Utility of a LangChain and OpenAI GPT-powered chatbot based on the international consensus statement on allergy and rhinology: Rhinosinusitis.

We created a LangChain/OpenAI API-powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR-RS). The ICAR-RS chatbot is able to provide direct and actionable recommendations. Utilization of consensus statements provides an opportunity for AI applications in healthcare.

Optimized Media Volumes Enable Homogeneous Growth of Mesenchymal Stem Cell-Based Engineered Cartilage Constructs.

Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time .

Neurostructural Heterogeneity in Youths With Internalizing Symptoms.

Background: Internalizing disorders such as anxiety and depression are common psychiatric disorders that frequently begin in youth and exhibit marked heterogeneity in treatment response and clinical course. Given that symptom-based classification approaches do not align with underlying neurobiology, an alternative approach is to identify neurobiologically informed subtypes based on brain imaging data.

Methods: We used a recently developed semisupervised machine learning method (HYDRA [heterogeneity through discriminative analysis]) to delineate patterns of neurobiological heterogeneity within youths with internalizing symptoms using structural data collected at 3T from a sample of 1141 youths.

The Opioid Epidemic and Psychiatry: The Time for Action Is Now.

The number of people with opioid use disorder and the number of overdose deaths in the United States have increased dramatically over the past 20 years. U.S.

Evidence for Dissociable Linkage of Dimensions of Psychopathology to Brain Structure in Youths.

Objective: High comorbidity among psychiatric disorders suggests that they may share underlying neurobiological deficits. Abnormalities in cortical thickness and volume have been demonstrated in clinical samples of adults, but less is known when these structural differences emerge in youths. The purpose of this study was to examine the association between dimensions of psychopathology and brain structure.

Spermine on Endothelial Extracellular Vesicles Mediates Smoking-Induced Pulmonary Hypertension Partially Through Calcium-Sensing Receptor.

Objective- This study aims to determine whether and how the enriched metabolites of endothelial extracellular vesicles (eEVs) are critical for cigarette smoke-induced direct injury of endothelial cells and the development of pulmonary hypertension, rarely explored in contrast to long-investigated mechanisms secondary to chronic hypoxemia. Approach and Results- Metabonomic screen of eEVs from cigarette-smoking human subjects reveals prominent elevation of spermine-a polyamine metabolite with potent agonist activity for the extracellular CaSR (calcium-sensing receptor). CaSR inhibition with the negative allosteric modulator Calhex231 or CaSR knockdown attenuates cigarette smoke-induced pulmonary hypertension in rats without emphysematous changes in lungs or chronic hypoxemia.

Acculturative Stress, Social Problem Solving, and Depressive Symptoms among Korean American Immigrants.

The present study examined the relationship among acculturative stress, social problem solving, and depressive symptoms among 107 Korean American immigrants. Hierarchical regression analysis showed that acculturative stress significantly predicted depressive symptoms controlling for different domains of acculturation. With regard to the role of social problem solving, among the five dimensions of social problem solving (i.

Impacts of maturation on the micromechanics of the meniscus extracellular matrix.

To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force microscopy (AFM)-nanoindentation. For circumferential fibers, we detected significant increase in the effective indentation modulus, E, with age. Such impact is in agreement with the increase in collagen fibril diameter and alignment during maturation, and is more pronounced in the outer zone, where collagen fibrils are more aligned and packed.

Individual variation in working memory is associated with fear extinction performance.

PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory.

Applicability of EULAR/ACR classification criteria for dermatomyositis to amyopathic disease.

Background: Existing classification systems for idiopathic inflammatory myopathies (IIMs) fail to permit classification and/or diagnosis of amyopathic dermatomyositis (ADM) in patients.

Objective: In light of the new European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM, we evaluated the likelihood of the skin variables included in the EULAR/ACR criteria (Gottron's sign, Gottron's papules, and heliotrope rash) to give a high probability of classifying patients with ADM.

Methods: This retrospective study evaluated 211 adult patients with dermatomyositis at the University of Pennsylvania.

Sex differences in estimated brain metabolism in relation to body growth through adolescence.

The human brain consumes a disproportionate amount of the body's overall metabolic resources, and evidence suggests that brain and body may compete for substrate during development. Using perfusion MRI from a large cross-sectional cohort, we examined developmental changes of MRI-derived estimates of brain metabolism, in relation to weight change. Nonlinear models demonstrated that, in childhood, changes in body weight were inversely related to developmental age-related changes in brain metabolism.

Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses.

The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology.

CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells.

Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural features to connexins and pannexins, has been implicated in ATP release from taste buds, but it has not been evaluated for a functional role in the airway.

Microsphere-Based Assessment of DNA Methylation for AML Prognosis.

Epigenetic dysregulation, including aberrant methylation of cytosine residues in DNA, is a hallmark of cancer and clearly results in oncogenic cellular alterations such as transcriptional attenuation of tumor suppressors and genomic instability. A number of studies have examined DNA methylation alterations in patients with acute myeloid leukemia (AML) and have shown that analysis of multilocus methylation patterns can identify biologically distinct AML subclasses and can predict patient prognosis. In order to utilize the prognostic capability of methylation analysis in a clinical setting, we have developed a microsphere-based HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP) assay to interrogate the methylation state of genomic multiple loci along with a random forest-based classification algorithm that correlates DNA methylation status with patient prognosis.

Large Animal Models of Meniscus Repair and Regeneration: A Systematic Review of the State of the Field.

Injury to the meniscus is common, but few viable strategies exist for its repair or regeneration. To address this, animal models have been developed to translate new treatment strategies toward the clinic. However, there is not yet a regulatory document guiding such studies.

Effects of ophthalmologic solutions on sinonasal ciliated epithelium.

Background: Off-label use of topical ophthalmologic formulations for treatment of rhinologic disease is cited in recent literature and is anecdotally prevalent among practicing otolaryngologists. Steroids, antibiotics, and other drugs designed for ocular use have subjective clinical efficacy in the nose and sinuses, but their specific effects on the ciliated epithelium are less well defined. This study examines 9 commercially available ophthalmologic drug formulations for effects on ciliary motility in sinonasal cultures, in an effort to characterize their utility as topical therapies for sinonasal diseases.

Relative susceptibility of airway organisms to antimicrobial effects of nitric oxide.

Background: Nitric oxide (NO) is released in the airway as a critical component of innate immune defense against invading pathogenic organisms. It is well documented that bacteriostatic and bactericidal effects of NO are concentration-dependent. However, few data exist comparing relative susceptibility of common pathogens to NO at physiologic concentrations.

Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes.

Background: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes.

Micromechanical anisotropy and heterogeneity of the meniscus extracellular matrix.

Unlabelled: To understand how the complex biomechanical functions of the meniscus are endowed by the nanostructure of its extracellular matrix (ECM), we studied the anisotropy and heterogeneity in the micromechanical properties of the meniscus ECM. We used atomic force microscopy (AFM) to quantify the time-dependent mechanical properties of juvenile bovine meniscus at deformation length scales corresponding to the diameters of collagen fibrils. At this scale, anisotropy in the elastic modulus of the circumferential fibers, the major ECM structural unit, can be attributed to differences in fibril deformation modes: uncrimping when normal to the fiber axis, and laterally constrained compression when parallel to the fiber axis.

Mechanical function near defects in an aligned nanofiber composite is preserved by inclusion of disorganized layers: Insight into meniscus structure and function.

Unlabelled: The meniscus is comprised of circumferentially aligned fibers that resist the tensile forces within the meniscus (i.e., hoop stress) that develop during loading of the knee.

Cause-specific mortality in patients with psoriatic arthritis and rheumatoid arthritis.

Objective: The objective of this study was to examine cause-specific mortality in patients with PsA compared with the general population and compared with patients with RA.

Methods: A cohort study was performed using The Health Improvement Network among patients aged 18-89 years with data from 1994 to 2010. PsA and RA were defined by medical codes, and up to 10 unexposed controls were matched on practice and start date within the practice.

The risk of fracture among patients with psoriatic arthritis and psoriasis: a population-based study.

Objective: To determine the risk of fracture and osteoporosis among patients with psoriatic arthritis (PsA) and psoriasis, compared with the general population and patients with rheumatoid arthritis (RA).

Methods: A population-based cohort study was performed in The Health Improvement Network in the UK using data from 1994 to 2014. Patients aged 18-89 years with PsA or psoriasis and up to five unexposed controls matched by practice and start date within that practice were included.

A SMART data analysis method for constructing adaptive treatment strategies for substance use disorders.

Aims: To demonstrate how Q-learning, a novel data analysis method, can be used with data from a sequential, multiple assignment, randomized trial (SMART) to construct empirically an adaptive treatment strategy (ATS) that is more tailored than the ATSs already embedded in a SMART.

Method: We use Q-learning with data from the Extending Treatment Effectiveness of Naltrexone (ExTENd) SMART (N = 250) to construct empirically an ATS employing naltrexone, behavioral intervention, and telephone disease management to reduce alcohol consumption over 24 weeks in alcohol dependent individuals.

Results: Q-learning helped to identify a subset of individuals who, despite showing early signs of response to naltrexone, require additional treatment to maintain progress.