Therapeutic Intervention Research Articles

A Pragmatic Approach to Fetal Monitoring via Cardiotocography Using Feature Elimination and Hyperparameter Optimization.

Cardiotocography (CTG) is used to assess the health of the fetus during birth or antenatally in the third trimester. It concurrently detects the maternal uterine contractions (UC) and fetal heart rate (FHR). Fetal distress, which may require therapeutic intervention, can be diagnosed using baseline FHR and its reaction to uterine contractions. Using CTG, a pragmatic machine learning strategy based on feature reduction and hyperparameter optimization was suggested in this study to classify the various fetal states (Normal, Suspect, Pathological). An application of this strategy can be a decision support tool to manage pregnancies. On a public dataset of 2126 CTG recordings, the model was assessed using various standard CTG dataset specific and relevant classifiers. The classifiers' accuracy was improved by the proposed method. The model accuracy was increased to 97.20% while using Random Forest (best classifier). Practically speaking, the model was able to correctly predict 100% of all pathological cases and 98.8% of all normal cases in the dataset. The proposed model was also implemented on another public CTG dataset having 552 CTG signals, resulting in a 97.34% accuracy. If integrated with telemedicine, this proposed model could also be used for long-distance "stay at home" fetal monitoring in high-risk pregnancies.

What are the essential determinants of human papillomavirus carcinogenesis?

Human papillomavirus (HPV) infection is the leading viral cause of cancer. Over the past several decades, research on HPVs has provided remarkable insight into human cell biology and into the pathology of viral and non-viral cancers. The HPV E6 and E7 proteins engage host cellular proteins to establish an environment in infected cells that is conducive to virus replication. They rewire host cell signaling pathways to promote proliferation, inhibit differentiation, and limit cell death. The activity of the "high-risk" HPV E6 and E7 proteins is so potent that their dysregulated expression is sufficient to drive the initiation and maintenance of HPV-associated cancers. Consequently, intensive research efforts have aimed to identify the host cell targets of E6 and E7, in part with the idea that some or all of the virus-host interactions would be essential cancer drivers. These efforts have identified a large number of potential binding partners of each oncoprotein. However, over the same time period, parallel research has revealed that a relatively small number of genetic mutations drive carcinogenesis in most non-viral cancers. We therefore propose that a high-priority goal is to identify which of the many targets of E6 and E7 are critical drivers of HPV carcinogenesis. By identifying the cancer-driving targets of E6 and E7, it should be possible to better understand the distinct roles of other targets, perhaps in the viral life cycle, and to focus efforts to develop anti-cancer therapies on the subset of virus-host interactions for which therapeutic intervention would have the greatest impact.

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.

With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29-45years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.

Posterior urethral valves: Clinical audits of presentation, diagnostic and therapeutic intervention in a nigerian teaching hospital.

We described our experience in the management of PUV at UNIOSUN Teaching Hospital, Osogbo, Osun State. This was a retrospective analysis of patients with diagnosis of PUV carried out over a 4year period (2019-2023). Demographic characteristics, clinical presentation, diagnosis and mode of therapeutic interventions were the variables analysed. A total of 17 patients with PUV were managed during the study period. Median age at presentation and surgery were 10months (range 3.0-48.0) and 13months (range 3.0-49.5), respectively. Most common presentation was poor urinary stream, 11 (64.7%). Mean PCV was 34.42%. Klebsiella aerogens was the predominant 9 (52.9%) organism isolated. A patient had prenatal USS diagnosis suggestive of PUV, majority (52.9%) had bilateral grade 1V hydronephrosis at presentation. Voiding cystogram was diagnostic in 14 patients, (82.4%) while urethrocystoscopy was done in 14 (82.4%) patients. Median creatinine level were 116, 76.5 and 51.0 (micromol/l) pre- and post-catheterization and 1month post-surgery, respectively. There was positive correlation between the age and post- surgery creatinine but a negative correlation between the PCV and grade of hydronephrosis. All patients had Mohans valvotomy. We had mortality in a patient from urosepsis. At 6months-1year follow-up, 15 patients had good urine stream with stable renal function. Early intervention assist in optimizing renal and bladder function and minimize risk of urosepsis. Where there is no facility for endoscopic valve ablation, Mohans valvotomy remains a viable treatment option.

Unveiling the Complexity of cis-Regulation Mechanisms in Kinases: A Comprehensive Analysis.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.

Over the past two decades, the "hallmarks of cancer" have revolutionized cancer research and highlighted the crucial roles of inflammation and immunity. Pro-tumorigenic inflammation promotes cancer development along with inhibition of anti-tumor immunity, shaping the tumor microenvironment (TME) towards a tumor-permissive state and further enhancing the malignant potential of cancer cells. This immunosuppressive TME allows tumors to evade immunosurveillance. Thus, understanding the complex interplay between tumors and the immune system within the TME has become pivotal, especially with the advent of immunotherapy. Although immunotherapy has achieved notable success in many malignancies, primary liver cancer, particularly hepatocellular carcinoma (HCC), presents unique challenges. The hepatic immunosuppressive environment poses obstacles to the effectiveness of immunotherapy, along with high mortality rates and limited treatment options for patients with liver cancer. In this review, we discuss current understanding of the complex immune-mediated mechanisms underlying liver neoplasms, focusing on HCC and liver metastases. We describe the molecular and cellular heterogeneity within the TME, highlighting how this presents unique challenges and opportunities for immunotherapy in liver cancers. By unraveling the immune landscape of liver neoplasms, this review aims to contribute to the development of more effective therapeutic interventions, ultimately improving clinical outcomes for patients with liver cancer.

The eATP/P2×7R Axis Drives Quantum Dot-Nanoparticle Induced Neutrophil Recruitment in the Pulmonary Microcirculation.

Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG-amine-QDs, but not carboxyl-QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP-gated receptor P2X7R induced expression of E-selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA-1 and MAC-1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

Orbit symmetry breaking in MXene implements enhanced soft bioelectronic implants.

Bioelectronic implants featuring soft mechanics, excellent biocompatibility, and outstanding electrical performance hold promising potential to revolutionize implantable technology. These biomedical implants can record electrophysiological signals and execute direct therapeutic interventions within internal organs, offering transformative potential in the diagnosis, monitoring, and treatment of various pathological conditions. However, challenges remain in improving excessive impedance at the bioelectronic-tissue interface and thus the efficacy of electrophysiological signaling and intervention. Here, we devise orbit symmetry breaking in MXene (a low-cost scalability, biocompatible, and conductive two dimensionally layered material, which we refer to as OBXene), which exhibits low bioelectronic-tissue impedance, originating from the out-of-plane charge transfer. Furthermore, the Schottky-induced piezoelectricity stemming from the asymmetric orbital configuration of OBXene facilitates interlayered charge transport in the device. We report an OBXene-based cardiac patch applied on the left ventricular epicardium of both rodent and porcine models to enable spatiotemporal epicardium mapping and pacing while coupling the wireless and battery-free operation for long-term real-time recording and closed-loop stimulation.

HMGB1 promotes M1 polarization of macrophages and induces COPD inflammation.

Chronic obstructive pulmonary disease (COPD) is a pervasive and incapacitating respiratory condition, distinguished by airway inflammation and the remodeling of the lower respiratory tract. Central to its pathogenesis is an intricate inflammatory process, wherein macrophages exert significant regulatory functions, and High mobility group box 1 (HMGB1) emerges as a pivotal inflammatory mediator potentially driving COPD progression. This study explores the hypothesis that HMGB1, within macrophages, modulates COPD through inflammatory mechanisms, focusing on its influence on macrophage polarization. Our investigation uncovered that HMGB1 is upregulated in the context of COPD, associated with an enhanced proinflammatory M1 macrophage polarization induced by cigarette smoke. This polarization is linked to suppressed cell proliferation and induced apoptosis, indicative of HMGB1's role in the disease's inflammatory trajectory. The study further implicates HMGB1 in the activation of the Nuclear factor kappa-B (NF-κB) signaling pathway and chemokine signaling within macrophages, which are likely to amplify the inflammatory response characteristic of COPD. The findings underscore HMGB1's critical involvement in COPD pathogenesis, presenting it as a significant target for therapeutic intervention aimed at modulating macrophage polarization and inflammation.

CD44: A Stemness Driver, Regulator and Marker - all in one?

Although the concept of cancer stem cells is still controversial, previous studies have shown that blood cancers, as well as specific types of solid cancers such as colorectal cancer, rely on stem cells during the onset of tumor growth and further tumor development. Moreover, resistance to therapeutic treatment in leukemias such as acute myeloid leukemia and in colorectal cancer can be attributed to a small population of cells with stemness properties known as minimal residual disease. In this review, we look back on the discovery of cancer stem cells and the contribution of the findings in blood cancer to a parallel discovery in solid cancers. We focus on CD44 as a stem cell marker, both in blood cancers and in several types of solid cancers, particularly of the gastro-intestinal tract. This review highlights newly discovered molecular mechanisms of action of CD44 which indicate that CD44 has indeed a function in stemness, stem cell maintenance and drug resistance. We attempt here to make the link between the functions of CD44 isoforms in stemness and their involvement in specific steps of tumor growth and metastasis.

Clinical characterization of children and adolescents with ADHD and sleep disturbances.

Sleep disturbances (SD) are commonly reported concerns among parents and caregivers of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). While it is widely acknowledged that SD can worsen various aspects of children and adolescents' well-being (e.g., academic performance and emotional/behavioral state), a comprehensive clinical characterization of ADHD and SD is currently lacking. To address this gap, 136 children and adolescents diagnosed with ADHD (aged 6 to 14 years) were retrospectively selected by reviewing electronic health records of hundreds of patients with neuropsychiatric disorders referred to the children's hospital. Participants were divided into two groups based on the presence of SD, assessed via a parent-report questionnaire (94 ADHD without SD and 42 ADHD with SD). Standardized measures of adaptive behavior, academic performance, ADHD-related and emotional/behavioral symptoms were collected. Results documented that the group of ADHD with SD obtained worse scores in specific aspects of adaptive behavior (conceptual and practical domains), academic performance (text comprehension, writing), ADHD symptoms (inattention) and emotional/behavioral difficulties (especially, mood/emotional regulation and stress) compared to those with ADHD without SD. In addition, our results established a relationship between sleep problems and diverse clinical aspects of children and adolescents with ADHD, while controlling for age, cognitive level, gender, ADHD symptoms severity, and Body Mass Index. From a clinical perspective, our study suggests that the presence of SD in patients with ADHD may serve as an indicator for strengths and weaknesses in this population, even demonstrating an independent relationship with specific clinical dimensions. Implications to improve clinical diagnostic and therapeutic interventions are discussed.

Clinical Impact of Radiologist’s Alert System on Patient Care for High-risk Incidental CT Findings: A Machine Learning-Based Risk Factor Analysis

Rationale and ObjectivesEfficient communication between radiologists and clinicians ordering computed tomography (CT) examinations is crucial for managing high-risk incidental CT findings (ICTFs). Herein, we introduced a Radiologist’s Alert and Patient Care Follow-up System (APCFS) for high-risk ICTFs. This study aimed to analyze the ICTFs detected by this system and the factors associated with them. Materials and MethodsThis retrospective study was approved by the institutional review board. We analyzed 52,331 CT examinations conducted between 2019 and 2021. In cases where high-risk ICTFs were identified, radiologists utilized APCFS to prompt ordering clinicians for further patient care. We assessed the frequency, affected body organs, presence or absence of therapeutic interventions, and diagnoses of high-risk ICTFs. An automated machine learning platform was employed to analyze the factors associated with high-risk ICTFs. ResultsAmong the 52,331 CT examinations, 507 (0.96%) revealed high-risk ICTFs, primarily affecting the lung (18.0%). Of these 507 high-risk ICTFs, 117 (23.1%) underwent therapeutic interventions, while 362 (71.4%) required only follow-up. Of the 117 cases undergoing interventions, 61 (52.1%) required surgery. Of the 219 high-risk ICTFs leading to a confirmed diagnosis, 146 (66.7%) were neoplastic lesions, including 88 (60.3%) malignancies, and 73 (33.3%) were non-neoplastic lesions. The top three risk factors associated with high-risk ICTFs in the regularized logistic regression model were the imaging protocol (especially aortic valve implantation planning protocol), imaging area (especially whole-body imaging), and clinical department (especially cardiology). ConclusionUtilizing APCFS, high-risk ICTFs were detected in approximately 1% of all CT examinations, likely associated with specific imaging protocols, areas, and clinical departments.

The causality between rheumatoid arthritis and postural deformities: bidirectional Mendelian randomization study and mediation analysis

BackgroundTo better understand the preventive or therapeutic clinical interventions that may be supported by the association between rheumatoid arthritis (RA) and postural deformities including hallux valgus, flat foot, and scoliosis, this study was conducted using Mendelian randomization (MR) analysis. It aimed to investigate whether RA is causally associated with postural deformities in European populations.MethodsSummary-level data on RA and postural deformities were obtained from the IEU OpenGWAS project and Finngen database, respectively. LDSC regression analysis was conducted to assess the genetic correlation between these diseases. The inverse variance weighting (IVW) method was employed as the primary approach for two-sample MR analyses to evaluate causality. Supplementary methods included MR-Egger, maximum likelihood, weighted median, and cML-MA. To test for potential horizontal pleiotropy, we performed the MR-Egger intercept test, cML-MA, and secondary analyses after excluding confounders. Additionally, mediation analyses were conducted using two-step MR.ResultsThe IVW method revealed RA to be causally associated with hallux valgus (OR 1.132, 95% CI 1.087-1.178, P < 0.001) and flat foot (OR 1.197, 95% CI 1.110-1.291, P < 0.001). Among postural deformities, hallux valgus was causally associated with flat foot (OR 1.823, 95% CI 1.569-2.119, P < 0.001) and scoliosis (OR 1.150, 95% CI 1.027-1.287, P < 0.05). No significant horizontal pleiotropy was detected. Moreover, mediation analyses indicated that hallux valgus mediates the effect of RA on flat foot (mediation effect 0.024, 95% CI 0.005-0.044, P < 0.05), with a mediation proportion of 41.31%.ConclusionThese findings indicate a potential causal association between genetically predicted RA and both hallux valgus and flat foot. Furthermore, hallux valgus serves as a mediator in the pathway from RA to flat foot. This underscores the importance of early screening and preventive treatment of foot deformities in RA patients. Further research is necessary to determine the applicability of these findings in non-European populations.

Tandem mass spectrometry-based assay for heparan-N-sulphatase in paediatric CSF: A potential pharmacodynamic biomarker for mucopolysaccharidosis type IIIA therapy

Mucopolysaccharidosis type IIIA is a lysosomal storage disorder caused by mutations in the gene coding for heparan-N-sulphatase, a crucial enzyme in the degradation of heparan sulfate. In mucopolysaccharidosis type IIIA, heparan sulfate accumulates in the lysosomes, predominantly affecting the central nervous system. It is the most common and most severe form of mucopolysaccharidosis type III, with onset typically before the age of ten years. There is an ongoing effort to develop therapies that aim at restoring enzyme function in the brain. This study introduces a novel tandem mass spectrometry method for assessing heparan-N-sulphatase activity in pediatric cerebrospinal fluid from healthy and disease individuals.Analysis of cerebrospinal fluid samples revealed marked differences in enzyme activity, with mucopolysaccharidosis type IIIA individuals exhibiting significantly reduced levels. This new method could serve as a valuable tool for evaluating the efficacy of future therapeutic interventions targeting sulphatase activity restoration in the brain.

New insights into prostate Cancer from the renin-angiotensin-aldosterone system.

Prostate cancer is among the most common malignancies found in men, with multifactorial changes occurring altogether to disrupt the pathophysiology of this gland. The Renin-Angiotensin-Aldosterone System (RAAS) is an extensively studied pathway that has newly attributed fundamental roles in cancer biology that impact cell growth, migration, metastasis, and death. These processes are significantly influenced by various components of the RAAS, including prorenin, AT1R, AT2R, and Ang 1–7/Mas receptors. Although the pathophysiology of prostate cancer is complex, targeting the RAAS shows promise as a therapeutic approach. RAAS dysregulation is evident in prostate cancer, and treatments traditionally used for cardiovascular diseases are being explored for cancer therapy. The RAAS pathway has significant effects on the formation of new blood vessels (angiogenesis), the spread of cancer cells to other parts of the body (metastasis), and cell proliferation. In this pathway, angiotensin II and its receptors have crucial functions. Angiotensin II stimulates angiogenesis and cell proliferation through the AT1R, whereas the AT2R has the opposite effect by inhibiting cell growth. Additional pathways involving ACE2/Ang 1–7/Mas also provide potential targets for therapeutic intervention, mitigating the impact of the traditional ACE/Angiotensin II/AT1R pathway. The components of the RAAS influence multiple signalling pathways, such as Androgen Receptor (AR), NF-κB, and PI3K/AKT/mTOR, which enhances our understanding of how it contributes to the progression of prostate cancer. This also provides new possibilities for therapeutic interventions.

Dynamic Transition of Regulatory T Cells to Cytotoxic Phenotype Amid Systemic Inflammation in Graves' Ophthalmopathy.

Graves' disease (GD) is an autoimmune condition that can progress to Graves' Ophthalmopathy (GO), leading to irreversible damage to orbital tissues and potential blindness. The pathogenic mechanism is not fully understood. In this study, we conducted single-cell multi-omics analyses on healthy individuals, GD patients without GO, newly diagnosed GO patients, and treated GO patients. Our findings revealed gradual systemic inflammation during GO progression, marked by overactivation of cytotoxic effector T cell subsets, and expansion of specific T cell receptor clones. Importantly, we observed a decline in the immunosuppressive function of activated regulatory T cells (aTreg) accompanied by a cytotoxic phenotypic transition. In vitro experiments revealed that dysfunction and transition of GO-autoreactive Treg were regulated by the yinyang1 (YY1) upon secondary stimulation of thyroid stimulating hormone receptor (TSHR) under inflammatory conditions. Furthermore, adoptive transfer experiments of GO mouse model confirmed infiltration of these cytotoxic Treg into the orbital lesion tissues. Notably, these cells were found to upregulate inflammation and promote pathogenic fibrosis of orbital fibroblasts (OFs). Our results revealed the dynamic changes in immune landscape during GO progression and provided novel insights into the instability and phenotypic transition of Treg, offering potential targets for therapeutic intervention and prevention of autoimmune diseases.

Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47.

Spastic paraplegia 47 (SPG47) is a neurological disorder caused by mutations in the adaptor protein complex 4 β1 subunit (AP4B1) gene leading to AP-4 complex deficiency. SPG47 is characterised by progressive spastic paraplegia, global developmental delay, intellectual disability and epilepsy. Gene therapy aimed at restoring functional AP4B1 protein levels is a rational therapeutic strategy to ameliorate the disease phenotype. Here we report that a single delivery of adeno-associated virus serotype 9 expressing hAP4B1 (AAV9/hAP4B1) into the cisterna magna leads to widespread gene transfer and restoration of various hallmarks of disease, including AP-4 cargo (ATG9A) mislocalisation, calbindin-positive spheroids in the deep cerebellar nuclei, anatomical brain defects and motor dysfunction, in an SPG47 mouse model. Furthermore, AAV9/hAP4B1-based gene therapy demonstrated a restoration of plasma neurofilament light (NfL) levels of treated mice. Encouraged by these preclinical proof-of-concept data, we conducted IND-enabling studies, including immunogenicity and GLP non-human primate (NHP) toxicology studies. Importantly, NHP safety and biodistribution study revealed no significant adverse events associated with the therapeutic intervention. These findings provide evidence of both therapeutic efficacy and safety, establishing a robust basis for the pursuit of an IND application for clinical trials targeting SPG47 patients.

Impact of Audio-Visual Complexity on Symptomatology of Laryngeal Dystonia: A Virtual Reality Study.

Laryngeal dystonia (LD) is an isolated focal dystonia characterized by involuntary spasms in laryngeal muscles selectively impairing speech production. Anecdotal observations reported the worsening of LD symptoms in stressful or vocally demanding situations. To examine the impact of surrounding audio-visual complexity on LD symptomatology for a better understanding of disorder phenomenology. We developed well-controlled virtual reality (VR) environments of real-life interpersonal communications to investigate how different levels of audio-visual complexity may impact LD symptoms. The VR experiments were conducted over five consecutive days, during which each patient experienced 10 h of 4100 experimental trials in VR with gradually increasing audio-visual complexity. Daily reports were collected about patients' voice changes, as well as their comfort, engagement, concentration, and drowsiness from using VR technology. After a weekly VR exposure, 82% of patients reported changes in their voice symptoms related to changes in background audio-visual complexity. Significant differences in voice symptoms were found between the first two levels of the audio-visual challenge complexity independent of study sessions or VR environments. This study demonstrated that LD symptoms are impacted by audio-visual background across various virtual realistic settings. These findings should be taken into consideration when planning behavioral experiments or evaluating the outcomes of clinical trials in these patients. Moreover, these data show that VR presents a reliable and useful technology for providing real-life assessments of the impact of various experimental settings, such as during the testing of novel therapeutic interventions in these patients. Level 3 Laryngoscope, 2024.

How the arts heal: a review of the neural mechanisms behind the therapeutic effects of creative arts on mental and physical health

BackgroundThe creative arts have long been known for their therapeutic potential. These modalities, which include dance, painting, and music, among others, appear to be effective in enhancing emotional expression and alleviating adverse physiological and psychological effects. Engagement in creative arts can be pursued as a personal hobby, in a classroom setting, or through a formal therapeutic intervention with a qualified therapist. Engagement can be active (i.e., creating) or passive (i.e., viewing, listening). Regardless of the modality and manner of engagement, the mechanisms explaining the therapeutic efficacy of creative arts remain poorly understood.ObjectiveThis study aims to systematically review research investigating the neurological mechanisms activated during active or passive engagement in creative arts, with a specific emphasis on the roles of the medial prefrontal cortex (mPFC) and the amygdala in emotional regulation (ER) and creative behaviors. The review seeks to provide preliminary evidence for the possible existence of common neural mechanisms underlying both phenomena, which could inform the development of targeted therapeutic interventions leveraging creative arts for ER.MethodsA systematic review was conducted following the Cochrane Collaboration guideline and PRISMA standards to identify studies examining the neurological mechanisms underlying creative activities.ResultsA total of six out of 85 records meet the inclusion criteria, with all being basic research studies. Preliminary findings suggest that active and passive engagement with creative arts consistently activate neural circuits implicated in adaptive emotional regulation, including the mPFC and amygdala. These activations mirror the neural pathways engaged in effective ER strategies, suggesting the possible existence of shared mechanisms between creative expression and emotional processing.ConclusionThe evidence underscores the potential of creative arts as a complementary therapeutic strategy alongside conventional care and other evidence-based mind-body modalities. By elucidating the shared neural mechanisms between creative arts engagement and ER, this review contributes to the theoretical and practical understanding of the role of creative arts in mental health. Future research is recommended to further explore these neural correlations and their implications for therapeutic practice.

Advances in Chiral Metabolomic Profiling and Biomarker Discovery.

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.