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The Explainable Modular Neural Network (XModNN) enables the identification of biomarkers, facilitating the classification of diseases and clinical parameters in transcriptomic datasets. The modules within XModNN represent specific pathways or genes of a functional hierarchy. The incorporation of biological insights into the architectural design reduced the number of parameters. This is further reinforced by the weighted multi-loss progressive training, which enables successful classification with a reduced number of replicates. The combination of this workflow with layer-wise relevance propagation ensures a robust post hoc explanation of the individual module contribution. Two use cases were employed to predict sex and neuroblastoma cell states, demonstrating that XModNN, in contrast to standard statistical approaches, results in a reduced number of candidate biomarkers. Moreover, the architecture enables the training on a limited number of examples, attaining the same performance and robustness as support vector machine and random forests. The integrated pathway relevance analysis improves a standard gene set overrepresentation analysis, which relies solely on gene assignment. Two crucial genes and three pathways were identified for sex classification, while 26 genes and six pathways are highly important to discriminate adrenergic–mesenchymal cell states in neuroblastoma cancer.
Background and Objectives
The most recent guidelines and recommendations regarding treatments of dental caries in children are shifting towards evidence-based minimal or non-invasive approaches aiming to preserve the vitality of teeth and potentially reduce the need for dental general anesthesia. This study investigated the treatment recommendations of dentists actively practicing pediatric dentistry in Germany regarding different patient cases with caries in primary teeth.
Materials and Methods
The questionnaire was distributed on paper or online to pediatric dentists and general dentists practicing pediatric dentistry. Five cases of children with dental treatment needs representing a variety of clinical situations were selected for the questionnaire. Considering four different scenarios regarding pain symptoms (yes/no) and cooperation level (good/low) for each case resulted in 20 questions, where the preferred treatment option could be chosen out of 21 options ranging from observation only to extraction with/without different sedation techniques. The answers were categorized into three categories for each case and scenario according to guidelines, recent scientific evidence, and recommendations (recommended, acceptable, or not recommended/contraindicated).
Results
In total, 222 participants responded to the survey (161 female; 72.5%). In 55.2% of the total 4440 answers, the participants chose a “recommended” treatment option, in 16.4% “acceptable”, but in 28.4%, a “not recommended” treatment, which ranged for the five cases between 18.7 and 36.1%. While pain and low cooperation levels led to more invasive and justified treatment choices (only 26.3% “not recommended”), less severe scenarios resulted more often in “not recommended” options (pain with good cooperation: 31.0%; or low cooperation without pain: 32.6%). The dentist’s age, experience, and educational background did not significantly correlate to choosing “not recommended” treatment options.
Conclusions
A child’s pain and cooperation level greatly impact the treatment decisions made by dentists, with a risk of too invasive treatment options in low-severity cases. Substantial disparities in treatment recommendations for caries in primary teeth persist among dental practitioners regardless of their age, experience, and educational background.
Among the physical decontamination methods, treatment with ultraviolet (UV) radiation is a suitable means of preventing viral infections. Mercury vapor lamps (254 nm) used for room decontamination are potentially damaging to human skin (radiation) and harmful to the environment (mercury). Therefore, other UV-C wavelengths (100–280 nm) may be effective for virus inactivation on skin without damaging it, e.g., far-UV-C radiation with a wavelength of 233 nm, which is absorbed in the outer layer of the skin and thus does not reach the deeper layers of the skin. For room disinfection, 275 nm UV-C LED lamps could be a more environmentally friendly alternative, since toxic mercury is avoided. A carrier test using multiple viruses was used to determine the TCID50/mL value on stainless steel, PVC, and glass carriers. In addition to the inactivation kinetics (233 nm), the necessary UV-C dose for 4 lg inactivation (275 nm) was investigated. The impact of irradiance on the inactivation efficacy was also assessed. The inactivation of the viruses was a function of the radiation dose. UV-C-radiation at 233 nm (80 mJ/cm2) inactivated from 1.49 ± 0.08 to 4.28 ± 0.18 lg depending on the virus used. To achieve a 4 lg inactivation (275 nm) for enveloped viruses, doses of up to 70 mJ/cm2 (SuHV-1) were sufficient. For non-enveloped viruses, a maximum dose of 600 mJ/cm2 (MS2) was necessary. Enveloped viruses were inactivated with lower doses compared to non-enveloped viruses. Higher radiation doses were required for inactivation at 275 nm in comparison to 254 nm. A more environmentally friendly alternative to mercury vapor lamps is available with 275 nm LED emitters. Radiation at 233 nm could serve as an additional prophylactic or therapeutic measure for virus inactivation in direct contact with human skin.
Background
The integration of artificial intelligence (AI) into radiology aims to improve diagnostic accuracy and efficiency, particularly in settings with limited access to expert radiologists and in times of personnel shortage. However, challenges such as insufficient validation in actual real-world settings or automation bias should be addressed before implementing AI software in clinical routine.
Methods
This cross-sectional study in a maximum care hospital assesses the concordance between diagnoses made by a commercial AI-based software and conventional radiological methods augmented by AI for four major thoracic pathologies in chest X-ray: fracture, pleural effusion, pulmonary nodule and pneumonia. Chest radiographs of 1506 patients (median age 66 years, 56.5% men) consecutively obtained between January and August 2023 were re-evaluated by the AI software InferRead DR Chest ® .
Results
Overall, AI software detected thoracic pathologies more often than radiologists (18.5% vs. 11.1%). In detail, it detected fractures, pneumonia, and nodules more frequently than radiologists, while radiologists identified pleural effusions more often. Reliability was highest for pleural effusions (0.63, 95%-CI 0.58–0.69), indicating good agreement, and lowest for fractures (0.39, 95%-CI 0.32–0.45), indicating moderate agreement.
Conclusions
The tested software shows a high detection rate, particularly for fractures, pneumonia, and nodules, but hereby produces a nonnegligible number of false positives. Thus, AI-based software shows promise in enhancing diagnostic accuracy; however, cautious interpretation and human oversight remain crucial.
Ventricular arrhythmias originating from the papillary muscle of the ventricles are complex clinical problems. Catheter ablation has the potential to cure these arrhythmias. However, the procedure is usually challenging due to the specific anatomy, catheter instability and difficulty in localization of the origin of the arrhythmias. Intracardiac echocardiography (ICE) has been reported to be the suitable imaging method for assessing the location of focus in papillary muscles. We used transthoracic echocardiography (TTE), as a noninvasive cost-effective imaging supporting modality, in combination with 3D mapping to guide the exact localization and successful ablation of papillary muscle-originating premature ventricular contractions (PVCs).
Active inference describes (Bayes-optimal) behaviour as being motivated by the minimisation of surprise of one’s sensory observations, through the optimisation of a generative model (of the hidden causes of one’s sensory data) in the brain. One of active inference’s key appeals is its conceptualisation of precision as biasing neuronal communication and, thus, inference within generative models. The importance of precision in perceptual inference is evident—many studies have demonstrated the importance of ensuring precision estimates are correct for normal (healthy) sensation and perception. Here, we highlight the many roles precision plays in action, i.e., the key processes that rely on adequate estimates of precision, from decision making and action planning to the initiation and control of muscle movement itself. Thereby, we focus on the recent development of hierarchical, “mixed” models—generative models spanning multiple levels of discrete and continuous inference. These kinds of models open up new perspectives on the unified description of hierarchical computation, and its implementation, in action. Here, we highlight how these models reflect the many roles of precision in action—from planning to execution—and the associated pathologies if precision estimation goes wrong. We also discuss the potential biological implementation of the associated message passing, focusing on the role of neuromodulatory systems in mediating different kinds of precision.
Background
Malnutrition is a common complication in chronic pancreatitis and associated with reduced quality of life and life expectancy. Nutritional support is considered mandatory in malnourished patients with chronic pancreatitis but there is only scarce evidence on optimal treatment modalities and the efficacy of nutrition therapy. Here, we investigated the feasibility and efficacy of an intensified nutritional intervention in malnourished patients with chronic pancreatitis and aimed to identify suitable indicators for monitoring nutritional status.
Methods
We performed a single-arm feasibility study, in which malnourished patients with chronic pancreatitis received an intensified trans-sectoral nutritional intervention for 6 months. Multimodal treatment comprised face-to-face dietary counseling, oral nutritional supplementation, and a complementary telephone-based nutrition and exercise coaching. Patients underwent follow-up examinations after 28, 90, and 180 days, when we assessed changes in anthropometric and body composition measures, muscle function, Chronic Pancreatitis Prognosis Score (COPPS), as well as blood parameters and intestinal microbiota composition.
Results
Eleven out of 73 patients initially screened for study participation were enrolled in the trial of which 9 subjects (age (mean ± SD): 56.2 (±14.8) years; male: 67%; alcoholic etiology: 44%) underwent the complete intervention. Patients gained a median of 5.3 kg (8.6%) body weight, including 1.6 kg skeletal muscle mass, and significantly increased gait speed ( p < 0.001). Ameliorated nutritional status and muscle function were associated with increased blood levels of IGF-1 and cholinesterase as well as altered gut microbiota composition on the phyla and genera level. Moreover, significant improvements in COPPS indicated reduced disease severity after 90 and 180 days.
Conclusion
Malnourished patients with chronic pancreatitis benefit from intensified nutritional therapy. Besides ameliorated nutritional status, a multimodal intervention can improve muscle function as well disease prognosis. Future studies are needed to prove superiority to standard-of-care and to validate potential biomarkers for prospective monitoring of nutritional status.
Clinical trial registration
https://clinicaltrials.gov/study/NCT04476056 , NCT04476056.
Background/Objective
Endoprostheses might fail due to complications such as implant loosening or periprosthetic infections. The surface topography of implant materials is known to influence osseointegration and attachment of pathogenic bacteria. Laser-Induced Periodic Surface Structures (LIPSS) can improve the surface topography of orthopedic implant materials. In this preclinical in vitro study, laser pulses with a wavelength in the ultraviolet (UV) spectrum were applied for the generation of LIPSS to positively influence formation of extracellular matrix by primary human Osteoblasts (hOBs) and to reduce microbial biofilm formation in vitro .
Methods
Laser machining was employed for generating UV-LIPSS on sample disks made of Ti6Al4V and Ti6Al7Nb alloys. Sample disks with polished surfaces were used as controls. Scanning electron microscopy was used for visualization of surface topography and adherent cells. Metal ion release and cellular metal levels were investigated by inductively coupled plasma mass spectrometry. Cell culture of hOBs on sample disks with and without UV-LIPSS surface treatments was performed. Cells were investigated for their viability, proliferation, osteogenic function and cytokine release. Biofilm formation was facilitated by seeding Staphylococcus aureus on sample disks and quantified by wheat germ agglutinin (WGA) staining.
Results
UV-LIPSS modification results in topographies with a periodicity of 223 nm ≤ λ ≤ 278 nm. The release of metal ions was found increased for UV-LIPSS on Ti6Al4V and decreased for UV-LIPSS on Ti6Al7Nb, while cellular metal levels remain unaffected. Cellular adherence was decreased for hOBs on UV-LIPSS Ti6Al4V when compared to controls while proliferation rate was unaffected. Metabolic activity was lower on UV-LIPSS Ti6Al7Nb when compared to the control. Alkaline phosphatase activity was upregulated for hOBs grown on UV-LIPSS on both alloys. Less pro-inflammatory cytokines were released for cells grown on UV-LIPSS Ti6Al7Nb when compared to polished surfaces. WGA signals were significantly lower on UV-LIPSS Ti6Al7Nb indicating reduced formation of a S. aureus biofilm.
Conclusion
Our results suggest that UV-LIPSS texturing of Ti6Al7Nb positively influence bone forming function and cytokine secretion profile of hOBs in vitro . In addition, our results indicate diminished biofilm formation on UV-LIPSS treated Ti6Al7Nb surfaces. These effects might prove beneficial in the context of long-term arthroplasty outcomes.
Background
Multipin dry electrodes (dry EEG) provide faster and more convenient application than wet EEG, enabling extensive data collection. This study aims to compare task-related time-frequency representations and resting-state connectivity between wet and dry EEG methods to establish a foundation for using dry EEG in investigations of brain activity in neuropsychiatric disorders.
Methods
In this counterbalanced cross-over study, we acquired wet and dry EEG in 33 healthy participants [ n = 22 females, mean age (SD) = 24.3 (± 3.4) years] during resting-state and an auditory oddball paradigm. We computed mismatch negativity (MMN), theta power in task EEG, and connectivity measures from resting-state EEG using phase lag index (PLI) and minimum spanning tree (MST). Agreement between wet and dry EEG was assessed using Bland–Altman bias.
Results
MMN was detectable with both systems in time and frequency domains, but dry EEG underestimated MMN mean amplitude, peak latency, and theta power compared to wet EEG. Resting-state connectivity was reliably estimated with dry EEG using MST diameter in all except the very low frequencies (0.5–4 Hz). PLI showed larger differences between wet and dry EEG in all frequencies except theta.
Conclusion
Dry EEG reliably detected MMN and resting-state connectivity despite a lower signal-to-noise ratio. This study provides the methodological basis for using dry EEG in studies investigating the neural processes underlying psychiatric and neurological conditions.
F. nucleatum, involved in carcinogenesis of colon carcinomas, has been described as part of the commensal flora of the female upper reproductive tract. Although its contribution to destructive inflammatory processes is well described, its role as commensal uterine bacteria has not been thoroughly investigated. Since carcinogenesis shares similar mechanisms with early pregnancy development (including proliferation, invasion, blood supply and the induction of tolerance), these mechanisms induced by F. nucleatum could play a role in early pregnancy. Additionally, implantation and placentation require a well-balanced immune activation, which might be suitably managed by the presence of a limited amount of bacteria or bacterial residues. We assessed the effect of inactivated F. nucleatum on macrophage-trophoblast interactions. Monocytic cells (THP-1) were polarized into M1, M2a or M2c macrophages by IFN-γ, IL-4 or TGF-β, respectively, and subsequently treated with inactivated fusobacteria (bacteria:macrophage ratio of 0.1 and 1). Direct effects on macrophages were assessed by viability assay, flow cytometry (antigen presentation molecules and cytokines), qPCR (cytokine expression), in-cell Western (HIF and P-NF-κB) and ELISA (VEGF secretion). The function of first trimester extravillous trophoblast cells (HTR-8/SVneo) in response to macrophage-conditioned medium was microscopically assessed by migration (scratch assay), invasion (sprouting assay) and tube formation. Underlying molecular changes were investigated by ELISA (VEGF secretion) and qPCR (matrix-degrading factors and regulators). Inflammation-primed macrophages (M1) as well as high bacterial amounts increased pro-inflammatory NF-κB expression and inflammatory responses. Subsequently, trophoblast functions were impaired. In contrast, low bacterial stimulation caused an increased HIF activation and subsequent VEGF-A secretion in M2c macrophages. Accordingly, there was an increase of trophoblast tube formation. Our results suggest that a low-mass endometrial/decidual microbiome can be tolerated and while it supports implantation and further pregnancy processes.