanisms of such interventions remain largely unexplored. The purpose of this study was to investigate a potential mechanistic process through which one hybrid digital mental health intervention (i.

Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally.

Importance: Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation regarding cannabis use, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship.

Objective: To elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function.

Unique Functional Neuroimaging Signatures of Genetic Versus Clinical High Risk for Psychosis.

Background: 22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms.

Positron emission tomography in the evaluation of endometriosis: A systematic review.

Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear.

Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety.

There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

Introduction: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry.

Improved Disabilities of the Arm, Shoulder and Hand scores after myoelectric arm orthosis use at home in chronic stroke: A retrospective study.

Background: Most stroke survivors have persistent upper limb impairments after completing standard clinical care. The resulting impairments can adversely affect their quality of life and ability to complete self-care tasks and remain employed, leading to increased healthcare and societal costs. A myoelectric arm orthosis can be used effectively to support the affected weak arm and increase an individual's use of that arm.

Pioglitazone reverses alcohol-induced alterations in alveolar macrophage mitochondrial phenotype.

Background: People with alcohol use disorder (AUD) have an increased risk of developing pneumonia and pulmonary diseases. Alveolar macrophages (AMs) are immune cells of the lower respiratory tract that are necessary for clearance of pathogens. However, alcohol causes AM oxidative stress, mitochondrial damage and dysfunction, and diminished phagocytic capacity, leading to lung injury and immune suppression.

Cucurbit[8]uril Binds Nonterminal Dipeptide Sites with High Affinity and Induces a Type II β-Turn.

In an effort to target polypeptides at nonterminal sites, we screened the binding of the synthetic receptor cucurbit[8]uril (Q8) to a small library of tetrapeptides, each containing a nonterminal dipeptide binding site. The resulting leads were characterized in detail using a combination of isothermal titration calorimetry, H NMR spectroscopy, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), and X-ray crystallography. The equilibrium dissociation constant values determined for the binding of Q8 to nonterminal dipeptide sites Lys-Phe (KF) and Phe-Lys (FK) were 60 and 86 nm, respectively.

Xist ribonucleoproteins promote female sex-biased autoimmunity.

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation.

The impact of guided versus supportive coaching on mental health app engagement and clinical outcomes.

Although mobile mental health apps have the unique potential to increase access to care, evidence reveals engagement is low unless coupled with coaching. However, most coaching protocols are limited in their scalability. This study assesses how human support and guidance from a Digital Navigator (DN), a scalable coach, can impact mental health app engagement and effectiveness on anxiety and depressive symptoms.

Variability in Cognitive Task Performance in Early Adolescence Is Associated With Stronger Between-Network Anticorrelation and Future Attention Problems.

Background: Intraindividual variability (IIV) during cognitive task performance is a key behavioral index of attention and a consistent marker of attention-deficit/hyperactivity disorder. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN)-thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are 1) associated with each other and 2) can predict future attention-related deficits has not been examined in a developmental, population-based cohort.

Myoelectric Arm Orthosis Assists Functional Activities: A 3-Month Home Use Outcome Report.

Objective: The objective was to compare task performance in individuals with upper limb impairments with and without a myoelectric arm orthosis.

Design: Three-month observational study. Participants met at 4 time points after receiving their myoelectric orthosis (2-Weeks, Month-1, Month-2, Month-3) to complete 4 standardized common daily tasks.

Ancestry-based differences in the immune phenotype are associated with lupus activity.

Systemic lupus erythematosus (SLE) affects 1 in 537 Black women, which is >2-fold more than White women. Black patients develop the disease at a younger age, have more severe symptoms, and have a greater chance of early mortality. We used a multiomics approach to uncover ancestry-associated immune alterations in patients with SLE and healthy controls that may contribute biologically to disease disparities.

An exploratory analysis of the effect size of the mobile mental health Application, mindLAMP.

Objectives: Despite the proliferation of mobile mental health apps, evidence of their efficacy around anxiety or depression is inadequate as most studies lack appropriate control groups. Given that apps are designed to be scalable and reusable tools, insights concerning their efficacy can also be assessed uniquely through comparing different implementations of the same app. This exploratory analysis investigates the potential to report a preliminary effect size of an open-source smartphone mental health app, mindLAMP, on the reduction of anxiety and depression symptoms by comparing a control implementation of the app focused on self-assessment to an intervention implementation of the same app focused on CBT skills.

Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.

Introduction: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis.

Autoantibodies are highly prevalent in non-SARS-CoV-2 respiratory infections and critical illness.

The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non-SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non-SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs).

Relapse prediction in schizophrenia with smartphone digital phenotyping during COVID-19: a prospective, three-site, two-country, longitudinal study.

Smartphone technology provides us with a more convenient and less intrusive method of detecting changes in behavior and symptoms that typically precede schizophrenia relapse. To take advantage of the aforementioned, this study examines the feasibility of predicting schizophrenia relapse by identifying statistically significant anomalies in patient data gathered through mindLAMP, an open-source smartphone app. Participants, recruited in Boston, MA in the United States, and Bangalore and Bhopal in India, were invited to use mindLAMP for up to a year.

Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution Across Peripheral Immune Cells in IBD.

Background And Aims: Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.

Methods: We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls].

Smartphone app engagement and clinical outcomes in a hybrid clinic.

Despite the growing prevalence of mental health-related smartphone apps, low real-world engagement has prevented these apps from transforming the mental health landscape. Integrating mental health apps into more traditional therapeutic models appears to support better clinical outcomes, but also raises questions about the relationship between app engagement, the app itself, and the coach or clinician. This study explores patient app engagement patterns and the associated clinical outcomes gathered from piloting a digital clinic.