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With the rapid spread and evolution of SARS-CoV-2, the ability to monitor its transmission and distinguish among viral lineages is critical for pandemic response efforts. The most commonly used software for the lineage assignment of newly isolated SARS-CoV-2 genomes is pangolin, which offers two methods of assignment, pangoLEARN and pUShER. PangoLEARN rapidly assigns lineages using a machine-learning algorithm, while pUShER performs a phylogenetic placement to identify the lineage corresponding to a newly sequenced genome. In a preliminary study, we observed that pangoLEARN (decision tree model), while substantially faster than pUShER, offered less consistency across different versions of pangolin v3. Here, we expand upon this analysis to include v3 and v4 of pangolin, which moved the default algorithm for lineage assignment from pangoLEARN in v3 to pUShER in v4, and perform a thorough analysis confirming that pUShER is not only more stable across versions but also more accurate. Our findings suggest that future lineage assignment algorithms for various pathogens should consider the value of phylogenetic placement.

Exome sequencing (ES) may identify and report secondary findings that are unrelated to the primary disease for which the patient underwent genetic testing, but are of potential value in patient care.In this study, we evaluated 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders. The variants identified were classified and reported following the 2015 ACMG Standards and Guidelines for the interpretation of sequence variants and the ACMG recommendations for reporting secondary findings (v3.2).We detected a total of 17 variants in 17 patients across 9 different genes as secondary findings. Seven heterozygous variants were found in BRCA1, MSH2, and PALB2 which are part of the cancer phenotype category. Nine heterozygous variants were found in MYH7, TTN, LDLR, DSC2, and DSP which are part of the cardiovascular phenotype category. Finally, one heterozygous variant was found in TTR which is part of the miscellaneous phenotype category. Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic.The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsKeratoconus (KC) is an asymmetrical bilateral corneal ectasia, of which the pathogenesis is unknown. Moreover, genetic factors play an important role. We reported ophthalmic findings in a Chinese family with monozygotic twins with KC to describe the clinical features and identify genetic variants.Comprehensive ophthalmic clinical assessments and examinations, including history, slit-lamp biomicroscopy, best-corrected visual acuity, corneal topography, anterior segment optical coherence tomography, and corneal biomechanics, were carried out on the twins and their parents. Whole-genome sequencing (WGS) was performed to identify variants in this family. SIFT, PolyPhen2, MutationTaster, and CADD were used to predict the effect of amino acid substitutions on the affected protein.The twins presented typical KC features. However, their mother did not meet the criteria for a KC diagnosis but exhibited KC subclinical manifestations. After screening, 12 potentially pathogenic variants in 10 genes were identified in both twins and emerged as candidate variants for this family. These genes included 1 previously reported KC-associated variant (ZNF469, c.4384 G>A); 8 variants in 6 KC-associated genes (GRHPR, c.337 G>A, c.862_863del; COL6A1, c.920 G>A; FLG, c.8753C>G; HSPG2, c.9503C>T; KRT82, c.1306 G>A; SCN9A, c.5702_5706del, c.641 G>A); and 3 variants in 3 non-KC-associated genes (PDE6G, c.6C>A; HAL, c.1724C>T; AGBL1, c.2381 G>A).The accumulation of these potentially pathogenic variants in twins may have caused KC in these twins. These results expand the spectrum of KC candidate variants and provide a basis for further studies on KC. [ABSTRACT FROM AUTHOR]

Background: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists, giving rise to new variants characterized by mutations in the spike protein. However, public data regarding the virus's evolutionary trend is not widely available after the downgrade of coronavirus disease 2019(COVID-19). Therefore, this study aimed to investigate the applicability of an in-house Sanger-based method for identifying SARS-CoV-2 variants, particularly focusing on newly emerged Omicron variants, and updating the epidemiology of COVID-19 during the 8th wave in Hiroshima Prefecture. Results: A total of 639 saliva samples of individuals who had tested positive for COVID-19, received from Hiroshima City Medical Association Clinical Laboratory Center between February 01, 2023, and March 12, 2024, were included in the study. SARS-CoV-2 variants were identified in 69.3% (443/639) with the mean viral titer 2 × 106 copies/mL, and high viral titer in Omicron variant XBC.1.6* (5 × 108 copies/mL) using RT-qPCR. By partial Spike gene-based sequencing using the Sanger Sequencing strategy, Omicron sub-lineages XXB.1, BA.5, and EG.1 were identified during different periods. A comprehensive phylogenetic analysis of 7383 SARS-CoV-2 strains retrieved from GISAID, collected in Hiroshima from the onset of the COVID-19 pandemic in early 2020 until July 2024, revealed the dynamic evolution of SARS-CoV-2 variants over time. The study found a similar pattern of variant distribution between the full genomes from GISAID, and the partial genomes obtained from our screening strategy during the same period. Conclusions: Our study revealed that all SARS-CoV-2 viruses circulated in Hiroshima were Omicron variants and their sub-lineages during the 8th wave outbreak in Hiroshima. Persistent molecular surveillance of SARS-CoV-2 is needed for the decision-making and strategic planning of the public promptly. Our study added evidence for the usefulness of SARS-CoV-2 spike gene partial sequencing-based SARS-CoV-2 variant identification strategy for mass screening and molecular surveillance even though the evolution of newly emerged various SARS-CoV-2 Omicron variants. [ABSTRACT FROM AUTHOR]

Background: The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases. The aim of the study was to genetically characterise a cohort of 265 Polish patients with MeDOC and to get insight into the skin lesions using transcriptome and lipid profile analyses. Results: We detected causal variants in 85% (226/265) patients. In addition to the primary gene defect, a pathogenic variant in another gene involved in MeDOC pathology was identified in 23 cases. We found 150 distinct variants in 33 genes, including 32 novel and 16 recurrent (present in > 5 alleles). In 43 alleles large rearrangements were detected, including deletions in the STS, SPINK5, CERS3 and recurrent duplication of exons 10–14 in TGM1. The RNA analysis using samples collected from 18 MeDOC patients and 22 controls identified 1377 differentially expressed genes - DEG. The gene ontology analysis revealed that 114 biological processes were upregulated in the MeDOC group, including i.e. epithelial cell differentiation, lipid metabolic process; homeostasis; regulation of water loss via skin; peptide cross-linking. The DEG between TGM1 and ALOX12B patients, showed that RNA profile is highly similar, though fatty acid profile in epidermal scrapings of those patients showed differences e.g. for the very long chain fatty acids (VLCFAs; FAs ≥ C20), the very long-chain monounsaturated fatty acids (VLC-MUFAs, FAs ≥ C20:1) and the n6 polyunsaturated fatty acids (n6 PUFAs). Conclusion: Our results show that NGS-based analysis is an effective MeDOC diagnostic tool. The Polish MeDOC patients are heterogenic, however recurrent variants are present. The novel variants and high number of TGM1 and SPINK5 copy number variations give further insight into molecular pathology of MeDOC. We show that secondary variants in MeDOC-related genes are present in a significant group of patients, which should be further investigated in the context of phenotype modifiers. Finally, we provide novel RNA and lipid data that characterise molecularly MeDOC epidermis. [ABSTRACT FROM AUTHOR]

A nanoplasmonic biosensor for the precise detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by leveraging advances in nanostructured sensing materials and highly selective monoclonal antibodies is presented. The sensor integrates plasmonic Au nanostructures optimized for surface‐enhanced Raman scattering (SERS), enhancing sensitivity through unique light interactions at the nanoscale. Coupled with exclusive antibodies that specifically target SARS‐CoV‐2 and its evolving variants, this sensor demonstrates remarkable selectivity and versatility. Validated with 270 clinical samples, it demonstrates a sensitivity of 98.9% and specificity of 100%. More importantly, the virus in nasopharyngeal swab samples collected over 3 years, marking the long‐term, large‐scale clinical validation of the nanoplasmonic biosensor for SARS‐CoV‐2 is been successfully detected. Furthermore, the integration of this sensor with face masks enables the detection of airborne SARS‐CoV‐2, highlighting its potential for routine management of coronavirus disease 2019 (COVID‐19). [ABSTRACT FROM AUTHOR]

Albinism is a phenotypically and genetically heterogeneous condition characterized by a variable degree of hypopigmentation and by ocular features leading to reduced visual acuity. Whereas numerous genotypic studies have been conducted throughout the world, very little is known about the genotypic spectrum of albinism in Africa and especially in sub‐Saharan Western Africa. Here we report the analysis of all known albinism genes in a series a 23 patients originating from Mali. Four were diagnosed with OCA 1 (oculocutaneous albinism type 1), 17 with OCA 2, and two with OCA 4. OCA2 variant NM_000275.3:c.819_822delinsGGTC was most frequently encountered. Four novel variants were identified (two in TYR, two in OCA2). A deep intronic variant was found to alter splicing of the OCA2 RNA by inclusion of a pseudo exon. Of note, the OCA2 exon 7 deletion commonly found in eastern, central, and southern Africa was absent from this series. African patients with OCA 1 and OCA 4 had only been reported twice and once, respectively, in previous publications. This study constitutes the first report of the genotypic spectrum of albinism in a western sub‐Saharan country. [ABSTRACT FROM AUTHOR]

Purpose. Arterial supply of thalamus is complex and highly variable. In particular, the distribution pattern of thalamoperforating arteries received more attention some decades ago than in recent years. Methods. We are presenting the case of a 46-year-old patient with wake-up drowsiness, complex oculomotor disorder and dysarthria. He was investigated in the acute phase using non-contrast brain Computed Tomography (NCCT), CT Angiography (CTA), and in the following days Digital Subtraction Angiography (DSA) was performed Results. The NCCT showed a subacute ischemic stroke in the right anterior thalamus and rostral midbrain with normal findings on CTA. DSA imaged a variant of thalamic supply (Percheron type III), constituted by perforating branches arising from an artery bridging the P1 segments of both Posterior Cerebral Arteries (PCAs). Results. The thalamus has a complex and variable arterial supply, mainly in the pattern of paramedian thalamic-mesencephalic perforating arteries. The most reported variant is Percheron type IIb and supplies the paramedian thalami and the rostral midbrain. Type IIb occlusion usually causes a bilateral paramedian thalamic stroke, but rostral midbrain and anterior thalamus are involved in 57% and 19% cases. The rarer Type III variant probably prevented the bilateral extension of infarction and involved the territory of tuberothalamic and paramedian perforating arteries. Conclusions. Currently, DSA allows directly imaging variants in thalamic vascularization and better understanding the stroke mechanisms. In particular, in the presented case, a medium-sized vessel occlusion rather than a small vessel occlusion mechanism might be raised, leading to a different diagnostic pathway. [ABSTRACT FROM AUTHOR]

From 2014–2023, infectious bronchitis virus (IBV) was detected in 6,589 samples from Canada, and partial nucleotide (nt) sequences of the IBV spike protein (S) gene were determined for 1,678 samples. Based on their S gene nt sequence identities and origin, Canadian IBVs could be classified into 4 groups: 1) 50.3% were variant viruses related to strains described in the United States; 2) 45.6% were vaccine-like viruses; 3) 2.1% were Eurasian viruses; 4) 2.0% were Canadian variants. Outbreaks with IBVs related to strains CAL1734/04, 4/91, and DMV/1639/11 were often associated with more severe disease in all chicken commodity groups. With the emergence of numerous IBV strains, the severity of infection and number of affected flocks increased. Outbreaks with various IBV strains overlapped in their emergence, peaked, and regressed, but the introduction of DMV/1639/11 has resulted in a continuous field challenge since its first detection in 2015. [ABSTRACT FROM AUTHOR]

The ACTA1 gene encodes skeletal muscle alpha‐actin, which forms the core of the sarcomeric thin filament in adult skeletal muscle. ACTA1 represents one of six highly conserved actin proteins that have all been associated with human disease. The first 15 pathogenic variants in ACTA1 were reported in 1999, which expanded to 177 in 2009. Here, we update on the now 607 total variants reported in LOVD, HGMD, and ClinVar, which includes 343 reported pathogenic/likely pathogenic (P/LP) variants. We also provide suggested ACTA1‐specific modifications to ACMG variant interpretation guidelines based on our analysis of known variants, gnomAD reports, and pathogenicity in other actin isoforms. Using these criteria, we report a total of 447 P/LP ACTA1 variants. From a clinical perspective, the number of reported ACTA1 disease phenotypes has grown from five to 20, albeit with some overlap. The vast majority (74%) of ACTA1 variants cause nemaline myopathy (NEM), but there are increasing numbers that cause cardiomyopathy and novel phenotypes such as distal myopathy. We highlight challenges associated with identifying genotype–phenotype correlations for ACTA1. Finally, we summarize key animal models and review the current state of preclinical treatments for ACTA1 disease. This update provides important resources and recommendations for the study and interpretation of ACTA1 variants. [ABSTRACT FROM AUTHOR]

Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future. [ABSTRACT FROM AUTHOR]

Background: Modifiers significantly impact disease phenotypes by modulating the effects of disease-causing variants, resulting in varying disease manifestations among individuals. However, identifying genetic interactions between modifier and disease-causing variants is challenging. Results: We developed MDVarP, an ensemble model comprising 1000 random forest predictors, to identify modifier ~ disease-causing variant combinations. MDVarP achieves high accuracy and precision, as verified using an independent dataset with published evidence of genetic interactions. We identified 25 novel modifier ~ disease-causing variant combinations and obtained supporting evidence for these associations. MDVarP outputs a class label ("Associated-pair" or "Nonrelevant-pair") and two prediction scores indicating the probability of a true association. Conclusions: MDVarP prioritizes variant pairs associated with phenotypic modulations, enabling more effective mapping of functional contributions from disease-causing and modifier variants. This framework interprets genetic interactions underlying phenotypic variations in human diseases, with potential applications in personalized medicine and disease prevention. [ABSTRACT FROM AUTHOR]

The domination problem and three of its variants (total domination, 2-domination, and secure domination) are considered. These problems have various real-world applications, including error correction codes, ad hoc routing for wireless networks, and social network analysis, among others. However, each of them is NP-hard to solve to provable optimality, making fast heuristics for these problems desirable. There are a wealth of highly developed heuristics and approximation algorithms for the domination problem; however, such heuristics are much less common for variants of the domination problem. We redress this gap in the literature by proposing a novel implementation of the cross-entropy method that can be applied to any sensible variant of domination. We present results from experiments that demonstrate that this approach can produce good results in an efficient manner even for larger graphs and that it works roughly as well for any of the domination variants considered. [ABSTRACT FROM AUTHOR]

To thrive on melting alpine and polar snow, some Chlorophytes produce an abundance of astaxanthin, causing red blooms, often dominated by genus Sanguina. The red cells have not been cultured, but we recently grew a green biciliate conspecific with Sanguina aurantia from a sample of watermelon snow. This culture provided source material for Oxford Nanopore Technology and Illumina sequencing. Our assembly pipeline exemplifies the value of a hybrid long- and short-read approach for the complexities of working with a culture grown from a field sample. Using bioinformatic tools, we separated assembled contigs into 2 genomic pools based on a difference in GC content (57.5 and 55.1%). We present the data as 2 assemblies of S. aurantia variants but explore other possibilities. High-throughput chromatin conformation capture analysis (Hi-C sequencing) was used to scaffold the assemblies into a 96-Mb genome designated as "A" and a 102-Mb genome designated as "B." Both assemblies are highly contiguous: genome A consists of 38 scaffolds with an N50 of 5.4 Mb, while genome B has 50 scaffolds with an N50 of 6.4 Mb. RNA sequencing was used to improve gene annotation. [ABSTRACT FROM AUTHOR]

Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain variants spread more easily, are more contagious, and pose a significant health menace to global populations. The replication kinetics of the Malaysian isolates of Alpha, Beta, Delta, and Omicron variants were studied in the Vero E6 cell line. Their replication kinetics were determined using the plaque assay, quantitative real-time PCR (qRT-PCR), and the viral growth curve. The Beta variant exhibited the highest replication rate at 24 h post-infection (h.p.i), as evidenced by the highest viral titers and lowest viral RNA multiplication threshold. The plaque phenotypes also varied among the variants, in which the Beta and Omicron variants formed the largest and smallest plaques, respectively. All studied variants showed strong cytopathic effects after 48 h.p.i. The whole-genome sequencing highlighted cell-culture adaptation, where the Beta, Delta, and Omicron variants acquired mutations at the multibasic cleavage site after three cycles of passaging. The findings suggest a strong link between the replication rates and their respective transmissibility and pathogenicity. This is essential in predicting the impacts of the upcoming variants on the local and global populations and is useful in designing preventive measures to curb virus outbreaks. [ABSTRACT FROM AUTHOR]

Appropriate growth curves can reflect more sophisticated growth patterns of animals than body weight, and thus, the identification of genes and variants related to the growth curve parameter traits contributes to revealing the fine growth and development characteristics of livestock. However, the ability of single genome-wide association analysis (GWAS) and transcriptome analyses to identify valuable genes and variants is limited. In this study, based on genome and transcriptome data, the growth curve parameter traits of hybrid pigs were analyzed, and a set of genes and variants were identified. The Gompertz–Laird growth curve model was optimized to reveal the growth pattern of F2 individuals of Duroc × Erhualian pigs over four time points. Five growth parameters were estimated, including initial body weight (W 0) , instantaneous growth rate per day (L), coefficient of relative growth or maturing index (k), body weight at inflection point (W i) , and average growth rate (GR). These five parameters were subjected to a genome-wide association study, differential gene expression analysis, and weighted gene co-expression network analysis (WGCNA). In the study, 336 pigs were genotyped, and 39,494 SNP markers were used for each pig in the analysis. Thirty of these pigs were also included in the transcriptomics analysis. Based on genome and transcriptome data, the integrated analyses identified five putative SNPs (including INRA0056566 on chromosome X, DRGA0004151 on chromosome 3, INRA0056460 on chromosome X, H3GA0049324 on chromosome 17, and H3GA0037747 on chromosome 13) and 15 candidate genes (PDGFA, VEGFD, CSPP1, EFHC1, PIK3C3, ZZZ3, GCC2, MAPK14, ZPR1, ISG15, ANG, CEBPD, ZHX3, CTBP2, and MYNN). The functional analysis indicated that these candidate genes played important roles in cell division and differentiation, development and aging, and skeletal muscle and fat formation. Our results provide insight into the genetic mechanisms underlying the growth and development of hybrid pigs and offer a theoretical basis for genomic breeding. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna's response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.5 strains. This approach, while commendable, is unfeasible in light of rapidly emerging mutated viral strains. PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2024. Articles included focused on specific themes such as the clinical history of recombinant protein vaccine development against different diseases, including COVID-19, the production of recombinant protein vaccines using different host expression systems, aspects to consider in recombinant protein vaccine development, and overcoming problems associated with large-scale recombinant protein vaccine production. In silico approaches to identify conserved and immunogenic epitopes could provide broad protection against SARS-CoV-2 VOCs but require validation in animal models. The recombinant protein vaccine development platform has shown a successful history in clinical development. Recombinant protein vaccines incorporating conserved epitopes may utilize a number of expression systems, such as yeast (Saccharomyces cerevisiae), baculovirus-insect cells (Sf9 cells), and Escherichia coli (E. coli). Current multi-epitope subunit vaccines against SARS-CoV-2 utilizing synthetic peptides are unfeasible for large-scale immunizations. Recombinant protein vaccines based on conserved and immunogenic proteins produced using E. coli offer high production yields, convenient purification, and cost-effective production of large-scale vaccine quantities capable of protecting against the SARS-CoV-2 D614G strain and its VOCs. [ABSTRACT FROM AUTHOR]

Background: Although there have been reports of COVID-19 breakthrough infections in vaccinated individuals, the vaccines have demonstrated a high efficacy in preventing severe illness and death. Nepal has reported fewer studies of COVID-19 breakthrough infections. Hence, this study has objective to assess the prevalence, and to describe clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) breakthrough infection. Methods: This descriptive study was conducted from January to December 2022. The study enrolled 200 individuals who had received the recommended doses of the COVID-19 vaccine and they were RT-PCR positive diagnosed with vaccine breakthrough infections after 14 days of completing the vaccination course. The patient's demographic and clinical profiles, as well as their outcomes in terms of severity, length of hospital stay, and mortality were recorded. Results: The prevalence of SARS-CoV2 infection was 6.3% (547/8682). Among fully vaccinated personnel, the prevalence of breakthrough infections was 6.2% (200/3175). This study found the Omicron variants in respondents. The mean age of the patients was 38.28 years, and 41.5% (83/200) of the breakthrough cases were healthcare workers. The mean time gap between the second dose of vaccination and a positive RT-PCR test was 354.68 days. Of the 200 breakthrough cases, 89% (178) had mild symptoms, 9% (17) had moderate symptoms requiring hospitalization, and 2% (4) were severe cases that required intensive care facility. Among the severe cases, 3 out 4 were above 60 years old. Furthermore, the patients greater than 60 years had longer hospital stays (p < 0.0001) however no deaths were recorded. Conclusion: Fully vaccinated individuals can experience COVID-19 breakthrough infections and the majority of cases present with mild symptoms. Elderly patients have a higher likelihood of severe disease and longer hospital stay compared to younger patients. The results of this study emphasize the importance of vaccination in mitigating the severity of the disease. [ABSTRACT FROM AUTHOR]

Summary: As a consequence of continuing demand for additional capacity and higher quality data transmission, channel coding as a key component of a digital communication network has progressed from a classical single pair, point‐to‐point information theoretic application to a class of coding techniques with diverse parameters. The heterogeneous requirements of B5G/6G networks technology have made flexibility of code parameters the main desired feature while designing channel codes. Owing to this, channel coding techniques have evolved to support enabling applications that depend on different factors such as latency, reliability, energy efficiency and throughput. We review and discuss the application of new techniques, modifications in the design and construction of modern channel coding schemes, including block, convolutional, rateless and space‐time codes. Further, the error correction performance of mainstream channel decoders for LDPC, polar and turbo codes is compared and analysed for their attainable error rate. The aim of this study is to highlight the adaptability of the discussed coding schemes for the forthcoming cellular network landscape. This article also addresses the implementational challenges of high throughput, low latency and machine type communication scenarios. Moreover, some recent studies exploring the role of machine learning for optimisation of B5G/6G networks are classified and discussed. Concluding, research areas pertaining to the scalability of error control coding for next generation networking are addressed. [ABSTRACT FROM AUTHOR]

Background: Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. Methods: As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. Results: The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. Conclusions: Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic is a global health concern and has persisted through the emergence of variants that have caused subsequent waves of COVID-19 due to the high dispersion and contagiousness of the virus. The aim of this work was to analyze the epidemiology of the cases of reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants during the third and fourth wave of the COVID-19 pandemic at the Hospital Juárez de México (HJM). Methodology: A prospective study of the cases of SARS-CoV-2 reinfection, variants detected, symptoms, and associated comorbidities was carried out on 1,347 patients who attended the HJM from September 2021 to July 2022. Results: 760 (56.4%) and 587 (43.6%) patients were negative and positive for SARS-CoV-2, respectively. The Omicron variant was the most frequent and the most common symptoms were: cough (80%), headache (61.32%), fever (51.6%), and dyspnea (40%). A higher proportion of females were vaccinated, ranging from one dose to the complete schedule. The factors that were associated with a greater risk of death from complications of SARS-CoV-2 reinfection were male gender, diabetes mellitus, and arterial hypertension. Conclusions: Females were the most susceptible to an Omicron reinfection event, even though they were vaccinated. However, the risk of death was higher when the patient was male; being male was a potential risk factor for death from COVID-19 and comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: The visual detection of the early-eluting unknown peaks (UPs) in the chromatogram of the high-performance liquid chromatography (HPLC) is essential for its being supplementary to the diagnostic workup of different phenotypes of ß-Thal, particularly in areas endemic to this disease. This study aimed to scrutinize and uncover the interaction of the level of UPs detected during HPLC analysis of hemoglobin (Hb) with the Hb-F, Hb-A2, Hb subunits levels, and ß-Thalassemia (ß-Thal) phenotypes. Materials and methods: A total of 161 respondents with ß-Thal and 52 healthy blood donors were included in this study. HPLC analysis of Hb and quantification of the Hb subunits were performed using the VARIANT II ß-Thalassemia Short Program and triple-quad mass spectrometry, respectively. The level of UPs was measured using the software ImageJ 1.53k. Results: The mean levels of UP2, UP3, and UP4 correlated positively with the quantities of Hb-A2 and Hb-F, mainly in Hb-E/ß-Thal and ß-Thal major groups. The mean level of UP4 showed a direct correlation with Hb-subunit gamma. Conclusion: The composition of the UP4 is gamma-globin in nature. Further exploration of other elements in these pre-integration UPs might uncover clinically valuable markers. Knowledge and awareness of how these UPs interact with the Hb variants in different ß-Thal and their compositions, especially in cases of ß-Thal major or Hb E/ß-thal, might contribute toward revealing molecular mechanisms in ß-Thal and reinforcing the hematopathologists' interpretation of the result of HPLC analysis of Hb in diagnosing different ß-Thal phenotypes. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the monitoring of SARS-CoV-2 RNA in wastewater was used to track the evolution and emergence of variant lineages and gauge infection levels in the community, informing appropriate public health responses without relying solely on clinical testing. As more sublineages were discovered, it increased the difficulty in identifying distinct variants in a mixed population sample, particularly those without a known lineage. Here, we compare the sequencing technology from Illumina and from Oxford Nanopore Technologies, in order to determine their efficacy at detecting variants of differing abundance, using 248 wastewater samples from various Quebec and Ontario cities. Our study used two analytical approaches to identify the main variants in the samples: the presence of signature and marker mutations and the co-occurrence of signature mutations within the same amplicon. We observed that each sequencing method detected certain variants at different frequencies as each method preferentially detects mutations of distinct variants. Illumina sequencing detected more mutations with a predominant lineage that is in low abundance across the population or unknown for that time period, while Nanopore sequencing had a higher detection rate of mutations that are predominantly found in the high abundance B.1.1.7 (Alpha) lineage as well as a higher sequencing rate of co-occurring mutations in the same amplicon. We present a workflow that integrates short-read and long-read sequencing to improve the detection of SARS-CoV-2 variant lineages in mixed population samples, such as wastewater. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses. [ABSTRACT FROM AUTHOR]

HPV16 is occasionally detected in vaccinated women who received the bivalent HPV16/18 vaccine, usually at low viral loads. This study explored potential differences in HPV16 variants between vaccinated and unvaccinated women. HPV16-postive viral loads were detected in 1.9% (17/875) and 13% (162/760) of vaccinated and unvaccinated women, respectively, showcasing the vaccine's high efficacy. The L1, E6, and URR regions of HPV16 were sequenced from genital swabs from 16 vaccinated and 25 unvaccinated women in the HAVANA (HPV Among Vaccinated And Non-vaccinated Adolescents) study. The majority of HPV16 variants from vaccinated and unvaccinated women clustered similarly with sub-lineages A1 and A2. Additionally, a separate cluster within lineage A was found, with the variants sharing the L1-located SNP A753G (synonymous) and the URR-located SNP T340C, which did not occur in the other variants. Furthermore, four variants from vaccinated women had relatively long branches, but were not characterized by specific SNPs. The frequency of G712A in the URR was the only SNP observed to be marginally higher among vaccinated women than unvaccinated women. Non-synonymous SNPs T266A in the FG-loop of L1 and L83V in E6 were common among variants from vaccinated and unvaccinated women, but present in similar frequencies. In conclusion, the detection of HPV16 in vaccinated (and unvaccinated) women seemed to be the result of random circulation within this study population. [ABSTRACT FROM AUTHOR]

Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We investigated 129 patients diagnosed with Chronic Myeloid Leukemia treated with imatinib as first choice therapy. The participants of the study are highly admixed, populations that exhibit genetic diversity and complexity due to the contributions of multiple ancestral groups. Thus, the aim of this work was to investigate the association of 30 SNVs in genes related to response to treatment with Imatinibe in CML. Our results indicated that for the rs2290573 of the ULK3 gene, patients with the recessive AA genotype are three times more likely to develop resistance over time (secondary resistance) (p = 0.019, OR = 3.19, IC 95%= 1.21–8.36). Finally, we performed interaction analysis between the investigated variants and found several associations between SNVs and secondary resistance. We concluded that the variant rs2290573 of the ULK3 gene may be relevant for predicting treatment response of CML with imatinib, as well as possible treatment resistance. The use of predictive biomarkers is an important tool for therapeutic choice of patients, improving their quality of life and treatment efficacy. [ABSTRACT FROM AUTHOR]

Histone variants are the paralogs of core histones (H2A, H2B, H3 and H4). They are stably expressed throughout the cell cycle in a replication-independent fashion and are capable of replacing canonical counterparts under different fundamental biological processes. Variants have been shown to take part in multiple processes, including DNA damage repair, transcriptional regulation and X chromosome inactivation, with some of them even specializing in lineage-specific roles like spermatogenesis. Several reports have recently identified some unprecedented variants from different histone families and exploited their prognostic value in distinct types of cancer. Among the four classes of canonical histones, the H2A family has the greatest number of variants known to date, followed by H2B, H3 and H4. In our prior review, we focused on summarizing all 19 mammalian histone H2A variants. Here in this review, we aim to complete the full summary of the roles of mammalian histone variants from the remaining histone H2B, H3, and H4 families, along with an overview of their roles in cancer biology and their prognostic value in a clinical context. [ABSTRACT FROM AUTHOR]

Exome sequencing (ES) has identified biallelic kinesin family member 12 (KIF12) mutations as underlying neonatal cholestatic liver disease. We collected information on onset and progression of this entity. Among consecutively referred pediatric patients at our centers, diagnostic ES identified 4 patients with novel, biallelic KIF12 variants using the human GRCh38 reference sequence, as KIF12 remains incompletely annotated in the older reference sequence GRCh37. A review of these and of 21 reported patients with KIF12 variants found that presentation with elevated serum transaminase activity in the context of trivial respiratory infection, without clinical features of liver disease, was more common (n = 18) than manifest cholestatic disease progressing rapidly to liver transplantation (LT; n = 7). Onset of liver disease was at age <1 year in 15 patients; LT was more common in this group. Serum gamma‐glutamyl transpeptidase activity (GGT) was elevated in all patients, and total bilirubin was elevated in 15 patients. Liver fibrosis or cirrhosis was present in 14 of 18 patients who were biopsied. The 16 different pathogenic variants and 11 different KIF12 genotypes found were not correlated with age of onset or progression to LT. Identification of biallelic pathogenic KIF12 variants distinguishes KIF12‐related disease from other entities with elevated GGT. [ABSTRACT FROM AUTHOR]

Piscine orthoreovirus‐1 (PRV‐1) is a prevalent agent in Atlantic salmon (Salmo salar) and the causative agent of heart and skeletal muscle inflammation (HSMI), an important disease in farmed Atlantic salmon. Investigations into the introduction and dissemination routes of PRV‐1 in a field setting have been limited. This study aimed to better understand PRV‐1 infections and HSMI‐associated mortality under field conditions. We tracked introduction and spread of PRV‐1 over one production cycle in a geographically isolated region in Norwegian aquaculture. From five sites, a total of 32 virus isolates were sequenced and genogrouped. The results indicated multiple introductions of PRV‐1 to the area, but also revealed a high level of genetic homogeneity among the virus variants. The variants differed from that of the previous production cycle at two out of three sites investigated, suggesting that synchronized fallowing can be a useful tool for preventing dissemination of PRV‐1 between generations of fish. Exposure to PRV‐1 at the freshwater stage was identified as a potential source of introduction. A low level of HSMI‐associated mortality was observed at all sites, with the onset of mortality showing some variation across PRV‐1 genogroups. However, the study highlighted the complexity of associating viral genogroups with mortality in a field setting. Overall, this study contributes valuable insights into PRV‐1 dynamics in a real‐world aquaculture setting, offering potential strategies for disease management and prevention. [ABSTRACT FROM AUTHOR]

Background: In previous studies, there was an increase in mortality with secondary coinfections in all COVID-19 variants. However, no prior study has explored the association of coinfection with outcomes of hospitalized patients among the COVID-19 variants (Alpha, Delta, and Omicron). Methods: This observational cohort study involved 21,186 patients hospitalized with COVID-19 in 25 hospitals in Texas. Patients were divided into groups by surges of COVID-19: Alpha (November 1, 2020–February 10, 2021), Delta (July 10, 2021–October 14, 2021), and Omicron (December 21, 2021–March 3, 2022). Data were collected from electronic health records using methodology from the Viral Respiratory Illness Universal Study COVID-19 registry (NCT04323787) of COVID-19 hospitalizations. Multivariable Cox-proportional hazard regression model assessed the adjusted effect of different surge periods on mortality. Results: Bacterial coinfections varied among hospitalization surges associated with Alpha (8.5%), Delta (11.7%), and Omicron (11.9%) variants. Adjusted analyses showed a higher 30-day and 90-day mortality in all variants when coinfections were present compared with isolated COVID-19 infection. In particular, 30-day and 90-day mortality were significantly worse with Delta compared to Alpha and Omicron. Conclusions: All variants were associated with a higher mortality when bacterial coinfections were present. Delta was associated with a higher risk-adjusted mortality at 30 days and thereafter. [ABSTRACT FROM AUTHOR]

Purpose of Review: Maturity-onset diabetes of the young (MODY) are monogenic forms of diabetes resulting from genetic defects, usually transmitted in an autosomal dominant fashion, leading to β-cell dysfunction. Due to the lack of homogeneous clinical features and univocal diagnostic criteria, MODY is often misdiagnosed as type 1 or type 2 diabetes, hence its diagnosis relies mostly on genetic testing. Fourteen subtypes of MODY have been described to date. Here, we review ABCC8-MODY pathophysiology, genetic and clinical features, and current therapeutic options. Recent Findings: ABCC8-MODY is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter subfamily C member 8 (ABCC8) gene, involved in the regulation of insulin secretion. The complexity of ABCC8-MODY genetic picture is mirrored by a variety of clinical manifestations, encompassing a wide spectrum of disease severity. Such inconsistency of genotype-phenotype correlation has not been fully understood. A correct diagnosis is crucial for the choice of adequate treatment and outcome improvement. By targeting the defective gene product, sulfonylureas are the preferred medications in ABCC8-MODY, although efficacy vary substantially. We illustrate three case reports in whom a diagnosis of ABCC8-MODY was suspected after the identification of novel ABCC8 variants that turned out to be of unknown significance. We discuss that careful interpretation of genetic testing is needed even on the background of a suggestive clinical context. Summary: We highlight the need for further research to unravel ABCC8-MODY disease mechanisms, as well as to clarify the pathogenicity of identified ABCC8 variants and their influence on clinical presentation and response to therapy. [ABSTRACT FROM AUTHOR]

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Abstract Background The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists, giving rise to new variants characterized by mutations in the spike protein. However, public data regarding the virus's evolutionary trend is not widely available after the downgrade of coronavirus disease 2019(COVID-19). Therefore, this study aimed to investigate the applicability of an in-house Sanger-based method for identifying SARS-CoV-2 variants, particularly focusing on newly emerged Omicron variants, and updating the epidemiology of COVID-19 during the 8th wave in Hiroshima Prefecture. Results A total of 639 saliva samples of individuals who had tested positive for COVID-19, received from Hiroshima City Medical Association Clinical Laboratory Center between February 01, 2023, and March 12, 2024, were included in the study. SARS-CoV-2 variants were identified in 69.3% (443/639) with the mean viral titer 2 × 106 copies/mL, and high viral titer in Omicron variant XBC.1.6* (5 × 108 copies/mL) using RT-qPCR. By partial Spike gene-based sequencing using the Sanger Sequencing strategy, Omicron sub-lineages XXB.1, BA.5, and EG.1 were identified during different periods. A comprehensive phylogenetic analysis of 7383 SARS-CoV-2 strains retrieved from GISAID, collected in Hiroshima from the onset of the COVID-19 pandemic in early 2020 until July 2024, revealed the dynamic evolution of SARS-CoV-2 variants over time. The study found a similar pattern of variant distribution between the full genomes from GISAID, and the partial genomes obtained from our screening strategy during the same period. Conclusions Our study revealed that all SARS-CoV-2 viruses circulated in Hiroshima were Omicron variants and their sub-lineages during the 8th wave outbreak in Hiroshima. Persistent molecular surveillance of SARS-CoV-2 is needed for the decision-making and strategic planning of the public promptly. Our study added evidence for the usefulness of SARS-CoV-2 spike gene partial sequencing-based SARS-CoV-2 variant identification strategy for mass screening and molecular surveillance even though the evolution of newly emerged various SARS-CoV-2 Omicron variants.

Objective To identify the clinical features and pathogenic variants in two unrelated families with gnathodiaphyseal dysplasia (GDD), a rare genetic bone disorder. Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members. Peripheral blood samples (3-4 mL) were collected from the probands and their parents. Genomic DNA was extracted by standard phenol-chloroform method. Whole exome sequencing (WES) was performed to screen for candidate pathogenic gene variants of the probands. PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members. The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families, evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis. Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands. In family 1, the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene, while in family 2, the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5. These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356 (p.Cys356Gly) and amino acid glycine with glutamic acid at position 518 (p.Gly518Glu) in the ANO5 protein, respectively. Conclusions This study first identified the pathogenic variant c.1 066T＞G (p.Cys356Gly) in Chinese population, provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.

Abstract Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.

Abstract Background Modifiers significantly impact disease phenotypes by modulating the effects of disease-causing variants, resulting in varying disease manifestations among individuals. However, identifying genetic interactions between modifier and disease-causing variants is challenging. Results We developed MDVarP, an ensemble model comprising 1000 random forest predictors, to identify modifier ~ disease-causing variant combinations. MDVarP achieves high accuracy and precision, as verified using an independent dataset with published evidence of genetic interactions. We identified 25 novel modifier ~ disease-causing variant combinations and obtained supporting evidence for these associations. MDVarP outputs a class label ("Associated-pair" or "Nonrelevant-pair") and two prediction scores indicating the probability of a true association. Conclusions MDVarP prioritizes variant pairs associated with phenotypic modulations, enabling more effective mapping of functional contributions from disease-causing and modifier variants. This framework interprets genetic interactions underlying phenotypic variations in human diseases, with potential applications in personalized medicine and disease prevention.

Abstract Background Although there have been reports of COVID-19 breakthrough infections in vaccinated individuals, the vaccines have demonstrated a high efficacy in preventing severe illness and death. Nepal has reported fewer studies of COVID-19 breakthrough infections. Hence, this study has objective to assess the prevalence, and to describe clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) breakthrough infection. Methods This descriptive study was conducted from January to December 2022. The study enrolled 200 individuals who had received the recommended doses of the COVID-19 vaccine and they were RT-PCR positive diagnosed with vaccine breakthrough infections after 14 days of completing the vaccination course. The patient’s demographic and clinical profiles, as well as their outcomes in terms of severity, length of hospital stay, and mortality were recorded. Results The prevalence of SARS-CoV2 infection was 6.3% (547/8682). Among fully vaccinated personnel, the prevalence of breakthrough infections was 6.2% (200/3175). This study found the Omicron variants in respondents. The mean age of the patients was 38.28 years, and 41.5% (83/200) of the breakthrough cases were healthcare workers. The mean time gap between the second dose of vaccination and a positive RT-PCR test was 354.68 days. Of the 200 breakthrough cases, 89% (178) had mild symptoms, 9% (17) had moderate symptoms requiring hospitalization, and 2% (4) were severe cases that required intensive care facility. Among the severe cases, 3 out 4 were above 60 years old. Furthermore, the patients greater than 60 years had longer hospital stays (p

Abstract Uganda is a developing low-income country with a low incidence of colorectal cancer, which is steadily increasing. Ugandan colorectal cancer (CRC) patients are young and present with advanced-stage disease. In our population, there is a scarcity of genetic oncological studies, therefore, we investigated the mutational status of CRC tissues, focusing in particular on the adenomatous polyposis coli (APC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and SMAD4 genes. Our objective was to determine whether there were any differences between other populations and Ugandan patients. We performed next-generation sequencing on the extracted DNA from formalin-fixed paraffin-embedded adenocarcinoma samples from 127 patients (mean (SD) age: 54.9 (16.0) years; male:female sex ratio: 1.2:1). Most tumours were located in the rectum 56 (44.1%), 14 (11%) tumours were high grade, and 96 (75.6%) were moderate grade CRC. Stage III + IV CRC tumours were found in 109 (85.8%) patients. We identified 48 variants of APC, including 9 novel APC mutations that were all pathogenic or deleterious. For PIK3CA, we found 19 variants, of which 9 were deleterious or pathogenic. Four PIK3CA novel pathogenic or deleterious variants were included (c.1397C > G, c.2399_2400insA, c.2621G > C, c.2632C > G). Three SMAD4 variants were reported, including two pathogenic or deleterious variants (c.1268G > T, c.556dupC) and one tolerant (c.563A > C) variant. One novel SMAD4 deleterious mutation (c.1268G > T) was reported. In conclusion, we provide clinicopathological information and new genetic variation data pertinent to CRC in Uganda.

Abstract Background Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. Methods As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. Results The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. Conclusions Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.

Cystic fibrosis (CF) is a genetic disease characterized by a wide spectrum of severity, resulting from the inheritance of a mutant allele of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). The aim of the study was to present a CFTR mutation analysis among the Albanian population and to identify rare variants.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the main cause of dementia. Its etiology remains largely unclear, though genetic and environmental factors appear to confer susceptibility to AD development. This study assessed the role of ATP-binding Cassette A Subfamily 7 (ABCA7) genetic polymorphisms, as ongoing research suggests they have a role in the development of AD. We conducted a PubMed, Google Scholar, and Scopus search to identify and assess all AD studies examining ABCA7 variants in different populations and ethnicities. The last search was conducted on February 8, 2023. Inclusion and exclusion criteria were applied and only the studies that met the inclusion criteria were included in this review. Seventeen studies were finally included. According to the results, ABCA7 variants infer different risks for AD among populations with different ancestries. African American populations show a higher risk for AD, carrying the five novel variants rs115550680, rs142076058, rs10405305, rs3764647, and rs567222111. Asian populations also have an increased risk for AD, harboring three variants. ABCA7 genetic variability contributes to AD development and shows racial disparities. African American and Asian populations seem to be at greater risk of developing AD. These results may assist future research efforts for the early and accurate diagnosis of AD. Moreover, further exploration of the mechanisms of ABCA7 in the context of AD could identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background and Purpose: Small‐fiber neuropathy (SFN) affects only unmyelinated and thin myelinated fibers. It may be caused by amyloidogenic mutations of the transthyretin (TTR) gene, but not all TTR gene variants are pathogenic. The nonamyloidogenic c.76G>A (rs1800458) and c.337‐18G>C (rs36204272) variants of TTR were recently reported to be associated with SFN. We investigated this putative association by analyzing TTR gene sequencing data retrospectively for two cohorts of patients, one with SFN and a control group. Methods: In this retrospective single‐center study, we analyzed the frequency of the c.76G>A and c.337‐18G>C TTR gene variants in a cohort of patients meeting a strict definition of SFN, with or without dysautonomia, a control cohort of patients investigated for nonneurological conditions, and the gnomAD international database. Results: We included 55 SFN patients in this study, 17 of whom had dysautonomia. The allelic frequencies of the two variants in our cohort of 55 SFN patients were 7.27% for c.76G>A TTR and 5.25% for c.337‐18G>C. The frequencies of both variants were statistically similar in the 337 control patients and the gnomAD database. Conclusions: The c.76G>A and c.337‐18G>C TTR gene variants are not associated with SFN. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor‐α (TNF‐α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF‐α promoter region are considered to influence its transcription and are associated with the TNF‐α level. Therefore, it is worth detecting the association of the variants in the TNF‐α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF‐α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p =.002, OR = 1.563; 95% CI: 1.18–2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log‐additive mode (p =.002, OR = 1.56; 95% CI: 1.17–2.07). The haplotypes analysis identified that the rs1799724‐rs1800629CA was associated with high risk of the development of T2DM (p =.002, OR = 1.559, 95% CI: 1.173–2.072). Conversely, the rs1799724‐rs1800629CG was a protective haplotype of T2DM (p =.001, OR = 0.732, 95% CI: 0.607–0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p =.017). Our results revealed that the rs1800629 in the TNF‐α gene promoter region was associated with T2DM in a Chinese Han population. [ABSTRACT FROM AUTHOR]

Given discrepancies identified in current veterinary anatomy textbooks, we aimed to re-examine the anatomic patterns of the extensor tendons of the manus considering their prevalence and measurements. This study was conducted based on the dissection of the right and left distal forelimbs of 22 domestic short-haired cats (12 females and 10 males), fixed in 10% formalin solution. In the most frequent specimens (23 of 44 distal limbs -52.3%-), the m. extensor digitorum lateralis consisted of three bellies which sent three tendons to digits III-V and a tendon branch to digit II, which united with the extensor digiti I et II tendon to that digit, or inserted onto the medial aspect of the metacarpophalangeal joint capsule of digit III in 9.1% of distal limbs. In other cases, the tendon branch to digit II was absent or arose directly from the most medial belly of this muscle in 25% and 13.6% of distal limbs, respectively. The m. extensor digiti I et II was found to have two unequal bellies, leading to two medial and lateral tendons. The tendons exhibited 5 different configurations. In the most common specimens (68.2%), the medial tendon was bifurcated into two branches to digit I and the medial aspect of digit II as well as the lateral tendon ran to the lateral aspect of digit II to join the corresponding tendon of the extensor digitorum communis. According to this study, the current concepts of veterinary anatomical texts about the common pattern of the extensor tendons of the manus of domestic cats need to be revised, which could greatly contribute to the teaching of veterinary anatomy. [ABSTRACT FROM AUTHOR]

The African Vultures Optimization Algorithm (AVOA) is a recently developed meta-heuristic algorithm inspired by the foraging behavior of African vultures in nature. This algorithm has gained attention due to its simplicity, flexibility, and effectiveness in tackling many optimization problems. The significance of this review lies in its comprehensive examination of the AVOA’s development, core principles, and applications. By analyzing 112 studies, this review highlights the algorithm’s versatility and the growing interest in enhancing its performance for real-world optimization challenges. This review methodically explores the evolution of AVOA, investigating proposed improvements that enhance the algorithm’s ability to adapt to various search geometries in optimization problems. Additionally, it introduces the AVOA solver, detailing its functionality and application in different optimization scenarios. The review demonstrates the AVOA’s effectiveness, particularly its unique weighting mechanism, which mimics vulture behavior during the search process. The findings underscore the algorithm’s robustness, ease of use, and lack of dependence on derivative information. The review also critically evaluates the AVOA’s convergence behavior, identifying its strengths and limitations. In conclusion, the study not only consolidates the existing knowledge on AVOA but also proposes directions for future research, including potential adaptations and enhancements to address its limitations. The insights gained from this review offer valuable guidance for researchers and practitioners seeking to apply or improve the AVOA in various optimization tasks. [ABSTRACT FROM AUTHOR]

Abstract Predicting epidemic evolution is essential for making informed decisions and guiding the implementation of necessary countermeasures. Computational models are vital tools that provide insights into illness progression and enable early detection, proactive intervention, and targeted preventive measures. This paper introduces Sybil, a framework that integrates machine learning and variant-aware compartmental models, leveraging a fusion of data-centric and analytic methodologies. To validate and evaluate Sybil’s forecasts, we employed COVID-19 data from several European and U.S. states. The dataset included the number of new and recovered cases, fatalities, and variant presence over time. We evaluate the forecasting precision of Sybil in periods in which there is a change in the trend of the pandemic evolution or a new variant appears. Results demonstrate that Sybil outperforms conventional data-centric approaches, being able to forecast accurately the changes in the trend, the magnitude of these changes, and the future prevalence of new variants.

Dupuytren’s contracture (DC) is a fibroproliferative disorder of the palmar fascia characterised by the digits’ flexion contractures and is associated with abnormal build-up of type III collagen. The prevalence of the disease is reported to be highest among Northern European descendants. However, the disease is widespread globally with varying prevalence. DC is a multifactorial disease, having both genetic and environmental factors contributing to the causality of the disease. Over the years, various studies have been conducted to understand the molecular mechanism and genetic aspects of DC but there is a lack of reports on the variants found in the exonic regions. Most reports are backdated making it necessary to re-evaluate the variants to further understand the genetic aetiology of DC. In this review, we first highlight the genetic aspects and previous genetic studies on DC. The report is followed by a discussion on the molecular pathways suggested to be associated with DC and a summary of the genetic variants in the exonic regions found in DC and their connections with the molecular pathways. A total of nine variants were reported originating from six genes comprising three pathways. Most variants reported are involved in the Wnt signalling pathway. Moreover, all variants identified are in European/Caucasian subjects and the variants found in the exonic regions are missense variants. A comparison of these findings with variants from populations of other regions can be conducted to identify the variants with the most occurrence to act as biomarkers or therapeutic targets for DC.

This paper discusses Alija Isakovic's commitment and contributions to the processes of reaffirmation Bosnian language within Serbo-Croatian linguistic unitarism in the second half of the 20th century. We have shown the historical context of the language policy and Isakovic's significant work for the selected theme. The focus of this paper is on the sociolinguistic text "Varijante na popravnom ispitu" and the lexicographic work Rječnik karakteristične leksike u bosanskome jeziku, which represents a kind of struggle for the specificity of the Bosnian variant and characteristic lexicon of Bosnian language in that linguistic norm. The results of Isakovic's work are noticeable in the Yugoslav period (partial change in the field of official language policy), but it's also noticeable in period of state independence when language policy was created based on Isaković's concepts.

Abstract Corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), claimed millions globally. After the report of the first incidence of the virus, variants emerged with each posing a unique threat than its predecessors. Though many advanced diagnostic assays like real-time PCR are available for screening of SARS-CoV-2, their applications are being hindered because of accessibility and cost. With the advent of rapid assays for antigenic screening of SARS-CoV-2 made diagnostics far easy as the assays are rapid, cost-effective and can be used at point-of-care settings. In the present study, a fusion construct was made utilising highly immunogenic B cell epitopes from the three important structural proteins of SARS-CoV-2. The protein was expressed; purified capture mAbs generated and rapid antigen assay was developed. Eight hundred and forty nasopharyngeal swab samples were screened for the evaluation of the developed assay which showed 37.14% positivity, 96.51% and 100% sensitivity and specificity respectively. The assay developed was supposed to identify SARS-CoV-2 wild-type as well as variants of concern and variants of importance in real-time conditions.