Gut Microbiome Signatures During Acute Infection Predict Long COVID.

Long COVID (LC), manifests in 10-30% of non-hospitalized individuals post-SARS-CoV-2 infection leading to significant morbidity. The predictive role of gut microbiome composition during acute infection in the development of LC is not well understood, partly due to the heterogeneous nature of disease. We conducted a longitudinal study of 799 outpatients tested for SARS-CoV-2 (380 positive, 419 negative) and found that individuals who later developed LC harbored distinct gut microbiome compositions during acute infection, compared with both SARS-CoV-2-positive individuals who did not develop LC and negative controls with similar symptomatology.

Genomic epidemiology reveals the dominance of Hennepin County in the transmission of SARS-CoV-2 in Minnesota from 2020 to 2022.

We analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission "sinks.

In vivo label-free optical signatures of chemotherapy response in human pancreatic ductal adenocarcinoma patient-derived xenografts.

Pancreatic cancer is a devastating disease often detected at later stages, necessitating swift and effective chemotherapy treatment. However, chemoresistance is common and its mechanisms are poorly understood. Here, label-free multi-modal nonlinear optical microscopy was applied to study microstructural and functional features of pancreatic tumors in vivo to monitor inter- and intra-tumor heterogeneity and treatment response.

Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022.

SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread, and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020-2022 and use Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest introduction into Minnesota was to Hennepin County from a domestic source around January 22, 2020; six weeks before the first confirmed case in the state.

The formation of interlocked grain in African mahogany (Khaya spp.) analysed by X-ray computed microtomography.

Interlocked grain occurs when the orientation of xylem fibres oscillates, alternating between left- and right-handed spirals in successive wood layers. The cellular mechanisms giving rise to interlocked grain, thought to involve the slow rotation of fusiform initials within the vascular cambium, remain unclear. We suggest that observations of wood structure at the cellular level, but over large areas, might reveal these mechanisms.

A mathematical framework for modelling cambial surface evolution using a level set method.

Background And Aims: During their lifetime, tree stems take a series of successive nested shapes. Individual tree growth models traditionally focus on apical growth and architecture. However, cambial growth, which is distributed over a surface layer wrapping the whole organism, equally contributes to plant form and function.

High detection rates of colorectal neoplasia by stool DNA testing with a novel digital melt curve assay.

Background & Aims: Current stool DNA tests identify about half of individuals with colorectal cancers and miss most individuals with advanced adenomas. We developed a digital melt curve (DMC) assay to quantify low-abundance mutations in stool samples for detection of colorectal neoplasms and compared this test with other approaches.

Methods: We combined a melt curve assay with digital polymerase chain reaction and validated the quantitative range.

Stool DNA and occult blood testing for screen detection of colorectal neoplasia.

Background: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting.

Objective: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm).

Altered DNA mismatch repair expression in synchronous and metachronous colorectal cancers.

Background & Aims: It is not clear what proportion of synchronous or metachronous colorectal cancers (CRCs) are associated with DNA mismatch repair (MMR) alterations or unsuspected Lynch syndrome. On the basis of tissue analyses, the aims were to evaluate DNA MMR expression in metachronous, synchronous, and isolated sporadic CRCs and to assess within-patient concordance of MMR expression in metachronous and synchronous CRCs.

Methods: Tissue was evaluated from 34 patients with metachronous CRC, 34 matched solitary CRC patients, and 40 patients with synchronous CRCs.

Highly methylated genes in colorectal neoplasia: implications for screening.

Discriminant markers are required for accurate cancer screening. We evaluated genes frequently methylated in colorectal neoplasia to identify the most discriminant ones. Four genes specifically methylated in colorectal cancer [bone morphogenetic protein 3 (BMP3), EYA2, aristaless-like homeobox-4 (ALX4), and vimentin] were selected from 41 candidate genes and evaluated on 74 cancers, 62 adenomas, and 70 normal epithelia.

Detection of colorectal disease by stool defensin assay: an exploratory study.

Background & Aims: Alpha-defensins 1-3 (human neutrophil peptides [HNP]1-3), reported to be elevated in tumor tissue and serum of patients with colorectal cancer (CRC), have not been studied in stool. We evaluated the neoplasm specificity of HPN1-3 and their discriminant value as stool markers for CRC.

Methods: Protein and mRNA expression of HPN1-3 were assayed in CRC cell lines, microdissected CRC and normal epithelium, and white blood cells.

A sensitive method to quantify human long DNA in stool: relevance to colorectal cancer screening.

Human long DNA in stool may reflect nonapoptotic exfoliation and has been used as a colorectal cancer (CRC) marker. Targeting human-specific Alu repeats represents a logical but untested approach. A real-time Alu PCR assay was developed for quantifying long human DNA in stool and evaluated in this study.

Aberrant methylation of the eyes absent 4 gene in ulcerative colitis-associated dysplasia.

Background & Aims: This study explored the eyes absent 4 (EYA4) gene promoter methylation in noncolitic colorectal tissues and assessed its discrimination for neoplasia in chronic ulcerative colitis (CUC).

Methods: The methylation status of noncolitic specimens was confirmed by direct bisulfite sequencing. Methylation-specific polymerase chain reaction (MSP) primers were designed to evaluate colorectal tissues, including 50 noncolitic patients comprising 24 normal epithelia, 14 polyps, and 12 cancers.

Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barrett's esophagus.

Hypermethylation of secreted frizzled-related proteins (SFRP) genes frequently occurs with several cancers but has not been studied in esophageal adenocarcinoma or its precursor-Barrett's esophagus. To explore the role of SFRP methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated SFRP genes as biomarkers for Barrett's esophagus and cancer, methylation of SFRP genes was determined in esophageal adenocarcinomas, Barrett's esophagus and normal epithelia using methylation-specific PCR. Protein expression of SFRP genes was then assessed in these tissues by immunohistochemistry.

Frequent methylation of eyes absent 4 gene in Barrett's esophagus and esophageal adenocarcinoma.

Most esophageal adenocarcinomas arise within Barrett's esophagus but the cause of this increasingly prevalent condition remains unknown. Early detection improves survival and discriminant screening markers for Barrett's esophagus and cancer are needed. This study was designed to explore the natural history of eyes absent 4 (EYA4) gene methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated EYA4 as a candidate marker.

Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia.

Objectives: Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia.

Detection of occult upper gastrointestinal tract bleeding: performance differences in fecal occult blood tests.

Objective: To compare rates of detection of occult upper gastrointestinal (GI) tract bleeding by guaiac (Hemoccult II [HO]), immunochemical (HemeSelect [HS]), and heme-porphyrin (HemoQuant [HQT]) fecal occult blood tests. PATIENTS, SUBJECTS, AND METHODS: In a cross-sectional study to detect native occult upper GI tract bleeding, single stools were collected from 56 patients with iron deficiency and a proven hemorrhagic GI tract lesion. In a longitudinal study to detect simulated occult upper GI tract bleeding, 3 stool samples were serially collected from 10 clinically normal subjects after ingestion of 5 and 15 mL of autologous blood.