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JMIR Mental Health Jul 2024Large language model (LLM)-powered services are gaining popularity in various applications due to their exceptional performance in many tasks, such as sentiment analysis...
Large language model (LLM)-powered services are gaining popularity in various applications due to their exceptional performance in many tasks, such as sentiment analysis and answering questions. Recently, research has been exploring their potential use in digital health contexts, particularly in the mental health domain. However, implementing LLM-enhanced conversational artificial intelligence (CAI) presents significant ethical, technical, and clinical challenges. In this viewpoint paper, we discuss 2 challenges that affect the use of LLM-enhanced CAI for individuals with mental health issues, focusing on the use case of patients with depression: the tendency to humanize LLM-enhanced CAI and their lack of contextualized robustness. Our approach is interdisciplinary, relying on considerations from philosophy, psychology, and computer science. We argue that the humanization of LLM-enhanced CAI hinges on the reflection of what it means to simulate "human-like" features with LLMs and what role these systems should play in interactions with humans. Further, ensuring the contextualization of the robustness of LLMs requires considering the specificities of language production in individuals with depression, as well as its evolution over time. Finally, we provide a series of recommendations to foster the responsible design and deployment of LLM-enhanced CAI for the therapeutic support of individuals with depression.
Topics: Humans; Artificial Intelligence; Depression; Language; Communication; Humanism
PubMed: 38958218
DOI: 10.2196/56569 -
Molecular Genetics & Genomic Medicine Jul 2024Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous...
BACKGROUND
Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin-1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan-like disorders.
PURPOSE
To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan-related genes in patients with MFS and ocular manifestations.
METHODS
We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel-based next-generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases.
RESULTS
We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan-related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families.
CONCLUSION
We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan-related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.
Topics: Humans; Marfan Syndrome; Female; Male; Fibrillin-1; Adult; Child; High-Throughput Nucleotide Sequencing; Adolescent; Mutation; Middle Aged; Child, Preschool; Eye Diseases; Pedigree; East Asian People; Adipokines
PubMed: 38958168
DOI: 10.1002/mgg3.2482 -
Journal of the American Heart... Jul 2024Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days...
BACKGROUND
Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH-90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy.
METHODS AND RESULTS
Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH-90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS-90) was assessed with in-person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59-79], median National Institutes of Health Stroke Scale score 14 [9-20]). Median DAOH-90 was 71 [29-84] and median mRS-90 score was 3 [2-5]. DAOH-90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho -0.44, <0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24, <0.001). There was a strong association between mRS-90 and DAOH-90 (Spearman rho correlation -0.79, <0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84-0.88), mRS score >1 was 0.88 (95% CI, 0.86-0.90) and mRS score >2 was 0.90 (95% CI, 0.89-0.92).
CONCLUSIONS
In patients with stroke treated with reperfusion therapies, DAOH-90 shows reasonable comparability to the more established outcome measure of mRS-90. DAOH-90 can be readily obtained from administrative databases and therefore has the potential to be used in large-scale clinical trials and comparative effectiveness studies.
PubMed: 38958146
DOI: 10.1161/JAHA.123.032321 -
Journal of the American Heart... Jul 2024Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of...
BACKGROUND
Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity.
METHODS AND RESULTS
Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; <0.001), and correlated negatively with diffuse fibrosis assessed by ECV (=-0.34, <0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, <0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (=-0.41, <0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels.
CONCLUSIONS
Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.
PubMed: 38958130
DOI: 10.1161/JAHA.124.035264 -
Dental and Medical Problems 2024Dentists, through inappropriate antibiotic prescription, may contribute to the global problem of antibiotic resistance (AR).
BACKGROUND
Dentists, through inappropriate antibiotic prescription, may contribute to the global problem of antibiotic resistance (AR).
OBJECTIVES
Understanding dentists' antibiotic prescription patterns, source of knowledge, and the driving forces behind their prescription practices may be crucial for the effective implementation of the rational use of antibiotics (RUA) in dentistry.
MATERIAL AND METHODS
Active members of the Turkish Dental Association were invited to participate in an electronic survey comprising questions focusing on their role, knowledge and perceptions regarding RUA, the perceived barriers to adapting RUA in daily dental work, and the actual antibiotic prescription practices. The potential impact of age, gender, professional experience, and the mode of dental practice was also evaluated. Dentists' prescription practices for periodontal disease/conditions were evaluated as well.
RESULTS
Based on 1,005 valid responses, there was consensus on the necessity of RUA (99.1%); however, its implementation was low. The main barriers were dentists' own safety concerns (74.4%), strong patients' demands (42.2%) and the fact that prescribing antibiotics became a professional habit (35.8%). Different educational background resulted in clear variances in everyday prescription practices.
CONCLUSIONS
The implementation of RUA was not sufficient and the perceived barriers had an impact on daily prescribing habits. Support for dental professionals through the efficient dissemination of evidencebased clinical guidelines and decision-making aids is likely to require additional help from professional organizations in order to actively combat AR.
Topics: Humans; Anti-Bacterial Agents; Practice Patterns, Dentists'; Surveys and Questionnaires; Male; Female; Adult; Middle Aged; Turkey; Health Knowledge, Attitudes, Practice; Attitude of Health Personnel; Inappropriate Prescribing
PubMed: 38958119
DOI: 10.17219/dmp/159490 -
Journal of Extracellular Vesicles Jul 2024Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication... (Meta-Analysis)
Meta-Analysis
Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof-of-concept of EV-therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state-of-the-art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta-analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV-based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%-CI: 0.1-5.2%), and adverse events (AE; 4.4% (95%-CI: 0.7-22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non-engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV-therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV-based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter-study comparison.
Topics: Humans; Extracellular Vesicles; Clinical Trials as Topic
PubMed: 38958077
DOI: 10.1002/jev2.12458 -
Aging Cell Jul 2024Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease...
Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome-wide meta-analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome-wide and proteome-wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single-cell transcriptome analysis was performed to link targets with cell types. Individual-level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically-elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome-wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single-cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP.
PubMed: 38958042
DOI: 10.1111/acel.14266 -
Physiological Research Jul 2024Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However,...
Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.
PubMed: 38957948
DOI: No ID Found -
Nursing Open Jul 2024To explore the assumptions and values that influence nursing health assessment practices among registered general nurses in general medical and surgical wards.
AIM
To explore the assumptions and values that influence nursing health assessment practices among registered general nurses in general medical and surgical wards.
DESIGN
The study was designed as a focused ethnography.
METHODS
A semi-structured interview guide was used to explore prevailing nursing health assessment practices of 13 registered general nurses in an attempt to explore the assumptions and values influencing health assessment practices in the study setting. Data were analysed inductively using an interpretive qualitative content analysis method.
RESULTS
Nursing health assessment practices, and underlying assumptions and values were underpinned by a central theme of a culture of low expectation relating to nursing health assessment. The culture of low expectation was highlighted in five themes: (1) Unsystematic Assessment of Health Status, (2) Purpose of Nursing Health Assessment, (3) The Role of Nursing Educational and Regulatory Institutions, (4) Ward Ethos and (5) The Role of Organizational and Ward Leadership.
IMPLICATION
The adoption of a holistic nursing health assessment framework with a clearly defined purpose of aiding nursing diagnoses can guide patient-centred care delivery and facilitate early recognition of physiological deterioration.
PATIENT OR PUBLIC CONTRIBUTION
Thirteen registered general nurses were interviewed, and the initial findings returned to them for validation.
CONCLUSION
The potential contribution of nursing health assessment to nursing practice and patient outcomes may not be fully realized if nursing health assessment is not situated within a holistic health assessment model with a clearly defined purpose for nursing practice.
Topics: Humans; Anthropology, Cultural; Qualitative Research; Tertiary Care Centers; Nursing Assessment; Female; Adult; Nursing Staff, Hospital; Male; Interviews as Topic; Nurses; Attitude of Health Personnel; Middle Aged
PubMed: 38957916
DOI: 10.1002/nop2.2237 -
Journal of the Indian Society of... Apr 2024Traditionally, pediatric endodontics lacked access to the full potential of rotary instruments. These instruments, designed for the permanent root canal system, often... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative evaluation of the efficacy of the Pro AF Baby Gold and Kedo-S pediatric endodontic files for canal instrumentation, transportation, and centering ratio - A systematic review and meta-analysis.
BACKGROUND
Traditionally, pediatric endodontics lacked access to the full potential of rotary instruments. These instruments, designed for the permanent root canal system, often presented limitations when used in primary teeth. To address this, exclusive pediatric rotary files with regular improvements have been introduced, featuring superior cutting efficiency with a focus on precise alignment. This design offers the advantage of reduced risk of ledges, perforations, instrument separation, and canal transportation. This study aimed to compare and evaluate the effectiveness of Pro AF Baby Gold and Kedo-S rotary files in preparing primary tooth root canals during pulpectomy procedures through a meta-analysis.
METHODOLOGY
The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The review searched electronic databases from 2000 to February 2024 for studies evaluating the efficacy of Pro AF Baby Gold and Kedo-S files in terms of canal instrumentation, transportation, and centering ratio. The Cochrane risk of bias (ROB)-2 tool assessed quality, with analyses conducted using RevMan software version 5.3. The standardized mean difference (SMD) served as the summary with a random effects model (P < 0.05).
RESULTS
Out of the five studies identified through the eligibility criteria, three were deemed suitable for a meta-analysis, while all five were included in a qualitative synthesis. The quality assessment revealed a presence of moderate-to-low ROB. The pooled analysis using SMD did not show any statistically significant differences between the files, except for the centering ratio in the mesiobuccal canal, where the Kedo-S file performed slightly better. In addition, the absence of any significant asymmetry in the funnel plot suggests that there is likely no publication bias present in the data.
CONCLUSION
Pro AF Baby Gold files can be used as an alternative adjunct in pediatric endodontics to Kedo-S files and manual files.Prospero Registration: CRD42023469406.
Topics: Humans; Root Canal Preparation; Equipment Design; Tooth, Deciduous; Child; Dental Instruments; Pulpectomy
PubMed: 38957903
DOI: 10.4103/jisppd.jisppd_526_23