An Efficient Numerical Scheme for Biological Models in the Frame of Bernoulli Wavelets

This article considers three types of biological systems:the dengue fever disease model,the COVID-19 virus model,and the transmission of Tuberculosis model.The new technique of creating the integration matrix for the Bernoulli wavelets is applied.Also,the novel method proposed in this paper is called the Bernoulli wavelet collocation scheme(BWCM).All three models are in the form system of coupled ordinary differential equations without an exact solution.These systems are converted into a system of algebraic equations using the Bernoulli wavelet collocation scheme.The numerical wave distributions of these governing models are obtained by solving the algebraic equations via the Newton-Raphson method.The results obtained from the developed strategy are compared to several schemes such as the Runge Kutta method,and ND solver in mathematical software.The convergence analyses are discussed through theorems.The newly implemented Bernoulli wavelet method improves the accuracy and converges when it is compared with the existing methods in the literature.

Dynamics of Advantageous Mutant Spread in Spatial Death-Birth and Birth-Death Moran Models

The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.

The relationship between compartment models and their stochastic counterparts:A comparative study with examples of the COVID-19 epidemic modeling

Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochastic models is not well understood.The present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2019 modeling literature.We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations.Based on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment.The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics.However,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs.Additionally,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents.This model offered a balance between computational efficiency and accuracy.The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling.Furthermore,the results had implications for the development of hybrid models that integrated the strengths of both frameworks.Overall,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

Background: Calotropis procera (C. procera), is an authentic plant naturally grown in the flora of Dead Sea region. Despite its toxicity, C. procera presents healing properties. However, it has not been implemented yet in cosmetics as an active ingredient. Objective: The biological effects of C. procera callus extract on skin were elucidated solely and in combination with Dead Sea water (DSW). Methods: The capability of C. procera extract to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by LPS and SDS addition respectively. Viability and cytokine secretion were evaluated. The combination of C. procera extract with Dead Sea water was tested on full thickness skin equivalents. Gene expression and relevant biochemical markers for glycolysis, hypoxia and extracellular matrix balance were tested. Results: C. procera extract exhibits a protective biological activity against skin irritation and inflammation at the biochemical level. Furthermore, a combination of C. procera extract and DSW demonstrates a potential contribution for skin wellbeing via enhance energy production, resistance to hypoxia and extracellular matrix balance. Conclusions: Topical application of C. procera callus extract might support skin balance and wellbeing at the molecular level. Hence, it is recommended for new cosmetic formulae as standalone or in combination with Dead Sea water, in the effort to achieve anti-aging bio-activity that is working beyond skin aging symptoms, especially via skin calming effects and skin energy enhancement.

Establishment of injury models in studies of biological effects induced by microwave radiation

Microwave radiation has been widely used in various fields,such as communication,industry,medical treatment,and military applications.Microwave radiation may cause injuries to both the structures and functions of various organs,such as the brain,heart,reproductive organs,and endocrine organs,which endanger human health.Therefore,it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation.The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies.In this article,we review the microwave exposure conditions,subjects used to establish injury models,the methods used for the assessment of the injuries,and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.

Combination of Neuro-Fuzzy Network Models with Biological Knowledge for Reconstructing Gene Regulatory Networks

Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly. In this paper, we propose a novel approach based on combining neuro-fu^zy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory nctworks＋ but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without lhctitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast, The results show that this approach can work effectively.

Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using^(18)F-FDG and^(18)F-FLT

Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.

Smaller & Smarter: Score-Driven Network Chaining of Smaller Language Models

With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily measured by the number of parameters, but also the subsequent escalation in computational demands, hardware and software prerequisites for training, all culminating in a substantial financial investment as well. In this paper, we present novel techniques like supervision, parallelization, and scoring functions to get better results out of chains of smaller language models, rather than relying solely on scaling up model size. Firstly, we propose an approach to quantify the performance of a Smaller Language Models (SLM) by introducing a corresponding supervisor model that incrementally corrects the encountered errors. Secondly, we propose an approach to utilize two smaller language models (in a network) performing the same task and retrieving the best relevant output from the two, ensuring peak performance for a specific task. Experimental evaluations establish the quantitative accuracy improvements on financial reasoning and arithmetic calculation tasks from utilizing techniques like supervisor models (in a network of model scenario), threshold scoring and parallel processing over a baseline study.

Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Use of machine learning models for the prognostication of liver transplantation: A systematic review

BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.

Economic Stress, Precariousness and Risk of High Blood Pressure: A Descriptive Survey of Life Models within Households of the Central Region of Cameroon

Context/Objective: High blood pressure (HBP) currently represents the most widespread chronic non-communicable disease in Cameroon. The increase in its prevalence in the country is the result of multiple factors including economic stress imposed by precariousness, poor living conditions, sources of anxiety, anguish, depression and other behavioral disorders. Economic stress is a globalizing concept that integrates into a purely hermeneutic approach, a particular functioning of the nervous system of an individual who faces employment problems and precarious remuneration conditions. The non-satisfaction by an individual of his basic needs due to insufficient financial means can cause him to become irritable, aggressive, and socially and symbolically isolated, thereby increasing the desire to resort to morbid life models such as excessive consumption of narcotics and other psychoactive substances often associated with high blood pressure. The fight against the emergence of BPH is a complex, multifaceted and multifactorial reality that requires taking into account economic stress. The main objective of this survey is to describe the situation of economic stress within the Cameroonian population, which imposes precariousness and life models at risk of high blood pressure. Specifically, we determined the level of household income and the sources of income. Methods: A cross-sectional survey with a descriptive aim among five hundred households in the Central Region of Cameroon was conducted. A probabilistic technique called simple randomness was used. The number of households to be surveyed was determined indirectly using the Cochrane formula. Data collection in face-to-face mode using a physical questionnaire took place from July 1 to August 31, 2023, after obtaining ethical clearance from the Regional Health Research Ethics Committee, Human from the Center and an administrative authorization for data collection. Regarding their processing, the data was grouped during processing in Excel sheets. Normality and reliability tests of the collected data were carried out. For this, the Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value. Descriptive analysis was possible using R software version 3.2, SPSS version 25.0, XLSTAT 2016, PAST and EXCEL programs from Microsoft Office 2013. Results: The main results highlight economic stress, with 45.60% of households surveyed earning less than US$154 per month;55% of household heads were women in single-parent families;14% of household heads were unemployed, 22% worked in the private sector and 19% were self-employed. This general economic situation leads to precarious living conditions, thereby increasing the risk of high blood pressure among the Cameroonian population.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

Animal models of hepatitis E infection: Advances and challenges

Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

In vitro engineered models of neurodegenerative diseases

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalmodels do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals andhumans.Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative diseases.Today,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating tissue.In THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.

Asymptotic normality of error density estimator in stationary and explosive autoregressive models

In this paper,we consider the limit distribution of the error density function estima-tor in the rst-order autoregressive models with negatively associated and positively associated random errors.Under mild regularity assumptions,some asymptotic normality results of the residual density estimator are obtained when the autoregressive models are stationary process and explosive process.In order to illustrate these results,some simulations such as con dence intervals and mean integrated square errors are provided in this paper.It shows that the residual density estimator can replace the density\estimator"which contains errors.

Contrasts of bimodal tropical instability waves(TIWs)-induced wind stress perturbations in the Pacific Ocean among observations,ocean models,and coupled climate models

The coupling between wind stress perturbations and sea surface temperature(SST)perturbations induced by tropical instability waves(TIWs)in the Pacific Ocean has been revealed previously and proven crucial to both the atmosphere and ocean.However,an overlooked fact by previous studies is that the loosely defined“TIWs”actually consist of two modes,including the Yanai wave-based TIW on the equator(hereafter eTIW)and the Rossby wave-based TIW off the equator(hereafter vTIW).Hence,the individual feedbacks of the wind stress to the bimodal TIWs remain unexplored.In this study,individual coupling relationships are established for both eTIW and v TIW,including the relationship between the TIW-induced SST perturbations and two components of wind stress perturbations,and the relationship between the TIW-induced wind stress perturbation divergence(curl)and the downwind(crosswind)TIW-induced SST gradients.Results show that,due to different distributions of eTIW and vTIW,the coupling strength induced by the eTIW is stronger on the equator,and that by the vTIW is stronger off the equator.The results of any of eTIW and vTIW are higher than those of the loosely defined TIWs.We further investigated how well the coupling relationships remained in several widely recognized oceanic general circulation models and fully coupled climate models.However,the coupling relationships cannot be well represented in most numerical models.Finally,we confirmed that higher resolution usually corresponds to more accurate simulation.Therefore,the coupling models established in this study are complementary to previous research and can be used to refine the oceanic and coupled climate models.

Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.