Search

KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S2MMAM). S2MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2MF-CN). S2MMAM facilitates the execution of the classification task by transferring the useful information captured in SMF-SN to the S2MF-CN to improve the model prediction accuracy. In SMF-SN, we propose a Triple Attention-guided Feature Aggregation module for obtaining segmentation features that incorporate high-level semantic abstract features and low-level semantic detail features. Segmentation features provide pre-guidance and key information expansion for S2MF-CN. S2MF-CN shares the encoder and decoder parameters of SMF-SN, which enables S2MF-CN to obtain rich classification features. S2MF-CN uses the proposed Intra and Inter Mutual Guidance Attention Fusion (I2MGAF) module to first guide segmentation and classification feature fusion to extract hidden multi-scale contextual information. I2MGAF then guides the multidimensional fusion of genetic data and CT image data to compensate for the lack of information in single modality data. S2MMAM achieved 83.27% AUC and 81.67% accuracy in predicting KRAS gene mutation status in NSCLC. This method uses medical image CT and genetic data to effectively improve the accuracy of predicting KRAS gene mutation status in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Mutations in PDE6A and PDE6B are known to cause autosomal recessive RP in humans, On the other hand, mutations in PDE6G are rare but can lead to severe early-onset RP. Case presentation: An 8-year-old Chinese boy was referred to our hospital for poor vision issues. Refraction with cycloplegia showed high hyperopia with astigmatism both eyes. Funduscopic examination revealed typical bone spicule-type pigment deposits in the periphery and midperiphery. The patient was given glasses and a whole exome sequencing containing mitochondrial genes was performed. The results of genetic testing showed that there was a heterozygous frameshift mutation and a segment deletion in the proband's PDE6G gene. Analysis of the parental genes showed that frameshift mutation was inherited from the proband's mother and segment deletion from his father. Conclusions: In this paper, we give a firsthand report that the complex heterozygous mutations of PDE6G gene can causes autosomal recessiveRP (arRP), which expands the understanding of the pathogenic genes of RP. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies. Highlights: Colorectal cancer (CRC) is one of the leading causes of death among patients. CRC has been characterized with changes at the genetic and epigenetic factors. The molecular factors can be used as diagnostic and prognostic factors in CRC. The cell death mechanisms demonstrate dysregulation in CRC. Autophagy has aberrant activation in CRC and exerts dual function. [ABSTRACT FROM AUTHOR]

Objective: In this paper we report how the United Kingdom's National Institute for Health and Care Excellence (NICE) search filters for treating and managing COVID-19 were validated for use in MEDLINE (Ovid) and Embase (Ovid). The objective was to achieve at least 98.9% for recall and 64% for precision. Methods: We did two tests of recall to finalize the draft search filters. We updated the data from an earlier peer-reviewed publication for the first recall test. For the second test, we collated a set of systematic reviews from Epistemonikos COVID-19 L.OVE and extracted their primary studies. We calculated precision by screening all the results retrieved by the draft search filters from a targeted sample covering 2020-23. We developed a gold-standard set to validate the search filter by using all articles available from the "Treatment and Management" subject filter in the Cochrane COVID-19 Study Register. Results: In the first recall test, both filters had 99.5% recall. In the second test, recall was 99.7% and 99.8% in MEDLINE and Embase respectively. Precision was 91.1% in a deduplicated sample of records. In validation, we found the MEDLINE filter had recall of 99.86% of the 14,625 records in the gold-standard set. The Embase filter had 99.88% recall of 19,371 records. Conclusion: We have validated search filters to identify records on treating and managing COVID-19. The filters may require subsequent updates, if new SARS-CoV-2 variants of concern or interest are discussed in future literature. [ABSTRACT FROM AUTHOR]

To date, the role of NODAL in normal and abnormal L-R asymmetry has been well established. In a recent paper, mutations of this gene have been reported in heterotaxy but also in transposition with D- or L-ventricular loop. The effects of NODAL and other laterality genes can be recognized separately in all three cardiac segments: for topology and septation of the atria, for ventricular looping, and for spiralization and alignment of the great arteries. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract malignancies, including cholangiocarcinoma (CCA) and gallbladder neoplasms, present intricate challenges in diagnosis and treatment. This comprehensive overview highlights the diversity of CCA subtypes, their genetic underpinnings, and the pivotal role of etiological factors. Despite diagnostic complexities, advancements in genomic sequencing reveal promising therapeutic targets, such as FGFR2 alterations and IDH1 mutations. Dr. James Cleary's insights underscore the potential of these targets in reshaping the treatment landscape. This paper provides insights into the conventional understanding of biliary tract malignancies and emphasizes the critical need for ongoing research to optimize outcomes in this challenging cancer subtype. By elucidating diverse FGFR2 alterations and the potential of IDH1 inhibition, the aim is to pave the way for targeted therapeutic interventions. As we delve deeper into understanding the intricate complexities of biliary tract malignancies, this research seeks to drive precision medicine forward, offering hope for improved treatment strategies and outcomes in the face of this formidable cancer. This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the latest developments in the emerging therapies for cholangiocarcinoma, with a focus on precision medicine, immunotherapy, and targeted therapies. We explore the potential of genomic profiling to tailor treatments to individual patients, as well as the promising results of immunotherapeutic agents in clinical trials. Furthermore, we examine the role of specific molecular targets and their inhibitors in slowing disease progression. The findings discussed in this paper offer hope for improved outcomes and prolonged survival in cholangiocarcinoma patients using more effective and personalized treatment strategies. Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies. [ABSTRACT FROM AUTHOR]

Genes, expressed as sequences of nucleotides, are susceptible to mutations, some of which can lead to cancer. Machine learning and deep learning methods have emerged as vital tools in identifying mutations associated with cancer. Thyroid cancer ranks as the 5th most prevalent cancer in the USA, with thousands diagnosed annually. This paper presents an ensemble learning model leveraging deep learning techniques such as Long Short-Term Memory (LSTM), Gated Recurrent Units (GRUs), and Bi-directional LSTM (Bi-LSTM) to detect thyroid cancer mutations early. The model is trained on a dataset sourced from asia.ensembl.org and IntOGen.org, consisting of 633 samples with 969 mutations across 41 genes, collected from individuals of various demographics. Feature extraction encompasses techniques including Hahn moments, central moments, raw moments, and various matrix-based methods. Evaluation employs three testing methods: self-consistency test (SCT), independent set test (IST), and 10-fold cross-validation test (10-FCVT). The proposed ensemble learning model demonstrates promising performance, achieving 96% accuracy in the independent set test (IST). Statistical measures such as training accuracy, testing accuracy, recall, sensitivity, specificity, Mathew's Correlation Coefficient (MCC), loss, training accuracy, F1 Score, and Cohen's kappa are utilized for comprehensive evaluation. [ABSTRACT FROM AUTHOR]

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer arises through the accumulation of somatic mutations in key biological pathways. This paper aims to develop a probabilistic approach to delineate the temporal order of mutations during cancer development based on mutation profile data from a cohort of patients. A unique feature of our method is that it incorporates intra-tumor heterogeneity (ITH) information, which refers to the heterogeneous cell populations within a tumor and characterizes the evolutionary history of the tumor. We showed that by integrating ITH, pathways, and functional annotation information, our method yielded high accuracy in inferring the temporal order of pathway mutations during carcinogenesis. The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this problem, we propose PATOPAI, a probabilistic approach to estimate the temporal order of mutations at the pathway level by incorporating ITH information as well as pathway and functional annotation information of mutations. PATOPAI uses a maximum likelihood approach to estimate the probability of pathway mutational events occurring in a specific sequence, wherein it focuses on the orders that are consistent with the phylogenetic structure of the tumors. Applications to whole exome sequencing data from The Cancer Genome Atlas (TCGA) illustrate our method's ability to recover the temporal order of pathway mutations in several cancer types. [ABSTRACT FROM AUTHOR]

The mutation rate is a pivotal biological characteristic, intricately governed by natural selection and historically garnering considerable attention. Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain, ushering in an unprecedented era of mutation rate research. This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates. It examines various types of mutations, explores the evolutionary dynamics and associated theories, and synthesizes both classical and contemporary hypotheses. Furthermore, this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies, mutational patterns, molecular mechanisms, and driving forces influencing variations in mutation rates across species and tissues. Finally, it proposes several potential research directions and pressing questions for future investigations. [ABSTRACT FROM AUTHOR]

Enamel formation is a highly complex and regulated process. However, specific genetic mutations can cause dysregulation, resulting in defects in the enamel quantity, structure and composition. Inherited disorders such as amelogenesis imperfecta exclusively affect the formation of enamel. Nevertheless, enamel defects can also present as a feature of many inherited systemic diseases and syndromes. The defects present in a spectrum of mild to severe enamel pitting, mottling and loss of email, causing psychological and functional concerns for patients. Early diagnosis and intensive caries prevention along with a multidisciplinary specialist input are required in most cases. In this paper, we provide a comprehensive discussion of inherited enamel defects. [ABSTRACT FROM AUTHOR]

In 1931, Hermann J. Muller's postdoctoral student, George D. Snell (Nobel Prize recipient––1980) initiated research to replicate with mice Muller's X-ray-induced mutational findings with fruit flies. Snell failed to induce the two types of mutations of interest, based on fly data (sex-linked lethals/recessive visible mutations) even though the study was well designed, used large doses of X-rays, and was published in Genetics. These findings were never cited by Muller, and the Snell paper (Snell, Genetics 20:545–567, 1935) did not cite the 1927 Muller paper (Muller, Science 66:84, 1927). This situation raises questions concerning how Snell wrote the paper (e.g., ignoring the significance of not providing support for Muller's findings in a mammal). The question may be raised whether professional pressures were placed upon Snell to downplay the significance of his findings, which could have negatively impacted the career of Muller and the LNT theory. While Muller would receive worldwide attention, and receive the Nobel Prize in 1946 "for the discovery that mutations can be induced by X-rays," Snell's negative mutation data were almost entirely ignored by his contemporary and subsequent radiation genetics/mutation researchers. This raises questions concerning how the apparent lack of interest in Snell's negative findings helped Muller professionally, including his success in using his fruit fly data to influence hereditary and cancer risk assessment and to obtain the Nobel Prize. [ABSTRACT FROM AUTHOR]

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. For lung adenocarcinoma, identifying specific gene mutations, fusions, and giving corresponding targeted drugs can greatly improve the survival time of the patients. Among them, anaplastic lymphoma kinase (ALK) fusion occurs in 3%-7% of non-small cell lung cancer (NSCLC). In clinical practice, a variety of detection methods can be used to determine the ALK fusion status, but false negative test results are possible. This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adenocarcinoma, judged the ALK fusion status by various detection methods. Among them, immunohistochemistry (IHC)(Ventana D5F3), RNA based next-generation sequencing (RNA-based NGS) confirmed positive echinoderm microtubule associated protein like 4 (EML4)-ALK fusion, while DNA-based NGS was negative. This paper analyzed the detection methods of ALK fusion, in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment. [ABSTRACT FROM AUTHOR]

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test ( α = 0.05 ). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis. [ABSTRACT FROM AUTHOR]

Mucosal melanoma (MM) is a rare and aggressive form of melanoma with a poorer prognosis compared to other subtypes. Recent large-scale next-generation sequencing studies, including our own research, have demonstrated that the molecular characteristics and potential oncogenic drivers of MM differ significantly from those of cutaneous melanoma. The emergence of selective CDK4/6 inhibitors, already approved for use in breast cancer and undergoing phase III clinical trials for other solid tumors, represents a promising development in the treatment of MM. Recent studies have shown that CDK4/6 inhibitors not only induce cell cycle arrest but also play a crucial role in facilitating the interaction between tumor cells and the host immune system. Moreover, our findings indicate that dysregulation of cell cycle progression due to cyclin‐dependent kinase 4 (CDK4) amplification is a significant genetic characteristic in a substantial portion of MM cases. Targeting CDK4 in specific MM patients shows promise for precision cancer therapy, utilizing molecularly characterized MM patient-derived xenograft (PDX) models and clinical trials. This paper provides an overview of existing literature on CDK4/6 dysregulation in MM, as well as preclinical and clinical investigations on CDK4/6 inhibitors and potential combination therapies for MM treatment. [ABSTRACT FROM AUTHOR]

Accurate models describing the relationship between genotype and phenotype are necessary in order to understand and predict how mutations to biological sequences affect the fitness and evolution of living organisms. The apparent abundance of epistasis (genetic interactions), both between and within genes, complicates this task and how to build mechanistic models that incorporate epistatic coefficients (genetic interaction terms) is an open question. The Walsh-Hadamard transform represents a rigorous computational framework for calculating and modeling epistatic interactions at the level of individual genotypic values (known as genetical, biological or physiological epistasis), and can therefore be used to address fundamental questions related to sequence-to-function encodings. However, one of its main limitations is that it can only accommodate two alleles (amino acid or nucleotide states) per sequence position. In this paper we provide an extension of the Walsh-Hadamard transform that allows the calculation and modeling of background-averaged epistasis (also known as ensemble epistasis) in genetic landscapes with an arbitrary number of states per position (20 for amino acids, 4 for nucleotides, etc.). We also provide a recursive formula for the inverse matrix and then derive formulae to directly extract any element of either matrix without having to rely on the computationally intensive task of constructing or inverting large matrices. Finally, we demonstrate the utility of our theory by using it to model epistasis within both simulated and empirical multiallelic fitness landscapes, revealing that both pairwise and higher-order genetic interactions are enriched between physically interacting positions. Author summary: An important question in genetics is how the effects of mutations combine to alter phenotypes. Genetic interactions (epistasis) describe non-additive effects of pairs of mutations, but can also involve higher-order (three- and four-way etc.) combinations. Quantifying higher-order interactions is experimentally very challenging requiring a large number of measurements. Techniques based on deep mutational scanning (DMS) represent valuable sources of data to study epistasis. However, the best way to extract the relevant pairwise and higher-order epistatic coefficients (genetic interaction terms) from this data for the task of phenotypic prediction remains an unresolved problem. The Walsh-Hadamard transform represents a rigorous computational framework for calculating and modeling epistatic interactions at the level of individual genotypic values. Critically, this formalism currently only allows for two alleles (amino acid or nucleotide states) per sequence position, hampering applications in more biologically realistic scenarios. Here we present an extension of the Walsh-Hadamard transform that overcomes this limitation and demonstrate the utility of our theory by using it to model epistasis within both simulated and empirical multiallelic genetic landscapes. [ABSTRACT FROM AUTHOR]

This paper focuses on the maximum speed at which biological evolution can occur. I derive inequalities that limit the rate of evolutionary processes driven by natural selection, mutations, or genetic drift. These rate limits link the variability in a population to evolutionary rates. In particular, high variances in the fitness of a population and of a quantitative trait allow for fast changes in the trait's average. In contrast, low variability makes a trait less susceptible to random changes due to genetic drift. The results in this article generalize Fisher's fundamental theorem of natural selection to dynamics that allow for mutations and genetic drift, via trade-off relations that constrain the evolutionary rates of arbitrary traits. The rate limits can be used to probe questions in various evolutionary biology and ecology settings. They apply, for instance, to trait dynamics within or across species or to the evolution of bacteria strains. They apply to any quantitative trait, e.g., from species' weights to the lengths of DNA strands. [ABSTRACT FROM AUTHOR]

Simple Summary: The 2021 WHO classification of central nervous system (CNS) tumors is challenging for neuroradiologists due to the central role of the molecular profile of tumors. We performed a scoping review of recent literature to assess the existing data on the power of novel data analysis tools to predict new tumor classes by imaging. We found room for performance improvement for subgroups with lower incidence (e.g., 1p/19q codeleted or IDH1/2 mutated gliomas) and patients with rare diagnoses (e.g., pediatric gliomas, midline gliomas). More data regarding functional MRI techniques need to be collected. Studies explicitly designed to assess the generalizability of AI-aided tools for predicting molecular tumor subgroups are lacking. The 2021 WHO classification of CNS tumors is a challenge for neuroradiologists due to the central role of the molecular profile of tumors. The potential of novel data analysis tools in neuroimaging must be harnessed to maintain its role in predicting tumor subgroups. We performed a scoping review to determine current evidence and research gaps. A comprehensive literature search was conducted regarding glioma subgroups according to the 2021 WHO classification and the use of MRI, radiomics, machine learning, and deep learning algorithms. Sixty-two original articles were included and analyzed by extracting data on the study design and results. Only 8% of the studies included pediatric patients. Low-grade gliomas and diffuse midline gliomas were represented in one-third of the research papers. Public datasets were utilized in 22% of the studies. Conventional imaging sequences prevailed; data on functional MRI (DWI, PWI, CEST, etc.) are underrepresented. Multiparametric MRI yielded the best prediction results. IDH mutation and 1p/19q codeletion status prediction remain in focus with limited data on other molecular subgroups. Reported AUC values range from 0.6 to 0.98. Studies designed to assess generalizability are scarce. Performance is worse for smaller subgroups (e.g., 1p/19q codeleted or IDH1/2 mutated gliomas). More high-quality study designs with diversity in the analyzed population and techniques are needed. [ABSTRACT FROM AUTHOR]

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease. [ABSTRACT FROM AUTHOR]

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD. [ABSTRACT FROM AUTHOR]

The emerging field of genomic medicine offers an opportunity for biology and anatomy teachers to bring the topics of DNA, genetics, molecular processes, and evolution together into one experience. Through the genomic medicine paradigm, students see the unbroken connection between small biological topics such as mutations and their potential connection to disease phenotypes. In this paper, we present as a main example cystic fibrosis, which is an often-studied genetic disease in general biology class, for examination through the genomic medicine lens. Concepts such as genes, the plasma membrane, variation, mutations, the nucleus, and chromosomes can be used in a narrative and visual approach to genetics through the genomic medicine standpoint to engage and connect students with next-generation genomics and with the fundamental unit of life—the cell. It is through the genomic medicine lens that the cell's context and relationship to the evolving world takes place. [ABSTRACT FROM AUTHOR]

In the early 1900s, mutation breeding to select varieties with desirable traits using spontaneous mutation was actively conducted around the world, including Japan. In rice, the number of fixed mutations per generation was estimated to be 1.38-2.25. Although this low mutation rate was a major problem for breeding in those days, in the modern era with the development of next-generation sequencing (NGS) technology, it was conversely considered to be an advantage for efficient gene identification. In this paper, we proposed an in silico approach using NGS to compare the whole genome sequence of a spontaneous mutant with that of a closely related strain with a nearly identical genome, to find polymorphisms that differ between them, and to identify the causal gene by predicting the functional variation of the gene caused by the polymorphism. Using this approach, we found four causal genes for the dwarf mutation, the round shape grain mutation and the awnless mutation. Three of these genes were the same as those previously reported, but one was a novel gene involved in awn formation. The novel gene was isolated from Bozu-Aikoku, a mutant of Aikoku with the awnless trait, in which nine polymorphisms were predicted to alter gene function by their whole-genome comparison. Based on the information on gene function and tissue-specific expression patterns of these candidate genes, Os03g0115700/LOC_Os03g02460, annotated as a shortchain dehydrogenase/reductase SDR family protein, is most likely to be involved in the awnless mutation. Indeed, complementation tests by transformation showed that it is involved in awn formation. Thus, this method is an effective way to accelerate genome breeding of various crop species by enabling the identification of useful genes that can be used for crop breeding with minimal effort for NGS analysis. [ABSTRACT FROM AUTHOR]

Viola suavis var. pannonica (Violaceae) from central Europe is described here as a new variety to science. It is most similar to the blue-flowered V. suavis var. suavis and the white-flowered V. suavis var. catalonica and V. suavis subsp. naqshii, but exhibits differences in several characters, such as petal colour, spur shape, fimbriae length on the stipules, bracteoles position on the peduncle and lamina sinus shape. Although the new taxon is often considered a colour mutation of V. suavis var. suavis, previous genetic analyses revealed that these white-flowered plants do not arise recurrently at different locations (having multiple origins), but rather form a monophyletic evolutionary lineage. To date, the occurrence of V. suavis var. pannonica has been reported in the Slovak Republic, the Czech Republic and western Ukraine. In this paper, we report its occurrence in Austria and Hungary. Notes on its etymology, distribution, ecology, origin and hybridization, as well as photographs of the new variety (including the holotype) are also provided. [ABSTRACT FROM AUTHOR]

In biological systems, impulses are often used to model mutations in gene expression. In order to describe the instantaneity of the impulse, this paper employs a hybrid‐index model of impulsive Boolean networks with state‐triggered impulses. Based on this model, the time‐domain output controllability is investigated. Using the quotient mapping method, the hybrid‐domain solutions of this model are mapped to the time‐domain solutions, mathematically. Then a necessary and sufficient condition for output controllability in the time domain is presented. Finally, an example is given to demonstrate the correctness and effectiveness of the obtained results. [ABSTRACT FROM AUTHOR]

Simple Summary: Oncolytic herpes simplex viruses (oHSVs) employ as natural entry receptors nectin1 or HVEM. In contrast, retargeted oHSVs (ReHVs) employ as an entry receptor a tumor-associated antigen that no longer interacts with nectin1/HVEM and, thus, spares normal cells. Prior to entry, both oHSVs and ReHVs attach to cells by interaction of gC and gB glycoproteins with heparan sulphates and chondroitin sulphates (glycosaminoglycans–GAGs). The systemic delivery of oncolytic viruses would be the ideal route for hard-to-reach or metastatic cancers that constitute unmet clinical needs. In an accompanying paper, we reported that the blood complement and the antiviral neutralizing antibodies represent the major blood factors that inactivate systemically administered ReHVs. Here, we asked whether ReHV adsorption to GAGs acts as a sink and subtracts the virus from circulation. We report that a genetic modification in gC, which reduced its interaction with GAGs, resulted in a longer half-life of circulating ReHV and a higher anticancer efficacy of systemically (but not intratumorally) administered ReHV. The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those of endothelial cells, blood cells, and off-tumor tissues. As a proof-of-principle approach, we deleted seven amino acids critical for interacting with GAGs from the glycoprotein C (gC) of R-337 ReHV. The modification in the resulting R-399 recombinant prolonged the half-life in the blood of systemically administered R-399 and enhanced its biodistribution to tumor-positive lungs and to the tumor-negative liver. Ultimately, it greatly increased the R-399 efficacy against metastatic-like lung tumors upon IV administration but not against subcutaneous tumors upon IT administration. These results provide evidence that the increased efficacy seen upon R-399 systemic administration correlated with the slower clearance from the circulation. To our knowledge, this is the first in vivo evidence that the partial impairment of the gC interaction with GAGs resulted in a prolonged half-life of circulating ReHV, an increase in the amount of ReHV taken up by tissues and tumors, and, ultimately, an enhanced anticancer efficacy of systemically administered ReHV. [ABSTRACT FROM AUTHOR]

MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor sterile alpha domain containing 9 (SAMD9) located on the arm of chromosome 7 (7q21.2). The syndrome is rare and is usually diagnosed in newborns and children with myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, hence the acronym MIRAGE. The aims of this paper are (1) to present fetal ultrasound features in a case where MIRAGE syndrome was diagnosed prenatally and (2) to review the existing literature records on prenatal manifestations of MIRAGE syndrome. In our case, the fetus had severe early fetal growth restriction (FGR) with normal Doppler studies, atypical genitalia, oligohydramnios, and hyperechogenic bowel at the routine mid-gestation anomaly scan. Amniocentesis excluded infections and numeric or structural chromosomal abnormalities while whole exome sequencing (WES) of the fetal genetic material identified the specific mutation. Targeted testing in parents was negative, suggesting the "de novo" mutation in the fetus. We could not identify other specific case reports in the literature on the prenatal diagnosis of MIRAGE syndrome. In cases reported in the literature where the diagnosis of MIRAGE syndrome was achieved postnatally, there are mentions related to the marked FGR on prenatal ultrasound. Severe early-onset FGR with no other apparent cause seems to be a central prenatal feature in these babies, and WES should be offered, especially if there are other structural abnormalities. Prenatal diagnosis of MIRAGE syndrome is possible, allowing for reproductive choices, improved counseling of parents, and better preparation of neonatal care. [ABSTRACT FROM AUTHOR]

Simple Summary: The cornerstone of successful treatment of hematologic diseases, including multiple myeloma (MM), is early diagnosis and establishing a prognosis for the patient. Therefore, it is necessary to identify sensitive and specific markers for this disease. Non-coding RNAs including miRNAs are increasingly being recognized as potential diagnostic, predictive, and prognostic markers. These molecules are non-coding, single-stranded RNAs that regulate the expression of many target genes involved in key biological processes, such as cell proliferation, differentiation, and apoptosis. This paper aims to identify the role of non-coding RNAs including miRNAs as potential markers for diagnosis and prognosis in patients with MM. Multiple myeloma (MM) is the second most common hematologic malignancy in the world and accounts for 15% of primary hemocytopathies, with an ever-increasing number of new cases. It is asymptomatic in 30% of instances; hence, the determination of highly sensitive and specific markers is necessary to make a proper diagnosis. In the last 20 years, miRNAs, involved in regulating the expression of genes responsible for cell proliferation and differentiation, including tumor cells, have been identified as potential diagnostic and prognostic markers. The main aim of the following review was to outline the role of miRNAs in the diagnosis and prognosis of MM, considering their role in the pathogenesis of the disease and identifying their target genes and pathways. For this purpose, publications dating from 2013–2023 have been reviewed. Based on the available data, it is concluded that non-coding RNAs including miRNAs could be potential markers in MM. Furthermore, they may serve as therapeutic targets for certain drugs. [ABSTRACT FROM AUTHOR]

Introduction. ADCY5-related dyskinesia is a rare neurological disease caused by mutations in the gene encoding the adenylyl cyclase 5 (ADCY5) isoform, a protein that plays an important role in intracellular transmission. Variants in ADCY5 are associated with a spectrum of neurological disease encompassing dyskinesia, chorea, and dystonia. State of the-art. ADCY5 mutations result in clinically heterogeneous manifestations which comprise a range of core and less to highly variable symptoms. Due to the heterogeneous nature and difficulty in diagnosis of the disorder, available treatments are highly limited. Clinical implications. ADCY5-related dyskinesia was reported in 52 individuals in the literature over a five-year period (January 2017 to January 2022). We have listed all the symptoms and their frequency. The most common symptom reported in these patients was dystonia. Over 50% of patients developed dyskinesia and chorea. We report two cases of familial occurrence of symptomatic ADCY5-related dyskinesia. A 45-year-old patient presented with involuntary movements which had been occurring since childhood. The proband's neurological examination revealed dysarthria, involuntary myoclonic twitches, and choreic movements. The patient's 9-year-old son had developed involuntary movements, mainly chorea and dystonia. Future directions. This paper aims to summarise the recent literature on ADCY5-related neurological disorders and to present a new case of a Polish family with ADCY5 mutation. Genetic diagnostics are important in the context of possible future targeted treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma (CCA) manifests as a complex interplay of genetic and environmental factors, necessitating personalized approaches. This review covers the various causes, risk factors, and molecular aspects of CCA in oncology. It explores current diagnostic methods and treatments, such as targeted therapies and immunotherapy. Additionally, it addresses emerging strategies like microbiota modulation and the use of natural compounds. This review paper provides a comprehensive understanding of CCA, offering insights into current and evolving approaches for effective interventions in oncological care. Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a certain class of mutations in genomic sequences by studying the evolution of the entropy and relative entropy associated with the base frequencies of a given genomic sequence. Even if the method is, in principle, applicable to every sequence which varies randomly, the case of SARS-CoV-2 RNA genome is particularly interesting to analyze, due to the richness of the available sequence database containing more than a million sequences. Our model is able to track known features of the mutation dynamics like the Cytosine–Thymine bias, but also to reveal new features of the virus mutation dynamics. We show that these new findings can be studied using an approach that combines the mean field approximation of a Markov dynamics within a stochastic thermodynamics framework. [ABSTRACT FROM AUTHOR]

Background: Niemann-Pick Disease type C is a fatal autosomal recessive lipid storage disorder caused by NPC1 or NPC2 gene mutations and characterized by progressive, disabling neurological deterioration and hepatosplenomegaly. Herein, we identified a novel compound heterozygous mutations of the NPC1 gene in a Chinese pedigree. Case presentation: This paper describes an 11-year-old boy with aggravated walking instability and slurring of speech who presented as Niemann-Pick Disease type C. He had the maternally inherited c.3452 C > T (p. Ala1151Val) mutation and the paternally inherited c.3557G > A (p. Arg1186His) mutation using next-generation sequencing. The c.3452 C > T (p. Ala1151Val) mutation has not previously been reported. Conclusions: This study predicted that the c.3452 C > T (p. Ala1151Val) mutation is pathogenic. This data enriches the NPC1 gene variation spectrum and provides a basis for familial genetic counseling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: NR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Although ~ 46.7% of BBSOAS patients present with epilepsy, which is always drug-resistant and associated with higher rates of behavioral and cognitive problems, the treatment and outcomes of NR2F1-related epilepsy have rarely been described. Here, we present new cases of BBSOAS-related epilepsy and summarize all previously reported cases to explore the effective treatment for this type of epilepsy. Methods: We identified six new Chinese cases of BBSOAS with epilepsy. Five different de novo heterozygous NR2F1 mutations were identified in these cases, including two novel mutations c.365G > T, p.Cys122Phe and c.449G > T, p.Gly150Val. By combining the six cases and 14 previously reported cases, we analyzed the characteristics and treatment outcomes of NR2F1-related epilepsy. Results: Twelve of the 20 patients (60%) had infantile epileptic spasms, while the other patients had generalized tonic/tonic-clonic, focal, myoclonic, absence, or unclassified seizures. Several anti-seizure medications, steroids, and a ketogenic diet were administered in these cases. However, seizures were controlled in only 50% of previously reported cases, while all of the six new cases became seizure-free after perampanel as an add-on treatment. The average time from the addition of perampanel to seizure control was 7.33 ± 4.59 months (range, 1–12 months). The median time to seizure freedom was 14 months (1–32 months, > 19 months in 3 cases). The average dosage of perampanel needed for epilepsy control was 0.22 ± 0.17 mg/kg per day. Conclusions: In this paper, we comprehensively summarized the clinical characteristics, treatments and outcomes of NR2F1-related epilepsy for the first time. Perampanel exhibits dramatic efficacy for NR2F1-related epilepsy. This will help optimize the treatment of this type of epilepsy and provide clues for its pathogenic mechanisms. The two novel mutations expand the genotype spectrum of this disease. [ABSTRACT FROM AUTHOR]

The two cell-adhesion molecules, Neurexin-1 and Neuroligin-1, are essential for synapse function in neural networks. Interruptions to the function of these two proteins are associated with predestination for cognitive disorders, such as Autism spectrum disorder (ASD). In this paper, we study the effects of genetic missense mutations located on the cell interface between NRXN-1 and NLGN-1 on the development of neurodevelopmental disorders by identifying and determining the effects of mutations on bond strengths between NRXN-1 and NLGN-1 on the synaptic interface by building a computational platform. This was done by mapping all ASD-associated point mutations found in a web-based database on the computationally modeled structure of NRXN-1, then determining which mutations interact with NLGN-1. Then, the binding strength of the two proteins without the influence of the mutations was compared to the binding strength with the mutations so that the effects of the mutation were established. Based on our structural models and calculations of binding free energy, we found that these mutations can change the binding affinity of Neurexin-neuroligin interaction. Thus, we suggest that the changes in bond strength between Neurexin and Neuroligin at neural synapses can affect neural circuits, leading to autism-associated symptoms. [ABSTRACT FROM AUTHOR]

Background: Pre‐implantation genetic testing for monogenic disorders (PGT‐M) is an effective approach to reducing the incidence of birth defects by preventing the transmission of inherited diseases to offspring. However, there are still controversies regarding the detection methods and transplantation of embryos. This paper aims to evaluate the effectiveness of different detection technologies applied to PGT‐M through a retrospective analysis of clinical detection data. Methods: The carrier status of pathogenic mutations and chromosomal copy number variants (CNVs) in 892 embryos was characterized using next‐generation sequencing (NGS), single‐nucleotide polymorphism (SNP) array, and PCR‐based detection technologies. Clinical data from PGT‐M cases were retrospectively analyzed to assess the effectiveness of these detection methods in identifying genetic abnormalities in embryos. Results: A total of 829 embryos were analyzed, with 63 being unsuccessful. Our study revealed that the success rate of detecting deletional mutations using Gap‐PCR 84.9%, which is lower than that of SNP array (98.7%) and NGS (92.5%). However, no significant difference was observed when detecting point mutations using any of the methods. These findings suggest that, when detecting deletional mutations, SNP array and NGS are more suitable choices compared to Gap‐PCR. While SNP array may have a lower resolution and success rate (80.5%) in analyzing CNVs compared to NGS (95.5%), it may still be useful for revealing certain abnormal types. Conclusion: In conclusion, this study found that SNP analysis is advantageous for identifying polygenic and deletional mutations, whereas NGS is more cost‐efficient for detecting common monogenic diseases. Additionally, SNP‐based haplotyping and PCR‐based direct detection of mutations can be used together to enhance the accuracy and success rates of PGT‐M. Our findings offer valuable insights for PGT technicians in choosing suitable detection methods for patients. [ABSTRACT FROM AUTHOR]

Introduction: Malignant melanoma most commonly occurs in the skin. Primary malignant melanoma of endometrium is quite rare. Its diagnosis depends on clinical characteristics and pathological examination. It usually exhibits high degree of tumor histology, early onset of distant metastases, and unfavorable prognoses. Case Presentation: In this paper, we report a case of a 73-year-old woman with primary malignant melanoma of endometrium. This patient denied a history of nevus removal or any family medical history of cancer. She was admitted to the hospital for irregular vaginal bleeding after menopause and performed an endometrial biopsy. Pathological of the scrapings suggested malignant melanoma. She subsequently underwent a radical surgery. The final pathology diagnosis was primary malignant melanoma of endometrium, and BRAF gene mutation was detected. The tumor staged as IVB according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Thus, she then started adjuvant chemotherapy. This patient is currently on oral targeted therapy and is still being followed up. Conclusion: Mucosal melanoma is infrequent, and primary malignant melanoma of endometrial is a rare subtype. To the best of our knowledge, malignant melanoma originating from endometrium has never been reported before. It has a high degree of malignancy and is prone to early metastasis. Further investigations are warranted to explore its underlying pathogenesis, management, and outcomes. [ABSTRACT FROM AUTHOR]

Copyright of Logopedia e Comunicazione is the property of Edizioni Centro Studi Erickson SpA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: This article focuses on the impairment of lysosomes in the context of lysosomal storage disorders. Lysosomal storage disorders are a group of rare diseases with different causes united by the malfunctioning of the lysosomes. Lysosomes are intracellular vesicles, and their main function is to decompose intracellular waste in a process known as autophagy. Besides this function, lysosomes participate in a wide range of essential mechanisms aimed to keep the internal balance within our cells, which is called homeostasis. Maintaining homeostasis is a fundamental goal of all biological systems, from the simplest to the most complex, and is essential for proper functioning. Many of these disorders are originated from single-gene mutations. This provides a valuable starting point for scientists to trace the path from a single molecule to disease symptoms across the complexity of living organisms. The purpose of this paper is to provide insights from the molecular to the clinical level on this group of diseases, focusing on changes in autophagy and the latest therapeutic approaches in the field. Lysosomes are the main organelles responsible for the degradation of macromolecules in eukaryotic cells. Beyond their fundamental role in degradation, lysosomes are involved in different physiological processes such as autophagy, nutrient sensing, and intracellular signaling. In some circumstances, lysosomal abnormalities underlie several human pathologies with different etiologies known as known as lysosomal storage disorders (LSDs). These disorders can result from deficiencies in primary lysosomal enzymes, dysfunction of lysosomal enzyme activators, alterations in modifiers that impact lysosomal function, or changes in membrane-associated proteins, among other factors. The clinical phenotype observed in affected patients hinges on the type and location of the accumulating substrate, influenced by genetic mutations and residual enzyme activity. In this context, the scientific community is dedicated to exploring potential therapeutic approaches, striving not only to extend lifespan but also to enhance the overall quality of life for individuals afflicted with LSDs. This review provides insights into lysosomal dysfunction from a molecular perspective, particularly in the context of human diseases, and highlights recent advancements and breakthroughs in this field. [ABSTRACT FROM AUTHOR]

Copyright of Actualidades Biológicas is the property of Universidad de Antioquia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Collodion Baby is a descriptive term for newborns with the entire surface of the body wrapped in a rigid yellowish membrane that resembles solid and translucent parchment paper. A rare disorder that often occurs in preterm babies with low birth weight. Collodion babies can have defects in protein and fat metabolism due to genetic mutations. Management with emollients, fluid and electrolyte balance and overcoming infection. Case Report: Reported newborn came to the emergency room of Soeselo Hospital referral from Puskesmas with Collodion Baby and low birth weight. Yellowish skin is obtained throughout the body such as translucent thick parchment, fissures with some erosion and ecropions in both eyes. The patient is placed in an incubator with a temperature of 30-32o C, emollient therapy, topical antibiotics on fissures and erosions, prophylactic antibiotics and antibiotic creams for ectropion. Discussion: Collodion baby is a condition at risk of serious complications including: risk of infection, hypernatremic dehydration, fluid and electrolyte imbalances and temperature instability caused by epidermal lipid disorders and protein homeostasis, resulting in increased transepidermal water loss (TEWL) caused by mutations in the transglutaminase 1-TGM1, ALOXE3 or ALOX12B, ABCA12, HIPAL4/ichthyin, ABHD5 genes responsible for epidermal homeostasis. Conclusion: Collodion Baby is a disorder with severe corneal damage. The importance of proper and comprehensive management with the aim of minimizing complications can reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

This document is a corrigendum for an article titled "Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient." The corrigendum addresses two sentences in the abstract section of the published paper that needed revision. The corrections involve clarifying the mutations and drug resistance observed in the study. The authors confirm that these changes are typographical errors and do not affect the interpretation of the results. [Extracted from the article]

Epigenetics in the form of DNA methylation and other processes is an established property of genotypes and a focus of empirical research. Yet, there remain fundamental gaps in the evolutionary theory of epigenetics. To support a comprehensive understanding of epigenetics, this paper investigates theoretically the combined effects of deleterious mutation and epimutation with and without inbreeding. Both spontaneous epimutation and paramutation are considered to cover a broader range of epigenetic phenomena. We find that inbreeding generally reduces the amount of segregating deleterious genetic and epigenetic variation at equilibrium, although interestingly inbreeding can also increase the amount of deleterious genetic or epigenetic variation. Furthermore, we also demonstrate that epimutation indirectly can cause increased or decreased deleterious genetic variation at equilibrium relative to classic expectations, which is particularly evident when paramutation is occurring. With the addition of deleterious epimutation, there may be significantly increased purging of deleterious variation in more inbred populations and a significantly increased amount of segregating deleterious variation in more outbred populations, with notable exceptions. [ABSTRACT FROM AUTHOR]

Objective: Sertoli–Leydig cell tumors (SLCTs) are rare neoplasms occurring in young women with 60% associated with DICER1 mutations. This is only the second published case series of patients with SLCTs with associated DICER1 gene alterations. DICER1 syndrome is a rare inherited tumor‐susceptibility syndrome affecting organs such as the ovaries. We use this case series to inform readers on this increasingly important condition in gynecology. Methods and Results: We present three young females presenting with secondary amenorrhoea, hirsutism, acne and in one case tonic–clonic seizures. All cases had high testosterone levels and an adnexal mass on ultrasound. Following surgical removal, pathology confirmed SLCTs and genetic testing followed. All three patients had DICER1 syndrome with two patients subsequently found to be related. Discussion: The prevalence of DICER1 syndrome in the population is estimated to be 1 in 10 000 with a spectrum of sex cord stromal tumors affecting young women. The associated pathological classifications and management. This paper describes the DICER1 gene and the associated tumor predisposition syndrome alongside a surveillance protocol for use in clinical practice. It promotes discussion over the importance of early clinical genetics involvement in sex‐cord stromal tumors and the associated difficulties in counseling in a young patient population. Genetic testing and early detection are imperative for targeted surveillance of at‐risk organs to be performed but despite this there is no international guidance. The cases highlight the psychological impact of tumors in young patients and provokes an ethical discussion over DICER1 gene's inclusion in preimplantation genetics. Conclusions: DICER1 syndrome is a rare but increasingly important condition in pediatric and adolescent gynecology with a paucity of published data and case reports. This makes international consensus on management and surveillance difficult. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aimed to report nine Charcot–Marie–Tooth disease (CMT) families with six novel IGHMBP2 mutations in our CMT2 cohort and to summarize the genetic and clinical features of all AR‐CMT2S patients reported worldwide. Methods: General information, clinical and neurophysiological data of 275 axonal CMT families were collected. Genetic screening was performed by inherited peripheral neuropathy related genes panel or whole exome sequencing. The published papers reporting AR‐CMT2S from 2014 to 2023 were searched in Pubmed and Wanfang databases. Results: In our CMT2 cohort, we detected 17 AR‐CMT2S families carrying IGHMBP2 mutations and eight were published previously. Among these, c.743 T > A (p.Val248Glu), c.884A > G (p.Asp295Gly), c.1256C > A (p.Ser419*), c.2598_2599delGA (p.Lys868Sfs*16), c.1694_1696delATG (p.Asp565del) and c.2509A > T (p.Arg837*) were firstly reported. These patients prominently presented with early‐onset typical axonal neuropathy and without respiratory dysfunction. So far, 56 AR‐CMT2S patients and 57 different mutations coming from 43 families have been reported in the world. Twenty‐nine of 32 missense mutations were clustered in helicase domain and ATPase region. The age at onset ranged from 0.11to 20 years (Mean ± SD: 3.43 ± 3.88 years) and the majority was infantile‐onset (<2 years). The initial symptoms included weakness of limbs (19, 29.7%), delayed milestones (12, 18.8%), gait disturbance (11, 17.2%), feet deformity (8, 12.5%), feet drop (8, 12.5%), etc. Interpretation: AR‐CMT2S accounted for 6.2% in our CMT2 cohort. We firstly reported six novel IGHMBP2 mutations which expanded the genotypic spectrum of AR‐CMT2S. Furthermore, 17 AR‐CMT2S families could provide more resources for natural history study, drug research and development. [ABSTRACT FROM AUTHOR]

One of the recent significant but challenging research studies in computational biology and bioinformatics is to unveil protein complexes from protein-protein interaction networks (PPINs). However, the development of a reliable algorithm to detect more complexes with high quality is still ongoing in many studies. The main contribution of this paper is to improve the effectiveness of the well-known modularity density ( ) model when used as a single objective optimization function in the framework of the canonical evolutionary algorithm (EA). To this end, the design of the EA is modified with a gene ontology-based mutation operator, where the aim is to make a positive collaboration between the modularity density model and the proposed gene ontology-based mutation operator. The performance of the proposed EA to have a high quantity and quality of the detected complexes is assessed on two yeast PPINs and compared with two benchmarking gold complex sets. The reported results reveal the ability of modularity density to be more productive in detecting more complexes with high quality when teamed up with a gene ontology-based mutation operator. [ABSTRACT FROM AUTHOR]

Sulfonate esters, one of the genetic impurities, have gained significant attention in recent years due to their potential to cause genetic mutations and cancer. In this study, we reported a novel on‐line column‐switching liquid chromatography method for the quantitative analysis of three p‐toluene sulfonate alkyl esters in active pharmaceutical ingredients (APIs). The sensitivity was improved by large‐volume injection. A diluting modulation‐based sampling procedure was specifically devised to mitigate the impact of solvent effects and resolve the poor stability of isopropyl p‐toluene sulfonate alkyl ester. The established method was validated in terms of linearity, sensitivity, accuracy, stability, and robustness. The limit of quantitation level was determined to be 1 ng/mL (equivalent to 1 ppm relative to 1 mg/mL API samples). Besides, the method was applied for four APIs Tosuloxacin toluene sulfonate, Lapatinib toluene sulfonate, Nirapalib toluene sulfonate, and Capecitabine. The recoveries of all target analytes in the four‐drug substances were within 89%–110%. The expanded uncertainties of the measurements ranged from 6.8% to 8.4% at a coverage level of k = 2 and a confidence level of approximately 95%. The method described in this paper was compared with other published literature, demonstrating its simplicity and ease of standardization which could be further applied in the quality control and safety assessment of drug substances. [ABSTRACT FROM AUTHOR]

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies. [ABSTRACT FROM AUTHOR]

Skin cancer is one of the most common types of cancer globally, by increasing occurrence rates each year. It is a predominant kind of cancer which rises from the uncontrolled growth of abnormal skin cells due to genetic mutations including various factors such as UV radiation, genetics and other factors. The death rate is decreased when skin cancer is detected at early stages. Therefore, this paper proposed a Convolutional Neural Network (CNN) with Coordinate Attention Module (CAM) for early detection of skin cancer. The data augmentation is utilized in this experiment for data pre-processing and fed into the Gray Level Co-occurrence Matrix (GLCM) based feature extraction technique. The Harris Hawk Optimization (HHO) is utilized for selecting features that have faster convergence and strong capability in local optima. The selected features are given as input to CNN with the CAM approach. This model is estimated on ISIC-2019 and ISIC-2020 datasets and attains better results using accuracy, precision, recall, specificity, and F1-score. The obtained result shows that the proposed model achieves better accuracy of 98.77% on the ISIC-2019 dataset and 99.51% on the ISIC-2020 dataset which ensures accurate detection compared to other existing methods like Inception-ResNet and Residual Deep Convolutional Neural Network (RDCNN). [ABSTRACT FROM AUTHOR]