Evolution medicine

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al...

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes ( SLITRK2 and FMR1 ) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice...

PURPOSE: Manual reconstruction (MR) of the vastus lateralis (VL) muscle cross sectional area (CSA) from sequential ultrasound (US) images is accessible, reproducible and has concurrent validity with magnetic resonance imaging. However, this technique requires numerous controls and procedures during image acquisition and reconstruction, making it laborious and time-consuming. The aim of this study was to determine the concurrent validity of VL CSA assessments between MR and computer vision-based automatic reconstruction (AR) of CSA from sequential images of the VL obtained by US...

BACKGROUND: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks...

BACKGROUND: Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables. METHODS: A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic...

Gated radionuclide angiography and myocardial perfusion imaging were developed in the United States and Europe in the 1970's and soon adopted in Canadian centers. Much of the early development of nuclear cardiology in Canada was in Toronto, Ontario and was quickly followed by new programs across the country. Clinical research in Canada contributed to the further development of nuclear cardiology and cardiac PET. The Canadian Nuclear Cardiology Society (CNCS) was formed in 1995 and became the Canadian Society of Cardiovascular Nuclear and CT Imaging (CNCT) in 2014...

The field of orthobiologics continues to advance at a rapid pace, and theoretically holds some promise to augment the biologic healing response in rotator cuff repair. However, the clinical evidence for use of substances such as platelet-rich plasma for rotator cuff repair remains inconclusive. Atelocollagen, as a synthetic collagen substitute, has been proposed as another alternative to provide more collagen substrate for healing, but outcomes data with this technique is lacking. As biologic augmentation options continue to push the envelope on indications, due diligence is required to carefully examine options for safety and efficacy...

The continued growth of data from biological screening and medicinal chemistry provides opportunities for data-driven experimental design and decision making in early-phase drug discovery. Approaches adopted from data science help to integrate internal and public domain data and extract knowledge from historical in-house data. Protein kinase (PK) drug discovery is an exemplary area where large amounts of data are accumulating, providing a valuable knowledge base for discovery projects. Herein, the evolution of PK drug discovery and development of small molecular PK inhibitors (PKIs) is reviewed, highlighting milestone developments in the field and discussing exemplary studies providing a basis for increasing data orientation of PK discovery efforts...

In view of the strong randomness and non-stationarity of complex system, this study suggests a hybrid multi-strategy prediction technique based on optimized hybrid denoising and deep learning. Firstly, the Sparrow search algorithm (SSA) is used to optimize Variational mode decomposition (VMD) which can decompose the original signal into several Intrinsic mode functions (IMF). Secondly, calculating the Pearson correlation coefficient (PCC) between each IMF component and the original signal, the subsequences with low correlation are eliminated, and the remaining subsequence are denoised by Wavelet soft threshold (WST) method to obtain effective signals...

Evolutionary maintenance of dioecy is a complex phenomenon and varies by species and underlying pathways. Also, different sexes may exhibit variable resource allocation (RA) patterns among the vegetative and reproductive functions. Such differences are reflected in the extent of sexual dimorphism. Though rarely pursued, investigation on plant species harbouring intermediate sexual phenotypes may reveal useful information on the strategy pertaining to sex-ratios and evolutionary pathways. We studied H. rhamnoides ssp...

The existence of large volumes of data has considerably alleviated concerns regarding the availability of sufficient data instances for machine learning experiments. Nevertheless, in certain contexts, addressing limited data availability may demand distinct strategies and efforts. Analyzing COVID-19 predictions at pandemic beginning emerged a question: how much data is needed to make reliable predictions? When does the volume of data provide a better understanding of the disease's evolution and, in turn, offer reliable forecasts? Given these questions, the objective of this study is to analyze learning curves obtained from predicting the incidence of COVID-19 in Brazilian States using ARIMA models with limited available data...

Digitally enabled higher education involves the in-depth use of new-generation digital technology, which has subverted and innovated the traditional teaching mode, driven the development of high-quality teaching and learning, and improved teachers' teaching experience, and increased efficiency. Based on ecosystem theory, this paper constructs a higher education ecosystem with the government, enterprises, and universities as the core participating subjects. It considers the participating subjects' effort level and the ecosystem's overall benefits under the three scenarios of noncooperative research and development (R&D), cost sharing, and cooperative R&D...

In the context of green and sustainable development and rural revitalization, analysis of the relationship between economic development and the evolution of carbon metabolism is of great significance for China's future transformation of development models. This study analyzed the spatial characteristics and spatiotemporal evolution pattern of the decoupling status between carbon metabolism and economic development of Laiwu during two periods from 2001 to 2018 at the village and town unit scales by using the Tapio decoupling model...

Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain...

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Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy...

BACKGROUND: Being a ubiquitous, highly contagious virus with a continuous mutation and a large number of evolutions worldwide, the infectious bronchitis virus (IBV) continues to wreak problems among Egyptian chickens and generate economic losses. The commonly applied IBV vaccination protocols in broilers include alternatives to classic and/or variant attenuated live virus vaccines. AIM: The current study targeted to assess the protective efficacy of concurrent and successive Ma5 and 4/91 vaccine strain regimens against the field variant II IBV strain (IBV-EGY-ZU/Ck-127/2021) in chickens...

OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last 3 years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorized or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022...

The diverse and unparalleled ecological landscape of Australasia has forged a unique environment for exotic animal practice, characterized by its rich biodiversity and stringent legislation. From its origins in the 1960s to its current status as a dedicated specialist niche, the exotic pet veterinary profession in Australasia has undergone a remarkable evolution. The profession faces hurdles in education and training, with limited dedicated institutes offering comprehensive programs, leading to a knowledge gap that employers must bridge...

This article explores the evolution, unique aspects, and challenges facing exotic animal practice in South Africa. This article delves into the slow emergence of dedicated exotic practices and the challenges faced by veterinarians in a vast and diverse landscape. The unique nature of the veterinary landscape is highlighted, emphasizing the impact of varied climates on species inhabiting different regions. The challenges are multifaceted, ranging from limited education infrastructure to dietary issues, unregulated feeds, and the complexities of herbal medicine use...