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The Chinese sleeper (Perccottus glenii), an invasive Asian fish, was first registered in Germany in 2009 (westernmost extent of its invasive range). We sampled Chinese sleepers from two localities on the Bücherlgraben creek (a tributary of the River Naab) in south-eastern Germany in November 2015 and examined them for parasite infection. Twelve taxa were registered, including ciliates (unidentified Trichodina), a monogenean, three cestode species, two digenean taxa, two acanthocephalan species, two nematode species and one mollusc glochidia. Infracommunities consisted of 1–5 species, with 10% of fish uninfected. Three parasite species (Acanthocephalus anguillae, Gyrodactylus luciopercae and Pseudocapillaria tomentosa) were recorded on Chinese sleepers for the first time. The results highlight the important role of the Chinese sleeper as a second intermediate host in the life cycle of heron and grebe parasites. The Chinese sleeper parasite community displayed low homogeneity at both localities sampled, with allogenic parasites (metacercariae and mesocercoids) mostly shared. Differences between localities were mainly caused by autogenic parasites. No invasive parasites associated with the Chinese sleeper were observed in the study area, all parasites being representatives of European fauna. This supports the hypothesis of introduction via the aquarium trade or through transport with commercial fish. [ABSTRACT FROM AUTHOR]

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD., Design: Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7 Δhep ) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics. We analysed the association of rs641738C>T genotype with liver inflammation and fibrosis in 846 NAFLD patients and obtained genotype-specific liver lipidomes from 280 human biopsies., Results: Allelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7 Δhep mice showed spontaneous steatosis characterised by increased hepatic cholesterol ester content after 10 weeks. After 6 weeks on a high fat, methionine-low, choline-deficient diet, mice developed increased hepatic fibrosis as measured by picrosirius staining (p < 0.05), hydroxyproline content (p < 0.05) and transcriptomics, while the inflammatory cell populations and inflammatory mediators were minimally affected. In a human biopsied NAFLD cohort, MBOAT7 rs641738C>T was associated with fibrosis (p = 0.004) independent of the presence of histological inflammation. Liver lipidomes of Mboat7 Δhep mice and human rs641738TT carriers with fibrosis showed increased total lysophosphatidylinositol levels. The altered lysophosphatidylinositol and phosphatidylinositol subspecies in MBOAT7 Δhep livers and human rs641738TT carriers were similar., Conclusion: Mboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Monoclonal antibodies (mAbs) are valuable tools both in therapy and in diagnostic. Their tendency to aggregate is a serious concern. Since a mAb drug substance (DS) is composed of different variants, it is important for manufacturers to know the behavior and stability not only of the mAb as a whole, but also of the variants contained in the product. We present a method to separate hydrophobicity variants of a mAb and subsequently analyzed these variants for stability and aggregation propensity. We identified a potentially aggregation prone hydrophilic variant which is interrelated with another previously identified aggregation prone acidic charge variant. Additionally, we assessed the risk posed by the aggregation prone variant to the DS by spiking hydrophobicity variants into DS and did not observe an enhanced aggregation propensity. Thus we present an approach to separate, characterize and analyze the criticality of aggregation prone variants in protein DS which is a step forward to further assure drug safety., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Biopharmaceutical products contain conformational and chemical variants, that are typically well characterized regarding identity and activity. However, little is known about their self-interaction propensity and tendency to unfold, which are critical characteristics for drug stability and safety. This study aimed to separate and compare charge variants of a monoclonal antibody (mAb) and to identify aggregation prone species. We show a semi-preparative cation exchange method, that we developed to separate the individual acidic and basic variants from the naïve mAb. Additionally, we demonstrate, that the yield and purity of the fractionated charge species, extracted by that method, were sufficient for subsequent analysis of aggregate content, conformation stability and self-interaction. Our analysis revealed a differently behaving acidic variant and confirmed its increased aggregation propensity by molecular modeling. During a stability study, the potentially aggregation prone charge variant posed a limited risk to the drug substance (DS). We are the first to look at the stability of single charge variants of biopharmaceuticals, and thus present manufacturers and regulatory authorities with a method to enhance drug safety., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the challenges with urgent evaluation of patients with acute respiratory distress syndrome (ARDS) in the emergency room (ER) is distinguishing between cardiac vs infectious etiologies for their pulmonary findings. We conducted a retrospective study with the collected data of 171 ER patients. ER patient classification for cardiac and infection causes was evaluated with clinical data and chest X-ray image data. We show that a deep-learning model trained with an external image data set can be used to extract image features and improve the classification accuracy of a data set that does not contain enough image data to train a deep-learning model. An analysis of clinical feature importance was performed to identify the most important clinical features for ER patient classification. The current model is publicly available with an interface at the web link: http://nbttranslationalresearch.org/ .

One in eight women develops invasive breast cancer in her lifetime. The frontline protection against this disease is mammography. While computer-assisted diagnosis algorithms have made great progress in generating reliable global predictions, few focus on simultaneously producing regions of interest (ROIs) for biopsy. Can we combine ROI-oriented algorithms with global classification of cancer status, which simultaneously highlight suspicious regions and optimize classification performance? Can the asymmetry of breasts be adopted in deep learning for finding lesions and classifying cancers? We answer the above questions by building deep-learning networks that identify masses and microcalcifications in paired mammograms, exclude false positives, and stepwisely improve performance of the model with asymmetric information regarding the breasts. This method achieved a co-leading place in the Digital Mammography DREAM Challenge for predicting breast cancer. We highlight here the importance of this dual-purpose process that simultaneously provides the locations of potential lesions in mammograms., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Background and Aims: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC., Approach and Results: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10 -6 ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10 -4 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10 -26 ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10 -23 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (OR allelic , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10 -4 )., Conclusions: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population., (© 2019 by the American Association for the Study of Liver Diseases.)

Background: Venous thromboembolism (VTE) chemoprophylaxis in breast surgery remains controversial. In 2012, we instituted a practice change of routine chemoprophylaxis for patients with invasive cancer undergoing mastectomy. Herein, we report the effects of this on rates of VTE and hematoma., Methods: Our 30-day rates of VTE and hematoma requiring reoperation among patients with mastectomy since the practice change were retrospectively collected from National Surgical Quality Improvement Program (NSQIP). The subsequent 5-year data (2012-2017) was compared with historic NSQIP data (2006-2010). We utilized information from our 30-day follow-up databank to assess patients not sampled by NSQIP., Results: After the practice change, the heparin prophylaxis rate rose from 19.5% to 95.6% (P < .001) and the VTE rate fell from 0.8% to 0% (P = .30). There was no significant change in reoperative hematoma rate (P = .39). The majority of the current NSQIP patient population (93.1%) had a Caprini score of 5 or greater. Among 663 patients obtained from 30-day postoperative follow-up, there were 2 VTE (0.3%) and 7 (1.1%) reoperations for hematoma., Conclusions: The practice change resulted in an increase of VTE chemoprophylaxis without significant change in hematoma incidence. Although not statistically significant, VTE incidence decreased. This supports the use of standardized VTE chemoprophylaxis in this population and warrants further study., (© 2019 Wiley Periodicals, Inc.)

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

BACKGROUNDSurgical site infections (SSIs) following colorectal surgery (CRS) are among the most common healthcare-associated infections (HAIs). Reduction in colorectal SSI rates is an important goal for surgical quality improvement.OBJECTIVETo examine rates of SSI in patients with and without cancer and to identify potential predictors of SSI risk following CRSDESIGNAmerican College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data files for 2011-2013 from a sample of 12 National Comprehensive Cancer Network (NCCN) member institutions were combined. Pooled SSI rates for colorectal procedures were calculated and risk was evaluated. The independent importance of potential risk factors was assessed using logistic regression.SETTINGMulticenter studyPARTICIPANTSOf 22 invited NCCN centers, 11 participated (50%). Colorectal procedures were selected by principal procedure current procedural technology (CPT) code. Cancer was defined by International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes.MAIN OUTCOMEThe primary outcome of interest was 30-day SSI rate.RESULTSA total of 652 SSIs (11.06%) were reported among 5,893 CRSs. Risk of SSI was similar for patients with and without cancer. Among CRS patients with underlying cancer, disseminated cancer (SSI rate, 17.5%; odds ratio [OR], 1.66; 95% confidence interval [CI], 1.23-2.26; P=.001), ASA score ≥3 (OR, 1.41; 95% CI, 1.09-1.83; P=.001), chronic obstructive pulmonary disease (COPD; OR, 1.6; 95% CI, 1.06-2.53; P=.02), and longer duration of procedure were associated with development of SSI.CONCLUSIONSPatients with disseminated cancer are at a higher risk for developing SSI. ASA score >3, COPD, and longer duration of surgery predict SSI risk. Disseminated cancer should be further evaluated by the Centers for Disease Control and Prevention (CDC) in generating risk-adjusted outcomes.Infect Control Hosp Epidemiol 2018;39:555-562.