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Excitons in the fractional quantum Hall effect
Joint response of surface subsidence and strong mine earthquake under high-positioned and thick-hard strata in deep coal mine
The AI tool that can interpret any spreadsheet instantly
The effects of teleconnections on water and carbon fluxes in the two South America’s largest biomes
Modeling suction of unsaturated granular soil treated with biochar in plant microbial fuel cell bioelectricity system
Pathological variants in HPV-independent vulvar tumours
AbstractVulvar cancer is a rare gynaecological disease that can be caused by infection with human papillomavirus (HPV). The mutational frequencies and landscape for HPV-associated and HPV-independent vulvar tumor development are supposedly two distinctly different pathways and more detailed knowledge on target biological mechanisms for individualized future treatments is needed. The study included formalin-fixed paraffin-embedded (FFPE) samples from 32 cancer patients (16 HPV-negative and 16 HPV-associated), treated in Örebro, Sweden from 1988 to 2008. The Oncomine™ Comprehensive Assay v3 was used to detect variants across 161 different tumor relevant genes. Data analysis included quality assessment followed by variant analysis of DNA with the Oncomine Comprehensive v3 workflow and with a custom filter using the VarSome Clinical software. The RNA-analysis was performed with the Oncomine Comprehensive v3 workflow. Totally, 94% of DNA libraries and 81% of RNA libraries were of adequate quality for further downstream analysis. With the Oncomine™ filter chain there was an increased number of variants in the HPV-negative group (2.5 variants) compared to the HPV-associated group (1.5 variants). Using custom filter and the Varsome Clinical software; additional single nucleotide variants (SNV) were detected where the vast majority were classified as likely benign/benign. HPV-negative tumors had a larger fraction of variants of unknown significance (VUS), and likely pathogenic/pathogenic compared to the HPV-associated tumours. The top 10 frequently mutated genes in HPV-indepentent tumors were TP53, POLE, PTCH1, BRCA2, CREBBP, NOTCH2, ARID1A, CDKN2A, MSH2, and NOTCH1. Three fusion genes were detected; TBL1XR1(1)::PIK3CA(2) (n = 2) and NF1(5)::PSMD11(2) (n = 1). Copy number variations (CNV) were more common in HPV-associated tumors (n = 13/16, 81%) compared to HPV-negative tumors (n = 9/14, 64%). The most frequent CNV was found in the cMYC gene, followed by CDK2 (n = 5) and CDK4 (n = 4). The main outcome of this study show that vulvar cancer harbour genetic variations of different types and specifically, HPV-independent tumours are molecularly very heterogeneous and harboured more SNVs while HPV-associated tumors more frequently presented with gene amplifications. The PI3K/AKT/mTOR1 pathway was affected in both the groups as well as the cell cycle regulation pathway. Similarly, the DNA repair gene POLE was found mutated in both vulvar cancer groups.
Author Correction: Mass spectroscopy reveals compositional differences in copepodamides from limnic and marine copepods
We need to talk about human genome editing
The impact of preschool children’s physical fitness evaluation under self organizing maps neural network
Technological evaluation of stones from the eastern region of the state of São Paulo, Brazil, for railway ballast
Permanent Nanobubbles in Water: Liquefied Hollow Carbon Spheres Break the Limiting Diffusion Current of Oxygen Reduction Reaction
Associations of personality traits with actigraphic sleep in middle-aged and older adults
Evaluation of external and radiological landmark methods for optimizing ultrasound-guided right internal jugular venous catheterization depth in cardiac surgery
The impact of brain-systemic oxygenation coupling in sleep-disordered breathing on cognitive function in elderly
Li2ZrF6-based electrolytes for durable lithium metal batteries
Relation between anatomical features of patent foramen ovale and residual shunt based on transesophageal echocardiography
The importance of trunk motion in wearable based infant spontaneous movement analysis
Exploratory disproportionality analysis of potentially drug-induced eosinophilic pneumonia using United States Food and Drug Administration adverse event reporting system
AbstractDrug-induced eosinophilic pneumonia (EP) is an uncommon adverse drug reaction. Many drugs have been reported to cause EP, the evidence mainly being in the form of case reports/case series. This study aims to conduct an exploratory analysis of the United States Food and Drug Administration adverse event reporting system (FAERS) database to identify previously unknown drugs that can cause EP and supplement the available evidence for known culprit drugs. A retrospective case–noncase study was conducted using individual case safety reports (ICSRs) reported to the US FAERS from the first quarter of 2004 to the second quarter of 2024. Cases of potentially drug-induced EP were identified using OpenVigil application by conducting a narrow and broad scope search using the Medical Dictionary of Regulatory Activities preferred terms. A base list of drugs described in select literature to have caused EP was used to categorize known and unknown drugs. A disproportionality analysis was performed, with a reporting odds ratio > 2, lower end of the 95% confidence interval > 1, and a minimum of 3 reported cases considered a signal of disproportionate reporting (SDR). During the study period, 8,702,548 individual case safety reports (ICSRs) were submitted to the FAERS. Of these, 855 ICSRs using the narrow scope search and 1411 ICSRs using the broad scope search reported EP. The three most commonly reported drugs with an SDR for EP using the narrow scope search were daptomycin, naltrexone, and prednisone. The most common indications for the use of the drugs were infections, immunological conditions, asthma, and central nervous system disorders. In total, there were 45 drugs with an SDR but no supporting literature evidence available. The number of drugs implicated in causing EP has increased over the years. Several antimicrobial agents, followed by drugs affecting the central nervous system and anticancer drugs, including monoclonal antibodies, can produce EP. The list of suspected drugs identified in this study, especially those with SDR and literature evidence, should be strongly considered as a possible cause in patients presenting with pneumonia not explained otherwise.
The importance of clinical experience in AI-assisted corneal diagnosis: verification using intentional AI misleading
AbstractWe developed an AI system capable of automatically classifying anterior eye images as either normal or indicative of corneal diseases. This study aims to investigate the influence of AI’s misleading guidance on ophthalmologists’ responses. This cross-sectional study included 30 cases each of infectious and immunological keratitis. Responses regarding the presence of infection were collected from 7 corneal specialists and 16 non-corneal-specialist ophthalmologists, first based on the images alone and then after presenting the AI’s classification results. The AI’s diagnoses were deliberately altered to present a correct classification in 70% of the cases and incorrect in 30%. The overall accuracy of the ophthalmologists did not significantly change after AI assistance was introduced [75.2 ± 8.1%, 75.9 ± 7.2%, respectively (P = 0.59)]. In cases where the AI presented incorrect diagnoses, the accuracy of corneal specialists before and after AI assistance was showing no significant change [60.3 ± 35.2% and 53.2 ± 30.9%, respectively (P = 0.11)]. In contrast, the accuracy for non-corneal specialists dropped significantly from 54.5 ± 27.8% to 31.6 ± 29.3% (P < 0.001), especially in cases where the AI presented incorrect options. Less experienced ophthalmologists were misled due to incorrect AI guidance, but corneal specialists were not. Even with the introduction of AI diagnostic support systems, the importance of ophthalmologist’s experience remains crucial.