Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases.

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has affected populations, societies, and lives for more than 2 years. Long-term sequelae of COVID-19, collectively termed the postacute COVID-19 syndrome, are rapidly emerging across the globe. Here, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen persistence underlies the postacute COVID-19 syndrome. METHODS: We performed an endoscopy study with 46 patients with inflammatory bowel disease (IBD) 219 days (range, 94-257) after a confirmed COVID-19 infection. SARS-CoV-2 antigen persistence was assessed in the small and large intestine using quantitative polymerase chain reaction of 4 viral transcripts, immunofluorescence of viral nucleocapsid, and virus cultivation from biopsy tissue. Postacute COVID-19 was assessed using a standardized questionnaire, and a systemic SARS-CoV-2 immune response was evaluated using flow cytometry and enzyme-linked immunosorbent assay at endoscopy. IBD activity was evaluated using clinical, biochemical, and endoscopic means. RESULTS: We report expression of SARS-CoV-2 RNA in the gut mucosa ∼7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8+ T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19, immunosuppressive therapy, and gut inflammation. We were unable to culture SARS-CoV-2 from gut tissue of patients with viral antigen persistence. Postacute sequelae of COVID-19 were reported from the majority of patients with viral antigen persistence, but not from patients without viral antigen persistence. CONCLUSION: Our results indicate that SARS-CoV-2 antigen persistence in infected tissues serves as a basis for postacute COVID-19. The concept that viral antigen persistence instigates immune perturbation and postacute COVID-19 requires validation in controlled clinical trials.

PUFA-Induced Metabolic Enteritis as a Fuel for Crohn's Disease.

BACKGROUND & AIMS: Crohn's disease (CD) globally emerges with Westernization of lifestyle and nutritional habits. However, a specific dietary constituent that comprehensively evokes gut inflammation in human inflammatory bowel diseases remains elusive. We aimed to delineate how increased intake of polyunsaturated fatty acids (PUFAs) in a Western diet, known to impart risk for developing CD, affects gut inflammation and disease course. We hypothesized that the unfolded protein response and antioxidative activity of glutathione peroxidase 4 (GPX4), which are compromised in human CD epithelium, compensates for metabolic perturbation evoked by dietary PUFAs. METHODS: We phenotyped and mechanistically dissected enteritis evoked by a PUFA-enriched Western diet in 2 mouse models exhibiting endoplasmic reticulum (ER) stress consequent to intestinal epithelial cell (IEC)-specific deletion of X-box binding protein 1 (Xbp1) or Gpx4. We translated the findings to human CD epithelial organoids and correlated PUFA intake, as estimated by a dietary questionnaire or stool metabolomics, with clinical disease course in 2 independent CD cohorts. RESULTS: PUFA excess in a Western diet potently induced ER stress, driving enteritis in Xbp1-/-IEC and Gpx4+/-IEC mice. ω-3 and ω-6 PUFAs activated the epithelial endoplasmic reticulum sensor inositol-requiring enzyme 1α (IRE1α) by toll-like receptor 2 (TLR2) sensing of oxidation-specific epitopes. TLR2-controlled IRE1α activity governed PUFA-induced chemokine production and enteritis. In active human CD, ω-3 and ω-6 PUFAs instigated epithelial chemokine expression, and patients displayed a compatible inflammatory stress signature in the serum. Estimated PUFA intake correlated with clinical and biochemical disease activity in a cohort of 160 CD patients, which was similarly demonstrable in an independent metabolomic stool analysis from 199 CD patients. CONCLUSIONS: We provide evidence for the concept of PUFA-induced metabolic gut inflammation which may worsen the course of human CD. Our findings provide a basis for targeted nutritional therapy.

[Use of subcutaneous Vedolizumab: A position paper issued by the Inflammatory Bowel Disease Working Group of the Austrian Society of Gastroenterology and Hepatology (ÖGGH)]. / Positionspapier der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der ÖGGH zum Einsatz von Vedolizumab subkutan.

The humanized monoclonal anti-α4ß7-integrin-antibody vedolizumab is one of several biologic therapeutic options in moderate-to-severe ulcerative colitis and Crohn's disease. Within the VISIBLE trial program, a novel subcutaneous application route was evaluated in addition to the already established intravenous form. In this position statement, the working group "Inflammatory Bowel Diseases" of the Austrian Society for Gastroenterology and Hepatology (OEGGH) summarizes the evidence regarding the subcutaneous application of vedolizumab. This work supplements a position paper on the value of vedolizumab as a first-line biologic that has already been published and offers useful recommendations for clinical practice.

An evaluation of the CARL manikin for use in "patient-free" real ear measurement: consistency and comparison to normative data.

OBJECTIVE: Simulation-based learning experiences provide low-risk opportunities for procedural training and practice in audiology. A series of real ear measurements (REM) were completed using Clinical Assistant for Research and Learning (CARL) manikins to determine expected responses and to compare to normative data. DESIGN: (1) Real-ear Unaided Response (REUR) curves were measured with one CARL and each of three ear styles. (2) Test/retest reliability was evaluated by repeating each REUR. (3) Real ear to coupler difference (RECD) values for foam-tip and custom earmolds were calculated. (4) The reliability across copies of the CARL heads was evaluated by comparing REUR measurement from one set of ears on 4 heads. STUDY SAMPLE: Four adult CARL manikins and thirty ears (5 sets of large, small, and bent). RESULTS: Within each ear category, the average difference across frequencies from one ear to the next was less than 2.5 dB with no significant individual difference more than 5.8 dB. Test/retest reliability was excellent. Typical REUR and RECD curves were created for each ear style and compared to published data on human ears. CONCLUSIONS: REM using the adult CARL head are predictable and repeatable making this simulator a good tool for audiological training.

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1.

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a ≥2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

Crystal Growth of Alkali Uranyl Borates from Molten Salt Fluxes: Characterization and Ion Exchange Behavior of A2(UO2)B2O5 (A = Cs, Rb, K).

A new family of layered alkali uranyl borates, A2(UO2)B2O5 (A = Cs, Rb, K), was synthesized as high quality single crystals via high temperature flux growth methods. At room temperature, the compounds are structurally closely related although they crystallize in different monoclinic space groups, specifically P21/c (Cs), C2/m (Rb), and C2/c (K). At a low temperature (100 K), Cs2(UO2)B2O5 becomes isostructural with K2(UO2)B2O5 as the result of a reversible structure transition by Cs2(UO2)B2O5. The title phases represent the first examples of uranyl borates resulting from high temperature flux growth utilizing alkali halide fluxes. The synthesis, structures, and thermal, optical, and ion exchange properties are reported, and modeling of the atomic structure and disorder of the ion exchanged phases is discussed.

Diverse patterns of constitutive and inducible overexpression of detoxifying enzyme genes among resistant Aphis glycines populations.

Understanding the mechanisms of pyrethroid resistance is essential to the effective management of pesticide resistance in Aphis glycines Matsumura (Hemiptera: Aphididae). We mined putative detoxifying enzyme genes in the draft genome sequence of A. glycines for cytochrome oxidase P450 (CYP), glutathione-S-transferase (GST) and esterases (E4 and carboxylesterases-CES). Aphids from clonal populations resistant to pyrethroids from three sites in Minnesota, USA, were screened against a diagnostic LC99 concentration of either λ-cyhalothrin or bifenthrin and detoxifying enzyme genes expression in survivors was analyzed by qPCR. Their expression profiles were compared relative to a susceptible clonal population. We found 61 CYP (40 full-length), seven GST (all full-length), seven E4 (five full-length) and three CES (two full-length) genes, including 24 possible pseudogenes. The detoxifying enzymes had different expression profiles across resistant aphid populations, possibly reflecting differences in the genetic background and pyrethroid selection pressures as the number of constitutively overexpressed detoxifying enzyme genes was correlated with the level of resistance. Our findings will strengthen the understanding of the pyrethroid resistance mechanisms in A. glycines.

Parasitism of Adult Pentatomidae by Tachinidae in Soybean in the North Central Region of the United States.

Stink bugs (Hemiptera: Pentatomidae) are agricultural pests of increasing significance in the North Central Region of the United States, posing a threat to major crops such as soybean. Biological control can reduce the need for insecticides to manage these pests, but the parasitism of stink bugs by Tachinidae (Diptera) is poorly characterized in this region. The objective of this study was to evaluate the rate of parasitism of stink bugs by tachinids over 2 yr from nine states across the North Central Region. Parasitism was assessed by quantifying tachinid eggs on the integument of stink bug adults. Parasitism rates (i.e., percent of adult stink bugs with tachinid eggs) were compared across stink bug species, states, stink bug sex, and years. The mean percent parasitism of stink bugs by tachinids was about 6% across the region and did not differ among stink bug species. Mean percent parasitism was significantly higher in Missouri than in northern and western states. In addition, male stink bugs had significantly higher mean percent parasitism than females. Stink bug species commonly found in soybean in the region showed some parasitism and are therefore potentially vulnerable to oviposition by these parasitoids. This is the first study to characterize the level of parasitism of stink bugs by tachinids across the North Central Region.

Thermodynamics and Electronic Properties of Heterometallic Multinuclear Actinide-Containing Metal-Organic Frameworks with "Structural Memory".

Thermodynamic studies of actinide-containing metal-organic frameworks (An-MOFs), reported herein for the first time, are a step toward addressing challenges related to effective nuclear waste administration. In addition to An-MOF thermochemistry, enthalpies of formation were determined for the organic linkers, 2,2'-dimethylbiphenyl-4,4'-dicarboxylic acid (H2Me2BPDC) and biphenyl-4,4'-dicarboxylic acid (H2BPDC), which are commonly used building blocks for MOF preparation. The electronic structure of the first example of An-MOF with mixed-metal AnAn'-nodes was influenced through coordination of transition metals as shown by the density of states near the Fermi edge, changes in the Tauc plot, conductivity measurements, and theoretical calculations. The "structural memory" effect (i.e., solvent-directed crystalline-amorphous-crystalline structural dynamism) was demonstrated as a function of node coordination degree, which is the number of organic linkers per metal node. Remarkable three-month water stability was reported for Th-containing frameworks herein, and the mechanism is also considered for improvement of the behavior of a U-based framework in water. Mechanistic aspects of capping linker installation were highlighted through crystallographic characterization of the intermediate, and theoretical calculations of free energies of formation (ΔGf) for U- and Th-MOFs with 10- and 12-coordinated secondary building units (SBUs) were performed to elucidate experimentally observed transformations during the installation processes. Overall, these results are the first thermochemical, electronic, and mechanistic insights for a relatively young class of actinide-containing frameworks.

[Neuroendocrine tumors in daily gastroenterology and endoscopy - a practice manual]. / Neuroendokrine Tumoren in der täglichen gastroenterologischen und endoskopischen Praxis ­ ein klinisch orientierter Leitfaden.

Neuroendocrine tumors of the gastrointestinal tract (GI-NET) are rare tumors. Functional tumors with hormonal syndromes (e. g., insulinoma, gastrinoma) are less common than non-functional tumors, which usually have an indolent course. Therapy for GI-NET is multimodal, including endoscopic or surgical procedures aiming at complete removal of tumor tissue. Patients in later stages may benefit from interventional radiology or medical therapy. This article gives an overview regarding the key aspects of GI-NET therapy in daily gastroenterology practice with emphasis on endoscopic diagnosis and therapy.

Free Quantum Fields in 4D and Calabi-Yau Spaces.

We develop general counting formulas for primary fields in free four dimensional (4D) scalar conformal field theory (CFT). Using a duality map between primary operators in scalar field theory and multivariable polynomial functions subject to differential constraints, we identify a sector of holomorphic primary fields corresponding to polynomial functions on a class of permutation orbifolds. These orbifolds have palindromic Hilbert series, which indicates they are Calabi-Yau orbifolds. We construct the unique top-dimensional holomorphic form expected from the Calabi-Yau property. This sector includes and extends previous constructions of infinite families of primary fields. We sketch the generalization of these results to free 4D vector and matrix CFTs.

Application of maximum entropy to statistical inference for inversion of data from a single track segment.

In this paper an approach is presented to estimate the constraint required to apply maximum entropy (ME) for statistical inference with underwater acoustic data from a single track segment. Previous algorithms for estimating the ME constraint require multiple source track segments to determine the constraint. The approach is relevant for addressing model mismatch effects, i.e., inaccuracies in parameter values determined from inversions because the propagation model does not account for all acoustic processes that contribute to the measured data. One effect of model mismatch is that the lowest cost inversion solution may be well outside a relatively well-known parameter value's uncertainty interval (prior), e.g., source speed from track reconstruction or towed source levels. The approach requires, for some particular parameter value, the ME constraint to produce an inferred uncertainty interval that encompasses the prior. Motivating this approach is the hypothesis that the proposed constraint determination procedure would produce a posterior probability density that accounts for the effect of model mismatch on inferred values of other inversion parameters for which the priors might be quite broad. Applications to both measured and simulated data are presented for model mismatch that produces minimum cost solutions either inside or outside some priors.

A two-way coupled mode formalism that satisfies energy conservation for impedance boundaries in underwater acoustics.

This paper shows that energy conservation and the derivation of the two-way coupled mode range equations can be extended in three dimensions to complex mode functions and eigenvalues. Furthermore, the energy in the coupled mode formulation is conserved for finite thickness fluid ocean waveguides with a penetrable bottom boundary beneath any range dependence. The derivations rely on completeness and a modified orthonormality statement. The mode coupling coefficients are specified solely and explicitly by the waveguide range dependence. The statement of energy conservation is applied to a numerical coupled mode calculation.

Stink Bug (Hemiptera: Heteroptera: Pentatomidae) Feeding and Phenology on Early-Maturing Soybean in Minnesota.

The invasion by Halyomorpha halys (Stål) and an increasing abundance of native Pentatomidae pose a threat to soybean, Glycine max (L.) Merrill, production in northern states. A risk assessment framework was used to provide an initial assessment of the risk of Pentatomidae affecting soybean production in northern states. A caged field study was performed over two years to assess the response of soybean to H. halys feeding. Cages placed over R4 soybean were infested with 0, 1, 2, 4, or 8 fourth-instar H. halys nymphs per 0.3 row-m, and the insects were allowed to feed for 15 to 16 days. Feeding by H. halys on soybean affected yield components, maturity, and quality (i.e., seed injury). Season-long monitoring of soybean fields was performed via sweep net sampling to assess the likelihood of herbivorous Pentatomidae occurring on soybean during plant growth stages susceptible to feeding injury. Adults of herbivorous species were collected at low densities in fields in mid- to late July before collection of herbivorous nymphs. Herbivorous nymphs were first collected in the R3 and R4 soybean growth stages and their abundance peaked during the R6 soybean growth stage. This preliminary assessment indicates that if populations of exotic and native herbivorous Pentatomidae continue to increase in abundance, they will pose a threat to northern soybean production.

Soybean Aphid (Hemiptera: Aphididae) Affects Soybean Spectral Reflectance.

Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is the most economically important insect pest of soybean in the north central United States. Scouting-based integrated pest management (IPM) programs could become more efficient and more widely adopted by using plant spectral reflectance to estimate soybean aphid injury. Our objective was to determine whether plant spectral reflectance is affected by soybean aphid feeding. Field trials were conducted in 2013 and 2014 using caged plots. Early-, late-, and noninfested treatments were established to create a gradient of soybean aphid pressure. Whole-plant soybean aphid densities were recorded weekly. Measurements of plant spectral reflectance occurred on two sample dates per year. Simple linear regression models were used to test the effect of cumulative aphid-days (CAD) on plant spectral reflectance at 680 nm (RED) and 800 nm (NIR), normalized difference vegetation index (NDVI), and relative chlorophyll content. Data indicated that CAD had no effect on canopy-level RED reflectance, but CAD decreased canopy-level NIR reflectance and NDVI. Canopy- and leaf-level measurements typically indicated similar plant spectral response to increasing CAD. CAD generally had no effect on relative chlorophyll content. The present study provides the first documentation that remote sensing holds potential for detecting changes in plant spectral reflectance induced by soybean aphid. The use of plant spectral reflectance in soybean aphid management may assist future IPM programs to reduce sampling costs and prevent prophylactic insecticide sprays.

Complementarity of statistical treatments to reconstruct worldwide routes of invasion: the case of the Asian ladybird Harmonia axyridis.

Inferences about introduction histories of invasive species remain challenging because of the stochastic demographic processes involved. Approximate Bayesian computation (ABC) can help to overcome these problems, but such method requires a prior understanding of population structure over the study area, necessitating the use of alternative methods and an intense sampling design. In this study, we made inferences about the worldwide invasion history of the ladybird Harmonia axyridis by various population genetics statistical methods, using a large set of sampling sites distributed over most of the species' native and invaded areas. We evaluated the complementarity of the statistical methods and the consequences of using different sets of site samples for ABC inferences. We found that the H. axyridis invasion has involved two bridgehead invasive populations in North America, which have served as the source populations for at least six independent introductions into other continents. We also identified several situations of genetic admixture between differentiated sources. Our results highlight the importance of coupling ABC methods with more traditional statistical approaches. We found that the choice of site samples could affect the conclusions of ABC analyses comparing possible scenarios. Approaches involving independent ABC analyses on several sample sets constitute a sensible solution, complementary to standard quality controls based on the analysis of pseudo-observed data sets, to minimize erroneous conclusions. This study provides biologists without expertise in this area with detailed methodological and conceptual guidelines for making inferences about invasion routes when dealing with a large number of sampling sites and complex population genetic structures.

Immature development and adult longevity of the soybean tentiform leafminer (Lepidoptera: Gracillariidae).

The leaf-mining microlepidopteran, Macrosaccus morrisella (Fitch) (Lepidoptera: Gracillariidae), has emerged as a new pest of soybean, Glycine max (L.) Merrill (Fabales: Fabaceae), in Canada and the United States, but little is known about its life history traits. Thus, this study was conducted to assess the immature developmental rate of M. morrisella, from egg to adult emergence, on soybean at different temperatures, and the longevity of adults supplied with water and/or honey at different temperatures. The time to 50% emergence of adults was 71.90, 36.33, 24.62, and 17.83 days at 15, 20, 25, and 30 °C, respectively. The lower developmental threshold of M. morrisella was estimated at 8.96 °C, with 425.04 degree-days required for egg-to-adult development. For adult longevity, time to 50% mortality at 25 °C was 15.00, 4.00, and 2.00 days when adults were provided with 25% (v/v) honey-water solution, water, or nothing, respectively. In a follow-up experiment, time to 50% mortality at 25 °C was 24.00, 6.00, 3.00, and 3.00 days when adults were provided with honey and water (offered separately), honey, water, or nothing, respectively, with a synergistic effect when honey and water were offered simultaneously as opposed to honey or water alone. Finally, when fed 25% (v/v) honey-water solution and maintained at 20, 25, and 30 °C, time to 50% mortality of adults was 26.50, 15.00, and 15.00 days. These results inform the understanding of the basic biology of M. morrisella and will help inform the future development of management programs for this insect in soybean.

Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition-A Prospective Multicenter Study.

BACKGROUND: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.