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Frontiers in Neuroscience 2024Glioblastoma (GBM) is a highly aggressive malignant tumor of the central nervous system that displays varying molecular and morphological profiles, leading to...
INTRODUCTION
Glioblastoma (GBM) is a highly aggressive malignant tumor of the central nervous system that displays varying molecular and morphological profiles, leading to challenging prognostic assessments. Stratifying GBM patients according to overall survival (OS) from H&E-stained whole slide images (WSI) using advanced computational methods is challenging, but with direct clinical implications.
METHODS
This work is focusing on GBM (IDH-wildtype, CNS WHO Gr.4) cases, identified from the TCGA-GBM and TCGA-LGG collections after considering the 2021 WHO classification criteria. The proposed approach starts with patch extraction in each WSI, followed by comprehensive patch-level curation to discard artifactual content, i.e., glass reflections, pen markings, dust on the slide, and tissue tearing. Each patch is then computationally described as a feature vector defined by a pre-trained VGG16 convolutional neural network. Principal component analysis provides a feature representation of reduced dimensionality, further facilitating identification of distinct groups of morphology patterns, via unsupervised k-means clustering.
RESULTS
The optimal number of clusters, according to cluster reproducibility and separability, is automatically determined based on the rand index and silhouette coefficient, respectively. Our proposed approach achieved prognostic stratification accuracy of 83.33% on a multi-institutional independent unseen hold-out test set with sensitivity and specificity of 83.33%.
DISCUSSION
We hypothesize that the quantification of these clusters of morphology patterns, reflect the tumor's spatial heterogeneity and yield prognostic relevant information to distinguish between short and long survivors using a decision tree classifier. The interpretability analysis of the obtained results can contribute to furthering and quantifying our understanding of GBM and potentially improving our diagnostic and prognostic predictions.
PubMed: 38831756
DOI: 10.3389/fnins.2024.1304191 -
Cell Communication and Signaling : CCS Jun 2024Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in...
BACKGROUND
Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in peripheral nociception remain unclear.
METHODS
Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca channels (T-type channels).
RESULTS
IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2.
CONCLUSION
Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.
Topics: Animals; Calcium Channels, T-Type; src-Family Kinases; Cyclic AMP-Dependent Protein Kinases; Trigeminal Ganglion; Male; Sensory Receptor Cells; Receptors, Interleukin; Mice; Signal Transduction; Mice, Inbred C57BL; Interleukins
PubMed: 38831315
DOI: 10.1186/s12964-024-01688-6 -
Asia Pacific Allergy Jun 2024Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome belong to a family of severe cutaneous adverse reactions that can be life-threatening and carry a risk of...
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome belong to a family of severe cutaneous adverse reactions that can be life-threatening and carry a risk of significant morbidity and potential mortality in the event of re-exposure. Lifelong avoidance of the culprit agent is mandated, which can lead to the exclusion of multiple medications if the trigger is unclear. This can result in adverse health outcomes analogous to that of a penicillin allergy label. We present a case in which the patient would progress to fatal myeloma in the absence of treatment, however, multiple medications were administered prior to the occurrence of TEN following previous chemotherapy. Available risk stratification tools including human leucocyte antigen assessment and the algorithm of drug causality for epidermal necrolysis scoring system were utilized followed by patch testing which identified a lesser-suspected agent as possibly causative. Further evidence-based in vivo testing and subsequent challenges allowed for the reintroduction of life-saving chemotherapy.
PubMed: 38827259
DOI: 10.5415/apallergy.0000000000000125 -
Cognition Aug 2024Perceptual decision-making often lacks explicit feedback, making confidence in our choices pivotal for guiding subsequent actions. Recent studies have highlighted the...
Perceptual decision-making often lacks explicit feedback, making confidence in our choices pivotal for guiding subsequent actions. Recent studies have highlighted the role of motor responses in modulating decision confidence. Two competing mechanisms have been proposed to elucidate this phenomenon. The "fluency hypothesis" posits that the ease and smoothness of executing a motor response can serve as a cue to enhance retrospective confidence. Conversely, the "monitoring hypothesis" suggests that the extent of action monitoring during response selection may boost retrospective confidence, with heightened monitoring potentially offsetting response fluency. We conducted a pre-registered experiment to directly test these hypotheses. Participants engaged in a perceptual task involving the discrimination of Gabor patch orientation. Perceptual responses required high or low motor precision, manipulated by the size of target circles that participants had to reach with the computer mouse to provide a response. Contrary to the "fluency hypothesis", our results showed that, in trials requiring higher precision (utilizing small circles), participants reported higher confidence levels compared to trials with less demanding responses (involving larger circles). Importantly, this increase in confidence did not coincide with any change in perceptual accuracy. These findings align with the "monitoring hypothesis," suggesting that the degree of action monitoring during response execution can indeed influence retrospective decision confidence.
Topics: Humans; Decision Making; Adult; Young Adult; Psychomotor Performance; Female; Male; Motor Activity; Metacognition
PubMed: 38824695
DOI: 10.1016/j.cognition.2024.105832 -
Dermatology Practical & Conceptual Apr 2024Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically...
INTRODUCTION
Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically relevant allergens.
OBJECTIVE
The aim of this study was to identify the most frequently observed allergens among Turkish children and adolescents patch-tested in 2013-2023.
METHODS
The patch test results of 160 patients (age ≤18) were analyzed retrospectively. The frequency of contact allergens and distribution of positive results in terms of sex, age group (children and adolescents), and the presence of atopic dermatitis (AD) were identified.
RESULTS
Forty-nine patients (30.6%) (34 girls and 15 boys) exhibited positive patch test reactions to a minimum of one allergen, and contact sensitivity was statistically significantly higher in girls (P=0.034). The five most frequent allergens were nickel sulfate (10.6%), MCI/MI (8.1%), cobalt chloride (5.6%), p-phenylenediamine (PPD) (5%), and MI (3.5%). No significant association was observed between patch test positivity and age groups (P>.05). Nickel sulfate sensitivity was significantly higher in girls than in boys (P=.043). A positive reaction was detected in 31.3% of patients with AD and in 33.7% of those without (P>.05), and a statistically significant relationship was observed between contact sensitivity to fragrance allergens and AD (P=.046).
CONCLUSION
Metals and preservatives represent the most frequent allergens in Turkish children and adolescents. Metal sensitivity is expected to decrease as legislation is enforced. Regulatory measures are now required to reduce MI and MCI/MI contact allergy in Turkey.
PubMed: 38810081
DOI: 10.5826/dpc.1402a151 -
BMC Pediatrics May 2024Celiac disease is one of the most common autoimmune disorders. This study aimed to evaluate the relationship between celiac disease and wheat sensitization.
INTRODUCTION AND AIM
Celiac disease is one of the most common autoimmune disorders. This study aimed to evaluate the relationship between celiac disease and wheat sensitization.
SUBJECTS AND METHODS
In the current study, children aged < 18 years with confirmed celiac disease were included. Data were analyzed using SPSS.
RESULTS
Gastrointestinal problems were the most common indication for evaluation in terms of celiac disease. Prick and patch tests were positive in 43.4% and 34% respectively.
CONCLUSION
Prick test and patch test for wheat sensitization were positive in about 30-45% of the children for celiac disease.
Topics: Humans; Celiac Disease; Child; Male; Female; Child, Preschool; Wheat Hypersensitivity; Patch Tests; Immunoglobulin E; Adolescent; Skin Tests; Triticum; Infant
PubMed: 38807087
DOI: 10.1186/s12887-024-04844-6 -
Cureus Apr 2024Drug-induced urticaria and angioedema cases are typically reversible upon discontinuation and can be triggered by antibiotics, angiotensin-converting enzyme inhibitors,...
Drug-induced urticaria and angioedema cases are typically reversible upon discontinuation and can be triggered by antibiotics, angiotensin-converting enzyme inhibitors, or nonsteroidal anti-inflammatory drugs. Piperacillin-tazobactam, a common broad-spectrum antimicrobial, has been linked to severe adverse reactions, such as thrombocytopenia, hemolytic anemia, and Steven Johnson syndrome in some cases. A 35-year-old male presented to the emergency department with fever, cough, and acute breathlessness, complicating his ongoing treatment for pulmonary tuberculosis with bedaquiline and delamanid. He was admitted and received supportive care. On the third day of intravenous piperacillin-tazobactam, he developed drug-induced urticaria and angioedema, which resolved upon discontinuing the drug. Piperacillin/tazobactam-induced hypersensitivity reaction is an immunologic and IgE-mediated immediate reaction. IgE-mediated immediate reactions to three major phenotypes of allergic patients with confirmed to piperacillin/tazobactam are either (1) sensitized to the β-lactam ring or (2) sensitized to the lateral chain of aminopenicillins or (3) selective to piperacillin/tazobactam alone. A skin patch test is advised, or prescribed to avoid hypersensitivity reactions due to piperacillin/tazobactam. This case underscores the challenges of non-adherence to anti-tubercular therapy, leading to drug resistance and prolonged, costly, and sometimes intolerable treatments. Regular patient follow-up, counseling, monitoring, and healthcare provider involvement are essential to enhance treatment adherence. Adverse drug reactions must be promptly reported and managed, and patient-centric approaches are crucial. Digital patient records and standardized data collection are recommended for program evaluation and global policy development. Causality assessment for piperacillin-tazobactam was diagnosed as the probable cause of drug-induced urticaria and angioedema. This case highlights the importance of adherence to tuberculosis treatment to prevent drug resistance. Overall, patient-centered care, monitoring adverse events of drug added, and better data collection are crucial for successful tuberculosis management.
PubMed: 38800261
DOI: 10.7759/cureus.58877 -
Journal of Clinical Medicine May 2024Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction...
Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction technique" to correct the narrowed remnant portal vein just or late after right lobe living donor hepatectomy. Demographic and clinical data of 12 living liver donors with narrowed remnant portal veins and treated with the "elbow patch reconstruction technique" were prospectively collected and retrospectively evaluated. Anatomic variation of the portal vein was defined in accordance with the Nakamura classification; six of the living liver donors had type A, three had type B, and the remaining three had type C. In eight of the living liver donors with a narrowed remnant portal vein, diagnosis was detected by intraoperative Doppler ultrasonography and visual inspection by experienced transplant surgeons in the living donor hepatectomy procedure. In the remaining four living liver donors, diagnosis was performed postoperatively when elevation of liver enzymes was noticed during the routine liver function test and Doppler US. The diagnosis was confirmed by multidetector computed tomography. Data from nine males and three females aged 18 to 54 years were analyzed. All of the living liver donors were followed up for a median of 1710 days (min-max: 1178-4447 days; IQR: 1516 days), and none of the living liver donors had any structural or functional complications in the portal vein. Narrowing remnant portal veins are rare, but they are a life-threatening complication in living liver donors, and this condition requires urgent management. Image guided interventions and narrowed segment resection with end-to-end anastomosis using a vascular graft carried a potential risk for thrombosis and restenosis. To avoid these complications, we shared a technique named "elbow patch reconstruction technique". This technique can be very effective in relieving the narrowing of the remnant portal vein after right lobe living donor hepatectomy.
PubMed: 38792466
DOI: 10.3390/jcm13102924 -
Journal of Imaging Apr 2024This paper introduces a self-attention Vision Transformer model specifically developed for classifying breast cancer in histology images. We examine various training...
This paper introduces a self-attention Vision Transformer model specifically developed for classifying breast cancer in histology images. We examine various training strategies and configurations, including pretraining, dimension resizing, data augmentation and color normalization strategies, patch overlap, and patch size configurations, in order to evaluate their impact on the effectiveness of the histology image classification. Additionally, we provide evidence for the increase in effectiveness gathered through geometric and color data augmentation techniques. We primarily utilize the BACH dataset to train and validate our methods and models, but we also test them on two additional datasets, BRACS and AIDPATH, to verify their generalization capabilities. Our model, developed from a transformer pretrained on ImageNet, achieves an accuracy rate of 0.91 on the BACH dataset, 0.74 on the BRACS dataset, and 0.92 on the AIDPATH dataset. Using a model based on the prostate small and prostate medium HistoEncoder models, we achieve accuracy rates of 0.89 and 0.86, respectively. Our results suggest that pretraining on large-scale general datasets like ImageNet is advantageous. We also show the potential benefits of using domain-specific pretraining datasets, such as extensive histopathological image collections as in HistoEncoder, though not yet with clear advantages.
PubMed: 38786562
DOI: 10.3390/jimaging10050108 -
Marine Pollution Bulletin Jun 2024Community-based marine debris removal efforts on the Hawaiian Islands of Kaua'i and Hawai'i, spanning 2013-2022, provided large datasets and documented remarkable...
Community-based marine debris removal efforts on the Hawaiian Islands of Kaua'i and Hawai'i, spanning 2013-2022, provided large datasets and documented remarkable variations in annual amounts of debris, mainly from abandoned, lost and derelict fishing gear. To test the hypothesis that the influx of marine debris on Hawaiian shores is determined by the proximity of the North Pacific garbage patch, whose pattern changes under the control of large-scale ocean dynamics, we compared these observational data with the output of an oceanographic drift model. The high correlations between the total mass of debris collected and the model, ranging between r = 0.81 and r = 0.84, validate the attribution of the strong interannual signal to significant migrations of the garbage patch reproduced in the model experiments. Synchronous variations in marine debris fluxes on the two islands, separated by >500 km, confirm the large scale of the interannual changes in the North Pacific marine debris system.
Topics: Hawaii; Pacific Ocean; Environmental Monitoring; Waste Products; Water Pollutants
PubMed: 38781802
DOI: 10.1016/j.marpolbul.2024.116484