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Salmonella enterica is one of the most commonly reported foodborne pathogens by public health agencies worldwide. In this study, the multilocus sequence typing (MLST) population structure and frequency of antimicrobial resistance (AMR) genes were evaluated in S. enterica strains from Mexico (n = 2561). The most common sources of isolation were food (44.28%), environment (27.41%), animal-related (24.83%), and human (3.48%). The most prevalent serovars were Newport (8.51%), Oranienburg (7.03%), Anatum (5.78%), Typhimurium (5.12%), and Infantis (4.57%). As determined by the 7-gene MLST scheme, the most frequent sequence types were ST23, ST64, and ST32. The core genome MLST scheme identified 132 HC2000 and 195 HC900 hierarchical clusters, with the HC2000_2 cluster being the most prevalent in Mexico (n = 256). A total of 78 diferent AMR genes belonging to 13 antimicrobial classes were detected in 638 genomic assemblies of S. enterica. The most frequent class was aminoglycosides (31.76%), followed by tetracyclines (12.53%) and sulfonamides (11.91%). These results can help public health agencies in Mexico prioritize their eforts and resources to increase the genomic sequencing of circulating Salmonella strains. Additionally, they provide valuable information for local and global public health eforts to reduce the impact of foodborne diseases and AMR. Key words: Salmonella, antimicrobial resistance genes, MLST, epidemiology, genomics, 1. Introduction Salmonella enterica is one of the primary pathogens causing foodborne diseases, which impact considerable morbidity, mortality, and economic costs worldwide, thus representing a tremendous global public health problem [...]

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here, we studied 20 patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and four male patients had a median age of 14 years (range 4-70). Tumors were uniformly extra-axial or intraventricular and located at the cerebral convexities (n = 7), falx (2), lateral ventricles (4), tentorium (2), cerebellopontine angle (4), and spinal cord (1). NGS demonstrated that eight tumors harbored EWSR1-ATF1 fusion, seven had EWSR1-CREB1, four had EWSR1-CREM, and one had FUS-CREM. Tumors were uniformly well circumscribed and typically contrast enhancing with solid and cystic growth. Tumors with EWSR1-CREB1 fusions more often featured stellate/spindle cell morphology, mucin-rich stroma, and hemangioma-like vasculature compared to tumors with EWSR1-ATF1 fusions that most often featured sheets of epithelioid cells with mucin-poor collagenous stroma. These tumors demonstrated polyphenotypic immunoprofiles with frequent positivity for desmin, EMA, CD99, MUC4, and synaptophysin, but absence of SSTR2A, myogenin, and HMB45 expression. There was a propensity for local recurrence with a median progression-free survival of 12 months and a median overall survival of greater than 60 months, with three patients succumbing to disease (all with EWSR1-ATF1 fusions). In combination with prior case series, this study provides further insight into intracranial mesenchymal tumors with FET-CREB fusion, which represent a distinct group of CNS tumors encompassing both intracranial myxoid mesenchymal tumor and angiomatoid fibrous histiocytoma-like neoplasms.

PurposeThe endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.MethodsWhole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data.ResultsAll patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele.ConclusionNGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

A 14-year-old boy underwent an allogenic bone marrow transplant (BMT) 4 months following diagnosis of acute myeloid leukemia. Three weeks after the BMT the patient was intubated secondary to presumed [...]

The patient was a 17-day-old male infant, who was born by cesarean section to a 27-year-old gravida 1, para 0 mother at 35 weeks' estimated gestational age; the infant weighed [...]

Abstract: Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present three pediatric patients with intracranial EWSR1‐rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next‐generation sequencing (NGS) were performed. A 12‐year‐old male (case 1), 14‐year‐old female (case 2), and 18‐year‐old male (case 3), presented with headaches, emesis, and seizures, respectively. The magnetic resonance images demonstrated tumors abutting the dura (cases 1 and 3) and in the third ventricle (case 2). All tumors were vascular, with solid sheets of monomorphic oval cells in a prominent myxoid/microcystic matrix. A thin fibrous pseudocapsule was present in all lesions, but definitive lymphocytic cuffing was absent. Morphologically, they closely resembled myxoid variant of angiomatoid fibrous histiocytoma. Mitoses were rare, and necrosis was absent. All tumors expressed desmin and GLUT1, and focal EMA and CD99. The proliferation index was low. FISH and NGS showed EWSR1–CREB1 fusion (cases 1 and 2), and EWSR1–CREM fusion (case 3). There were no FUS (16p11.2) or NR4A3 (9q22.33) rearrangements in case 3. Gains of 5q (including KCNIP1) and 11q (including CCND1) were present in cases 1 and 2. There were no common pathogenic genomic changes other than EWSR1 rearrangements across cases. CNS myxoid mesenchymal neoplasms with histological and immunophenotypic similarities to myxoid variant of AFH are rare, diagnostically challenging, and harbor EWSR1–CREB1 and also a novel EWSR1–CREM fusion not yet described in AFH. Therefore, it is uncertain if these tumors represent variants of AFH or a new entity. The copy number and mutational changes presented here provide support for future studies to further clarify this issue. [ABSTRACT FROM AUTHOR]