Pathological Variables Research Articles

Predicting disease-free survival following curative-intent resection of right-sided colon cancer using a pre- and post-operative monogram: a prospective observational cohort study.

Disease prognostication can be achieved through the derivation of biologically and clinically integrated prediction models. The present study reports 1, 3 and 5-year disease-free survival (DFS) in patients undergoing right hemicolectomy for curative intent and both derives and validates a pre- and post-operative prediction tool for DFS for prognostication and risk stratification purposes. Consecutive patients undergoing right-sided curative-intent resection for colorectal cancer (2010-2020) in a tertiary care unit were followed-up prospectively for recurrence and survival outcomes. Survival analyses were used to derive pre- and post-operative models predicting 1, 3 and 5-year DFS. Calibration was reported and internal validation was performed using bootstrapping. A total of 822 patients underwent resection and 528 had ≥ 5-year follow-up. The 1, 3 and 5-year DFS rates were 85.6%, 72.5% and 57.6%, respectively. Variables associated with death/recurrence included: increasing age (HR >1.95, p=0.037), male gender (HR 1.62, p<0.001), ASA ≥3 (HR 1.79, p<0.001), low albumin (HR 1.54, p<0.001), T4 stage (HR 2.35, p=0.023), R1 status (HR 1.63, p=0.024),≥4 positive lymph nodes (HR>1.74, p<0.001) and Clavien-Dindo ≥3 (HR 2.83, p<0.001). The pre- and post-operative models contained 9 and 13 demographic, clinical, biochemical, operative and pathological variables, respectively (C-index 0.75 and 0.78, respectively). Excluding demographic, clinical and operative variables significantly reduced the C-index of the pre- (0.62) and post-operative models (0.69). The presented prediction tools for DFS will help clinicians stratify risk, offer appropriate adjuvant treatment and predict long-term survival following curative-intent right-sided colon cancer resection.

Investigating hyperostosis frontalis interna: a computed tomography analysis and predictive model for Hershkovitz classification.

Axial computed tomography (CT) cross-sections offer an accessible model for assessing diverse pathologies associated with hyperostosis frontalis interna (HFI) based on the Hershkovitz classification. To delineate the CT characteristics of HFI, emphasizing a radiological description using the Hershkovitz classification. It investigated whether the Hershkovitz classification can be predicted using density, a variable unexplored in the literature. HFI thickness and the presence of concurrent hyperostosis beyond the frontal bone (HBFB) were evaluated across varying degrees of the Hershkovitz classification. This retrospective study evaluated characteristics of HFI on CT. Each case was assigned a Hershkovitz classification. Density and thickness of the HFI along with the presence of concurrent HBFB were evaluated and correlated with the Hershkovitz classification. Axial CT of 77 patients with HFI was evaluated. Patient characteristics including sex were uncorrelated with CT measurements (P > 0.25) and Hershkovitz classification (P > 0.06). Increasing HFI thickness was associated with a higher Hershkovitz classification (odds ratio [OR] = 1.863, 95% confidence interval [CI] = 1.452-2.389; P < 0.001), and increasing density of HFI was associated with a lower Hershkovitz classification (OR = 0.995, 95% CI = 0.992-0.998; P = 0.002). Higher Hershkovitz classification was also found to be associated with the presence of concurrent HBFB (OR = 31.694, 95% CI = 6.483-154.938; P < 0.001). In our cohort, Hershkovitz classification on axial CT correlated with increased HFI thickness, presence of HBFB, and lower HFI density.

Addressing Ethnicity in the Design and Evaluation of an Educational Intervention on Interindividual Variation in Pharmacokinetics.

Interindividual variation in pharmacokinetics can occur due to diet, environmental or lifestyle factors, underlying pathology, and gene variants, typically single nucleotide polymorphisms (SNPs). Genetic mechanisms have received the most attention in research and education about ethnic differences in pharmacokinetics. Making this connection between genetics and ethnicity is problematic because it could reinforce the erroneous idea that there is a biological basis to ethnicity. The aim of this work was to design an educational intervention about interindividual variation in pharmacokinetics, explore how students perceive ethnicity and genetic differences prior to the educational intervention, and then assess the impact of the intervention and whether it could influence any misconceptions students might have about ethnicity and genetic similarity. Through the use of questionnaires and focus groups, we found that students typically refer to ethnicity to mean culture and place of origin, whereas in the pharmacological literature, ethnicity is synonymous with racial groups, that is, Black, White, and Asian. Prior to the educational intervention, students tended to expect a genetic mechanism for ethnic differences in drug metabolism and this was reduced after the intervention when a range of other nongenetic mechanisms were presented for interindividual variation. However, students' views about possible underlying mechanisms for ethnic differences in hypertension and about ethnicity more generally were unaffected by the intervention. This highlights the importance of reevaluating the way ethnicity is presented across the medical and medical sciences curriculums to be clear that ethnicity is socially constructed and avoid implying a biological basis.

Primary malignant bone and soft-tissue tumours of the spine and appendicular sacrum.

The aim of the present study was to analyze the oncological and neurological outcome of patients undergoing interdisciplinary treatment for primary malignant bone and soft-tissue tumours of the spine within the last seven decades, and changes over time. We retrospectively analyzed our single-centre experience of prospectively collected data by querying our tumour registry (Medical University of Vienna). Therapeutic, pathological, and demographic variables were examined. Descriptive data are reported for the entire cohort. Kaplan-Meier analysis and multivariate Cox regression analysis were applied to evaluate survival rates and the influence of potential risk factors. A total of 119 consecutive patients (mean age 38 years (SD 37; 1 to 83), mean follow-up 66 months (SD 26; 0 to 505) were investigated. Histological entities included Ewing's sarcoma (EWS; 33), chondrosarcoma (CSA; 20), osteosarcoma (OSA; 22), and soft-tissue sarcoma (STS; 44). Surgery was performed in 88 patients (74%). Neurological parameters improved in 18 patients (20%) after surgery. Overall, 32 patients (36%) suffered from surgical complications requiring revision. The median survival was 42 months (IQR 10 to 204). The one-, five-, and ten-year survival rates were 73%, 47%, and 39%, respectively. Corresponding five-year survival rates for EWS, CSA, OSA, and STS were 63%, 61%, 40%, and 32%, respectively. The decade of diagnosis, histological entity, surgical intervention, resection margin, and the presence of metastases had significant influence on survival. (Neo-)adjuvant therapies alone had no significant influence on overall survival. Our study clearly demonstrates the positive impact of improved surgical techniques, as well as refined imaging methods and evolved adjuvant therapy options, on survival rate in all tumour entities. However, despite a multimodal treatment plan, the long-term mortality of these tumours remains high.

Intelligent Drug Delivery: Pioneering Stimuli-Responsive Systems to Revolutionize Disease Management- An In-depth Exploration.

In recent years, there has been an escalating interest in stimuli-responsive drug delivery systems (SRDDS) due to their ability to revolutionize the delivery of therapeutics. SRDDSs offer a multitude of benefits in comparison to conventional drug delivery systems (DDS), including spatiotemporal control of drug release, targeted delivery, and improved therapeutic efficacy. The development of various classes of stimuli-responsive DDS, such as pH-responsive, temperature-responsive, photo-responsive, redox responsive systems, has been propelled by advances in materials science, nanotechnology, and biotechnology. These systems exploit specific environmental or physiological cues to trigger drug release in a precisely controlled manner, making them highly promising for the treatment of various diseases. In this review article, an in-depth exploration of the principles, mechanisms, and applications of SRDDS in the context of diverse pathologies such as cancer, arthritis, Alzheimer's disease, atherosclerosis and tissue engineering has been provided. Furthermore, this article delves into the discussion of recent patents, market overview and the progress of research in clinical trials. Overall, this article underscores the transformative potential of SRDDS in enabling personalized, precise, and effective drug delivery for the treatment of the above-mentioned diseases.

Pediatric Teledermatology in the General Teledermatology Practice: Population Variances in Contrasting Health Care Scenarios.

Introduction: Pediatric dermatology access is limited. Pediatric teledermatology (TD) opens the opportunity to explore diverse dermatological pathology promptly. Different TD modalities and providers may influence the consulting population. This study compares a synchronous TD from a private provider with the asynchronous TD of the public sector in Chile's health care system. Methods: A descriptive and inferential analysis of 168 synchronous and 239 asynchronous pediatric teleconsultations, responded from January 2023 to August 2023. Results: Pediatric teleconsultations accounted for nearly one-fifth of all consultations in both models. The synchronous group was significantly older (p = 0.0065; 10.18 years ± 5.43 [0-18 years]) than the asynchronous group (8.65 years ± 5.74 [0-18 years]). June marked the highest and lowest teleconsultation volumes in synchronous and asynchronous platforms, respectively. The most frequent diagnostic group in both modalities was the noninfectious inflammatory pathology. Significant differences were noted within this group (p < 0.0001), with acne and dermatitis being predominant in the synchronous model. Significant differences also emerged within the infectious inflammatory group (p = 0.002), with bacterial and fungal infections being more common in the synchronous modality, whereas chronic viral infections predominated in the asynchronous group. Discussion: Pediatric TD is an emerging tool that optimizes access, manages the demand, and reduces waiting times. Seasonal variations may influence caregiver preferences for a specific attention model. The consulting population using synchronous and asynchronous modalities differs significantly in age and diagnostic distributions. Understanding these differences is crucial for effectively addressing specific practice gaps in each attention model.

Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery.

Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.

Pathophysiology and Potential Clinical Significance of Il-5: A Review Article

Interleukins belong to the group of cytokines that play a key role in immune system cell signaling. Among them, Interleukin-5 (IL-5) gains paramount significance in the regulation of eosinophils, which are thinly scattered in most allergic as well as inflammatory conditions, especially asthma. A biochemical characterization of IL-5 is a prerequisite for understanding the basic aspects of its function and finding a precise treatment. Interleukin-5 (IL-5) is a critical cytokine that primarily drives the development and differentiation of eosinophils and B cells, playing a key role in the allergic response and the pathogenesis of asthma. Therefore, the knowledge of its biochemical structure is a prerequisite for any plan to develop targeted therapies for eosinophilia-related diseases. The clinical relevance of interleukins resides in their regulatory capabilities of immune responses, with an ever-growing recognition in diverse pathologies such as allergic manifestations, autoimmune diseases, or neoplastic processes. Interleukins in clinical application should be the focus of research, specifically IL-5, synthesizing observable from the latest related studies and knowledge deficits that should entice future research in the same line. This paper, therefore, gives a review based on already existing research findings concerning the biochemical structure of IL-5.

Stress Granule Induction in Rat Retinas Damaged by Constant LED Light.

Stress granules (SGs) are cytoplasmic biocondensates formed in response to various cellular stressors, contributing to cell survival. Although implicated in diverse pathologies, their role in retinal degeneration (RD) remains unclear. We aimed to investigate SG formation in the retina and its induction by excessive LED light in an RD model. Rat retinas were immunohistochemically analyzed for SG markers G3BP1 and eIF3, and SGs were also visualized by RNA fluorescence in situ hybridization. Additionally, SGs were induced in primary retinal cell and eyeball cultures using sodium arsenite. Light exposure experiments used LED lamps with a color temperature of 5500 K and 200 lux intensity for short-term or two- to eight-day exposures. SGs were predominantly detected in retinal ganglion cells (RGCs) and inner nuclear layer (INL) cells, with arsenite-induction verified in RGCs. SG abundance was higher in animals exposed to light for 2-8 days compared to light/dark cycle controls. RGCs consistently exhibited more SGs than INL cells, and INL cells more than outer nuclear layer (ONL) cells (Scheirer-Ray-Hare test: H = 13.2, P = 0.0103 for light condition, and H = 278.2, P < 0.00001 for retinal layer). These observations were consistent across four independent experiments, each with three animals per light condition. This study characterizes SGs in the mammalian retina for the first time, with increased prevalence after excessive LED light exposure. RGCs and INL cells showed heightened SG formation, suggesting a potential protective mechanism against photodamage. Further investigations are warranted to elucidate the role of SGs in shielding against light stress and their implications in retinopathies.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5-7. Here we used deep learning methods to de novo design proteins to bind short-chain and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtained protein designs with remarkable thermal stability, high binding affinity and near-atomic-level agreement with the computational models. The designed proteins effectively neutralized all three 3FTx subfamilies in vitro and protected mice from a lethal neurotoxin challenge. Such potent, stable and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our results highlight how computational design could help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for the development of therapies for neglected tropical diseases.

Large-scale audiometric phenotyping identifies distinct genes and pathways involved in hearing loss subtypes.

Age-related hearing loss affects one-third of the population over 65 years. However, the diverse pathologies underlying these heterogenous phenotypes complicate genetic studies. To overcome challenges associated with accurate phenotyping for older adults with hearing loss, we applied computational phenotyping approaches based on audiometrically measured hearing loss. This novel phenotyping strategy uncovered distinct genetic variants associated with sensory and metabolic hearing loss. Sex-stratified analyses of these sexually dimorphic hearing loss phenotypes revealed a novel locus of relevance to sensory hearing loss in males, but not females. Enrichment analyses revealed that genes involved in frontotemporal dementia were implicated in metabolic hearing loss, while genes relating to sensory processing of sound by hair cells were implicated in sensory hearing loss. Our study has enhanced our understanding of these two distinct hearing loss phenotypes, representing the first step in the development of more precise treatments for these pathologically distinct hearing loss phenotypes.

Pilot Study Examining the Use of DCE MRI With Pharmacokinetic Analysis to Evaluate Hypoxia in Prostate Cancer

Purpose: This study aimed to investigate the association between tumor hypoxia, assessed through anti-HIF (hypoxia-inducible factor) staining, and aggressiveness in prostate cancer using a pharmacokinetic model, particularly those derived from the Tofts model, in predicting tumor aggressiveness. Material and Methods: From January 2019 to April 2021, we conducted a retrospective search of patients with confirmed prostate cancer and a previous magnetic resonance imaging (MRI) examination. After exclusions, a total of 57 consecutive patients were enrolled. Patient data, including demographic, laboratory, and pathologic variables, were collected. MRI acquisition followed PI-RADS guidelines, encompassing T2-weighted, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. An experienced abdominal radiologist conducted both morphologic and quantitative MRI analyses, evaluating parameters such as lesion size, apparent diffusion coefficient values, and the Tofts pharmacokinetics (TF) model. The histopathologic analysis included the International Society of Uropathology (ISUP) score and hypoxia marker immunohistochemistry. Results: There were no significant demographic and imaging differences between hypoxic and nonhypoxic tumors, except for elevated prostate-specific antigen levels in the latter and decreased normalized apparent diffusion coefficient in the former. Morphologic assessments revealed larger lesions in the hypoxia group. While K trans showed a positive association with hypoxia, it did not independently predict high-risk lesions. Conclusions: Our results suggest that pharmacokinetic analysis by the Tofts model was associated with tumors with hypoxia. However, this parameter was not an independent predictor of more aggressive tumors. Further studies, with a larger number of patients, multi-institutional and prospective, are needed to verify this possible association.

Cellular and organismal function of choline metabolism.

Choline is an essential micronutrient critical for cellular and organismal homeostasis. As a core component of phospholipids and sphingolipids, it is indispensable for membrane architecture and function. Additionally, choline is a precursor for acetylcholine, a key neurotransmitter, and betaine, a methyl donor important for epigenetic regulation. Consistent with its pleiotropic role in cellular physiology, choline metabolism contributes to numerous developmental and physiological processes in the brain, liver, kidney, lung and immune system, and both choline deficiency and excess are implicated in human disease. Mutations in the genes encoding choline metabolism proteins lead to inborn errors of metabolism, which manifest in diverse clinical pathologies. While the identities of many enzymes involved in choline metabolism were identified decades ago, only recently has the field begun to understand the diverse mechanisms by which choline availability is regulated and fuelled via metabolite transport/recycling and nutrient acquisition. This review provides a comprehensive overview of choline metabolism, emphasizing emerging concepts and their implications for human health and disease.

Interpretable machine learning models for predicting skip metastasis in cN0 papillary thyroid cancer based on clinicopathological and elastography radiomics features.

Skip lymph node metastasis (SLNM) in papillary thyroid cancer (PTC) involves cancer cells bypassing central nodes to directly metastasize to lateral nodes, often undetected by standard preoperative ultrasonography. Although multiple models exist to identify SLNM, they are inadequate for clinically node-negative (cN0) patients, resulting in underestimated metastatic risks and compromised treatment effectiveness. Our study aims to develop and validate a machine learning (ML) model that combines elastography radiomics with clinicopathological data to predict pre-surgical SLNM risk in cN0 PTC patients with increased risk of lymph node metastasis (LNM), improving their treatment strategies. Our study conducted a retrospective analysis of 485 newly diagnosed primary PTC patients, divided into training and external validation cohorts. Patients were categorized into SLNM and non-SLNM groups based on follow-up outcomes and postoperative pathology. We collected preoperative clinicopathological data and extracted, standardized radiomics features from elastography imaging to develop various ML models. These models were internally validated using radiomics and clinicopathological data, with the optimal model's feature importance analyzed through the Shapley Additive Explanations (SHAP) approach and subsequently externally validated. In our study of 485 patients, 67 (13.8%) exhibited SLNM. The extreme gradient boosting (XGBoost) model, integrating elastography radiomics with clinicopathological data, demonstrated superior performance in both internal and external validations. SHAP analysis identified five key determinants of SLNM: three radiomics features from elastography images, one clinical variable, and one pathological variable. Our evaluation highlights the XGBoost model, which integrates elastography radiomics and clinicopathological data, as the most effective ML approach for the prediction of SLNM in cN0 PTC patients with increased risk of LNM. This innovative model significantly enhances the accuracy of risk assessments for SLNM, enabling personalized treatments that could reduce postoperative metastases in these patients.

Associations among externalizing psychopathology, personality, and behavioral traits: Models of an externalizing spectrum in youth.

Consistent evidence has documented the cross-sectional and longitudinal associations of externalizing psychopathology with personality and behavioral traits, suggesting the presence of a broad, underlying liability to externalizing. In one of the first studies of its kind, we use a large, representative sample of youth (N = 2,245 twins and their siblings) to evaluate the evidence of an externalizing spectrum model, which includes psychopathology, personality, and behavioral traits and spans normal and pathological variation. We examine evidence for the inclusion of 15 candidate traits, from the domains of general and pathological personality, temperament, and aggression, in a model that includes dimensions of common childhood externalizing psychopathology. Using a combination of structural equation modeling and item response theory analyses, we found strong to moderate evidence for including the narcissism and impulsivity dimensions of psychopathic traits; reactive, proactive, and relational aggression; and agreeableness and conscientiousness from the five-factor model of personality. These traits were reliable indicators of the externalizing spectrum, as evidenced by their shared variance with externalizing symptoms, strong factor loadings, and high information. In addition, these traits indexed the externalizing spectrum at higher and lower levels of the latent trait relative to the symptoms alone, highlighting the value of including them. Many of our findings replicate and extend work conducted in adult samples, suggesting developmental continuity of externalizing. Broadly speaking, these findings have important implications for the conceptualization, measurement, and treatment of externalizing in youth. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Laparoscopic adrenalectomy in children with diverse adrenal pathologies: the impact of pre-operative imaging in decision making process.

The aim of this study was to assess the impact of pre-operative imaging regarding selecting cases of children's who underwent laparoscopic adrenalectomy due to adrenal masses in two tertiary medical centers. We performed a retrospective review of all laparoscopic adrenalectomy performed at two tertiary medical centers in Israel between 2017 and 2023. Sixteen (n=16) patients, 10 girls and six boys, underwent laparoscopic adrenalectomy through a transperitoneal approach. The median age was 10 years (range: eight months to 17.3 years). Six masses were incidentalomas. Preoperative imaging (ultrasonography, CT, and MRI) demonstrated a mass in the right adrenal (n=9) and left adrenal (n=7), with tumor sizes ranging from 1.8 to 5.3 cm in maximum diameter. Operative results showed minimal blood loss and no conversions to laparotomy. There were no postoperative complications. Pathological diagnoses included neuroblastoma (n=8), cortical hormone-secreting tumors (n=3), pheochromocytoma (n=2), adrenal cortical adenoma (n=2), and adrenal metastatic Ewing sarcoma (n=1). Eleven masses were defined as benign and five as malignant tumors. Laparoscopic adrenalectomy appears to be a safe and effective technique in selected cases with adrenal masses. Among our cohort, malignant masses were more common compared to the predominantly benign adrenal masses seen in adults. Vascular encasement was a major factor in determining the feasibility of the laparoscopic approach, with preoperative imaging playing a critical role in this assessment.

NKAP: A new m6A RNA binding protein predicts prognosis and immunotherapy response in head and neck squamous cell carcinoma.

This study aimed to investigate whether NKAP (nuclear factor κB activating protein) serves as a prognostic marker and predictive biomarker for immunotherapy response in head and neck squamous cell carcinoma (HNSCC). A retrospective cohort study combined with in vitro analyses was conducted. NKAP mRNA expression levels were assessed in 520 HNSCC tumor tissues and 44 normal tissues from the TCGA dataset and validated in a clinical cohort (n = 32). Clinical correlations with overall survival and immunotherapy outcomes were analyzed. The key pathological variables included tumor stage, grade, HPV status, and TP53 mutation. Appropriate statistics were calculated at a significant level (P<0.05). In this study, we have collected tissue samples from HNSCC patients (mean age: 52.65 ± 7.76; males 66%, females 34%). NKAP was upregulated in HNSCC tissues compared to adjacent normal tissues (P < 0.001). The high expression of NKAP correlated with advanced tumor stage, grade, and reduced survival (P < 0.05). High expression levels of NKAP were also associated with anti-PD-L1 therapy response (P < 0.05). Functional enrichment analysis revealed NKAP involvement in cell cycle regulation, mRNA processing, and chromatin remodeling pathways critical for cancer progression. NKAP represents a promising prognostic marker and therapeutic target for immunotherapy in HNSCC. Prospective studies are warranted to confirm these findings.

Harnessing machine learning in diagnosing complex hoarseness cases

PurposeTraditional vocal fold pathology recognition typically requires expertise of laryngologists and advanced instruments, primarily through direct visualization. This study aims to augment this conventional paradigm by introducing a parallel diagnostic procedure. Our objective is to harness a machine-learning algorithm designed to discern intricate patterns within patients' voice recordings to distinguish not only between healthy and hoarse voices but also among various specific disorders. Materials and methodsWe employed a machine-learning algorithm, utilizing transfer learning on the HuBERT model with Saarbruecken Voice Database samples. The study was conducted in two stages: a binary classifier distinguishes healthy and hoarse voices, while a subsequent multi-class classifier identifies specific voice disorders. Data from 2103 sessions, including over 25,000 components, representing diverse pathologies and healthy individuals, was analyzed. The models were trained, validated, and tested with a focus on robustness and accuracy in diagnosis. ResultsThe binary classifier achieved 82 % accuracy in distinguishing healthy from pathological voices. The multi-class algorithm which aims to identify specific laryngeal disorders obtained the highest accuracy (>93 %) for Laryngeal Dystonia. Noteworthy is the persistent challenge posed by Laryngeal Dystonia, a condition lacking a definitive diagnostic modality. ConclusionsOur findings demonstrate the feasibility of utilizing machine-learning algorithms to process voice samples, categorizing them into distinct pathologies. This approach holds potential for enhance patient triage, streamline diagnostics, and elevate overall patient care. Particularly valuable for challenging diagnoses, such as Laryngeal Dystonia, this method underscores the transformative role of machine learning in optimizing healthcare practices.

Stimuli-responsive nanoscale drug delivery system for epilepsy theranostics.

Epilepsy is a common neurological disease characterized by distinct pathological changes in the epileptogenic zone. Antiseizure drugs (ASDs) are widely used as the primary treatment for epilepsy. To improve the efficiency of ASDs medication, stimuli-responsive nanoscale drug delivery systems (nanoDDSs), triggered by either endogenous or exogenous factors, have been developed and been considered as a noninvasive and spatial-temporal approach to epilepsy theranostics. In this review, we introduce the pathological variations observed in epileptic lesions such as dysregulated neurotransmitter systems, disrupted ion homeostasis, and dynamic inflammatory cytokine networks. Furthermore, we summarize the recent advances in functional nano-assemblies that could be activated by endogenous stimuli of pathological alterations or exogenous stimuli such as electricity, light, and other interventions. Finally, we discuss the remaining challenges and prospect the insight into perspective of future development in this field. In summary, this review aims to highlight the potential of stimuli-responsive nanoDDSs as precise, controllable and efficient strategies for addressing unresolved issues in epilepsy theranostics. STATEMENT OF SIGNIFICANCE: This review summarizes recent progress in pathological changes such as dysregulated neurotransmitter system, disrupted ion homeostasis and dynamic inflammatory cytokine network, and emphasizes endogenous/exogenous stimuli-responsive nanoscale platforms including neurotransmitter-, ion-, and other stimuli-responsive nanoDDSs, providing the prospects of smart nanoDDSs applications and discussing the challenges to offer generalized guideline for further development of epilepsy theranostics.

Characterization of four structurally diverse inhibitors of SUR2-containing KATP channels

ABSTRACT Vascular smooth muscle ATP-sensitive potassium (KATP) channels play critical roles in modulating vascular tone and thus represent important drug targets for diverse cardiovascular pathologies. Despite extensive research efforts spanning several decades, the search for selective inhibitors that can discriminate between vascular KATP (i.e. Kir6.1/SUR2B) and pancreatic and brain KATP (i.e. Kir6.2/SUR1) channels has, until recently, been unsuccessful. Our group therefore carried out a high-throughput screen of chemically diverse compounds with the goal of discovering specific Kir6.1/SUR2B inhibitors. This screen identified several novel classes of Kir6.1/SUR2B inhibitors, including the first potent (IC50 ~100 nM) and selective inhibitor published to date, termed VU0542270. Here, we expand on this work by disclosing the identity and pharmacological properties of four additional Kir6.1/SUR2B inhibitors that are structurally unrelated to Kir to VU0542270. These inhibitors, named VU0212387, VU0543336, VU0605768, and VU0544086, inhibit Kir6.1/SUR2B with IC50 values ranging from approximately 100 nM to 1 µM and exhibit no apparent inhibitory activity toward Kir6.2/SUR1. Functional analysis of heterologously expressed subunit combinations of Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B and demonstrated that all four inhibitors act on SUR2 to induce channel inhibition. Interestingly, VU0543336 and VU0212387 exhibit paradoxical stimulatory effects on Kir6.2/SUR1 at higher doses. This study broadens our understanding of KATP channel pharmacology, generally, and reveals novel chemical matter for the development of Kir6.1/SUR2-selective drugs, specifically.