Search

Objective: The 2013 TCGA identified four molecular subgroups of endometrial cancer; however, the data results for most of the pathological features were varied and of low value for clinical application. Therefore, a meta-analysis of articles related to the clinicopathological features of molecular typing was performed to observe how the prevalence of the four subgroups varied across different pathological features and whether they were associated with certain specific pathological features and to understand how molecular typing may influence current pathological assessments. Methods: PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP were searched from the time of library construction until May 2024, and the following data were extracted: histological type, FIGO grade, FIGO stage, LVSI, depth of muscularis propria infiltration, and lymph node status of each TCGA group. Two reviewers used the Cochrane Diagnostic Research Scale assessment, and the data were analyzed using Review Manager 5.4.1 and Stata 14.0. Results: Fourteen diagnostic research papers were included in this study, with a total of 4,776 patients with endometrial cancer. Non-estrogen-related endometrial carcinoma (NEEC) vs. estrogen-related endometrial carcinoma (EEC) was low in polymerase epsilon (POLE) (OR = 0.49), microsatellite instability (MSI) (OR = 0.45), and copy number low (CNL) (OR = 0.11), while it was high in CNH (OR = 26.76). G3 EEC vs. G1–2 EEC POLE (OR = 1.98), MSI (OR = 1.74), and CNH (OR = 5.57) were high, whereas it was low in CNL (OR = 0.23), low in FIGO II–IV vs. FIGO I in POLE (OR = 0.39) and CNH (OR = 0.64), and high in FIGO II–IV vs. FIGO I in CNH (OR = 3.05). There was no difference in MSI prevalence in FIGO II–IV vs. FIGO I. POLE (OR = 0.64) and CNL (OR = 0.75) were low in myometrial invasion depths ≥50% and lower in myometrial invasion depths <50%, and CNL (OR) was higher in CNH (OR) than in myometrial invasion depths <50%. There was no difference in MSI between different myometrial invasion depths. MSI (OR = 1.69) and CNH (OR = 2.12) were higher in lymphatic vascular infiltration (LVSI) vs. no LVSI; CNL (OR = 0.39) was lower in LVSI than in no LVSI. There was no difference in POLE in the presence or absence of LVSI. Lymph node metastasis with and without lymph node metastasis in POLE (OR = 0.25) and CNL (OR = 0.31) were lower, and CNH (OR = 3.06) was higher in lymph node metastasis than in no lymph node metastasis. There was no difference in MSI in the presence or absence of lymph node metastasis. Conclusions: POLE patients predominated in pathological features of early-stage endometrial cancer and had better prognosis. MSI patients were more likely to be found in EEC and G3 EEC as well as LVSI. Nearly half of G3 EEC as well as LVSI were present in MSI patients, and CNH patients were more likely to be found to have pathological features of advanced endometrial cancer and poor prognosis, providing evidence that CNH is a high-risk cancer. Patients with CNL were more likely to be found to have pathological features of early-stage endometrial cancer and good prognosis, and CNL was present in large numbers in both early-stage and late-stage endometrial cancers. CNL does not yet have a precise prognostic value. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024563661. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS). Methods 97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types (P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% (Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% (Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect. [ABSTRACT FROM AUTHOR]

Background: The genus Bartonella is composed of Gram-negative, fastidious, facultative intracellular bacteria that can cause bacteremia in mammals and various disorders in humans. Rodents have been reported as reservoirs of more than 30 Bartonella species, seven of which cause zoonotic infections. Materials and Methods: In the present study, the isolation of Bartonella sp. was attempted from 150 spleen samples from 13 rodent species (mostly Apodemus species) from three geographically different regions in Turkey. Results:Bartonella sp. was successfully isolated from 65 of these 150 samples (43%). The prevalences of Bartonella sp. in tested rodents in the regions of Giresun, Yozgat, and Burdur were 68%, 44%, and 16%, respectively. Using polymerase chain reaction/sequence analysis of the citrate synthase-coding gene (gltA), Bartonellaisolates were classified seven species including B. taylorii, B. grahamii, B. birtlesii, B. mastomydis, and three putatively new Bartonella species. We performed further identification techniques for one of the three Bartonella species that were different from the validated Bartonella species according to the gltA sequence analysis. Conclusion: Here, we report the genomic and phenotypic characterization of Bartonella sp. strain G70 that was isolated from the splenic tissue of an Apodemus uralensis (Pallas 1881), the Ural field mouse, captured in the Giresun region of northeastern Turkey. Bartonella sp. strainG70 (RSKK 22001) was characterized by whole genome and partial gene (gltA, 16S ribosomal RNA) sequencing and comparison, scanning electron microscopy, biochemical tests, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. This novel Bartonella is a Gram-negative, rod-shaped bacterium and has neither flagella nor pili. The genome from strain G70 was 1,606,969-bp-long with a G + C content of 35.7%. Bartonella rochalimae was found to be the closest phylogenetic relative of strain G70 (OrthoANI = 90.5%, digital DNA–DNA hybridization = 41.4%). We therefore propose that this new species be named Bartonella bilalgolemii sp. nov. with strain G70T as the type strain. [ABSTRACT FROM AUTHOR]

The article discusses a rare case of recurrent metastatic spermatocytic tumor successfully treated with salvage systemic chemotherapy. Spermatocytic tumors are a rare subtype of testicular neoplasm, with less than 1% of all testicular neoplasms being of this type. The patient in the case study had an aggressive form of the tumor but showed a favorable response to second-line chemotherapy, highlighting the need for further research and collaboration in understanding the molecular landscape of rare tumors like spermatocytic tumors. [Extracted from the article]

Objective of this study was to identify pharmaceuticals and natural products utilized in clinical practice that have the potential to inhibit the expression of Cellular-myelocytomatosis oncogene (c-Myc), based on a review of the current literature. The aim was to assess the effect of the specified drugs on c-Myc expression in TNBC cells, determine the most potent inhibitor, and evaluate its impact on TNBC cell proliferation, invasive migration, and apoptosis, as well as the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) at both the gene and protein levels. Explore its potential for treatment or adjuvant therapy for triple-negative breast cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify gene and protein expression levels. Flow cytometry was employed to measure cell proliferation and apoptosis, while the Transwell assay was utilized to assess cell invasion and migration. Results: Harmaline emerged as the strongest inhibitor, significantly decreasing the expression of c-Myc at both the gene and protein levels in TNBC cells. It also inhibited cell proliferation, invasion, and migration while promoting apoptosis in TNBC cells. Additionally, there was a varying increase in the expression of ER and PR genes and proteins. While the expression of the HER-2 gene was elevated, there was no significant change in HER-2 protein levels. Notably, the expression of the phosphorylated HER-2 protein increased. Conclusion: Harmaline was found to promote apoptosis and inhibit cell proliferation, invasion, and migration in TNBC cells by targeting the inhibition of c-Myc. It also induced the re-expression of the ER, PR, and HER-2 genes, as well as the ER and PR proteins. [ABSTRACT FROM AUTHOR]

The changing epidemiological profile of invasive Haemophilus influenzae infections (IIHi) is noted in the post-vaccination era. The aim of this study was to characterize phenotypically and genotypically invasive Haemophilus influenzae (Hi) isolates detected in Tunisian pediatric patients. A retrospective study was conducted in the microbiology laboratory of the Children's Hospital of Tunis over ten years (2013–2023). All IIHi cases were included. Molecular identification and serotyping were conducted through qPCR. Molecular typing and analysis of resistance genes were extracted from whole genome sequencing data. Fifty-three IIHi cases were collected. Children under five years old were the most affected (81%). Non-typable isolates (NTHi) were predominant (79%) followed by serotype b (17%) and serotype a (4%). Genetic diversity was observed, essentially among NTHi isolates. Resistance of Hi isolates to ampicillin, amoxicillin–clavulanic acid and cefotaxime (CTX) were 42%, 20% and 4%, respectively. Thirteen isolates (29%) produced a beta-lactamase and 14 carried the blaTEM-1 gene (kappa = 0.95). For non-enzymatic resistance, group 3 (n = 12) showed resistance to ampicillin. Groupe 4 (n = 9, NTHi) showed discordances with resistance to CTX. The emergence of resistance to CTX is concerning. Continuous surveillance through molecular tools in conjunction with phenotypic and clinical data is necessary to ensure better management of these infections. [ABSTRACT FROM AUTHOR]

Abstract Objective The study aimed to identify distinct molecular subtypes of endometrial cancer (EC) by immunohistochemistry and to analyze their pathological characteristics, independent prognostic factors, and patient survival outcomes for potential clinical applications. Method 576 patients with preoperative EC confined to the uterus were divided into three subgroups based on the immunohistochemical detection method: MMR-deficiency (MMRd), P53 wild type (P53wt) and P53 abnormal (P53abn). These subgroups were retrospectively analyzed, and their pathological characteristics, prognostic factors and survival outcomes were compared. Results We identified 401 (69.6%), 123 (21.4%), and 52 (9%) cases of P53wt, MMRd, and P53abn subgroups, respectively. A significant difference was observed in the median age of onset, tumor stage, high-grade tumor differentiation, non-endometrioid carcinoma, myometrial invasion, lymphovascular invasion, the incidence of lymph node metastasis postoperative, and expression of ER and PR receptors among the three groups. Pathological type, lymphovascular invasion, ER and PR expression were identified as independent prognostic factors for disease-free survival (DFS). Additionally, pathological type, lymphovascular invasion, myometrial invasion, and PR expression were recognized as independent prognostic factors for overall survival (OS) in the study cohort. However, the survival outcome for P53abn was the worst, with lymphovascular invasion identified as an independent prognostic factor for DFS. Lymph node status, FIGO stage, and ER expression were identified as independent prognostic factors for OS. Conclusion The study concludes that immunohistochemical detection-based subtyping of EC holds clinical practicality and can be employed to explore both pathological and clinical prognoses for EC patients.

Abstract Background Scabies, an infestation of the mite Sarcoptes scabiei, has seen an increase in clinical diagnoses in the Netherlands since 2011. This study aimed to analyse PCR-positive S. scabiei skin samples through partial genome sequencing and to link findings to patient epidemiological characteristics. Methods Skin samples were collected from individuals in the Netherlands between January 2016 and January 2023. On the PCR-positive S. scabiei skin samples, partial mitochondrial cytochrome c oxidase subunit 1 gene (cox1) sequencing was performed to assess genetic variability. Epidemiological information was collected through interviews. We examined associations between cox1 subtypes, epidemiological factors and treatment outcomes. Results Sequencing results were obtained from 128 patients, with epidemiological information available for 55 (43%) of these patients. Fifteen distinct cox1 subtypes were identified. Subtype 01 was most prevalent (45%) and present across all age groups and social settings. The remaining subtypes were less common and not consistently found in all contexts. Five clusters were identified, each with identical cox1 subtypes. Comparative analysis with GenBank sequences revealed genetic similarities with strains from Australia, the USA and China, suggesting the global distribution and transmission of specific subtypes. A substantial proportion (73%) of patients with scabies required multiple treatments to eradicate the infestation, with no subtype-related differences. Conclusions This is the first study linking S. scabiei sequencing results to patient epidemiological data. Several subtypes clustered in specific geographic regions and social contexts, underscoring localised transmission patterns. Further research with larger sample sizes is needed to enhance our understanding of the transmission of this mite. This study provides valuable insights that will strengthen scabies control efforts. Graphical Abstract

Abstract Objectives To determine the prevalence, trends, and potential nosocomial transmission events of the hidden reservoir of rectal carriage of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). Methods From 2013 to 2022, yearly point prevalence surveys were conducted in a large Dutch teaching hospital. On the day of the survey, all admitted patients were screened for ESBL-E rectal carriage using peri-anal swabs and a consistent and sensitive selective culturing method. All Enterobacterales phenotypically suspected of ESBL production were analysed using whole genome sequencing for ESBL gene detection and clonal relatedness analysis. Results On average, the ESBL-E prevalence was 4.6% (188/4,119 patients), ranging from 2.1 to 6.6% per year. The ESBL-prevalence decreased on average 5.5% per year. After time trend correction, the prevalence in 2016 and 2020 was lower compared to the other year. Among the ESBL-E, Escherichia coli (80%) and CTX-M genes (85%) predominated. Potential nosocomial transmission events could be found in 5.9% (11/188) of the ESBL-E carriers. Conclusions The ESBL-E rectal carriage prevalence among hospitalized patients was 4.6% with a downward trend from 2013 to 2022. The decrease in ESBL-E prevalence in 2020 could have been due to the COVID-19 pandemic and subsequent countrywide measures as no nosocomial transmission events were detected in 2020. However, the persistently low ESBL-E prevalences in 2021 and 2022 suggest that the decline in ESBL-E prevalence goes beyond the COVID-19 pandemic, indicating that overall ESBL-E carriage rates are declining over time. Continuous monitoring of ESBL-E prevalence and transmission rates can aid infection control policy to keep antibiotic resistance rates in hospitals low.

Abstract Introduction The global increase of multidrug-resistant organisms (MDROs) is one of the most urgent public health threats affecting both humans and animals. The One Health concept emphasizes the interconnectedness of human, animal and environmental health and highlights the need for integrated approaches to combat antimicrobial resistance (AMR). Although the sharing of environments and antimicrobial agents between companion animals and humans poses a risk for MDRO transmission, companion animals have been studied to a lesser extent than livestock animals. This study therefore used core genome multilocus sequence typing (cgMLST) to investigate the genetic relationships and putative transmission of MDROs between humans and pets. Methods This descriptive integrated typing study included 252 human isolates, 53 dog isolates and 10 cat isolates collected from 2019 to 2022 at the Charité University Hospital in Berlin, Germany. CgMLST was performed to characterize methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant gram-negative bacteria. The genetic diversity of the MDROs of the different host populations was determined and compared based on sequence type and core genome complex type. Results Within this study the majority of samples from pets and humans was genetically distinct. However, for some isolates, the number of allelic differences identified by cgMLST was low. Two cases of putative household transmission or shared source of VR E. faecium and MDR E. coli between humans and pets were documented. Conclusions The interaction between humans and their pets appears to play a minor role in the spread of the MDROs studied. However, further research is needed. This study emphasizes the importance of comprehensive molecular surveillance and a multidisciplinary One Health approach to understand and contain the spread of MDROs in human and animal populations. Trial Registration The study is registered with the German Clinical Trials Register (DRKS00030009).

Coagulase-negative staphylococci (CoNS) colonize human skin and mucosal membranes, which is why they are considered harmless commensal bacteria. Two species, Staphylococcus epidermidis and Staphylococcus haemolyticus belong to the group of CoNS species and are most frequently isolated from nosocomial infections, including device-associated healthcare-associated infections (DA-HAIs) and local or systemic body-related infections (FBRIs). Methicillin resistance, initially described in Staphylococcus aureus, has also been reported in CoNS species. It is mediated by the mecA gene within the staphylococcal cassette chromosome (SCCmec). SCCmec typing, primarily using PCR-based methods, has been employed as a molecular epidemiological tool. However, the introduction of whole genome sequencing (WGS) and next-generation sequencing (NGS) has enabled the identification and verification of new SCCmec types. This review describes the current distribution of SCCmec types, subtypes, and variants among CoNS species, including S. epidermidis, S. haemolyticus, and S. capitis. The literature review focuses on recent research articles from the past decade that discuss new combinations of SCCmec in coagulase-negative Staphylococcus. The high genetic diversity and gaps in CoNS SCCmec annotation rules underscore the need for an efficient typing system. Typing SCCmec cassettes in CoNS strains is crucial to continuously updating databases and developing a unified classification system. [ABSTRACT FROM AUTHOR]

The Staphylococcus genus comprises multiple pathogenic and opportunistic species that represent a risk to public health. Epidemiological studies require accurate taxonomic classification of isolates with enough resolution to distinguish clonal complexes. Unfortunately, 16 S rRNA molecular analysis and phenotypic characterization cannot distinguish all species and do not offer enough resolution to assess intraspecific diversity. Other approaches, such as Multilocus Sequence Tagging, provide higher resolution; however, they have been developed for Staphylococcus aureus and a few other species. Here, we developed a set of genus-targeted primers using five orthologous genes (pta, tuf, tpi, groEs, and sarA) to identify all Staphylococcus species within the genus. The primers were initially evaluated using 20 strains from the Collection of Microorganisms of Interest in Animal Health from AGROSAVIA (CMISA), and their amplified sequences were compared to a set of 33 Staphylococcus species. This allowed the taxonomic identification of the strains even on close species and the establishment of intraspecies diversity. To enhance the scope and cost-effectiveness of the proposed strategy, we customized the primer sets for an Illumina paired-end amplicon protocol, enabling gene multiplexing. We assessed five genes across 177 strains, generating 880 paired-end libraries from the CMISA. This approach significantly reduced sequencing costs, as all libraries can be efficiently sequenced in a single MiSeq run at a fraction (one-fourth or less) of the cost associated with Sanger sequencing. In summary, this method can be used for precise identification and diversity analysis of Staphylococcus species, offering an advancement over traditional techniques in both resolution and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Combined large cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine carcinoma, accounting for approximately 10% of large cell neuroendocrine carcinoma (LCNEC). Mainly composed of coexisting adenocarcinoma components, with strong invasiveness and poor prognosis. The treatment regimen for CLCNEC mainly refers to complete surgical resection as the first choice in the early stage, while patients with stage II or higher require adjuvant treatment. At present, research on CLCNEC is mostly small sample and retrospective, and there is no consensus on whether molecular typing and treatment should be carried out. There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Antimicrobial resistance represents a challenge to public health systems because of the array of resistance and virulence mechanisms that lead to treatment failure and increased mortality rates. Although for years the main driver of carbapenem resistance in Italy has been the Klebsiella pneumoniae KPC carbapenemase, recent years have seen an increase in VIM and NDM metallo-beta-lactamases (MBLs). We conducted a five-year survey of New Delhi Metallo-beta-Lactamase (NDM)-producing Klebsiella pneumoniae (NDM-Kpn) clinical isolates from the Lazio region, Italy; the study aimed to elucidate the molecular mechanisms underpinning their resistant and virulent phenotype. Methods: Antimicrobial susceptibility was evaluated by automated systems and broth microdilution. In silico analysis of acquired resistance and virulence genes was performed using whole-genome sequencing (WGS), molecular typing through MLST, and core genome multi-locus sequence typing (cgMLST). Conclusions: A total of 126 clinical NDM-Kpn isolates were collected from 19 distinct hospitals in the Lazio region. Molecular analysis highlighted the existence of NDM-1 (108/126) and NDM-5 (18/126) variants, 18 Sequence Types (STs), and 15 Cluster Types (CTs). Notably, 31/126 isolates displayed a virulence score of 4, carrying ybt, ICEKp, iuc, and rmp genes. This study identified a variety of NDM-Kpn STs, mainly carrying the blaNDM-1 gene, with a significant number linked to high-risk clones. Of these isolates, 24.6% showed high-level resistance and virulence, emphasizing the risk of the spread of strains that combine multi-drug-resistance (MDR) and virulence. Proactive surveillance and international collaborations are needed to prevent the spread of high-risk clones, as well as further research into new antimicrobial agents to fight antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with the incidence and prognosis of various malignancies, most notably endometrial cancer (EC). This study investigated the connection between diabetes and EC, with a specific focus on elucidating the biological implications of the diabetes mellitus (DM)-related gene WFS1. Methods: Using the CTD, GeneCards, and GSEA databases, we identified WFS1 as a diabetes-related gene and then conducted an extensive investigation focusing on WFS1 in the context of EC. First, we identified WFS1 as the target gene and obtained EC data from the TCGA database. Then, comprehensive analyses and verification experiments, including differential expression analysis, prognostic modeling, functional enrichment analysis, gene mutation profiling, assessment of immune cell infiltration, immunophenoscore (IPS), tumor stemness index scoring, drug sensitivity analysis, single-cell transcriptomic analysis, glycolytic pathway analysis, and clinical verification, were performed to comprehensively evaluate the clinical value of WFS1 in EC. Results: The EC group had significantly lower WFS1 expression, with an AUC of 0.857 for the ROC diagnostic curve. Overall survival analysis revealed that WFS1 was an independent risk factor for EC; low WFS1 expression was correlated with a poor prognosis. Stemness index analysis revealed that decreased WFS1 expression was associated with increased tumor grade and enhanced tumor stemness, suggesting increased malignancy of EC. In addition, WFS1 expression was correlated with tumor microenvironment features such as immune cell infiltration. WFS1 was also associated with tumor drug resistance. Conclusion: EC patients with low WFS1 expression have a worse prognosis. WFS1 can be used as diagnostic and prognostic marker for EC. [ABSTRACT FROM AUTHOR]

Background: Scabies, an infestation of the mite Sarcoptes scabiei, has seen an increase in clinical diagnoses in the Netherlands since 2011. This study aimed to analyse PCR-positive S. scabiei skin samples through partial genome sequencing and to link findings to patient epidemiological characteristics. Methods: Skin samples were collected from individuals in the Netherlands between January 2016 and January 2023. On the PCR-positive S. scabiei skin samples, partial mitochondrial cytochrome c oxidase subunit 1 gene (cox1) sequencing was performed to assess genetic variability. Epidemiological information was collected through interviews. We examined associations between cox1 subtypes, epidemiological factors and treatment outcomes. Results: Sequencing results were obtained from 128 patients, with epidemiological information available for 55 (43%) of these patients. Fifteen distinct cox1 subtypes were identified. Subtype 01 was most prevalent (45%) and present across all age groups and social settings. The remaining subtypes were less common and not consistently found in all contexts. Five clusters were identified, each with identical cox1 subtypes. Comparative analysis with GenBank sequences revealed genetic similarities with strains from Australia, the USA and China, suggesting the global distribution and transmission of specific subtypes. A substantial proportion (73%) of patients with scabies required multiple treatments to eradicate the infestation, with no subtype-related differences. Conclusions: This is the first study linking S. scabiei sequencing results to patient epidemiological data. Several subtypes clustered in specific geographic regions and social contexts, underscoring localised transmission patterns. Further research with larger sample sizes is needed to enhance our understanding of the transmission of this mite. This study provides valuable insights that will strengthen scabies control efforts. [ABSTRACT FROM AUTHOR]

Introduction: Mammals are the main hosts for Brucella sp., agents of worldwide zoonosis. Marine cetaceans and pinnipeds can be infected by Brucella ceti and B. pinnipedialis, respectively. Besides classical bacteriological typing, molecular approaches such as MLVA, MLSA, and whole-genome sequencing (WGS) can differentiate these species but are cumbersome to perform. Methods: We compared the DNA and genome sequences of 12 strains isolated from nine marine mammals, with highly zoonotic B. melitensis, B. abortus, and B. suis, and the publicly available genomes of B. ceti and B. pinnipedialis. In silico pipelines were used to detect the antimicrobial resistance (AMR), plasmid, and virulence genes (VGs) by screening six open-source and one home-made library. Results and discussion: Our results show that easier-to-use HRM-PCR, Bruceladder, and Suis-ladder can separate marine Brucella sp., and the results are fully concordant with other molecular methods, such as WGS. However, the restriction fragment length polymorphism (RFLP) method cannot discriminate between B. pinnipedialis and B. ceti B1-94-like isolates. MLVA-16 results divided the investigated strains into three clades according to their preferred host, which was confirmed in WGS. In silico analysis did not find any AMR and plasmid genes, suggesting antimicrobial susceptibility of marine Brucella, while the presence of the VGs btpA gene was variable dependent on the clade. Conclusion: The HRM-PCR and Suis-ladder are quick, easy, and cost-effective methods to identify marine Brucella sp. Moreover, in silico genome analyses can give useful insights into the genetic virulence and pathogenicity potential of marine Brucella strains. [ABSTRACT FROM AUTHOR]

The incidence of brain tumors among children is second only to acute lymphoblastic leukemia, but the mortality rate of brain tumors has exceeded that of leukemia, making it the most common cause of death among children. Medulloblastoma (MB) is the most common type of brain tumor among children. Malignant brain tumors have strong invasion and metastasis capabilities, can spread through cerebrospinal fluid, and have a high mortality rate. In 2010, the World Health Organization first divided MB into four molecular subtypes based on molecular markers: WNT, Sonic hedgehog (SHH), Group 3, and Group 4. MB is a highly heterogeneous tumor. Different molecular subtypes of MB have significantly different clinical, pathological, and molecular characteristics. The prognosis of MB varies significantly among patients with different subtypes of this cancer. Thus, it is needed to study new diagnostic and therapeutic strategies. Metabolomics is an advanced analytical technology that uses various spectroscopic, electrochemical, and data analysis technologies to study and analyze the body’s metabolites. By detecting changes in metabolite types and quantities in different types of samples, it can sensitively discover the physiological and pathological changes in the body. It has great potential for clinical application and personalized medicine. It is promising and can help develop personalized treatment strategies based on the metabolic profiles of individuals. It can unravel the unique metabolic profiles of MB, which may revolutionize our understanding of the disease and improve patients’ outcomes. [ABSTRACT FROM AUTHOR]

Group A rotaviruses (RVAs) are widespread in humans and many animal species and represent the most epidemiologically important rotavirus group. The aim of the study was the identification of the genotype pattern of human RVA strains circulating in Poland, assessment of their phylogenetic relationships to pig RVAs and identification of reassortant and zoonotic virus strains. Human stool samples which were RVA positive (n = 166) were collected from children and adults at the age of 1 month to 74 years with symptoms of diarrhoea. Identification of the G and P genotypes of human RVAs as well as the complete genotype of reassortant and zoonotic virus strains was performed by the use of an RT‐PCR method. The G (G1–G4, G8 or G9) and/or P (P[4], P[6], P[8] or P[9]) genotypes were determined for 148 (89.2%) out of 166 RVA strains present in human stool. G1P[8] RVA strains prevailed, and G4P[8] (20.5%), G9P[8] (15.7%) and G2P[4] (13.3%) human RVA strains were also frequently identified. The full genome analysis of human G4P[6] as well as pig G1P[8] and G5P[6] RVAs revealed the occurrence of porcine–human reassortants and zoonotic RVAs. Detection of G4P[6] in pigs confirms their role as a reservoir of zoonotic RVAs. [ABSTRACT FROM AUTHOR]

Introduction: The global increase of multidrug-resistant organisms (MDROs) is one of the most urgent public health threats affecting both humans and animals. The One Health concept emphasizes the interconnectedness of human, animal and environmental health and highlights the need for integrated approaches to combat antimicrobial resistance (AMR). Although the sharing of environments and antimicrobial agents between companion animals and humans poses a risk for MDRO transmission, companion animals have been studied to a lesser extent than livestock animals. This study therefore used core genome multilocus sequence typing (cgMLST) to investigate the genetic relationships and putative transmission of MDROs between humans and pets. Methods: This descriptive integrated typing study included 252 human isolates, 53 dog isolates and 10 cat isolates collected from 2019 to 2022 at the Charité University Hospital in Berlin, Germany. CgMLST was performed to characterize methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant gram-negative bacteria. The genetic diversity of the MDROs of the different host populations was determined and compared based on sequence type and core genome complex type. Results: Within this study the majority of samples from pets and humans was genetically distinct. However, for some isolates, the number of allelic differences identified by cgMLST was low. Two cases of putative household transmission or shared source of VR E. faecium and MDR E. coli between humans and pets were documented. Conclusions: The interaction between humans and their pets appears to play a minor role in the spread of the MDROs studied. However, further research is needed. This study emphasizes the importance of comprehensive molecular surveillance and a multidisciplinary One Health approach to understand and contain the spread of MDROs in human and animal populations. Trial Registration: The study is registered with the German Clinical Trials Register (DRKS00030009). [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence, trends, and potential nosocomial transmission events of the hidden reservoir of rectal carriage of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). Methods: From 2013 to 2022, yearly point prevalence surveys were conducted in a large Dutch teaching hospital. On the day of the survey, all admitted patients were screened for ESBL-E rectal carriage using peri-anal swabs and a consistent and sensitive selective culturing method. All Enterobacterales phenotypically suspected of ESBL production were analysed using whole genome sequencing for ESBL gene detection and clonal relatedness analysis. Results: On average, the ESBL-E prevalence was 4.6% (188/4,119 patients), ranging from 2.1 to 6.6% per year. The ESBL-prevalence decreased on average 5.5% per year. After time trend correction, the prevalence in 2016 and 2020 was lower compared to the other year. Among the ESBL-E, Escherichia coli (80%) and CTX-M genes (85%) predominated. Potential nosocomial transmission events could be found in 5.9% (11/188) of the ESBL-E carriers. Conclusions: The ESBL-E rectal carriage prevalence among hospitalized patients was 4.6% with a downward trend from 2013 to 2022. The decrease in ESBL-E prevalence in 2020 could have been due to the COVID-19 pandemic and subsequent countrywide measures as no nosocomial transmission events were detected in 2020. However, the persistently low ESBL-E prevalences in 2021 and 2022 suggest that the decline in ESBL-E prevalence goes beyond the COVID-19 pandemic, indicating that overall ESBL-E carriage rates are declining over time. Continuous monitoring of ESBL-E prevalence and transmission rates can aid infection control policy to keep antibiotic resistance rates in hospitals low. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the application of TCGA molecular typing in endometrial carcinoma, compare the relationship between molecular typing and clinicopathologic features, and provide a new idea for individual treatment of patients.MethodsA total of 146 EC patients who underwent surgical treatment and TCGA molecular typing in Beijing Hospital from December 2019 to March 2023 were collected. The clinicopathologic features, immunohistochemistry, and prognosis of the four TCGA molecular types were analyzed retrospectively.ResultAmong the 146 patients with endometrial cancer (EC), 8 patients (5.5%) exhibited the POLE hypermutant type, 29 patients (19.9%) displayed the MSI-H type, 94 patients (64.4%) presented the low copy-number type, and 15 patients (10.3%) manifested the high copy-number type. A comparative analysis of the four TCGA types and age yielded statistically significant results (p = 0.012). Notably, significant associations were observed between menopausal status, the expression of ER, PR, and the four TCGA types. However, no significant difference was observed in CA125 levels before surgery among the four TCGA types (p = 0.587). There were significant differences observed among the four TCGA types and pathological types, pathological grades, FIGO stage, lymph node metastasis, and LVSI. The progression-free survival (PFS) rates of patients with POLE hypermutation, MSI-H type, CNL type, and CNH type were 100%, 100%, 93.62%, and 73.3%, respectively. There was a statistically significant difference between the four groups(p=0.006). POLE mutant and MSI-H type patients have higher PFS, while high copy type patients have the lowest.ConclusionsTCGA molecular typing has feasibility and application value in the clinical application of endometrial cancer, and has a certain predictive effect on the prognosis of EC patients. It has a certain guiding significance for the individual treatment of patients with endometrial cancer.

ObjectiveThe 2013 TCGA identified four molecular subgroups of endometrial cancer; however, the data results for most of the pathological features were varied and of low value for clinical application. Therefore, a meta-analysis of articles related to the clinicopathological features of molecular typing was performed to observe how the prevalence of the four subgroups varied across different pathological features and whether they were associated with certain specific pathological features and to understand how molecular typing may influence current pathological assessments.MethodsPubMed, Embase, Web of Science, CNKI, Wanfang, and VIP were searched from the time of library construction until May 2024, and the following data were extracted: histological type, FIGO grade, FIGO stage, LVSI, depth of muscularis propria infiltration, and lymph node status of each TCGA group. Two reviewers used the Cochrane Diagnostic Research Scale assessment, and the data were analyzed using Review Manager 5.4.1 and Stata 14.0.ResultsFourteen diagnostic research papers were included in this study, with a total of 4,776 patients with endometrial cancer. Non-estrogen-related endometrial carcinoma (NEEC) vs. estrogen-related endometrial carcinoma (EEC) was low in polymerase epsilon (POLE) (OR = 0.49), microsatellite instability (MSI) (OR = 0.45), and copy number low (CNL) (OR = 0.11), while it was high in CNH (OR = 26.76). G3 EEC vs. G1–2 EEC POLE (OR = 1.98), MSI (OR = 1.74), and CNH (OR = 5.57) were high, whereas it was low in CNL (OR = 0.23), low in FIGO II–IV vs. FIGO I in POLE (OR = 0.39) and CNH (OR = 0.64), and high in FIGO II–IV vs. FIGO I in CNH (OR = 3.05). There was no difference in MSI prevalence in FIGO II–IV vs. FIGO I. POLE (OR = 0.64) and CNL (OR = 0.75) were low in myometrial invasion depths ≥50% and lower in myometrial invasion depths

Purpose: This study aimed to evaluate a radiomics model using Photoacoustic/ultrasound (PA/US) imaging at intra and peri-tumoral area to differentiate Luminal and non-Luminal breast cancer (BC) and to determine the optimal peritumoral area for accurate classification. Materials and methods: From February 2022 to April 2024, this study continuously collected 322 patients at Shenzhen People’s Hospital, using standardized conditions for PA/US imaging of BC. Regions of interest were delineated using ITK-SNAP, with peritumoral regions of 2 mm, 4 mm, and 6 mm automatically expanded using code from the Pyradiomic package. Feature extraction was subsequently performed using Pyradiomics. The study employed Z-score normalization, Spearman correlation for feature correlation, and LASSO regression for feature selection, validated through 10-fold cross-validation. The radiomics model integrated intra and peri-tumoral area, evaluated by receiver operating characteristic curve(ROC), Calibration and Decision Curve Analysis(DCA). Results: We extracted and selected features from intratumoral and peritumoral PA/US images regions at 2 mm, 4 mm, and 6 mm. The comprehensive radiomics model, integrating these regions, demonstrated enhanced diagnostic performance, especially the 4 mm model which showed the highest area under the curve(AUC):0.898(0.78–1.00) and comparably high accuracy (0.900) and sensitivity (0.937). This model outperformed the standalone clinical model and combined clinical-radiomics model in distinguishing between Luminal and non-Luminal BC, as evidenced in the test set results. Conclusion: This study developed a radiomics model integrating intratumoral and peritumoral at 4 mm region PA/US model, enhancing the differentiation of Luminal from non-Luminal BC. It demonstrated the diagnostic utility of peritumoral characteristics, reducing the need for invasive biopsies and aiding chemotherapy planning, while emphasizing the importance of optimizing tumor surrounding size for improved model accuracy.

Brucellosis is an infectious disease of animals that can infect humans. The disease causes significant economic losses and threatens human health. A timely and accurate disease diagnosis plays a vital role in the identification of brucellosis. In addition to traditional diagnostic methods, molecular methods allow diagnosis and typing of the causative agent of brucellosis. This review will discuss various methods, such as Bruce-lаdder, Suiladder, high-resolution melt analysis, restriction fragment length polymorphism, multilocus sequence typing, multilocus variable-number tandem repeat analysis, and whole-genome sequencing single-nucleotide polymorphism, for the molecular typing of Brucella and discuss their advantages and disadvantages.

Abstract Background The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer. Methods A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves. Results In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability. Conclusion The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.

ObjectiveTo provide scientific value for effective prevention of Salmonella infection and treatment， the drug resistance spectrum and drug resistance characteristics of Salmonella enteritidis in Lanzhou was exploreed and a database of some genotypes of Salmonella was established.MethodsA total of 94 strains of Salmonella were isolated from foodborne active surveillance in Lanzhou from 2019 to 2021 by serotyping and biochemical analysis. The drug resistance of 41 strains of Salmonella enteritidis was detected by drug susceptibility testing and pulsed field gel electrophoresis. BioNumerics （Version 7.6） software was used to cluster the PFGE profiles of 41 strains of Salmonella enteritidis.ResultsA total of 94 strains of Salmonella could be classified into 20 serotypes， with Salmonella enteritidis as the dominant serogroup， accounting for 43.62% （41/94）. 41 strains of Salmonella enteritidis were generally resistant to quinolone nalidixic acid bacteria （100.00%）， followed by up to 80.49%（33/41） resistance to penicillin ampicillin， the resistance rate to cefazolin was 39.02%（16/41）， and the resistance rates to ampicillin/sulbactam and tetracycline were 31.71%（13/41）. But the drug resistance rates were all 0.00% to imipenem and cefoxitin. Twenty-six （63.41%） of the strains showed multi-drug resistance， resulting in eighteen multi-drug resistance profiles. Lastly， A total of 19 bands were obtained by Xba Ⅰ digestion of 41 strains of Salmonella enteritidis， and the similarity between the bands was 74.20%~100.00%. The number of strains contained in each band type was different， and the homology between strains of the same year was highly and they have 100.00% identical bands.ConclusionSalmonella serotypes in Lanzhou are diverse and PFGE band types are complex， and its dominant serogroup Salmonella enteritidis is highly resistant and multi-drug resistant seriously.

ObjectiveTo provide scientific basis for the prevention and control， early warning， tracing and clinical treatment of diarrheal diseases caused by Salmonella， the serotype distribution， drug resistance and molecular typing characteristics of Salmonella isolates from infectious diarrhea patients in Huzhou City were analyzed.MethodsA total of 126 isolates of Salmonella were collected from 6 sentinel hospitals in Huzhou City from 2021 to 2022. The isolates were characterized by serovar determination， antimicrobial susceptibility tests， and pulsed-field gel electrophoresis （PFGE） typing.ResultsThe 126 strains of Salmonella could be divided into 28 serotypes. The dominant serotypes were Salmonella typhimurium monophasic variant （32.5%， 41/126）， Salmonella enteritidis （24.6%， 31/126） and Salmonella typhimurium （15.1%， 19/126）. Salmonella typhimurium had different resistance characteristics to 15 antibiotics. The resistance rate of Salmonella typhimurium monophasic variant to tetracycline was 73.3% （44/60）， ampicillin and sulfamethoxazole were all 56.7% （34/60）. The resistance rate of Salmonella typhimurium to tetracycline and sulfamethoxazole was higher with 68.4% （13/19） and 52.6% （10/19）， respectively. The highest resistance rate of Salmonella enteritidis to ampicillin/sulbactam was 54.8% （17/31） and that of other Salmonella to tetracycline was the highest wih 51.4%（18/35）. The overall multidrug resistance rate was 62.7% （79/126）， showing 20 multidrug resistance spectra. The PFGE fingerprints of Salmonella typhimurium and Salmonella enteritidis were obtained 46 and 15 kinds types after digested by Xba Ⅰ enzyme.ConclusionThe predominant serotypes of Salmonella infection in Huzhou City are Salmonella typhimurium and Salmonella enteritidis. The multi-drug resistance of Salmonella bacteria is serious. PFGE zone types are both diverse and dominant.

Abstract Background Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. Methods We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. Results Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. Conclusion The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets. Graphical Abstract

ObjectiveTo comprehend the epidemiological and molecular characteristics of diarrheagenic Escherichia coli （DEC） in a specific district of Beijing City from 2018 to 2022， aiming to provide evidence for the prevention and control of related diseases.MethodsStool specimens of 1 600 diarrhea cases were collected from 3 surveillance sentinel hospitals in one district of Beijing from 2018 to 2022， and DEC strains were isolated from the specimens. The virulence genes were detected by multiplex PCR， and the pathogenic types were obtained. The epidemiological and clinical data were analyzed. Simultaneously， pulsed-field gel electrophoresis （PFGE） was used to ascertain the molecular types of the strains. Cluster analysis was performed on the fingerprints of ETEC， EPEC， and EAEC strains.ResultsDEC strains were isolated in 144 of 1 600 specimens from one district of Beijing from 2018 to 2022， with a detection rate of 9.00% （144/1 600）. The primary pathogenic type was ETEC， followed by EPEC， EAEC， and EHEC， no EIEC cases were detected. The male-to-female ratio of DEC infection cases was 1.48∶1， with the highest detection rate occurring in the 31~45 age group （11.15%， 59/529）. The year 2019 exhibited the highest positive detection rate of DEC， with the highest rates consistently observed during the summer months. Significant differences in the positive detection rate of DEC were observed among different age groups and years. Most of the DEC-positive patients suffered diarrhea， dehydration， abdominal pain and watery stool. The 144 DEC strains yielded 111 bands， with homology ranging from 13.07% to 100.00%. Isolates of the same type ranged from 2 to 7 strains， and their separation intervals varied from the same day to several years.ConclusionETEC and EPEC were the predominant pathogenic types of DEC in this area， while EHEC infections persisted. DEC exhibited a high incidence during the summer and was more frequently detected in young adults. The PFGE bands exhibited a highly polymorphic distribution.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) belonging to clonal complex 45 (CC45-MRSA) is rare in Kuwait. This study aimed to characterize MRSA isolates identified as CC45-MRSA by DNA microarray for antibiotic resistance and genetic backgrounds. METHODS: A total of 91 CC5-MRSA isolates obtained from clinical samples between 2016 and 2022 were investigated. Antibiotic resistance was determined by disc diffusion, and MIC determination. Staphylococcal protein A (Spa) typing was used to investigate genetic relatedness. RESULTS: The isolates were resistant to penicillin G (n=91), fusidic acid (n=71), erythromycin (n=16), inducible clindamycin (n=15), ciprofloxacin (n=11), trimethoprim (n=4) and gentamicin (n=2), and harbored blaZ, fusC, erm(C), dfrS1, and aacA-aphD. The isolates belonged to 25 spa types, dominated by t362 (29.6%), t132 (14.2%), followed by t004 (3.3%), t026 (2.2%), t050 (2.2%), t1575 (2.2%) and t2674 (2.2%), and nine genotypes with CC45-MRSA-IV+SCCfus (n=27), CC45-MRSA-[VI +fus] (n=22), CC45-MRSA-IV, Berlin EMRSA (n=17) and CC45-MRSA-[IV+fus] (n=9) constituting 93.4% of the isolates, CC45/agrIV-MRSA-V (n=5), CC45-MRSA-IV(tst1+) (n=3), CC45-MRSA-V (n=3), CC45-MRSA-V [tst1+], WA MRSA-4 (n=4), and CC45-MRSA-V [PVL+] (n=1). Eighty-six (94.5%) isolates belonged to accessory gene regulator type 1, while five belonged to type IV. All CC45-MRSA isolates harbored genes for capsular polysaccharide type 8, immune evasion cluster (staphylokinase, chemotaxis-inhibiting protein, and staphylococcal complement inhibitor), but harbored varied enterotoxins, and toxic shock syndrome toxin genes. One isolate was positive for Panton-Valentine Leukocidin. CONCLUSIONS: The diverse genetic backgrounds suggest independent acquisition of the CC45-MRSA isolates. The high prevalence of fusidic acid resistance in the dominant genotypes is disturbing.

Serratia marcescens is known to cause outbreaks in neonatal intensive care units (NICUs). Traditionally epidemiological data, antimicrobial resistance patterns and epidemiological typing have been used to guide infection prevention methods. Whole-genome sequencing (WGS) applications such as core-genome multi-locus sequence typing (cgMLST) applied during an outbreak would potentially yield more information. To use cgMLST to acquire detailed information on the source and spread of bacteria, enabling more efficient control measures during an S. marcescens outbreak at a NICU. Neonates admitted to the NICU of the Leiden University Medical Center (LUMC) during an outbreak between September 2023 and January 2024, with S. marcescens being cultured, were included. Environmental samples were taken to search for a common source, antibiotic susceptibility testing was performed, and antimicrobial resistance genes were analysed. S. marcescens strains from 17 of the 20 positive patients were available for molecular typing. The cgMLST scheme revealed five different complex types consisting of four separate clusters. Multiple clusters made an unidentified persistent environmental source as cause of the outbreak less likely, leading to a quick downscaling of infection prevention measures. Differences were shown in aminoglycoside resistance patterns of isolates within the same complex types and patients. The use of ad-hoc cgMLST provided timely data for rational decision-making during an S. marcescens outbreak at the NICU. Antibiotic phenotyping alone was found not to be suitable for studying clonal spread during this outbreak with S. marcescens. [ABSTRACT FROM AUTHOR]

Although rhinoviruses play a major role in exacerbations of childhood asthma, the presence of rhinovirus (RV) RNA in plasma, referred to as viremia, has been investigated in a few studies. The aim of the study was to investigate the presence of rhinovirus viremia at the time of asthma exacerbation and to describe the molecular characteristics of rhinoviruses associated with viremia. We conducted an observational, prospective, multicenter study in eight pediatric hospitals (VIRASTHMA2). Preschool‐aged recurrent wheezers (1–5 years) hospitalized for a severe exacerbation were included. Reverse‐transcription polymerase chain reaction (RT‐PCR) and molecular typing for RV/enteroviruses (EV) were performed on nasal swabs and plasma. Plasma specimens were available for 105 children with positive RT‐PCR for RV/EV in respiratory specimens. Thirty‐six (34.3%) had positive viremia. In plasma, 28 (82.4%) of the typable specimens were RV‐C, five (14.7%) were EV‐D68, and one was RV‐A (2.9%). In all cases, the RV/EV type was identical in the plasma and respiratory specimens. In conclusion, RV/EV viremia is frequent in severe exacerbations of preschool recurrent wheezers, particularly in RV‐C infections. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the expression of tcdA, tcdB, and binary toxin genes (cdtA and cdtB) by Real-Time PCR and molecular typing of Clostridioides difficile isolated from patient diarrhea samples from Hamadan Hospitals, west of Iran. Background: The concentration of C. difficile toxins (CDTs) is associated with the severity of the disease and the mortality rate. Measuring CDT levels could provide a reliable and objective means of determining the severity of C. difficile infection (CDI). Methods: From November 2018 to September 2019, 130 diarrhea samples were collected from hospitalized patients in three hospitals in Hamadan. C. difficle isolates were detected by culture and PCR. The presence of the genes encoding the toxin was identified by PCR, whereas the measurement of toxin expression was conducted using a relative Real-Time PCR technique. Genetic linkage of the isolates was also assessed by Ribotyping and Repetitive Extragenic Palindromic (rep-PCR) methods. Results: Among 130 diarrhea samples, 16 (12.3%) were positive for C. difficile. Genes encoding cdtA and tcdB were detected in all isolates, and 8 (50%) and 6 (37.5%) isolates were positive for the cdtA and cdtB genes. Real-time PCR results showed different expression levels of the toxin genes. A significant increase in the expression of the tcdA gene was observed compared with the control strain (P<0.05). Besides, more expression of cdtA gene was observed in the strains compared with cdtB gene. Ribotyping and rep-PCR results showed high genetic diversity of C. difficile among hospitals investigated. Conclusion: We encountered toxigenic C. difficile strains with various toxin expression levels, ribotypes, and rep types based on the findings of this study. This indicated that various clones from various sources circulate in the hospitals and among patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer. Methods: A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves. Results: In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability. Conclusion: The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition. [ABSTRACT FROM AUTHOR]

Aims To investigate the genetic profile and characterize antimicrobial resistance, including the main β-lactam antibiotic resistance genes, in Acinetobacterbaumannii isolates from a tertiary hospital in Recife-PE, Brazil, in the post-COVID-19 pandemic period. Methods and Results Acinetobacter baumannii isolates were collected between 2023 and 2024 from diverse clinical samples. Antimicrobial resistance testing followed standardized protocols, with β-lactamase-encoding genes detected via PCR and sequencing. Investigation into ISAba1 upstream of bla OXA-carbapenemase and bla ADC genes was also conducted. Genetic diversity was assessed through ERIC-PCR. Among the 78 A. baumannii , widespread resistance to multiple antimicrobials was evident. Various acquired β-lactamase-encoding genes (bla OXA-23,-24,-58,-143, bla VIM, and bla NDM) were detected. Furthermore, this is the first report of bla VIM-2 in A. baumannii isolates harboring either the bla OXA-23-like or the bla OXA-143 gene in Brazil. Molecular typing revealed a high genetic heterogeneity among the isolates, and multi-clonal dissemination. Conclusion The accumulation of genetic resistance determinants underscores the necessity for stringent infection control measures and robust antimicrobial stewardship programs to curb multidrug-resistant strains. [ABSTRACT FROM AUTHOR]

Background and Objectives: Klebsiella pneumoniae is a healthcare-associated infections agent and could be an extended spectrum ß-lactamase (ESBL) producer. Understanding the transmission of this bacterium in a hospital setting needs accurate typing methods. An antibiogram is used to detect the resistance pattern of the isolates. Random Amplified Polymorphic DNA (RAPD) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR are rapid, technically simple, and easy-to-interpret DNA typing methods. This study aimed to evaluate the use of antibiotyping, RAPD-, and ERIC-PCR to investigate the heterogeneity of K. pneumoniae isolated from clinical specimens. Materials and Methods: The antibiograms of 46 K. pneumoniae clinical isolates were determined by Vitek® 2 Compact. All isolates underwent RAPD-PCR using AP4 primer and ERIC-PCR using ERIC-2 primer. The dendrogram was generated using the GelJ software and analyzed to determine its similarity. The analysis of antibiogram and the molecular typing diversity index was calculated using the formula of the Simpson's diversity index. Results: About 71.7% of the isolates were ESBL-producers, and more than 80% of isolates were susceptible to amikacin, ertapenem, and meropenem. The antibiotyping produced 32 diverse types with DI = 0.964. In addition, the RAPD-PCR produced 47 different types with DI = 1, while ERIC-PCR was 46 (DI=0.999). Conclusion: Antibiotyping, RAPD- and ERIC-PCR showed powerful discrimination power among the isolates, supported the diversity of K. pneumoniae isolates in current study. These combination could be promising tools for clonal relationship determination, including in tracking the transmission of the outbreak's agent in hospital setting. [ABSTRACT FROM AUTHOR]

In 2013, the Cancer Genome Atlas (TCGA) research center completed the molecular classification endometrial carcinoma (EC), categorizing patients into POLE (DNA polymerase epsilon) mutation type, microsatellite instability-high (MSI-H) type, copy number low (CN-L) type, and copy number high (CN-H) type. Subsequently Western scholars refined this into the ProMisE and Trans-PORTEC classification to better suit clinical applications. Patients with POLE mutation EC have excellent prognosis and lower recurrence rate, allowing for a reduction in surgical scope and a deescalation of treatment. Patients with MSI-H or CN-H are still POLE mutant. MSI-H type patients have a high burden of tumor mutations and significant benefits from immunotherapy. CN-L type patients are the most common, with a prognosis second only to POLE mutant patients. These patients have a higher response rate to hormone therapy to preserve fertility. CN-H type patients have the worst prognosis, with invasive features and a high risk of recurrence. For these patients, postoperative supplementary treatment is necessary to avoid inadequate treatment. However, there are some studies have shown that targeted therapy is more effective for CN-H type patients. The TCGA molecular typing of EC has overcome the limitations of traditional pathological and histological classification for evaluating prognosis, providing new insights into the pathological characteristics, prognosis, clinical diagnosis and treatment decisions of EC. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma is the most common malignancy of the female reproductive system. Recent years have witnessed pivotal developments in the diagnosis and treatment, including the quantitative assessment of lymphovascular space invasion, the ultrastaging of sentinel lymph nodes, and the molecular stratification of endometrial carcinoma, all progressively integrated into clinical practice. These new insights have been incorporated into the 2023 version of the staging system by the International Federation of Gynecology and Obstetrics (FIGO), heralding a new era of clinical adoption. The importance of precise pathological evaluation cannot be overstated, serving as a linchpin for prognosticating patient outcomes and steering the course of adjuvant therapies. Through the lens of the updated 2023 FIGO staging for endometrial carcinoma, this discourse aims to elevate the paradigm of pathological diagnosis, promoting a benchmark of standardization and precision for pathologists, thereby empowering clinicians with a deeper and more accurate application of the staging system. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. Methods: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. Results: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. Conclusion: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets. [ABSTRACT FROM AUTHOR]

Despite numerous studies on Escherichia coli (E. coli) from sheep, there have been few reports on the characterization of E. coli isolates from various organs of individual sheep until now. The present study conducted molecular typing, antibiotics resistance, biofilm formation, and virulence genes on E. coli isolated from 57 freshly slaughtered apparently healthy sheep carcasses, gallbladders, fecal samples, and mesenteric lymph nodes (MLNs). The results demonstrated that the detection rate of R1 LPS core type in E. coli isolated from fecal samples (70.83%) was higher than that from other organs, but the detection rate of antibiotic resistance genes was lower (P < 0.05). The predominant phylogenetic group of E. coli isolated from the carcasses was group B1 (93.33%), and the detection rate of multidrug-resistance phenotype (80%) and the resistance rate of E. coli was higher than that from other organs (P < 0.05). Interestingly, the intensity of biofilm formation of E. coli isolated from MLNs was higher than that from other organs (P < 0.05). However, except for ibeB, the detection rates of virulence genes did not differ in E.coli isolated from different organs. In conclusion, differences were noted in these parameters of E. coli isolated from different organs of individual sheep. Therefore, the data may contain considerable mistakes concerning the actual situation in the host if we only analyze the data of E. coli isolated from feces or carcasses. [ABSTRACT FROM AUTHOR]

Although mobile phones as a rapid communication vehicle can lead to improved quality of healthcare, they can also facilitate the transmission of pathogens to patients. This current research focuses on genetic diversity, and genes involved in resistance and biofilm production of Staphylococcus aureus isolates from mobile phones of medical students. Antibiotic resistance profiling and polymerase chain reaction (PCR) amplification of antibiotic resistance and biofilm-related genes were investigated and statistically analyzed. Staphylococcal cassette chromosome mec (SCC mec) types were analyzed by multiplex PCR, and S. aureus protein A gene typing (spa typing) was done using PCR and sequencing. Sixty-four S. aureus isolates (16.8%) were obtained from 380 medical students' mobile phones who were working in hospitals. The findings showed that 71.9% of the isolates were MRSA and 78.1% were classified as MDR. All isolates exhibited sensitivity to vancomycin and linezolid. Overall, 7.8% of the isolates displayed an inducible clindamycin resistance phenotype, while 26.7% showed resistance to mupirocin. The results indicated that 68.8% of the isolates were biofilm producers, with 7 isolates (15.9%) classified as strong producers, 22 isolates (50%) as moderate producers, and 15 isolates (34.1%) as weak producers. The most prevalent type was CC8-MRSA III/t030 (18.7%), followed by CC8-MRSA III/t037 (12.5%), CC/ST22-MSSA/t790 (10.9%), CC1-MRSA IV-t114 (9.4%), CC1-MRSA IV-t127 (7.8%), CC8-MRSA V/t064 (7.8%), CC/ST15-MSSA-t360 (7.8%), CC30-MSSA/t021(6.3%), MRSA V-t355 (6.3%), CC8-MRSA III/t421 (4.7%), CC1-MRSA V-t267 (4.7%), and CC/ST15-MSSA-t084 (3.1%). The genetic diversity and prevalent multidrug resistance indicate that the resistance situation of S. aureus recovered from mobile phones in Tehran is severe, posing a potential threat to patients, the community, and healthcare settings. [ABSTRACT FROM AUTHOR]

Combined large cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine carcinoma, accounting for approximately 10% of large cell neuroendocrine carcinoma (LCNEC). Mainly composed of coexisting adenocarcinoma components, with strong invasiveness and poor prognosis. The treatment regimen for CLCNEC mainly refers to complete surgical resection as the first choice in the early stage, while patients with stage II or higher require adjuvant treatment. At present, research on CLCNEC is mostly small sample and retrospective, and there is no consensus on whether molecular typing and treatment should be carried out. There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

IntroductionMammals are the main hosts for Brucella sp., agents of worldwide zoonosis. Marine cetaceans and pinnipeds can be infected by Brucella ceti and B. pinnipedialis, respectively. Besides classical bacteriological typing, molecular approaches such as MLVA, MLSA, and whole-genome sequencing (WGS) can differentiate these species but are cumbersome to perform.MethodsWe compared the DNA and genome sequences of 12 strains isolated from nine marine mammals, with highly zoonotic B. melitensis, B. abortus, and B. suis, and the publicly available genomes of B. ceti and B. pinnipedialis. In silico pipelines were used to detect the antimicrobial resistance (AMR), plasmid, and virulence genes (VGs) by screening six open-source and one home-made library.Results and discussionOur results show that easier-to-use HRM-PCR, Bruce-ladder, and Suis-ladder can separate marine Brucella sp., and the results are fully concordant with other molecular methods, such as WGS. However, the restriction fragment length polymorphism (RFLP) method cannot discriminate between B. pinnipedialis and B. ceti B1-94-like isolates. MLVA-16 results divided the investigated strains into three clades according to their preferred host, which was confirmed in WGS. In silico analysis did not find any AMR and plasmid genes, suggesting antimicrobial susceptibility of marine Brucella, while the presence of the VGs btpA gene was variable dependent on the clade.ConclusionThe HRM-PCR and Suis-ladder are quick, easy, and cost-effective methods to identify marine Brucella sp. Moreover, in silico genome analyses can give useful insights into the genetic virulence and pathogenicity potential of marine Brucella strains.