Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease.

Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls.

Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease.

Background & Aims: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment.

Endobronchial Ultrasound for the Screening of Pulmonary Embolism in Patients with Suspected Lung Cancer: A Prospective Cohort Study.

Background: Patients with lung cancer exhibit increased risk of pulmonary embolism (PE). While the contrast phase of computed tomography of the chest in the diagnostic work-up of suspected chest malignancy does not allow reliable detection of PE, it may be feasible to screen for present PE during endobronchial ultrasound (EBUS) examination.

Objectives: The aim of this study was to establish if screening during EBUS for PE in patients with suspected lung cancer is feasible and if positive findings are predictive of PE.

Identification of gluten T cell epitopes driving celiac disease.

CD4 T cells specific for cereal gluten proteins are key players in celiac disease (CeD) pathogenesis. While several CeD-relevant gluten T cell epitopes have been identified, epitopes recognized by a substantial proportion of gluten-reactive T cells remain unknown. The identification of such CeD-driving gluten epitopes is important for the food industry and in clinical settings.

The genetic history of Scandinavia from the Roman Iron Age to the present.

We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden.

When Pulmonologists Are Novice to Navigational Bronchoscopy, What Predicts Diagnostic Yield?

Predicting factors of diagnostic yield in electromagnetic navigation bronchoscopy (ENB) have been explored in a number of previous studies based on data from experienced operators. However, little is known about predicting factors when the procedure is carried out by operators in the beginning of their learning curve. We here aim to identify the role of operators' experience as well as lesion- and procedure characteristics on diagnostic yield of ENB procedures in the hands of novice ENB operators.

The population genomic legacy of the second plague pandemic.

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.

The prevalence of acromegaly is higher than previously reported: Changes over a three-decade period.

Objective: To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control.

Methods: A total of 107 patients with acromegaly were identified by healthcare registries and subsequently validated by patient chart review over a three-decade period (1992-2021). A systematic literature review focusing on the incidence and prevalence of acromegaly was performed identifying 31 studies.

KIRCD8 T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19.

In this work, we find that CD8 T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49CD8 regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 T cells efficiently eliminated pathogenic gliadin-specific CD4 T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIRCD8 T cells, but not CD4 regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis.

Phenotype-Based Isolation of Antigen-Specific CD4 T Cells in Autoimmunity: A Study of Celiac Disease.

The pathogenic immune response in celiac disease (CeD) is orchestrated by phenotypically distinct CD4 T cells that recognize gluten epitopes in the context of disease-associated HLA-DQ allotypes. Cells with the same distinct phenotype, but with elusive specificities, are increased across multiple autoimmune conditions. Here, whether sorting of T cells based on their distinct phenotype (Tphe cells) yields gluten-reactive cells in CeD is tested.

Learning Curves for Electromagnetic Navigation Bronchoscopy Using CUSUM Analysis.

Background: Electromagnetic navigation bronchoscopy (ENB) is a relatively new and technically demanding procedure for the guidance of bronchoscopic biopsy to help locate small lung lesions. The results in experienced hands are well described. However, we do not know the results in unexperienced hands-in other words, we have no knowledge about how fast you can learn the procedure.

Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T-Cell-Directed Therapies.

Gluten-specific CD4 T cells being drivers of celiac disease (CeD) are obvious targets for immunotherapy. Little is known about how cell markers harnessed for T-cell-directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In-depth characterization of gluten-specific CD4 T cells and CeD-associated (CD38 and CD103 ) CD8 and γδ T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported.

Adult pedestrian and cyclist injuries in Lilongwe, Malawi: a cross-sectional study.

Background: Pedestrian and cyclist injuries are a major concern globally, but especially in low-income countries. Locally conducted research is needed to measure the size of the problem and advise policy on road safety interventions. We wanted to investigate the precise circumstances of these injuries in Lilongwe, Malawi and to identify risk factors for severe injuries.

Comprehensive Analysis of CDR3 Sequences in Gluten-Specific T-Cell Receptors Reveals a Dominant R-Motif and Several New Minor Motifs.

Gluten-specific CD4+ T cells are drivers of celiac disease (CeD). Previous studies of gluten-specific T-cell receptor (TCR) repertoires have found public TCRs shared across multiple individuals, biased usage of particular V-genes and conserved CDR3 motifs. The CDR3 motifs within the gluten-specific TCR repertoire, however, have not been systematically investigated.

Geographical mapping of road traffic injuries in Lilongwe, Malawi.

Background: Road traffic injuries are a leading cause of death and disability, especially in low- and middle-income countries. Identifying injury hotspots are valuable for introducing preventive measures. This is usually accomplished by using police data, but these are often unreliable in low-income countries.

Circulating CD103 γδ and CD8 T cells are clonally shared with tissue-resident intraepithelial lymphocytes in celiac disease.

Gut intraepithelial γδ and CD8 αβ T lymphocytes have been connected to celiac disease (CeD) pathogenesis. Based on the previous observation that activated (CD38), gut-homing (CD103) γδ and CD8 αβ T cells increase in blood upon oral gluten challenge, we wanted to shed light on the pathogenic involvement of these T cells by examining the clonal relationship between cells of blood and gut during gluten exposure. Of 20 gluten-challenged CeD patients, 8 and 10 had increase in (CD38CD103) γδ and CD8 αβ T cells, respectively, while 16 had increase in gluten-specific CD4 T cells.

Single-cell TCR repertoire analysis reveals highly polyclonal composition of human intraepithelial CD8 αβ T lymphocytes in untreated celiac disease.

We compared the αβ T-cell receptor repertoires of CD8 αβ intraepithelial lymphocytes from celiac disease patients and healthy subjects by single-cell sequencing. We demonstrate that the repertoires of untreated celiac disease patients were more polyclonal and more diverse than what was observed in both treated patients and healthy subjects.

The Effect of Catalogue Lead Time on Medium-Term Earthquake Forecasting with Application to New Zealand Data.

'Every Earthquake a Precursor According to Scale' (EEPAS) is a catalogue-based model to forecast earthquakes within the coming months, years and decades, depending on magnitude. EEPAS has been shown to perform well in seismically active regions like New Zealand (NZ). It is based on the observation that seismicity increases prior to major earthquakes.

Prevalence of alcohol use among road traffic crash victims presenting to a Malawian Central Hospital: A cross-sectional study.

Background: Alcohol consumption is a well-known risk factor for sustaining road traffic injuries worldwide. Malawi is a low-income country with a large and increasing burden of road traffic injuries. It has generally been viewed as a country with relatively little alcohol consumption.

Multi-omic detection of in archaeological human dental calculus.

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway.