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1.
Biochim Biophys Acta Proteins Proteom ; 1873(1): 141044, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39218139

RESUMO

Bacteriophages have evolved different mechanisms of infection and penetration of bacterial cell walls. In Siphoviridae-like viruses, the inner tail proteins have a pivotal role in these processes and often encode lytic protein domains which increase infection efficiency. A soluble lytic transglycosylase (SLT) domain was identified in the minor tail protein gp15 from the BFK20 bacteriophage. Six fragments containing this SLT domain with adjacent regions of different lengths were cloned, expressed and purified. The biophysical properties of the two best expressing fragments were characterized by nanoDSF and CD spectroscopy, which showed that both fragments had a high refolding ability of 90 %. 3D modeling indicated that the bacteriophage BFK20 SLT domain is structurally similar to lysozyme. The degradation activity of these SLT proteins was evaluated using a lysozyme activity assay. BFK20 might use its transglycosylase activity to allow efficient phage DNA entry into the host cell by degrading bacterial peptidoglycan.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39242408

RESUMO

PURPOSE: Volume injected for glottic insufficiency is paramount in achieving desired outcome. Factors that determine the required volume have not been thoroughly investigated and may correlate with outcome. The first objective of this investigation was to evaluate the association between injectable volume and various parameters, including lifestyle characteristics, pre-procedural factors, and voice measures, while the second aim assessed the correlation of volume to clinical outcomes in patients who underwent injection laryngoplasty. METHODS: For the first objective, a one-way ANOVA and univariate linear regression were used to analyze data from 124 patients (injected material, pre-operative diagnosis, previous voice therapy, age etc.). One-sample t-tests and Pearson correlational coefficients were employed for statistical analysis of aim 2 in a subgroup of 28 patients that had pre- and post-injection voice evaluations (e.g., acoustic and aerodynamic analysis, perceptual assessment, questionnaires). RESULTS: Average injection volume was 0.39 ± 0.062 mL (range: 0.1-1.6mL). No pre-procedural or lifestyle factor significantly affected injection volume (p > 0.05). There was no relationship between pre-procedural voice outcomes and injection volume (p > 0.05). Of the factors that were significantly improved post-injection laryngoplasty (GFI, VHI, and GRBAS), there were no significant correlations between the magnitude of improvement in these measures and injection volume (p > 0.05). CONCLUSION: Injection volume does not appear to be affected by pre-procedural or lifestyle factors. In addition, injection volume does not significantly impact clinical outcomes assessed through voice analysis or patient-reported questionnaires. Our results underscore the complexity of factors at play in injection laryngoplasty for glottic insufficiency.

3.
J Voice ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39244387

RESUMO

The elastic properties of the folds govern the characteristics of vocal fold vibrations. This study addresses existing gaps by investigating the Young's modulus along the anterior-posterior direction in excised canine and cadaveric human vocal folds. Micro-indentation testing was conducted on six excised canines and three cadaveric human larynges. Multiple points along the medial glottal wall were indented to determine force-displacement, stress-strain relationships, and Young's modulus as a function of Green's strain. A vertical stiffness gradient was consistently observed in both canine and human samples, with higher stiffness in the inferior aspect compared with the superior aspect. The stiffness increased toward both the anterior and posterior directions from the mid-coronal plane, with a more pronounced increase at the posterior edge. Human vocal folds generally exhibited lower stiffness at low strains but were comparable to canine vocal folds at higher strains. These findings suggest that the canine larynx model is a reasonable representation of the human laryngeal tissues' elastic property trends. This analysis of the vertical stiffness gradient in canine and human vocal folds provides valuable data for improving experimental and numerical models of phonation.

4.
Laryngoscope ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264157

RESUMO

OBJECTIVE: This study aims to evaluate the clinical outcomes of patients receiving in-office vocal fold steroid injections (VFSI), highlighting relatively new measures around vocal pitch. METHODS: Patients with a diagnosis of vocal fold scar who received in-office VFSI from 2013 to 2024 were evaluated. Pre- and post-steroid Voice Handicap Index (VHI-10) scores, stroboscopic vibratory parameters, acoustic measures of cepstral peak prominence (CPP), and fundamental frequency coefficient of variation (F0CoV) during sustained phonation were analyzed using Wilcoxon signed-rank tests and McNemar's tests. RESULTS: Twenty-two patients had follow-up data 1-3 months after steroid injection. The median decrease in VHI-10 after one injection was 4 points (p = 0.02). We found no difference in CPP and F0CoV measures at follow-up. Forty-five percent of patients improved in mucosal wave and amplitude of at least one vocal fold. Earlier presentation from vocal injury was associated with improvement in mucosal wave and amplitude of the left vocal fold (p = 0.03). We found no difference in sex, tobacco smoking history, singing status, secondary diagnosis, and baseline VHI-10 score between patients who improved in vibratory parameters and those who did not. CONCLUSION: This single-center study is one of the largest exploring patient outcomes following in-office VFSI. Though patients reported modest improvement in voice use after VFSI, this may not be as impactful as previously believed. Improvement in videostroboscopy is expected in about half of the patients, with recency from vocal injury a likely predictor of success. These partially negative results provide insight into counseling patients regarding benefits from in-office VFSI. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

5.
Laryngoscope ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283010

RESUMO

BACKGROUND: Unilateral vocal fold pseudocysts have been hypothesized to result from vocal fold paresis, but no explanation has been proposed for bilateral lesions. This study compares patients with unilateral to those with bilateral pseudocysts for insights into pathogenesis. METHODS: Adults with unilateral and bilateral pseudocysts evaluated between 2018 and 2023 were retrospectively studied. Patient demographics, laryngeal stroboscopic findings, management strategies employed, and treatment outcomes were recorded. Fisher's exact and student's t-tests were performed to assess unilateral and bilateral cohorts for differences. RESULTS: One hundred ninety-six patients (109 with bilateral and 87 with unilateral pseudocysts) were studied. The average age was 29 years (bilateral: 29 years, unilateral: 30 years; p = 0.3846). The groups differed with respect to sex (172 females: 105 bilateral, 67 unilateral; 24 males: 4 bilateral, 20 unilateral; p < 0.0001) and clinical diagnosis of paresis (bilateral: 13.8%, unilateral: 34.5%; p = 0.0010). Treatment was similar between cohorts for rates of voice therapy (bilateral: 67.0%, unilateral 63.2%; p = 0.6511) and surgery (bilateral: 12.8%, unilateral 17.2%; p = 0.4228). There were a total of six recurrences (bilateral: 2, unilateral: 4; p = 0.3898). CONCLUSIONS: Bilateral pseudocysts occur almost exclusively in women and with a relative absence of paresis. Unilateral pseudocysts are more likely to occur in the presence of paresis and in a significantly higher proportion of men. This suggests that unilateral and bilateral disease evolve in different clinical conditions, although they may share glottic insufficiency as a predisposing factor. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

6.
J Mol Evol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297932

RESUMO

Many polymerases and other proteins are endowed with a catalytic domain belonging to the nucleotidyltransferase fold, which has also been deemed the non-canonical palm domain, in which three conserved acidic residues coordinate two divalent metal ions. Tertiary structure-based evolutionary analyses provide valuable information when the phylogenetic signal contained in the primary structure is blurry or has been lost, as is the case with these proteins. Pairwise structural comparisons of proteins with a nucleotidyltransferase fold were performed in the PDBefold web server: the RMSD, the number of superimposed residues, and the Qscore were obtained. The structural alignment score (RMSD × 100/number of superimposed residues) and the 1-Qscore were calculated, and distance matrices were constructed, from which a dendogram and a phylogenetic network were drawn for each score. The dendograms and the phylogenetic networks display well-defined clades, reflecting high levels of structural conservation within each clade, not mirrored by primary sequence. The conserved structural core between all these proteins consists of the catalytic nucleotidyltransferase fold, which is surrounded by different functional domains. Hence, many of the clades include proteins that bind different substrates or partake in non-related functions. Enzymes endowed with a nucleotidyltransferase fold are present in all domains of life, and participate in essential cellular and viral functions, which suggests that this domain is very ancient. Despite the loss of evolutionary traces in their primary structure, tertiary structure-based analyses allow us to delve into the evolution and functional diversification of the NT fold.

7.
Trop Anim Health Prod ; 56(7): 250, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225879

RESUMO

This study was designed to predict the post-weaning weights of Akkaraman lambs reared on different farms using multiple linear regression and machine learning algorithms. The effect of factors the age of the dam, gender, type of lambing, enterprise, type of flock, birth weight, and weaning weight was analyzed. The data was collected from a total of 25,316 Akkaraman lambs raised at multiple farms in the Çiftlik District of Nigde province. Comparative analysis was conducted by using multiple linear regression, Random Forest, Support Vector Machines (and Support Vector Regression), Extreme Gradient Boosting (XGBoost) (and Gradient Boosting), Bayesian Regularized Neural Network, Radial Basis Function Neural Network, Classification and Regression Trees, Exhaustive Chi-squared Automatic Interaction Detection (and Chi-squared Automatic Interaction Detection), and Multivariate Adaptive Regression Splines algorithms. In this study, the test dataset was divided into five layers using the K-fold cross-validation method. The performance of models was compared using performance criteria such as Adjusted R-squared (Adj-[Formula: see text]), Root Mean Square Error (RMSE), Mean Absolute Deviation (MAD), and Mean Absolute Percentage Error (MAPE) by utilizing test populations in the predicted models. Additionally, the presence of low standard deviations for these criteria indicates the absence of an overfitting problem. [Formula: see text]The comparison results showed the Random Forest algorithm had the best predictive performance compared to other algorithms with Adj-[Formula: see text], RMSE, MAD, and MAPE values of 0.75, 3.683, 2.876, and 10.112, respectively. In conclusion, the results obtained through Multiple Linear Regression for the live weights of Akkaraman lambs were less accurate than the results obtained through artificial neural network analysis.


Assuntos
Peso Corporal , Aprendizado de Máquina , Carneiro Doméstico , Animais , Modelos Lineares , Feminino , Masculino , Carneiro Doméstico/fisiologia , Carneiro Doméstico/crescimento & desenvolvimento , Índia , Algoritmos , Ovinos , Peso ao Nascer
8.
Laryngoscope ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39315496

RESUMO

OBJECTIVE: The aim of this study is to report on experience acquired during the laryngeal electrophysiological assessment with Co-MEP and L-EMG in pediatric patients with acquired, congenital, and syndromic vocal fold paralysis (VFP), and correlate our findings with patients' characteristics, their comorbidities, and VFP etiology. METHODS: Pediatric patients with suspected or previously diagnosed unilateral or bilateral VFP underwent electrophysiological records under general anesthesia; corticobulbar motor-evoked potentials (Co-MEPs) and laryngeal electromyography (L-EMG) of thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were recorded. RESULTS: Statistical analysis revealed a statistically significant correlation between early gestational age at childbirth and TA muscle intensity (p = 0.002) and PCA muscle intensity (p = 0.002); tracheostomy presence and TA muscle intensity (p = 0.002) and PCA muscle intensity (p = 0.002); presence of genetic anomalies with intensity and latency for TA muscle and latency for PCA muscle (TA latency p = 0.015, TA intensity p = 0.021, PCA latency p = 0.035); congenital presentation of VFP and an increased intensity for TA muscle (p = 0.04); latency and intensity for TA muscle (p = 0.024); TA muscle intensity and PCA intensity (p = 0.005). CONCLUSION: Intraoperative Co-MEPs and L-EMG are two complementary tools for evaluating the functional integrity of the structures involved in conveying signals from the motor cortex to TA and PCA muscles in children with vocal fold paralysis. Further studies are needed to establish their ability to predict the recovery of VF mobility, which could potentially lead to decannulation. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39316129

RESUMO

OBJECTIVES: To stratify the severity of cricoarytenoid joint fixation (CAJF) by surgery and understand the role of it played in the bilateral vocal fold immobility (BVFI). The second objective emphasizes on the significance of the preoperative differential diagnosis from neurogenic immobility with medical history and endoscopic findings. METHODS: A retrospective review was conducted of 74 patients between 2005 and 2022. Careful medical history inquiry, and videolaryngoscopy are conducted to recruit the appropriate surgical candidates. All patients underwent arytenoid remobilization (AR) followed by vocal fold medialization with arytenoid adduction (AA) or lateralization with suture lateralization (SL). The severity of CAJF is graded during the operation or inferred based on the period from operation to recurrence. RESULT: A total of 18 patients, aged between 18 and 76 years, were analyzed. Among them, 14 cases were classified as the adducted type with ventilation problems, with three presenting with dyspnea, and 11 requiring artificial airways. Additionally, four patients presented with the abducted type, characterized by aphonia. Meanwhile, two additional cases were considered for comparison but were not included in this cohort of 18 subjects due to incorrect diagnosis and inappropriate management. Using AR procedure, the AA procedure offered three aphonia subjects a voiced sound without airway impairment and the SL procedure decannulated 100% (11/11) of the artificial airways and improved the airway patency in 100% (3/3) of the non-tracheostomized subjects despite the severity of CAJF. The severity of joint ankylosis was distributed as follows: In the aphonia group, there were three subjects with grade I, one subject with grade II, and 0 subjects with grade III. In the ventilation group, there was one subject with grade I, seven subjects with grade II, and six subjects with grade III. In contrast, the two cases used for comparison experienced recurrent dyspnea and failed decannulation because the AR procedure was not performed. The follow-up period was averaged in 58 and 14 months at least. CONCLUSION: From this experience, it is the accurate preoperative diagnosis instead of the severity of CAJF that determines the successful rate in airway patency and voiced phonation if the AR procedure is utilized. Careful medical history inquiry and videolaryngoscopic examination can correctly differentiate the mechanical from neurogenic origin without the help of EMG. Evidence of level: 4.

10.
Diagnostics (Basel) ; 14(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39272628

RESUMO

Nail capillaroscopic examination is an inexpensive and easily applicable method to identify capillary morphological changes in patients with conditions such as systemic sclerosis and Raynaud's. The detection of changes in capillaries makes an important contribution to diagnosing these diseases. Capillary morphology is important in the symptoms of these diseases, and capillary diameter, visibility, distribution, length, microbleeds, blood flow, and density are important indicators in capillaroscopic evaluation. Manual examination to determine these parameters is subjective, causes inconsistent results, and is labor-intensive and time-consuming. To overcome these problems, a YOLOv8s-based system was proposed in this paper to detect the number, thickness, and density of capillaries in the nail bed. The system's components include database systems that store the analysis results, artificial intelligence-based software that runs on the SBC (Single-Board Computer), and recorded microscope images. mAP and F1_score parameters were used to evaluate the system's performance, and values of 0.882 and 0.83 were obtained. The proposed system is promising in improving the diagnosis process of diseases such as systemic sclerosis and Raynaud's by providing objective measurements and the early diagnosis and monitoring of diseases.

11.
Laryngoscope ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276031

RESUMO

INTRODUCTION: Glucocorticoids (GCs) are commonly prescribed for laryngeal indications due to their potent anti-inflammatory properties. However, GCs effect on vocal fold (VF) epithelial morphology and barrier function following injury is overlooked and may be key to efficacy. In this study, the effects of GCs on epithelial morphology and barrier function were quantified in injured VFs. We seek to increase our understanding of biochemical processes underlying GC mechanisms to refine therapeutic strategies. METHODS: Microflap injury was induced in 65 rabbits. Seven days after injury, animals received bilateral 20 µL intracordal injections of saline, dexamethasone, methylprednisolone, or triamcinolone (n = 15 per condition). Five rabbits in each condition were euthanized 1, 7, or 60 days following treatment. An additional five animals served as non-injured/untreated controls. To quantify transepithelial electrical resistance (TEER), 1 mm epithelial biopsies were placed in an Ussing chamber. The contralateral VF was processed for transmission electron microscopy and epithelial depth analysis. RESULTS: At 60 days, GC treatment maintained TEER levels similar to non-injured/untreated controls. However, triamcinolone reduced TEER compared with saline-treated conditions. Acutely, epithelial hyperplasia typically persisted in all injured VFs. At 60 days, only dexamethasone and triamcinolone increased epithelial depth in injured VFs; all GCs increased epithelial depth compared with non-injured/untreated controls. CONCLUSION: Acutely, GCs did not alter TEER. Additionally, GCs did not alter epithelial depth compared with saline treatment, indicating alignment with natural healing responses. At 60 days, GCs exhibited varying degrees of TEER restoration and epithelial hyperplasia, possibly due to distinct pharmacodynamic profiles. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

12.
J Clin Med ; 13(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39274455

RESUMO

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing.

13.
Biomed Mater ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288796

RESUMO

The larynx is responsible for breathing, producing sound, and protecting the trachea against food aspiration through the cough reflex. Nowadays, scaffolding surgery has made it easier to regenerate damaged tissues by facilitating the influx of cells and growth factors. This review provides a comprehensive overview of the current knowledge on tissue engineering of the larynx and vocal folds. It also discusses the achievements and challenges of data sources. In conducting a literature search for relevant papers, we included sixty-eight studies from January 2000 to November 2023, sourced from PubMed and Scholar Google databases. We found a need for collaboration between voice care practitioners, voice scientists, bioengineers, chemists, and biotechnologists to develop safe and clinically valid solutions for patients with laryngeal and vocal fold injuries. It is crucial for patients to be knowledgeable about the available choices of laryngeal tissue engineering for successful tissue repair. Although few human trials have been conducted, future works should build upon previously completed in-vivo studies in an effort to move towards more human models. .

14.
J Voice ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39289086

RESUMO

BACKGROUND: Vocal fold nodules are most common in women and patients with vocal fold nodules represent the largest group in voice clinics. The prevalence of vocal fold nodules is particularly high in professions where the voice is used on a regular basis. The quality of the voice is influenced by a number of factors, including temperament, stress, and emotional state. These factors can influence the physiological conditions of phonation. The objective of this study was to assess the acoustic parameters of voice in patients with vocal nodules in comparison to healthy controls, and to determine whether voice quality is influenced by emotional state and coping with stress. METHODS: A total of 32 patients admitted to the ENT Department of the University Medical School with voice disorders between March and June 2007 constituted the study group. All patients were found to have a vocal nodule on physical and stroboscopic examination. The control group consisted of 30 healthy individuals who did not report any voice disorders. All subjects underwent voice recordings in the voice laboratory. Following the completion of the voice evaluation form, an aerodynamic assessment (a, s, and s/z-time), an index of vocal impairment, the Rosenbaum's Learned Resourcefulness Scale, and the Temperament and Characteristics Inventory (Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionaire), all subjects underwent further assessment. Acoustic analysis was conducted using the CSL program in Multidimensional voice program analysis and the Vocal Assessment component of Dr. Speech. RESULTS: The decrease in maximum phonation time in the study group was statistically significant. There were statistically significant differences in the parameters Mean Fundamental Frequence, Jitter, Relative Avarage Perturbation, Pitch Perturbation Quotient, Shimmer in dB, Shimmer, Amplitude Perturbation Quotient, Noise Hormonic Ratio, Soft Phonation Index from the Multidimensional voice program analysis, Jitter, Shimmer% from the voice assessment, and the perceptual rating (H, R, and B) from Dr. Speech's voice assessment analysis. The differences in the dimensions of anxious temperament and the examination of stress problem-solving strategies were significant between the study group and the control subjects. Differences in aerodynamic and acoustic parameters were found between disordered and healthy groups, as well as between individuals with different personalities. Overall, those with nodules were less likely to manage stress well than those without nodules. CONCLUSIONS: The study group and the control subjects showed significant differences in anxious temperament dimensions and stress problem-solving strategies. There were also differences in aerodynamic and acoustic parameters between the disordered and healthy groups, as well as between the groups with and without personality temperament differences. Overall, those with nodules were less likely to manage stress well than those without nodules. This finding indicates that stress management options are not effectively utilized in patients with vocal fold nodules. So, it might be a good idea to look into some kind of therapeutic approach and patient education for stress management.

15.
Laryngoscope ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291643

RESUMO

Despite tracheotomy being a routine procedure, it is not rare to encounter anatomic irregularities that can compromise its success. In this report, we describe a case in which a high riding innominate artery was identified within the surgical trajectory moments before incision, which ultimately necessitated airway securement using an alternative laryngological procedure. Laryngoscope, 2024.

16.
J Mol Biol ; : 168791, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39260686

RESUMO

The vastness of unexplored protein fold universe remains a significant question. Through systematic de novo design of proteins with novel αß-folds, we demonstrated that nature has only explored a tiny portion of the possible folds. Numerous possible protein folds are still untouched by nature. This review outlines this study and discusses the prospects for design of functional proteins with novel folds.

18.
J Math Biol ; 89(4): 38, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240340

RESUMO

Matsuda and Abrams (Theor Popul Biol 45(1):76-91, 1994) initiated the exploration of self-extinction in species through evolution, focusing on the advantageous position of mutants near the extinction boundary in a prey-predator system with evolving foraging traits. Previous models lacked theoretical investigation into the long-term effects of harvesting. In our model, we introduce constant-effort prey and predator harvesting, along with individual logistic growth of predators. The model reveals two distinct evolutionary outcomes: (i) Evolutionary suicide, marked by a saddle-node bifurcation, where prey extinction results from the invasion of a lower forager mutant; and (ii) Evolutionary reversal, characterized by a subcritical Hopf bifurcation, leading to cyclic prey evolution. Employing an innovative approach based on Gröbner basis computation, we identify various bifurcation manifolds, including fold, transcritical, cusp, Hopf, and Bogdanov-Takens bifurcations. These contrasting scenarios emerge from variations in harvesting parameters while keeping other factors constant, rendering the model an intriguing subject of study.


Assuntos
Evolução Biológica , Cadeia Alimentar , Conceitos Matemáticos , Modelos Biológicos , Dinâmica Populacional , Comportamento Predatório , Animais , Dinâmica Populacional/estatística & dados numéricos , Extinção Biológica , Simulação por Computador , Mutação , Ecossistema
19.
Front Comput Neurosci ; 18: 1388504, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309755

RESUMO

Late-onset Alzheimer disease (AD) is a highly complex disease with multiple subtypes, as demonstrated by its disparate risk factors, pathological manifestations, and clinical traits. Discovery of biomarkers to diagnose specific AD subtypes is a key step towards understanding biological mechanisms underlying this enigmatic disease, generating candidate drug targets, and selecting participants for drug trials. Popular statistical methods for evaluating candidate biomarkers, fold change (FC) and area under the receiver operating characteristic curve (AUC), were designed for homogeneous data and we demonstrate the inherent weaknesses of these approaches when used to evaluate subtypes representing less than half of the diseased cases. We introduce a unique evaluation metric that is based on the distribution of the values, rather than the magnitude of the values, to identify analytes that are associated with a subset of the diseased cases, thereby revealing potential biomarkers for subtypes. Our approach, Bimodality Coefficient Difference (BCD), computes the difference between the degrees of bimodality for the cases and controls. We demonstrate the effectiveness of our approach with large-scale synthetic data trials containing nearly perfect subtypes. In order to reveal novel AD biomarkers for heterogeneous subtypes, we applied BCD to gene expression data for 8,650 genes for 176 AD cases and 187 controls. Our results confirm the utility of BCD for identifying subtypes of heterogeneous diseases.

20.
Heliyon ; 10(18): e37669, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309835

RESUMO

This study investigates modeling the dynamics of a 3D translational parallel manipulator with closed chains using feedforward neural networks (FFNNs). The dataset exceeds 50,000 samples, incorporating experimental data collected from a robot prototype using MATLAB® real-time workshop and the National InstrumentsTM DAQ toolbox, as well as CAD simulation data from MSC ADAMS software. While achieving satisfactory mean squared error (MSE), some predictions did not fully capture the manipulator's dynamics, with small overfitting observed. A Deep Neural Network (DNN) was tested but faced overfitting and high computational costs, despite being trained on a subset of the dataset. This highlighted the limitations of DNNs for modeling such complicated parallel robots with closed chains and parallelograms. FFNNs were preferred for their simplicity and lower overfitting risk. L2 regularization and k-fold validation were applied to improve performance. Transfer learning (TL) was also employed, fine-tuning a new network with weights from pre-trained FFNNs using a smaller, unseen dataset. This approach significantly reduced MSE and completely eliminated overfitting, demonstrating the effectiveness of TL in refining model performance for forward and inverse dynamics. These findings suggest that FFNNs, combined with TL, L2 regularization, and k-fold validation, offer a robust method for accurately modeling complex robotic dynamics, enhancing control and optimization strategies for complicated robotic systems. Training for all networks was conducted within the MATLAB® environment.

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