Spatial relations between tumor cells and host-infiltrating cells are increasingly important in both basic science and clinical research. In this study we have tested the feasibility of using standard methods of immunohistochemistry (IHC) in a multiplex staining system using a newly developed set of chromogenic substrates for the peroxidase and alkaline phosphatase enzymes. Using this approach we have developed a set of chromogens characterized by 1) providing fine cellular detail, 2) non-overlapping spectral profiles, 3) absence of interactions between chromogens, 4) stable upon storage, and 5) compatible with current standard immunohistochemistry practices. When viewed microscopically under brightfield illumination the chromogens yielded the following colors; red, black, blue, yellow, brown, and green. By selecting compatible color combinations we have shown feasibility for four-color multiplex staining. Depending on the particular type of analysis being performed, visual analysis, without the aid of computer assisted image analysis, was sufficient to differentiate up to four different markers.

Introduction: Biliary Atresia (BA) is a common cause of neonatal cholestatic jaundice which, if recognized and treated early, can be life-saving for the infant. If the liver biopsy suggests the presence of BA, exploratory laparotomy is then carried out to confirm the diagnosis, along with the Kasai procedure to provide drainage to the bile secreted by the liver. The purpose of this study is to get a deep dive into all the various imaging modalities that can diagnose BA more effectively and with absolute certitude, thus helping prevent several children from a grave prognosis.Methodology: For the collection of the data, a search was done by two individuals using PubMed, Google Scholar, and Cochrane Library databases for all relevant literature. Each qualifying paper was evaluated independently by two reviewers. Each article was analyzed for the number of patients, their age, procedure modality, complexity of ethology, and incidence of the pre-decided complications. The statistical software packages RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20), Google Sheets, and Excel in Stata 14 were used to perform the statistical analyses. The data was obtained and entered into analytic software.Results: A total of 39 studies with 3,679 subjects were selected for the study, out of which 7 studies showed sensitivity above or equal to 95%, and an astounding 14 studies showed specificity above 95%. The value of True Positive (TP) was 1280, that of True Negative (TN) was 1817, that of False Positive (FP) was 239, and that of False Negative (FN) was 343. With a confidence interval of 95%, sensitivity, specificity, and positive predictive values were calculated. The sensitivity of Ultrasonography for Biliary Atresia is 0.79, with a CI of 95% in a range of 0.77 to 0.81. The specificity of Ultrasonography for Biliary Atresia is 0.88, with a CI of 95% in a range of 0.87 to 0.90. Conclusion: Even though several radiological techniques at present help to detect BA, USG of the abdomen proves to be an effective diagnostic and a modest screening test for the detection of BA.

The article explores the concept of 'synthetic man' (SM) in the context of 'synthetic biology' (SB), analysing the potential, challenges, and ethical implications of these achievements. Through dialogue with ChatGPT 4, an in-depth understanding of the evolution, contributions of SM, ChatGPT's contribution, and concerns associated with SM is sought, providing insight into how this technology could affect our society. Our study uses a structured dialogue framework with ChatGPT that addresses essential SM questions regarding SM history, contributions, challenges, and concerns. ChatGPT responses are analysed to extract relevant information and identify trends and insights. The ChatGPT dialogue reveals that MS is still a theoretical and speculative concept with significant advances in gene therapy and genetic engineering. The potential contributions of SM in addressing global challenges such as health, environment and education are identified. Ethical and social concerns such as health risks and psychological impact are also highlighted. Differences in ChatGPT responses were observed between different sessions or even within the same session, which highlighted the limitations in the replicability of the research and sometimes the need for clarification of the questions. The article is distinguished by its unique approach of using an advanced language model to explore a complex and speculative topic. The LLM Dialogue Framework on Technology (LLM-DFonTech) framework proposal for structured dialogue with ChatGPT on various technological topics related to the original contribution provides an adaptable tool for interdisciplinary research in emerging technologies. This methodology opens up new possibilities for analyzing and developing trends in technology and society.

The theories of Evolution and Big Bang have brought a major impact upon the scientific and societal perception upon the origins, abilities and roles of mankind on Earth. It is conclusively evident that Mother Nature and the physical realm is autonomous and all phenomena in the world occur without an imposition against the “free will” of such events and patterns. Nevertheless, this extent of freedom does not imply that life on Earth represents an accident and has no purpose. By careful analysis of ancient religious texts, it can be suggested even otherwise, that it is especially free will that is offered as a gift from outside of the physical dimensions of existence, with the purpose of a continuous edification and improvement of the overall life conditions and of the human perception. It may be that the multi-generational focus on improvement and progress have been misattributed as a long-term evolution of species, that humans came from animal ancestors and that there is a blurred line associating humans with animals. Furthermore, it may be that scientists based their suggestions that no outside Creator would have brought the Earth into existence on physical perspectives, when the extra-dimensional process of Creation implies that all elements of the physical existence undergo a process of Creation from the outside, where time, space and physical matter do not exist, in spite of such elements possibly reflecting unseen elements of the meta-physical world. Finally, there is the following example that deserves attention within the scientific community; just because all living cells - human, animal and plant - contain DNA chromosomes, ribosomes, mitochondria and a plasma membrane, it does not indicate that humans are animals, just as this does not indicate that plants are animals. In Science, there is a golden statement, that correlation does not imply causation. This example is in complete agreement with the verses of the Book of Genesis in the Holy Scriptures regarding the origins of life; namely, that animals could have been created by an Author of all life on Earth so that man would experience companionship. An improved scientific perception of the timeline of life on Earth may be reached via an approach that combines molecular biology with quantum physics, given that the three layers of Science - Biology, Chemistry and Physics - together with their foundational layer of Mathematics, are in fact situated in a relationship of complete harmony.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the Microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

In the absence of a treaty protocol or verification regime, the Biological and Toxin Weapons Convention (BWC) instituted Confidence-Building Measures (CBMs) as a mechanism to increase confidence in compliance, by enhancing transparency and mitigating ambiguities regarding states parties’ biological activities. While a promising tool to support treaty compliance, low participation, concerns regarding the completeness and accuracy of CBM submissions, a dearth of analysis, and restricted access to many submissions have limited CBMs’ value. Through interviews with 53 international experts—38 from BWC delegations and 15 independent experts—we identified concrete opportunities to increase CBMs’ value while mitigating the burden on states parties. This study supports states parties’ efforts in the BWC Working Group on the Strengthening of the Convention, as part of a series of research on BWC assurance that aims to characterize challenges around BWC verification and increase certainty in BWC compliance.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

With the inclusion of Internet Gaming Disorder (IGD) in both the DSM-5 and ICD-11, understanding the prevalence and diagnostic discrepancies is crucial for developing appropriate interventions. This study presents a meta-analysis of the prevalence of IGD based on two diagnostic criteria. We systematically searched PubMed, Web of Science databases. 17 studies were included in the final analysis, The analysis incorporated studies employing the DSM-5 and ICD-11 criteria and focused on the impact of various factors, including study location, sample size, and quality score, on the reported prevalence rates using a random-effects model. Heterogeneity and publication bias were analyzed using an I2 test and Galbraith plots , The prevalence of IGD varied among the selected studies, with a general pooled prevalence of 5% (95% CI: 3%–7%). Subgroup analysis indicated that the prevalence rates of IGD (DSM-5 criteria) and GD (ICD-11 criteria) do not show significant differences. DSM-5-based scales yielded varied results, while heterogeneity among the studies was high (I2 = 98.50). In contrast, ICD-11-based scales produced more consistent and less variable findings. Our findings highlight that assessment scales, not diagnostic criteria, impact IGD prevalence. This underscores the importance of adopting standardized methodologies to guide public health interventions. However, given the limited research based on ICD-11 diagnostic criteria, further investigation is necessary to determine the variations in prevalence rates of IGD under different diagnostic standards.

This investigation aimed to explore the impact of acute and regular physical exercise on Brain-Derived Neurotrophic Factor (BDNF) levels in individuals with obesity. Using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) approach, the inclusion criteria were defined as follows: i) population - individuals with overweight or obesity of any age or gender; ii) intervention - acute or chronic interventions involving aerobic or anaerobic methodologies; iii) comparator - for acute effect studies, pre- and post-evaluations served as comparators, while interventions included at least one experimental group or the inclusion of a control group; iv) outcome - BDNF variability concerning the applied methodology; v) study design - restricted to experimental studies exclusively. Conducted in August 2022, the searches were carried out on PubMed, Academic Search Complete, and Web of Science. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies (RoBANS) tool. Out of 98 potentially relevant articles, 16 met the eligibility criteria, encompassing 23 trials. Substantial heterogeneity was observed for both acute (I2 = 80.4%) and long-term effects (I2 = 88.7%). Additionally, RoBANS analysis indicated a low risk of bias for the included studies. The study's findings revealed a significant increase in the concentration of circulating BDNF in individuals with obesity compared to the control group following acute exercise. However, such an effect was not evident in the context of long-term physical exercise, with a small effect size (ES = 0.49) recorded in the latter scenario. The observed significant increase in BDNF levels post-acute exercise suggests a potential acute response mechanism contributing to the intricate interplay between exercise and neurotrophic factors in this population. Nevertheless, the absence of a similar effect in the context of long-term physical exercise implies a potential adaptation or ceiling effect. These findings underscore the importance of considering both the duration and nature of exercise interventions when exploring the neurobiological responses associated with obesity and exercise. The study provides valuable insights for future research and clinical implications in understanding the nuanced relationship between exercise, neurotrophic factors, and obesity.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Graph databases (GDBs) are becoming increasingly popular across scientific disciplines, being highly suitable to store and connect complex heterogeneous data. In systems biology, they are used as a backend solution for biological data repositories, ontologies, networks, pathways, and knowledge graph (KG) databases. In this review, we analyse all publications using or mentioning graph databases retrieved from PubMed and PubMed Central full-text search, focusing on the top 16 available GDB technologies. Relevant publications are then categorised according to their domain and application. We detail different approaches and highlight advantages of outstanding resources, such as UniProtKB, Disease Ontology, and Reactome, which provide graph-based solutions. We discuss ongoing efforts of the systems biology community to standardise and harmonise KG creation and the maintenance of integrated resources. Outlining prospects, including the use of GDBs as a way of communication between biological data repositories, we conclude that efficient design, querying, and maintenance of GDBs will be key for knowledge generation in systems biology and other research fields with heterogeneous data.

Colorectal cancer (CRC) with KRAS mutation is prone to develop metachronous metastasis. However, effective measures for prediction and prevention of such clinical issue are currently unavailable. In this study, we confirmed that KRAS mutation is a risk factor for CRC metachronous metastasis through meta-analysis and public database analysis. Based on the ICGC-AGRO database, we have constructed a risk scoring model for predicting metachronous metastasis in KRAS-mutant CRC using machine learning, which was validated in public datasets. Furthermore, we discovered that KRAS inhibitors can effectively suppress the migration and invasion capabilities of high risk CRC cells by wound healing assay and transwell experiment, which was validated ex vivo and in vivo using organoids and splenic liver metastatic mouse model. Finally, RNA sequencing, RT-qPCR, and western blots have proven that KRAS inhibitors can suppress the epithelial-mesenchymal transition (EMT) and transforming growth factor beta (TGF-beta) signaling pathway in CRC. Collectively, our study suggests that KRAS inhibitors may inhibit the metastatic ability of CRC by suppressing EMT and the TGF-beta pathway, suggesting their potential for the prevention of metachronous metastasis in CRC with KRAS mutation.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

Recently, there has been considerable research on deepfake detection. However, most existing methods face challenges in adapting to the advancements in new generative models within unknown domains. In addition, the emergence of new generative models capable of producing and editing high-quality images, such as Diffusion, Consistency, and LCM, poses a challenge for traditional deepfake training models. These advancements highlight the need for adapting and evolving existing deepfake detection techniques to effectively counter the threats posed by sophisticated image manipulation technologies. In this paper, our objective is to detect deepfake videos in unknown domains using unlabeled data. Specifically, our proposed approach employs Meta Pseudo Labels (MPL) with Supervised Contrastive Learning, so-called SupCon-MPL, allowing the model to be trained on unlabeled images. MPL involves the simultaneous training of both a Teacher model and a Student model, where the Teacher model generates Pseudo Labels utilized to train the Student model. This method aims to enhance the adaptability and robustness of deepfake detection systems against emerging unknown domains. Supervised Contrastive Learning utilizes labels to compare samples within similar classes more intensively, while encouraging greater distinction from samples in dissimilar classes. This facilitates the learning of features in a diverse set of deepfake images by the model, consequently contributing to the performance of deepfake detection in unknown domains. When utilizing the ResNet50 model as the backbone, SupCon-MPL exhibited an improvement of 1.58% in accuracy compared to traditional MPL in known domain detection. Moreover, in the same generation of unknown domain detection, there was a 1.32% accuracy enhancement, while in the detection of post-generation unknown domains, there was an 8.74% increase in accuracy.

Spontaneous, unwilled subjective imagery and symbols often emerge in psychotherapy that can appear baffling and confound interpretation. Moreover, early psychoanalytic theories seemed to diverge as often as they agreed on the meaning of such content. Nevertheless, reviewing key findings in the empirical science of spontaneous thought, as well as insights gleaned from neurosciences and especially embodied cognition, it is now possible to construct a more coherent theory of interpretation that is clinically useful. Given that thought is so thoroughly embodied, it is possible to demonstrate that universalities in human physiology yield universalities in thought. Such universalities can then be demonstrated to form a kind of biologically directed universal “code” for understanding spontaneous symbolic expressions that emerge in psychotherapy. An example is given that illustrates how this can be applied to clinical encounters.

DNA barcoding has emerged as a powerful tool in the field of taxonomy, transforming the way we identify and classify species. This review article aims to provide an up-to-date overview of the advancements in DNA barcoding techniques, their applications, and their impact on taxonomy and biodiversity studies. We will explore the evolution of DNA barcoding, the development of standardized barcode regions, and the challenges and limitations associated with this methodology. Additionally, we will delve into the diverse range of taxonomic groups for which DNA barcoding has been applied, highlighting key case studies and their contributions to our understanding of biodiversity. Furthermore, we will discuss the integration of DNA barcoding with other molecular and bioinformatic approaches, such as metabarcoding and machine learning, to enhance species identification and biodiversity assessment. This review aims to provide a comprehensive perspective on how DNA barcoding is reshaping the field of taxonomy and its implications for conservation, ecology, and evolutionary biology.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Today, LLMs are not good at personalization providing recommendation. They advise physicians and financial advisors to ask professionals in respective fields for help, even having user information available. Answering questions of software professionals, LLM needs to deliver in-depth answers with codes or algorithms, whereas for professionals in other fields would need definitions and main concepts. The intent of this chapter is to make LLM answer tailored to the needs of users, taking into account available information about them. To do that, we need to generalize available information about a person like her health record, maintaining the privacy of this person. We rely on meta-learning techniques to design a LLM prompt to produce a personalization prompt to obtain a suitable relevant information. Such “meta-prompt” is produced by generalization operation applied to available documents for the user. These documents need to be de-identified so that they are sufficient for personalization on one hand and will maintain user privacy on the other hand. The second neuro-symbolic technique to support personalization is abductive reasoning, acting in parallel to LLM fine-tuning. Traditional recommendation and personalization techniques as well as modern, deep learning – based are presented, and the comparison is drawn to the proposed approach. We also share the evaluation and comparative analyses of these approaches. We consider an example for how to build personalization LLM systems coming from Langchain platform. We will explore how to construct chains to form a personalization profile for a user and apply it to user search and recommendation requests.

Multimodal remote sensing data classification can enhance the model’s ability to distinguish land features through multimodal data fusion. In this context, how to help models understand the relationship between multimodal data and target tasks is the focus of researchers. Inspired by human feedback learning mechanisms, causal reasoning mechanisms, and knowledge induction mechanisms, this paper integrates causal learning, reinforcement learning, and meta learning into a unified remote sensing data classification framework and proposed the causal meta-reinforcement learning (CMRL). First, based on feedback learning mechanisms, we have overcome the limitations of traditional implicit optimization of fusion features and customized a reinforcement learning environment for multimodal remote sensing data classification tasks. Through feedback interactive learning between agents and the environment, we help them understand the complex relationships between multimodal data and labels, thereby achieving full mining of multimodal complementary information. Second, based on the causal inference mechanism we designed causal distribution prediction action, classification reward, and causal intervention reward, capturing pure causal factors in multimodal data and cutting off false statistical associations between non-causal factors and class labels. Finally, based on the knowledge induction mechanism, we designed a bi-layer optimization mechanism based on meta-learning. By constructing a meta training task and meta validation task simulation model in the generalization scenario of unseen data, we helped the model induce cross-task shared knowledge, thereby improving its generalization ability for unseen multimodal data. The experimental results on multiple sets of multimodal datasets show that the proposed method achieved state-of-the-art performance in multimodal remote sensing data classification tasks.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Trimeresurus albolabris, also known as the white-lipped pit viper or white-lipped tree viper, is a highly venomous snake distributed across Southeast Asia and the cause of many snakebite cases. In this study, we report the first whole genome assembly of T. albolabris obtained with next-generation sequencing from a specimen collected in Mengzi, Yunnan, China. After genome sequencing and assembly, the genome of this male T. albolabris individual was 1.51 Gb in length and included 38.42% repeat-element content. Using this genome, 21,695 genes were identified, and 99.17% of genes could be annotated using gene functional databases. Our genome assembly and annotation process was validated using a phylogenetic tree, which included six species and focused on single-copy genes of nuclear genomes. This research will contribute to future studies on Trimeresurus biology and the genetic basis of snake venom.

Over recent years, the swine industry has witnessed the withdrawal of antibiotics and continuous regulation of zinc and copper oxides in the early-life nutrition of piglets. Due to this development, alternative ingredients or additives from plant sources have been tremendously explored. Therefore, this study's objective was to evaluate the effect of dietary supplementation with tannins on weaned piglets’ growth performance, serum antioxidant capacity, and immune status using a meta-analysis approach. With only the inclusion of non-challenged weaned piglets, a total of 16 studies with parameters of interest were deemed eligible after a two-step screening process following a comprehensive literature search in the scientific databases of Web of Science, Scopus, ScienceDirect, PubMed, and Google Scholar. Two main categories of data, including the study’s characteristics and response variables (growth performance, serum antioxidant, and immune indices), were extracted. Applying the random-effects models, Hedges’ g effect size of supplementation with tannins was calculated using the R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (PSMD 0.05, I2 50%, n ≥10). Supplementation with tannin reduced average daily gain (p = 0.20) and feed conversion ratio (p 0.01); however, it increased average daily feed intake (p = 0.07) and final body weight (p 0.01). Meta-regression models indicated that tannin dosage and supplementation duration were directly associated with tannins' effectiveness on productive performance. In the serum, the concentration of glutathione peroxidase, superoxide dismutase, and total antioxidant capacity were elevated (p 0.01) in response to tannins supplementation, while malondialdehydes was reduced (p 0.01). Likewise, decreased immunoglobin A (p = 0.47) and increased immunoglobin M and G levels (p 0.01) were detected. In conclusion, dietary supplementation with tannins, particularly with chestnut and grape seed proanthocyanidins, increases the productivity of weaned piglets. At the same time, it is a possible nutritional strategy to mitigate oxidative stress and stimulate gut health. Thus, supplementing chestnut and grape seed proanthocyanidin tannins in the early phase of swine production could be used to alleviate the incidence of diarrhea.

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Although initially described as a tumor-cytotoxic agent, over time, it has also been recognized as an essential pro-inflammatory cytokine implicated in the pathogenesis of different autoimmune diseases, such as multiple sclerosis (MS). Several studies have shown an increase in TNF expression both in acute and chronic active MS brain lesions, as well as its involvement in maintaining a chronic inflammatory intrathecal process known as “compartmentalized inflammation”, which contributes to disease progression and disability accumulation in MS, even more than acute inflammatory activity. Indeed, high TNF levels were observed in the serum and cerebrospinal fluid of subjects with MS and correlated to disease severity, promoting axonal damage and, consequently, neurodegeneration. In this review we discuss the current knowledge of TNF and its receptors involvement in MS progression, focusing on disability progression independent of relapse activity (PIRA), meant as the disability accumulation evident in relapsing MS patients not related to acute inflammatory events.

Microfluidic systems offer precise control over physiological, biochemical, and mechanical stimuli in cell culture, allowing in vitro emulation of tissue or tumor microenvironments. This study aims to advance our understanding of tumor biology and contribute to personalized therapy development. Overcoming challenges in cell culture, including cell density and microfluidic device properties, is essential for this purpose. We designed a microfluidic system to facilitate the interaction of diverse cell lineages, incorporating human brain microvascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes (ScienceCells 1800). Post-fabrication, we assessed the system's functionality and systematically evaluated cell inoculation conditions. Photographic acquisitions comprehensively captured cell culture and their interactions. The device successfully enabled assessment of cellular proliferation, invasion, and migration, supporting the growth of monolayers and tumor organoids. Importantly, each channel demonstrated independence in study processes while allowing cellular intercommunication, both physically and biochemically. In conclusion, the functional microfluidic device facilitated the study of cell migration, tumor invasion, and organoid growth, faithfully replicating biological features observed in a tumor microenvironment. This research contributes to advancing our understanding of tumor biology for the development of personalized therapies.

Asian giant hornet, Vespa mandarinia, is an invasive species that could potentially destroy local honeybee industry in North America. It has been observed to nest in the coastal regions of British Columbia in Canada and Washington State in USA. What is the source population of the immigrant hornets? The identification of the source population can not only shed light on the route of immigration, but also on the similarity between the native habitat and the potential new habitat in the Pacific Northwest. We analyzed mitochondrial COX1 sequences of specimens sampled from multiple populations in China, South Korea, Japan and the Russian Far East. V. mandarinia exhibits phylogeographic patterns, forming monophyletic clades for 16 specimens from China, six specimens from South Korea and two specimens from Japan. The two mitochondrial COX1 sequences from Nanaimo, British Columbia are identical to the two sequences from Japan. The COX1 sequence from Blaine, Washington State, clustered with those from South Korea, and is identical to one sequence from South Korea (GenBank accession MN716828). Our geophylogeny, which allows visualization of genetic variation over time and space, provides evolutionary insights on the evolution and speciation of three closely related vespine species (V. tropica, V. soror and V. mandarinia). The geophylogeny also highlights a strong insufficiency in sample collection in China. The existing sequenced specimens from mainland China with geographic coordinates were represent only four provinces, missing populations along the coastal regions in East China. One therefore cannot exclude the possibility that the Asian giant hornet found in Canada and USA may also be identical to V. mandarinia in Eastern China. We strongly recommend more extensive DNA barcoding data with geographic information and longer DNA barcode (e.g., the entire mitochondrial genome) so that critical questions on invasive species and environmental conservation can be addressed more accurately than what is possible with existing data.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

The use of video in education has become ubiquitous as technological developments have markedly improved the ability and facility to create, deliver and view videos. The concomitant pedagogical transformation has created a sense of urgency regarding how video may be used to advance learning. Initial reviews have suggested only limited potential for the use of video in higher education. More recently, a systematic review of studies on the effect of video use on learning in higher education, published in the prestigious Review of Educational Research, found, overall, effects to be positive. In the present paper we critique this study and provide some needed clarity to the state of research on learning via video in higher education. We reveal significant gaps in the study methodology and write-up and use a cognitive processing lens to critically assess and reanalyse study data. We found results of this study to be only applicable to learning requiring lower-level cognitive processing and conclude, consistent with prior research, learning benefits remain limited.

Аnalysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that holds potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods. The source code can be accessed at https://github.com/zajakin/sRNAflow under the GPL3 licence.

Interdisciplinary conferences play a vital role in advancing explainable Artificial Intelligence (AI) within increasingly intersecting healthcare and computational biology arenas. Challenges result-ing from algorithmic bias and the necessity for domain-specific Explainable AI (XAI) techniques underscore the increasing significance of transparent and interpretable AI systems used in patient care. Collaborative efforts between clinicians, data scientists, and various stakeholders are nec-essary to innovate solutions tailored to healthcare needs. Specialized conferences may foster these interdisciplinary interactions, providing platforms for knowledge exchange, networking, and collaborative partnerships. The legal, ethical, and societal dimensions of medical AI advocate for an integrative approach that aligns technological advancements with patient-centered care val-ues. The role of specialized conferences is therefore essential for shaping future directions in ex-plainable AI and computational biology that contribute to improved patient outcomes and healthcare innovations.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN- between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. In summary, our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

The study also found that older age was a protective factor in prospective studies. The consistency of results across different study designs and sensitivity analyses further supported the robustness of the findings. It is important to note that the existing literature on revictimization in women facing intimate partner violence is limited and exhibits significant heterogeneity in terms of methodology and conceptual frameworks.

Telomeres are specialized structures at the ends of linear chromosomes that protect them from degradation and fusion. Telomere replication is a complex process that involves both DNA polymerases and a specialized enzyme called telomerase. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA by using an internal RNA template. However, telomerase alone cannot fully replicate the telomeric DNA, and requires the cooperation of other factors, such as shelterin, CST, and DNA repair proteins. Moreover, telomere replication is tightly regulated by various mechanisms, such as cell cycle checkpoints, telomere length homeostasis, and telomere position effect. Dysregulation of telomere replication can lead to genomic instability, cellular senescence, and cancer. Therefore, understanding the molecular details of telomere replication is crucial for elucidating the role of telomeres in aging and disease.

Purpose: Understanding how older adults perceive and interpret emotional cues in speech prosody contributes to our knowledge of cognitive aging. This study provides a systematic review with meta-analysis to investigate the extent of the decline in affective prosody recognition (APR) among older adults in terms of overall and emotion-specific performance and explore potential moderators that may cause between-study heterogeneity. Method: Incorporated into the literature search were six electronic databases, with a specific emphasis on studies comparing the APR performance of older adults with that of younger adults. This comparison was focused on basic emotions. Meta-regression analyses were executed to pinpoint potential moderators related to demographic and methodological characteristics. Results: A total of 19 studies were included in the meta-analysis, involving 560 older adults with a mean age of 69.15 years. The findings indicated a substantial negative effect size (g = －1.21). Furthermore, the magnitude of aggregated effect sizes showed a distinct valence-related recognition pattern with positive prosody exhibiting smaller effect sizes. Years of education were found to moderate the overall performance effect estimate while age and gender significantly influenced the effect estimate of happiness. Conclusions: The results confirmed a significant decline in APR ability among older adults, but this decline was unbalanced across basic emotions. Educational level emerged as a significant factor influencing APR ability. Moreover, participants with a higher mean age exhibited notably poorer performance in recognizing happy prosody. These findings underscore the need to further investigate the neurobiological mechanisms for APR decline associated with aging.

Cells execute biological functions to support phenotypes such as growth, migration, and secretion. Complementarily, each function of a cell has resource costs that constrain phenotype. Resource allocation by a cell allows it to manage these costs and optimize their phenotypes. In fact, the management of resource constraints (e.g., nutrient availability, bioenergetic capacity, and macromolecular machinery production) shape activity and ultimately impact phenotype. In mammalian systems, quantification of resource allocation provides important insights into higher-order multicellular functions; it shapes intercellular interactions and relays environmental cues for tissues to coordinate individual cells to overcome resource constraints and achieve population-level behavior. Furthermore, these constraints, objectives, and phenotypes are context-dependent, with cells adapting their behavior according to their microenvironment, resulting in distinct steady-states. This review will highlight the biological insights gained from probing resource allocation in mammalian cells and tissues.

About half of the world's population is at risk of dengue infection. Epidemics of dengue fever caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines, and searching multiple databases including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years). Cochrane Collaboration criteria were used for quality assessment, with thematic data synthesis and meta-analysis. Among 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. CYD-TDV (Dengvaxia®), and Tekade (TAK-003) vaccines demonstrated strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines demonstrated promising efficacy and immune response, particularly against severe manifestations.

For a number of reasons, a curative treatment for most chronic diseases is still unrealized [2–4] and the incidence of many chronic diseases is rapidly increasing [5–9]. A new model is offered as a solution; that being the individualized diagnosis of homeostasis, leading to the correction of epimutations. Individuals with chronic diseases are increasingly being defined by their epigenetic signatures [10,11]. Modern innovations in toxicogenomic studies are also becoming more accurate in their ability to identify the unique epigenetic signature of each toxin [12–14]. Hormesis studies (over 5,000) [15] suggest a universal principle, that a small dose is always a stimulant [16–18].These three facts present an opportunity; a method to diagnose and reverse chronic disease tendencies. This new model requires a paradigm shift in our understanding of disease origins: that dysfunctions in homeostasis [19,20] are the primary and deepest level of chronic disease causation. This is the level where the diagnosis needs to be made and where the corrections need to take place [21].

The task of conveying scientific research to individuals with varying levels of knowledge and understanding can prove to be quite challenging for a research scientist. The difficulty is further compounded when the exchange of information must be conducted within a limited timeframe. Notwithstanding, the 'elevator pitch' is a valuable tool that enables researchers to navigate these potential obstacles. An effective elevator pitch not only facilitates the communication of a researcher's scientific findings but also highlights the individual's skills and the significance of their research. Moreover, a well-crafted elevator pitch is a critical career development tool, serving as a means of networking and paving the way for future communications, scientific collaborations, and funding opportunities. This article examines the value of a scientific elevator pitch and provides step-by-step guidelines for developing and constructing an impactful pitch. Furthermore, we provide resources and an example of a successful elevator pitch delivered by a Fellow from the NIH-funded Accelerating Career Transitions (ACT) program, a professional development program established and managed by the American Society for Cell Biology (ASCB).

Few-shot fine-grained image classification (FSFGIC) methods refer to machine learning methods which aim to classify images (e.g., bird species, flowers, and airplanes) belonging to subordinate object categories of the same entry-level category with only a few samples. It is worth to note that feature representation learning is used not only to represent training samples, but also to construct classifiers for performing various FSFGIC tasks. In this paper, starting from the definition of FSFGIC, a taxonomy of feature representation learning for FSFGIC is proposed. According to this taxonomy, we discuss key issues on FSFGIC (including data augmentation, local or/and global deep feature representation learning, class representation learning, and task specific feature representation learning). The existing popular datasets and evaluation standards are introduced. Furthermore, a novel classification performance evaluation mechanism is designed with a 0.95 confidence interval for judging whether the classification accuracy obtained by a certain specified method is good or bad. Moreover, current challenges and future trends of feature representation learning on FSFGIC are elaborated.

This paper presents a concise exploration of the synthetic biology currently to artificially 1 create life, juxtaposed against natural life’s emergence over Earth’s 4.5-billion-year history. It explores 2 the complexities of life’s origins, sustaining factors, and the consequences of synthetic life creation, 3 addressing key scientific milestones such as the Urey-Miller experiment and Jacques Monod’s pro- 4 posals. The narrative navigates through the roles of energy, Maxwell’s demons, bifurcations, and 5 genetic information in the emergence and evolution of complex biological systems. Despite significant 6 strides in genetic engineering, the challenge of creating life from scratch persists, necessitating a deep 7 understanding of diverse scientific disciplines. While synthetic biology holds promise for medicine 8 and biotechnology, the creation of truly autonomous synthetic life forms raises ethical concerns. The 9 paper also stresses the imperative for careful ethical evaluation of the societal and environmental 10 implications arising from these advancements.

Vector-borne disease (VBD) accounts for more than 17% of the global infectious disease burden, disproportionately affecting developing nations within tropical and subtropical areas. As Aedes aegypti mosquitoes are the principal vector for the transmission of many Public Health pathogens, our study examined their population dynamics within the seasonal context of tropical dry biomes in El Salvador as incidence of VBD in this region has increased in recent years. Species that rely on sexual reproduction must maintain a balanced sex ratio (1:1) to support their population dynamics, however, our phenological analysis of field-collected A. aegypti specimens revealed significant sex ratio variations during dry and wet seasons. Interestingly, we detected a seasonal shift that favored female mosquitoes during the dry season, highlighting the dynamic nature of mosquito populations in highly urbanized environments like El Salvador. By linking sex ratio distortions to anthropogenic factors, our study underscores the importance of comprehensively characterizing the urban ecology of vectors for the development of effective biocontrol strategies. As such, we advocate for more nuanced vector control approaches that consider ecological factors as well as the human behaviors that influence mosquito breeding habitats to effectively combat the rise of VBDs amid global climate changes.

Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phag-es). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being pro-teinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacte-ria are highly diverse and, for the majority, remain poorly understood. Their long, flexible and multi-domain encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined by X-ray crystallography.

Peanuts, owing to their composition of complex carbohydrates, plant protein, unsaturated fatty acids, and essential minerals (magnesium, iron, zinc, and potassium), hold significant potential as a vital component of the human diet. Additionally, their low water requirements and nitrogen fixation capacity make them an appropriate choice for cultivation in adverse environmental conditions. The germination ability of seeds profoundly impacts the final yield of the crop, assessing seed viability of extreme importance. Conventional methods for assessing seed viability and germination are both time-consuming and costly. To address these challenges, this study investigated Visible-Near Infrared Spectroscopy (Vis/NIR) in the wavelength range of 500-1030 nm as a non-destructive and rapid method to determine the viability of two varieties of peanut seeds: North Carolina-2 (NC-2) and Spanish flower (Florispan). The study subjected the seeds to three levels of artificial aging through heat treatment, involving incubation in a controlled environment at a relative humidity of 85% and a temperature of 50°C over 24-hour intervals. The absorbance spectra noise was significantly mitigated and corrected to a large extent by combining the Savitzky-Golay (SG) and Multiplicative Scatter Correction (MSC) methods. To identify the optimal wavelengths for seed viability assessment, a range of meta-heuristic algorithms were employed, including world competitive contest (WCC), league championship algorithm (LCA), Genetics (GA), Particle Swarm Optimization (PSO), Ant Colony Optimization (ACO), imperialist competitive algorithm (ICA), learning automata (LA), heat transfer optimization (HTS), forest optimization (FOA), discrete symbiotic organisms search (DSOS), and cuckoo optimization (CUK). These algorithms offer powerful optimization capabilities for effectively extracting relevant wavelength information from spectral data. Results revealed that all the algorithms demonstrated remarkable accuracy in predicting the allometric coefficient of seeds, achieving correlation coefficients exceeding 0.985 and errors below 0.0036, respectively. In terms of execution time, the ICA (2.3635 seconds) and LCA (44.9389 seconds) algorithms exhibited the most and least efficient performance, respectively. Conversely, the FOA and the LCA algorithms excelled in identifying the least number of optimal wavelengths (10 wavelengths). Subsequently, the seeds were classified based on the wavelengths selected by the FOA (10 wavelengths) and (DSOS (16 wavelengths) methods, in conjunction with logistic regression (LR), decision tree (DT), Multilayer Perceptron (MP), support vector machine (SVM), k-nearest neighbor (K-NN), and NaiveBayes (NB) classifiers. The DSOS-DT and FOA-MP methods demonstrated the highest accuracy, yielding values of 0.993 and 0.983, respectively. Conversely, the DSOS-LR and DSOS-KNN methods obtained the lowest accuracy, with values of 0.958 and 0.961, respectively. Overall, our findings demonstrated that Vis/NIR spectroscopy, coupled with variable selection algorithms and learning methods, presents a suitable and non-destructive approach for detecting seed viability.

Chronic Low Back Pain (CLBP), defined as pain persisting for at least 12 weeks, is a significant public health issue, with prevalence intensifying due to an ageing global population, amassing approximately 619 million cases in 2020 and projected to escalate to 843 million by 2050. Given the multitude of therapeutic modalities available for CLBP, this research sought to ascertain their respective efficacies in ameliorating pain and disability. We specifically scrutinized Multidisciplinary Biopsychosocial Rehabilitation (MBR) among adults enduring non-specific low back pain for over 12 weeks, excluding acute pain conditions and pre-study surgical interventions. MBR is an approach encompassing various modalities, including exercise, behavioral therapies, educational programs, and work conditioning aspects, necessitating a comprehensive Network Meta-Analysis (NMA) to fully grasp the extensive scope of its impact. The constructed network comprised diverse MBR modalities (behavioral, educational, and work conditioning) alongside exercise therapy (ET), minimal intervention, and usual care, serving as controls with pain and disability as outcomes. Through the analysis of 4,619 initially identified studies, 93 were included, encompassing a total of 8,059 participants. The NMA conducted substantiated that both ET and MBR modalities were notably effective in alleviating CLBP, with education-oriented MBR emerging as the most efficacious for pain mitigation and behavior-focused MBR for disability reduction. Nevertheless, the discerned differences amongst the treatments were minimal and uncertain, highlighting that no modality was definitively superior to the others. The analysis revealed low global and local inconsistency within the network, underscoring the reliability of the observed outcomes. Given the intricate nature of CLBP, embodying various facets, our findings advocate for a combined therapeutic approach to optimize treatment efficacy. Nonetheless, the presence of high study heterogeneity and potential biases necessitates cautious interpretation of the results, prompting future research.

Constraint-based metabolic modeling approaches have enhanced our knowledge and understanding of the metabolism of prokaryotes and eukaryotes. This approach highly depends on the reconstruction process of genome-scale metabolic models (Mmodels). M-models can guide effective experimental design and yield new insights into the function and control of biological systems. Despite the recent advances in the automated generation of draft metabolic network reconstructions, the manual curation of these networks remains a labor-intensive and challenging task. Thus, these ten quick tips for the manual curation process are essential for optimizing high-quality metabolic model generation in less time. This collection of tips describes in great detail the resources and methods to ensure successful reconstruction. Furthermore, it increases the scope of other protocols of metabolic modeling by including resources to reconstruct eukaryotic organisms. Thus, all tips are applicable to a wide range of eukaryotic organisms. We believe this manuscript will interest a broad audience and researchers from different disciplines, spanning from microbiology and systems biology to biotechnology.

The methods used to introduce CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing into fruit species, as well as the impacts of the application of this technology to activate and knock out of target genes in different fruit trees species including tree development, yield, fruit quality, and tolerance to biotic and abiotic stresses have been firstly described in this review. The application of this gene editing technology could allow the development of new generations of fruit crops with improved traits by targeting different genetic segments or even could facilitate the introduction of traits in elite cultivars without changing other traits. However, at this moment, the scarcity of efficient regeneration and transformation protocols in some species, the fact that many of those procedures are the genotype-dependent or the convenience of segregating the transgenic parts of the CRISPR system represent the main handicaps limiting the potential of genetic editing techniques for fruit trees. Finally, latest news on the legislation and regulations about the use of plants modified through CRISPR/Cas systems has been also discussed.

To systematically assess the effect size of different methods for patients with low back pain. PubMed, Cochrane Library, Web of Science, and Google Scholar. databases were searched in January 2023. This study has been developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The key search terms were: “Low back pain”, “Back pain”, “SF-36”, “VAS”, “VASP”, “Roland-Morris”, “Oswestry Disability Index”, and “conservative treatment”. The risk of bias was determined for each randomized trial using the Cochrane Risk of Bias Tool, and the methodological index for non-randomized studies (MINORS). The outcomes included SF-36 Mental, SF-36 Physical, VAS, Roland-Morris, and Oswestry Disability Index. R 4.0.5 software was used, and standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes, random model. Twenty-five studies were included. Depending on the outcome being measured, the effect size of different methods in treating low back pain varies from small to large as follows: SF-36 Mental (SMD = 0.39, p < 0.0001), SF-36 Physical (SMD = 0.55, p < 0.0001), VAS (SMD = -0.84, p < 0.0001), Roland-Morris (SMD = -0.45, p < 0.0001), and Oswestry Disability Index (SMD = -0.61, p < 0.0001). Our meta-analysis indicates the positive effects of applying different methods in the treatment of low back pain. PROSPERO registration number: CRD42022371282

Objectives: Accumulating evidence suggests that physical activity (PA) is an efficient intervention to maintain functional capabilities and mitigate physiological changes in the older population. However, an attempt has yet to be made to comprehensively investigate the published landscape on the subject. Methods: This study had two aims. The first aim was to perform a bibliometric analysis for two keywords, “aging” and “PA”, to analyze the research trend. Since ‘frailty’ is the most noticeable co-occurring keyword with the two keywords, the second aim was to investigate the effects of PA, particularly resistance training (RT), on frailty via meta-analysis to provide a summary of the current evidence base. Results: Bibliometric analysis revealed that the number of publications on this research topic has gradually increased, highlighting the importance of understanding the role of PA in aging. A meta-analysis found that RT had significant beneficial effects on physical frailty factors, including handgrip strength, lower limb strength, balance, gait speed, and stair climbing ability. Conclusion: These findings demonstrate that RT is an effective intervention for improving physical function in frail populations; thus it has important implications for the development of PA programs for older adults with frailty. Future research is warranted to explore the optimal dose, frequency, and duration of RT programs for older adults, as well as the potential benefits of combining RT with other forms of PA, such as aerobic or balance exercises.

A rapid synthesis of chiral sulfoxide-functionalized meta-terphenyl derivatives by a 2,5-[C4+C2] ring transformation reaction of pyrylium salts with in-situ generated enantio-merically pure .alpha.-sulfinylacetaldehydes is described. This synthetic method demonstrates for the first time the use of .alpha.-sulfinylacetaldehydes in a reaction sequence initiated by nu-cleophilic attack of pyrylium salts by .alpha.-sulfinylcarbanions to generate chiral aromatic systems. The method presented shows broad applicability starting with various methyl sulfoxides and a number of functionalized pyrylium salts, furnishing meta-terphenyls with complex substitution patterns from readily accessible starting compounds.

This article provides a general overview of the bio-inspired computing method called DNA-Based Computing (DBC), including its theory and applications. The main theme of DBC is the central dogma of molecular biology (once information of DNA/RNA has got into a protein, it can’t get out again), i.e., DNA to RNA (sequences of four types of nucleotides) and DNA/RNA to protein (sequence of twenty types of amino acids) are allowed, not the reverse ones. Thus, DBC transfers few-element information (DNA/RAN-like) to many-element information (protein-like), solving a given cognitive problem. DBC can take many forms; this article elucidates two main forms, denoted as DBC-1 and DBC-2. Using arbitrary numerical examples, it is shown that DBC-1 can solve the following cognitive problems: “similarity indexing between seemingly different but inherently identical objects” and “recognizing regions of an image separated by a complex boundary.” DBC-2 can solve the following cognitive problem: “pattern recognition when the relevant information is insufficient.” Smart manufacturing-based systems (digital twins and big data analytics) must solve the abovementioned problems to make the manufacturing enablers (machine tools and monitoring systems) more self-reliant and autonomous. Consequently, DBC can improve the cognitive problem-solving ability of smart manufacturing-relevant systems and, thereby, can enhance its biologicalization.

The possibility of abrupt transitions threatens to poise ecosystems into irreversibly degraded states. Recently, it has been proposed the use of engineered microbiomes in endangered ecosystems to prevent them to cross tipping points and avoid collapse. Potential targets for such interventions include some of the most prominent life-support systems in the biosphere: drylands and coral reefs. Since engineering can require the introduction of microorganisms not present in resident communities, how can we weight the potential outcomes? One way is to use general models of species interactions where the "synthetic" strain is incorporated into a standard multispecies model. Here we follow this approach by modelling a resource-consumer community where one of the species is a modified one that acts by preserving some key resource. We show how the indirect effect of damping the decay of shared resources results in biodiversity increase, and last but not less, the successful incorporation of the synthetic within the ecological network. Further extensions and implications for future restoration and terraformation strategies are discussed.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

Glioblastoma (GBM) is a representative malignant brain tumor characterized by a dismal prognosis, with survival rates of less than 2 years and high recurrence rates. Despite surgical resection and several alternative treatments, GBM remains a refractory disease due to its aggressive invasiveness and resistance to anticancer therapy. In this report, we explore the role of fibronectin type III domain containing 3B (FNDC3B) and its potential as a prognostic and therapeutic biomarker in GBM. GBM exhibited a significantly higher cancer-to-normal ratio compared to other organs, and patients with high FNDC3B expression had a poor prognosis (p < 0.01). In vitro studies revealed that silencing FNDC3B significantly reduced the expression of Survivin, an apoptosis inhibitor, and also reduced cell migration, invasion, extracellular matrix adhesion ability, and stem cell properties in GBM cells. Furthermore, we identified that FNDC3B regulates PTEN/PI3K/Akt signaling in GBM cells using MetaCore integrated pathway bioinformatics analysis and a proteome profiler phospho-kinase array with sequential western blot analysis. Collectively, our findings suggest FNDC3B as a potential biomarker for predicting GBM patient survival and for the development of treatment strategies for GBM.

CagY is the largest and most complex protein from Helicobacter pylori's type IV secretion system (T4SS) and may participate in the modulation of gastric tissue inflammation. A three-dimensional structure has been reported for only two segments of the protein. To build a more complete model, particularly the region that spans between the outer membrane (OM) and the inner membrane (IM), we employed different approaches, including homology modeling, ab initio, and deep learning techniques. For the long-middle repeat region (MRR), modeling was performed using deep learning techniques and Molecular Dynamics. The modeled segments were assembled into a chain of 1595 aa, and a 14-chain CagY multimer structure was composed by structural alignment. The final multimer structure correlated with previously published struc-tures and allows to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric epithelial cells. The model further confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain probably functions as a contractile region that may play an essential role in the modulatory activity of CagY on tissue inflammation.

Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from from northeastern India to eastern China. Genomics research can help provide much insight in understanding venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China, producing a highly continuous reference genome, with the length of 1.53 Gb and 41.18% repeat element content. From this 24,799 genes were identified, and 97.97% genes could be annotated. Nuclear genome single-copy genes phylogenetic tree including 6 species verified the validity of our genome assembly and annotation process. This research will contribute to further study on Protobothrops biology and the genetic basis of the snake venom.

Dengue virus infection is caused by a positive stranded RNA virus called Dengue virus, which is spread by arthropods. It is a fast growing acute febrile disease with potentially lethal consequences that is a global public health problem, mostly in tropical and subtropical countries. In Ethiopia dengue fever is understudied despite the fact that the virus is still being transmitted and viral infection rates are rising. This systematic review and meta-analysis was aimed to estimate the pooled prevalence of DENV infection in Ethiopia. A literature search was done on PubMed, Hinari and Google Scholar databases to identify studies published before July, 2023. Random effects and fixed effects models were used to estimate pooled prevalence of all the three markers. The Inconsistency Index was used to assess the level of heterogeneity. A total of 11 articles were included in this review. Majority of the studies had moderate risk of bias and no study had a high risk of bias. A meta-analysis estimated pooled IgG prevalence of 21% (95% CI: 19-23), a pooled prevalence of IgM 9% (95%CI: 4-13) and a pooled DENV-RNA prevalence of 48% (95% CI: 33-62). There is evidence of possible publication bias in IgG but not found in the rest of markers. The prevalence of DENV infection is high in Ethiopia. Healthcare providers, researchers and policymakers should give more attention to dengue fever.

The generation and maintenance of membrane potential is considered a fundamental element of the cellular machinery. They are based on elements of physics and chemistry. Mathematics is used to validate the equations and evaluate the results. However, this computation process can lead to a misunderstanding of the phenomena involved or to the masking of crucial events. It is even possible that the calculation no longer corresponds to the hypothesis considered. Membrane theory is no exception to these trivial considerations, which are essential for normal theory validation.

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, a carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses. RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

The dynamics of hydrological lateral nutrient fluxes contribute to our understanding of ecological functions related to energy, materials, and organism flows across various spatiotemporal scales. To explore the connectivity between multiple spatial flow processes, we conducted a one-year field measurement to assess lateral hydrologic carbon (C) and nitrogen (N) fluxes over the continental shelf in the Yangtze estuary. We observed a significant correlation between the differences in remote sensing-based estimates of gross primary production (GPP) (∆GPPMODIS) and the differences in eddy covariance (EC) tower-based GPP (∆GPPEC) at both high-elevation and low-elevation sites. Over the course of a year, our predicted daily maximum tidal elevation (TE) closely matched the observed values in the creek, which facilitated the development of theoretical models to simulate biogeochemical cycling processes and aquatic ecosystem functions. Our findings indicate that the studied saltmarsh acts as a net exporter of dissolved total C (DTC) while serving as a net sink for dissolved total N (DTN). Furthermore, there is a significant correlation in the total dissolved stoichiometry of the C/N ratio between imports and exports. These findings highlight the importance of integrating ecological stoichiometric principles to gain a deeper understanding of the complex relationships between physical, chemical, and biological processes, particularly within the context of the meta-ecosystem framework. Additionally, when considering reciprocal hydrological lateral C and N flows, single ecosystem can function both as sources and sinks within the meta-ecosystem framework.

Objective The aim of this study was to explore the prognosis and influencing factors of recurrent ependymoma in children. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched to collect studies on survival outcomes and influencing factors of recurrent ependymoma in children. The search time frame was from the establishment of the database to September 2023. Two evaluators independently screened the literature, extracted data, and evaluated the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. Results A total of 11 studies involving 1120 patients were included. The integrated results of mOS from the 11 studies showed significant heterogeneity (I2 = 92%). Therefore, a random-effects model was used for merging, and the results showed statistically significant differences (P < 0.00001). In all the studies, the pooled estimate of median OS from the time of recurrence was 15.54 months (95% CI 8.80-27.45; P < 0.00001), and the combined median progression-free survival (PFS) from the time of first recurrence was 6.7 months (95% CI 5.59-7.64; P < 0.0001). The median OS for patients who underwent surgery at the time of recurrence was 20.7 months (95% CI 12.40–34.72; P < 0.00001), while the mOS for patients who received radiation therapy was 29.5 months (95% CI 18.97–46.00; P < 0.0001), and for patients who received chemotherapy mOS was 18.0 months (95% CI 8.62–37.75; P < 0.00001). The mOS for patients under 3 years old at the time of recurrence was 20.1 months (95% CI 1.98-204.50; P < 0.00001), while for patients over 3 years old at the time of recurrence mOS was 16.6 months (95% CI 9.40-29.35; P < 0.00001). Conclusion The results of the study show poor prognosis for children with recurrent ependymoma, and there are significant differences in these results. The influencing factors include patient age, tumor recurrence location, and treatment methods. These findings can further guide clinical research on new treatment methods and strategies to improve the prognosis of this population.

Membrane potential generation and maintenance are fundamental parts of membrane theory. However, since its inception, theories and assumptions have remained simple, whereas the amount of knowledge available has only grown. Unfortunately, this simplification and reductionism lead to its loss of validity on both microscopic and macroscopic scales. This article shows that assumptions made outside the context of factual reality lead to contradictions that cannot be compared with science. Membrane theory must be thoroughly revised, taking into account all forgotten and unanswered assumptions and questions to conform to facts and science to maintain credibility.

ABSTRACTBackground: Crohn's disease (CD) is a chronic inflammatory bowel disorder with limited treatment options. Mitochondrial dysfunction has been implicated in CD pathogenesis, and mitochondrial-based interventions have emerged as a potential therapeutic avenue. This systematic review aimed to assess the efficacy of mitochondrial-based interventions in the management of CD.Methods: A systematic search of multiple databases was conducted to identify relevant studies in accordance with the PRISMA protocol. Inclusion criteria encompassed studies investigating mitochondrial-targeted interventions in CD patients. Methodological quality and risk of bias assessments were performed. Data synthesis involved both quantitative meta-analysis and qualitative narrative synthesis.Results: A total of 23 studies were included in this review, comprising randomized controlled trials, observational studies, and case reports. Mitochondrial-based interventions encompassed nutraceuticals, probiotics, exercise, and dietary modifications. However, the overall quality of evidence was moderate, primarily due to methodological limitations in some studies.Conclusion: This systematic review suggests that mitochondrial-based interventions hold promise as adjunctive therapies for CD management. They appear to contribute to clinical remission and amelioration of disease activity. Nevertheless, the moderate quality of evidence underscores the need for further well-designed clinical trials to substantiate these findings and delineate optimal intervention strategies.

Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in the last years, it was observed a huge increase in the number of MPs solved by cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB). However, sample preparation remains a significant challenge in the field. Here, we evaluated in the MPs solved by cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å the most critical parameters for sample preparation: i) the surfactant used for protein extraction from the membrane, ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, iii) the vitrification method employed, and iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs, but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.

Polycystic ovary syndrome (PCOS) is a prevalent condition characterized by manifestations that can influence self-image and potentially result in psychological distress; however, data from literature on sexual function (SF) in PCOS women are contradictory. We aimed to evaluate sexual dysfunction (SD) in PCOS women by carrying out a systematic review and meta-analysis, using the gold-standard assessment tool SD-diagnosis (Female Sexual Function Index:FSFI). Seven databases were analyzed until August-2023; study quality was assessed by risk of bias and Newcastle Ottawa Scale. Our analysis encompassed 25 case-control studies (9933 women). PCOS group presented significantly lower scores in arousal (MD= -0.36 CI95%-0.60;-0.11), lubrication (MD= -0.52 CI95%-0.75;-0.28), orgasm (MD= -0.39 CI95%-0.57;-0.20), satisfaction (MD= -0.32 CI95%-0.50;-0.14) and pain subdomains (MD= -0.46 CI95%-0.75;-0.16), as in overall FSFI score (MD= -2.27 CI95%-3.23;-1.31). Overweight/obese (OW/O) patients exhibited significantly higher overall FSFI than OW/O controls (MD=1.98 CI95%0.68;3.27), particularly in lubrication (MD= -0.34), orgasm (MD= -0.26) and satisfaction (MD= -0.25) subdomains. These findings offer insights regarding SD in PCOS women and emphasize the need to incorporate SF assessment into multidisciplinary care. By this way, PCOS can be also considered a gateway diagnosis to other long-term consequences. Further research should focus on controlling variables, as ethnicity, culture, religion and economic disparities.

This study investigates the impact of temperature-induced quantum proton tunneling probability on DNA amplification during polymerase chain reactions (PCR). Using a simulation model based on a Gaussian wavefunction and finite-difference time-domain method, quantum tunneling of protons across square potential barriers is examined. The results unveil consistent probability distributions for quantum tunneling across various PCR temperatures, with distinct oscillation patterns emerging post-barrier crossing. Acknowledging limitations in initial conditions due to temperature-dependent proton energy, the study highlights the need for refined models and experimental validation. These findings accentuate the potential interplay between quantum mechanics and biological systems, prompting further research to understand quantum tunnelling’s comprehensive effect on genetic variations and molecular processes.

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

To determine the impacts of metabolizable energy levels on the performance indices of geese and to forecast the ideal range of dietary metabolizable energy levels, this study was carried out. Literature on the effects of dietary metabolized energy level on the performance of geese was searched from CNKI, Wanfang, VIP, PubMed, Web of Science, and ScienceDirect databases from January 1, 2000, to December 31, 2022. A dose-response meta-analysis was performed by STATA (14.0), data were calculated by the robust error meta-regression model (REMR), and nonlinear dose-effect curves were plotted by the restricted cubic spline method (RCS). 29 papers were chosen from the 1,475 literatures that fit the criteria and were included in the dose-response meta-analysis. There were 6,079 geese included in the sample. The following production performance indices included average daily gain (ADG), average daily feed intake (ADFI), feed-to-gain ratio (F/G), dressed percentage, percentage of half-eviscerated yield, percentage of eviscerated yield, percentage of breast muscle, percentage of leg muscle and percentage of abdominal fat. The Egger test assessed publication bias, while sensitivity analysis was used to examine the heterogeneity. The verified results are consistent and reliable. The results indicated that for each group, the optimal dietary metabolizable energy level was about 13 to 13.5MJ/kg for medium-sized geese aged 0 to 4 weeks, 12 to 13MJ/kg for medium-sized geese aged above 5 weeks, 12.5 to 13MJ/kg for small-sized geese aged 0 to 4 weeks, and 13 to 13.5MJ/kg for mall-sized geese over 5 weeks of age. Future research should be conducted on related diets of large-sized geese, small-sized geese, and higher metabolizable energy levels.

Background: Gestational diabetes is a common complication during pregnancy that can lead to numerous adverse outcomes. Some studies suggest that probiotics may be used to treat gestational diabetes, however, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the effect of probiotics on blood glucose and pregnancy outcomes in women with gestational diabetes. Methods: A systematic search of PubMed, Embase, and Cochrane databases was performed (start date to August 22, 2023). Primary outcomes included fasting blood sugar (FBS), fasting serum insulin (FSI), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). Secondary outcomes included pregnancy and neonatal outcomes. Results: 15 articles (n = 1006 women) met the inclusion criteria and were included in the analysis. Compared to a placebo, probiotics can decrease FBS (MD -2.58, 95% CI -4.38 to -0.79, p &lt; 0.01), FSI (MD -2.29, 95% CI -3.40 to -1.18, p &lt; 0.01), HOMA-IR (MD -0.56, 95% CI -0.81 to -0.32, p &lt; 0.01), birthweight (MD -101.20, 95% CI -184.62 to -17.77, p = 0.02), neonatal intensive care unit (NICU) (RR 0.60, 95% CI 0.40 to 0.89, p = 0.01), and hyperbilirubinemia (RR 0.31, 95% CI 0.16 to 0.61, p &lt; 0.01), alongside higher QUICKI (MD 0.01, 95% CI 0.00 to 0.01, p &lt; 0.01). However, no other significant results were obtained. Conclusion: Probiotics may improve blood glucose indicators and reduce neonatal hyperbilirubinemia, NICU admissions, and birth weight in women with GDM.

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regula-tion of the microtubule cytoskeleton and may thus represent valuable molecular markers contrib-uting to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B, KIFC1, AURKB, KIF2C, GTSE1, KIF15, KIF11, RACGAP1, STMN1) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B) are overexpressed by more than 10-fold in tumor samples and four of them (KIF11, AURKB, TPX2 and KIFC1) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (MAST4, MAPT and MTUS1) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Together our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer.

Due to the variation of the body coloration and the similarity of the related species, there are still some unresolved problems and debates in the taxonomic study of the genus Sycanus in China. We conducted the inter-specific phylogenetic analyses and the species delimitation for Sycanus in China based on DNA barcoding dataset of the mitochondrial cytochrome c oxidase subunit I gene of 81 samples and partial 28S rDNA sequences of 34 samples. The result showed that all the samples were divided into twelve species by integrating the results of DNA barcoding and morphological comparison. In the present paper, the genus Sycanus in China was reviewed systematically, all species were described or re-described, keyed, illustrated and photographed, among them, Sycanus taiwanensis Zhao & Cai sp. nov., Sycanus flavicorius Li & Cai sp. nov. and Sycanus hainanensis Wang & Cai sp. nov. were described as new to science. The biological informations of Sycanus falleni Stål, 1863 and Sycanus croceus Hsiao, 1979 were briefly recorded.

With an ever increasing amount of research data available, it becomes constantly more important to possess data literacy skills to benefit from this valuable resource. An integrative course was developed to teach students the fundamentals of data literacy through an engaging genome sequencing project. Each cohort of students performed planning of the experiment, DNA extraction, nanopore sequencing, genome sequence assembly, prediction of genes in the assembled sequence, and assignment of functional annotation terms to predicted genes. Students learned how to communicate science through writing a protocol in the form of a scientific paper, providing comments during a peer-review process, and presenting their findings as part of an international symposium. Many students enjoyed the opportunity to own a project and to work towards a meaningful objective.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

Aims: The aims of this meta-analysis were to assess: the prevalence of Post-Acute COVID-19 sequalae in HIV positive patients; average time of diagnosis; and meta-regress for possible moderators of PACS.Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database to get the best relevant results. These included Medline indexed journals; PubMed Central; NCBI Bookshelf and publishers' Web sites in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “long COVID-19 or post-acute COVID-19 syndrome/sequalae”, “persons living with HIV or HIV. The criteria for inclusion were published clinical articles reporting HIV in association with long COVID-19, further, the average time to an event of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Egger's tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The review/trial was PROSPERO registered (CRD42022328509).Results: A total of 43 studies reported post-acute COVID-19 syndrome. Of those, five reported post-acute COVID-19 sequalae in PLHIV. Prevalence of post-acute COVID-19 sequalae was 43.1% (95% CI 20.5% to 68.9%) in persons living with HIV (PLWH). The average time to PACS diagnosis was 4 months at 64% [0.64 (95% CI 0.230, 0.913) (P < 0.0000), I²= 93%] and at one year to PACS diagnosis was at 70 %, however with non-significant correlation (P > 0.05). On comorbidities, asthenia was associated with PACS at 17.6 % [0.176 (95% CI 0.067, 0.385) (P = 0.008), I²= 86%] while fatigue at 82%, however not related with PACS event incidence (P < 0.05). Americas, Asian and European regions showed PACS events rates of 82%, 43% and 19 % respectively (P<0.05) relative to HIV infection. Conclusion: PACS prevalence in PLWH was 43% occurring at an average time of 4 months at 64% and 70 % at 12 months however non-significant with PACS. Asthenia was significantly associated with PACS at 17.6 % while fatigue at 82%, however not related with PACS event incidence. Americas recorded the highest PACS event rates in PLWH.

In response to the issue of vehicle escape guidance, this manuscript proposes a unified intelligent control strategy synthesizing optimal guidance and Meta Deep Reinforcement Learning (DRL). Optimal control with minor energy consumption is introduced to meet terminal latitude, longitude and altitude. Maneuvering escape is realized by adding longitudinal and lateral direction maneuver overloads. Maneuver command decision model is calculated based on Soft-Actor-Critic (SAC) networks. Meta learning is introduced to enhance autonomous escape capability, which improves generalization performance to time-varying scenarios not encountered in the training process. In order to obtain training samples at a faster speed, this manuscript uses the prediction method to solve reward values, which avoiding a large number of numerical integration. The simulation results manifest that the proposed intelligent strategy can achieve high precise guidance and effective escape.

The Oriental ratsnake Ptyas mucosa is a common non-venomous snake of the colubrid family, with a wide geographic range spanning much of South and Southeast Asia. P. mucosa is widely cultivated dut to it used in traditional medicine, scientific research, and handicrafts. Therefore, genome resources could play an important role in the efficacy of traditional medicine and the analysis of the living environment of the species. We collected a snake sample in Hezhou, Guangxi, China, which was identified as P. mucosa by morphological identification. Here we present a highly continuous P. mucosa genome with a genome size of 1.74Gb. The scaffold N50 length is 9.57Mb and the maximal length of scaffold is 78.3Mb, the P. mucosa genome has a CG content of 37.9% and the integrity of the gene reached 86.6%.Assembled using long-reads, the total length of the repeat sequence in the genome reached 735 Mb, and its repeat content was as high as 42.19%. A total of 24,869 functional genes were annotated. This study will assist in the understanding of the P. mucosa, and also provide a basis for medicinal research.

Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

This paper discusses complexity theory, that is, the many theories that have been proposed for emergence of complexity from the underlying physics. Our aim is to identify which aspects have turned out to be the more fundamental ones as regards the emergence of biology, engineering, and digital computing, as opposed to those that are in fact more peripheral in these contexts. In the cases we consider, complexity arises via adaptive modular hierarchical structures that are open systems involving broken symmetries. Each emergent level is causally effective because of the meshing together of upwards and downwards causation that takes place consistently with the underlying physics. Various physical constraints limit the outcomes that can be achieved. The underlying issue concerns the origin of consciousness and agency given the basis of life in physics, which is structured starting from symmetries and variational principles with no trace of agency. A possible solution is to admit that consciousness is an irreducible emergent property of matter.

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about one million cases and 784 000 deaths worldwide in 2018). CG is lately diagnosed and guarantees a poor prognosis for GC (the 5-year survival rate is less than 20%, but in early detection can reach 90%). This study evaluated the transcriptional profile in tumor gastric samples to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data was collected at Gene Expression Omnibus (GEO) bank to obtain 3 dataset matrices that analyze gastric tumor tissue versus normal gastric tissue, performed microarray using GPL570 platform, and from different sources. The genes found in silico analysis were confirmed in several lines of GC cells by RT-qPCR. The protein data bank was used to find the correspondent proteins. Then a structural-based virtual screening was done to find molecules, and docking analysis was done using the DockThor server. Our results of transcriptomic analysis, together with RT-qPCR, confirm the high expression of the genes AJUBA, FBXL13, CCDC69, CD80 and NOLC1 in GC lines. Based on that, the correspondent proteins were used in SBVS analysis. Five molecules, one each target, MCULE-2386589557-0-6, MCULE-7343047040-0-1, MCULE-5230409338-0-3, MCULE-9178344200-0-1 and MCULE -5881513100-0-29. All molecules have favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS, and molecular docking analysis provided a suitable approach to find genes involved in GC and work the correspondent protein to strive for new molecules with anticancer properties.

Diminished ovarian reserve can be regarded as a sentinel indicator to foreshadow severe follicular loss and, ultimately, systemic aging. The negative slope of human ovulatory fidelity begins with a robust follicular endowment which gradually declines over time. In contrast, the youthful ovarian phenotype requires the coordinated work of endothelial, granulosa, immune, perivascular, stromal and possibly germline stem cells. Such a diverse tissue matrix can, in general, be influenced by platelet (PLT)-derived factors but this has not yet been specifically confirmed in the ovary after platelet-rich plasma (PRP). How could a comparable response be validated? Here a prospective, experimental study is proposed whereby eligible patients already undergoing scheduled laparoscopy provide ovarian tissue via biopsy submitted for co-culture with autologous Ca⁺² activated PRP. Recognizing the interlocking, central roles of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α), incubated samples would be assessed for these in vitro before vs. after PRP exposure, in addition to stereomicroscopy. A mathematical model is available to track NF-κB oscillations and estimate gene expression, cell development, growth, apoptosis, and key immune and inflammatory actions. Since NF-κB and TNF-α are discharged in activated PLT releasate (or react to its cargo proteins) this audit permits extraction of response markers observed post-stimulus, thus linking discrete signals to transcriptional output, cellular fitness, and ovarian cytoarchitecture. From this, a hypothesis could emerge where intraovarian PRP is found to make no direct impact on follicles, although modified ovarian field function and curtailed local entropy incidentally favor optimized oocyte competence as a secondary effect.

The minimum dominating tree (MDT) problem consists of finding a minimum weight sub-graph from an undirected graph, such that each vertex not in this sub-graph is adjacent to at least one of the vertices in it, and the sub-graph is connected without any ring structures. This paper presents a Dual Neighborhoods Search (DNS) algorithm for solving the MDT problem, which integrates several distinguishing features, such as two neighborhoods collaboratively working for optimizing the objective function, a fast neighborhood evaluation method to boost the searching effectiveness, and several diversification techniques to help the searching process jump out of the local optimum trap thus obtaining better solutions. DNS improves the previous best-known results for 4 public benchmark instances while providing competitive results for the remaining ones. Several ingredients of DNS are investigated to demonstrate the importance of the proposed ideas and techniques.

Reinforcement Learning (RL) has demonstrated considerable potential in solving challenges across various domains, notably in autonomous driving. Nevertheless, implementing RL in autonomous driving comes with its own set of difficulties, such as the overestimation phenomenon, extensive learning time, and sparse reward problems. Although solutions like Hindsight Experience Replay (HER) have been proposed to alleviate these issues, the direct utilization of RL in autonomous vehicles remains constrained due to the intricate fusion of information and the possibility of system failures during the learning process. In this paper, we present a novel RL-based autonomous driving system technology that combines Obstacle Dependent Gaussian (ODG) RL, Soft Actor-Critic (SAC), and meta-learning algorithms. Our approach addresses key issues in RL, including the overestimation phenomenon and sparse reward problems, by incorporating prior knowledge derived from the ODG algorithm. We evaluated our proposed algorithm on official F1 circuits, using high-fidelity racing simulations with complex dynamics. The results demonstrate exceptional performance, with our method achieving up to 89% faster learning speed compared to existing algorithms in these environments.

The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

This study aimed to evaluate the diagnostic roles of various immunohistochemical markers in urothelial carcinoma in situ (uCIS) through a meta-analysis and review of diagnostic test accuracy. Immunohistochemical markers CK20, CD44, AMACR, and p53 were evaluated in the present study. We analyzed the expression rates of immunohistochemical markers and compared their diagnostic accuracies. The estimated expression rates were 0.803 (95% confidence interval [CI]: 0.726–0.862), 0.142 (95% CI: 0.033–0.449), 0.824 (95% CI: 0.720–0.895), and 0.600 (95% CI: 0.510–0.683) for CK20, CD44, AMACR, and p53, respectively. In the comparison between uCIS and reactive/normal urothelium, the expression of CK20, AMACR, and p53 in uCIS was significantly higher than in reactive/normal urothelium. CD44 showed significantly lower expression in uCIS than in the reactive/normal urothelium. Among the markers, AMACR had the highest sensitivity, specificity, and diagnostic odds ratio. The AUC on SROC was the highest for CK20. In conclusion, immunohistochemical markers, such as CK20, CD44, AMACR, and p53, can be useful in differentiating uCIS from reactive/normal urothelium.

Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.

Living beings are composite thermodynamic systems in non-equilibrium conditions. Within this context, there are a number of thermodynamic potential differences (forces) between them and the surroundings, as well as internally. These forces lead to flows, which, ultimately, are essential to life itself. Living beings are under the pressures of natural selection, thus are biological flows as well. At the same time, the maintenance of homeostatic conditions, the tenet of physiology, demands regulation of these flows by control of variables. However, due to the very nature of these systems, regulation of flows and control of variables become entangled in closed loops. Therefore, the search for adaptation in flows takes a different path than the search for adaptation in morphological traits. Being at the roots of transfer processes, thermodynamic criteria turn out to be as natural physical candidates. Likewise, being at the roots of physiology, control turns out to be as a natural biological candidate in that path. Here we show how to combine entropy generation, with respect to a generalized process, and control of parameters (in such a generalized process) in order to create a criterium of optimal ways to regulate changes in generalized flows.

The idea that the Earth system self-regulates in a habitable state was proposed in the 1970s by James Lovelock, who conjectured that life plays a self-regulatory role on a planetary-level scale. A formal approach to such hypothesis was presented afterwards under a toy model known as the Daisyworld. The model showed how such life-geosphere homeostasis was an emergent property of the system, where two species with different properties adjusted their populations to the changing external environment. So far, this ideal world exists only as a mathematical or computational construct, but it would be desirable to have a real, biological implementation of Lovelock's picture beyond our one Biosphere. Inspired in the exploration of synthetic ecosystems using genetic engineering and recent cell factory designs, here we propose such a living, microbial Daisyworld. This is based on a synthetic microbial ecosystem using pH as the external, abiotic control parameter. Several case studies are considering, including two, three and multiple species assemblies. Despite that oscillatory dynamics and chaos emerge in the latter case, it is shown that global regulation is also achieved in most cases as species diversity increases. The alternative implementations and their implications of this model in other synthetic biology scenarios, including ecosystem engineering, are outlined.

RNA polymerase III (RNAP III) holoenzyme activity and its products processing have been linked to several metabolic dysfunction in lower and in higher eukaryotes. Alterations in the activity of RNAP III driven synthesis of non-coding RNA, causes extensive changes in the glucose metabo-lism. Increased RNAP III activity in S.cerevisiae maf1Δ strain, manifests with lethality when grown on non-fermentable carbon source. This lethal phenotype is suppressed by reducing tRNA syn-thesis. The cause for the lack of growth neither the underlying molecular mechanism has not been deciphered and has been awaiting a scientific explanation for a decade. Our previous proteomics data suggested mitochondrial dysfunction of the strain. Using model mutant strains maf1Δ (with increased tRNA abundance) and rpc128-1007 (with reduced tRNA abundance) we collected data showing major changes in TCA cycle metabolism of the mutants that explain the phenotypic ob-servations. The present study, based on 13C flux data and analysis of TCA enzymes activities, identifies the flux constraints in the mitochondrial metabolic network. The lack of growth is associated with the de-crease in TCA cycle activity and downregulation of the flux towards glutamate, aspartate and phosphoenolopyruvate (PEP), the metabolic intermediate feeding gluconeogenic pathway. rpc128-1007, the strain that is unable to increase tRNA synthesis due to a mutation in C128 subunit, has increased activity of TCA cycle under non-fermentable conditions. To summarize, cells with non-optimal activity of RNAP III, undergo substantial adaptation to a new metabolic state, that make them vulnerable under specific growth conditions. Our results strongly suggest that balanced, non-coding RNA synthesis that is coupled to glucose signaling is a fundamental requirement to sustain cell’s intracellular homeostasis and flexibility under changing growth conditions. Presented results provide insight into the possible role of RNAP III in mito-chondrial metabolism of other cell types.

Background and Objectives: Angioembolization has emerged as an effective therapeutic approach for pelvic hemorrhages; however, its exact effect size remains uncertain. Therefore, we conducted this systematic review and meta-analysis to investigate the effect size of embolization-related pelvic complications after nonselective angioembolization compared to that after selective angioembolization in patients with pelvic injury accompanying hemorrhage. Materials and Methods Relevant articles were collected by searching the PubMed, EMBASE, and Cochrane databases until June 24, 2023. Meta-analyses were conducted using odds ratios (ORs) for binary outcomes. Quality assessment was conducted using the risk of bias tool in non-randomized studies of interventions. Results: Five studies examining 357 patients were included in the meta-analysis. Embolization-related pelvic complications did not significantly differ between patients with nonselective and selective angioembolization (OR 1.581, 95% confidence interval [CI] 0.592 to 4.225, I2 = 0%). However, in-hospital mortality was more likely to be higher in the nonselective group (OR 2.232, 95% CI 1.014 to 4.913, I2 = 0%) than in the selective group. In the quality assessment, two studies were found to have a moderate risk of bias, whereas two studies exhibited a serious risk of bias. Conclusions: Despite the favorable outcomes observed with nonselective angioembolization concerning embolization-related pelvic complications, determining the exact effect sizes was limited owing to the significant risk of bias and heterogeneity. Nonetheless, the low incidence of ischemic pelvic complications appears to be a promising result.

The aims of this paper are 1) to explore the type of industry of SMEs that can survive for more than 5 years in ASEAN, and 2) to analyze the success factors of SMEs in ASEAN to be able to survive for more than 5 years. This paper employs a qualitative method, with a literature review and meta-analysis. From 2007 to 2017, data was extracted from Google Scholar, Emerald Insight, Sage Pub, and EBSCO databases. There are 14 factors that influence the success of SMEs in the main sectors, 20 factors in the manufacturing sectors, and 14 factors in the service sectors, depending on the type of industry. For instance: eCommerce, technology, and social media, international oriented, good management system, government support, working condition /environment, skill and competency labour/owner, market penetration/selection, policy, organizational performance, and characteristics, networking with government /supplier / customer, networking with government /supplier /customer, planned /strategy (business /market /operational /organizational). The findings of this literature review reveal several important factors that are critical to the success of SMEs in competing with other industries and can be developed for a longer period.

As cancer remains resistant to several modes of treatment, novel therapeutics are still under active investigation to overcome treatment inefficacy in cancer. Given the high attrition rate of de novo drug discovery, drug screening, and drug repurposing have offered time- and cost-effective alternative strategies for the identification of potentially effective therapeutics. In contrast to large-scale drug screens, computational approaches for drug repurposing leverage the increasing amounts of biomedical data to predict candidate therapeutic agents prior to testing in biological models. Current studies in drug repurposing for cancer therapy prediction have increasingly focused on the prediction of combination therapies, as combination therapies have numerous advantages over monotherapies. These include increased effect from synergistic interactions, reduced toxicity from lowered drug doses, and a reduced risk of resistance due to multiple non-overlapping mechanisms of action. This review provides a summary of several classes of computational methods used for drug combination therapy prediction in cancer research, including networks, regression-based machine learning, classifier machine learning models, and deep learning approaches, with the goal of presenting current progress in the field, particularly to non-computational cancer biologists. We conclude by discussing the need for further advancements in technologies that incorporate disease mechanisms, drug characteristics, multi-omics data, and clinical considerations to generate effective patient-specific drug combinations, as holistic data integration will inevitably result in optimal targeted therapeutics for cancer.

This study aimed to evaluate the diagnostic and prognostic roles of GATA3 immunohistochemistry in urothelial carcinoma (UC) through a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704–0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727–0.818) and 0.614 (95% CI: 0.426–0.774), respectively. The GATA expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938–0.980) and 0.644 (95% CI: 0.581–0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883–0.967 vs. 0.753, 95% CI: 0.645–0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724–0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311–0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes and it is careful interpreting GATA3 expression.

As recently as 2002 programmed aging in mammals was widely thought to be theoretically impossible based on generally accepted concepts regarding the evolution process. However, as described in this article, genetics discoveries, results of selective breeding, and other direct evidence strongly support the idea that aging creates an evolutionary advantage and that therefore complex biological mechanisms evolved that control mammal aging. Like similar life-cycle programs that control reproduction, growth, and menopause the aging program can adjust the aging trait during an individual’s life to compensate for temporary or local changes in external conditions that alter the optimum lifespan for a particular species population. In addition, genetics discoveries strongly support the evolvability concept to the effect that sexually reproducing species can evolve design features that increase their ability to evolve, and that aging is one such feature.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1R and AT2R on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1R and 2.97% through 4.57% for AT2R. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.