bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations
Authors: Dubinsky Vadim , Reshef Leah , Rabinowitz Keren , Wasserberg Nir , Dotan Iris , Gophna Uri 
Published: May 2022

Abstract

Background and Aims
Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages.

Methods
We investigated E. coli genomes from patients with ulcerative colitis [UC], Crohn’s disease [CD] or a pouch, and healthy subjects. The majority of genomes were reconstructed from metagenomic samples, including newly sequenced faecal metagenomes. Clinical metadata were collected. Functional analysis at the gene and mutation level were performed and integrated with IBD phenotypes and biomarkers.

Results
Overall, 530 E. coli genomes were analysed. The E. coli B2 lineage was more prevalent in UC compared with other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Host mucin utilisation enzymes were present in a single lineage and depleted in patients with a pouch, whereas those involved in inulin hydrolysis were enriched in patients with a pouch. E. coli strains from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or a pouch. Strikingly, patients with a pouch showed the highest inferred E. coli growth rates, even in the presence of antibiotics. Faecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific non-synonymous mutations in E. coli genes encoding for bacterial cell envelope components.

Conclusions
Comparative genomics indicates that E. coli is a commensal species adapted to the overactive mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.
Estimate of inbreeding depression on growth and reproductive traits in a Large White pig population
Authors: Zhang Yu , Zhuo Yue , Ning Chao , Zhou Lei , Liu Jian-Feng 
Published: May 2022

Abstract
With the broad application of genomic information, SNP-based measures of estimating inbreeding have been widely used in animal breeding, especially based on runs of homozygosity. Inbreeding depression is better estimated by SNP-based inbreeding coefficients than pedigree-based inbreeding in general. However, there are few comprehensive comparisons of multiple methods in pigs so far, to some extent limiting their application. In this study, to explore an appropriate strategy for estimating inbreeding depression on both growth traits and reproductive traits in a Large White pig population, we compared multiple methods for the inbreeding coefficient estimation based on both pedigree and genomic information. This pig population for analyzing the influence of inbreeding was from a pig breeding farm in the Inner Mongolia of China. There were 26,204 pigs with records of age at 100 kg (AGE) and back-fat thickness at 100 kg (BF), and 6,656 sows with reproductive records of the total number of piglets at birth (TNB), and the number of alive piglets at birth (NBA), and litter weight at birth. Inbreeding depression affected growth and reproductive traits. The results indicated that pedigree-based and SNP-based inbreeding coefficients had significant effects on AGE, TNB, and NBA, except for BF. However, only SNP-based inbreeding coefficients revealed a strong association with inbreeding depression on litter weight at birth. Runs of homozygosity-based methods showed a slight advantage over other methods in the correlation analysis of inbreeding coefficients and estimation of inbreeding depression. Furthermore, our results demonstrated that the model-based approach (RZooRoH) could avoid miscalculations of inbreeding and inbreeding depression caused by inappropriate parameters, which had a good performance on both AGE and reproductive traits. These findings might improve the extensive application of runs of homozygosity analysis in pig breeding and breed conservation.
Increased supply of methionine during a heat-stress challenge in lactating holstein cows alters mammary tissue mTOR signaling and its response to lipopolysaccharide
Authors: Coleman Danielle Nicole , Vailati-Riboni Mario , Pate Russell T , Aboragah Ahmad , Luchini Daniel , Cardoso Felipe C , Loor Juan J 
Published: May 2022

AbstractThe first objective was to investigate the effects of feeding rumen-protected methionine (RPM) during a heat stress (HS) challenge on abundance and phosphorylation of mechanistic target of rapamycin (mTOR)-related signaling proteins in mammary gland. The second objective was to investigate how HS and RPM may modulate the response of mammary gland explants to an inflammatory challenge using lipopolysaccharide (LPS). Thirty-two multiparous, lactating Holstein cows (184 ± 59 DIM) were randomly assigned to 1 of 2 environmental treatment groups, and 1 of 2 dietary treatments [TMR with RPM (Smartamine M; Adisseo Inc.; 0.105% DM as top dress) or TMR without RPM (CON)] in a crossover design. There were two periods with two phases per period. In phase 1 (9 d), all cows were in thermoneutral conditions (TN) and fed ad libitum. During phase 2 (9 d), group 1 (n = 16) cows were exposed to HS using electric heat blankets, whereas group 2 cows (n = 16) remained in TN but were pair-fed to HS counterparts to control for DMI decreases associated with HS. After a washout period (14 d), the study was repeated (period 2). Environmental treatments were inverted in period 2 (sequence), whereas dietary treatments remained the same. Mammary tissue was harvested via biopsy at the end of both periods. Tissue was used for protein abundance analysis and also for incubation with 0 or 3 μg/mL of LPS for 2 h and subsequently used for mRNA abundance. Data were analyzed using PROC MIXED in SAS. Analysis of protein abundance data included the effects of diet, environment and their interaction, and period and sequence to account for the crossover design. The explant data model also included the effect of LPS and its interaction with environment and diet. Abundance of phosphorylated mTOR and ratio of phosphorylated eukaryotic translation elongation factor 2 (p-EEF2) to total EEF2 in non-challenged tissue was greater with RPM supplementation (P = 0.04 for both) and in both cases tended to be greater with HS (P = 0.08 for both). Regardless of RPM supplementation, incubation with LPS upregulated mRNA abundance of IL8, IL6, IL1B, CXCL2, TNF, NFKB1, and TLR2 (P &lt; 0.05). An environment × LPS interaction was observed for NFKB1 (P = 0.03); abundance was greater in LPS-treated explants from non-HS compared with HS cows. Abundance of CXCL2, NFKB1, NOS2, NOS1, and SOD2 was lower with HS (P &lt; 0.05). Although LPS did not alter mRNA abundance of the antioxidant transcription factor NFE2L2 (P = 0.59), explants from HS cows had lower abundance of NFE2L2 (P &lt; 0.001) and CUL3 (P = 0.04). Overall, RPM supplementation may alter mTOR activation in mammary tissue. Additionally, although HS reduced explant immune and antioxidant responses, RPM did not attenuate the inflammatory response induced by LPS in vitro.
Mast Cell (MC)‐Induced Cholestasis is Dependent on Apical Sodium Bile Acid Transporter (ASBT) Expression
Authors: Meadows Vik , Kundu Debjyoti , Zhou Tianhao , Owen Travis , Meyer Alison , Kyritsi Konstantina , Chen Lixian , Kennedy Lindsey , Alpini Gianfranco , Francis Heather 
Published: May 2022

BackgroundImpaired bile flow is a characteristic of primary sclerosing cholangitis (PSC). Up to 80% of PSC patients present with irritable bowel disease (IBD). Mast cell (MC) injection into normal or MC‐deficient mice increases ductular reaction (DR), biliary senescence, liver fibrosis and total bile acid (TBA) levels in liver and serum. MCs infiltrate the liver, activating cholangiocytes and hepatic stellate cells (HSCs), and in the intestine, MCs increase intestinal permeability in PSC and IBD patients, respectively. Bacterial translocation and leaky gut have been proposed to initiate cholestatic injury. BA circulation is dependent on apical sodium BA transporter (ASBT) expression in ileum and cholangiocytes, and inhibition of ASBT by Vivo‐Morpholino blocks cholehepatic and enterohepatic BA circulation and reduces hepatic and ileal MC infiltration in cholestatic mice.AimWe aimed to investigate the role of ASBT and disruption of BA circulation in a model of MC‐induced cholestasis.MethodsWT and ASBT knockout (KO) mice, 14‐16 wks of age, received sterile 1X PBS or 5x106 MCs (MC/9 ATCC CRL8306) via tail vein injection. Three days after injection we collected liver, colon, and isolated hepatocytes and cholangiocytes and supernatants from all mice. Hepatic damage was determined by H&E staining and liver TBA content. DR was determined with CK‐19 immunohistochemistry (marker of cholangiocytes) and semi‐quantification. Hepatic inflammation was assessed by immunohistochemistry, and semi‐quantification of F4/80. Hepatic fibrosis was determined by fast green‐Sirius red staining and semi‐quantification of collagen deposition. Cholehepatic shunting was determined by TBA levels in isolated cholangiocyte and hepatocyte supernatant. Intestinal permeability was determined by colon ZO‐1 immunostaining and hepatic bacterial translocation by quantification of colony forming units (CFUs) from liver homogenates.ResultsMC injection increased liver damage, DR, hepatic inflammation, and fibrosis in WT mice that was reduced in ASBT KO + MC mice. Cholehepatic shunting increased in WT + MC mice demonstrated by enhanced TBA content in isolated hepatocyte and cholangiocyte supernatants compared to WT mice that was reduced in ASBT KO + MC mice. MC injection lowered colonic ZO‐1 expression in WT mice, but no change was noted in ASBT KO + MC mice. MC injection increased bacterial translocation in WT mice, yet ASBT KO + MC mice had reduced bacterial translocation similar to WT and ASBT KO mice.ConclusionMC injection increases PSC phenotypes in WT mice that are reduced when BA circulation is disrupted by KO of ASBT. Regulation of ASBT is a potential therapeutic strategy for PSC and PSC‐IBD patients.
In the Absence of YAP, TAZ Contributes to Hepatocyte Adaptation in Chronic Cholestasis in Females
Authors: Molina Laura M. , Gabdulkhakova Adelya , Zhu Junjie , Liu Silvia , Poddar Minakshi , Singh Sucha , Ma Xiaochao , Singhi Aatur , Ko Sungjin , Monga Satdarshan P. 
Published: May 2022

We previously demonstrated that loss of Yes‐associated protein 1 (YAP1) in early liver development (YAP1 KO) leads to an Alagille syndrome‐like phenotype with absence of intrahepatic bile ducts and severe cholestasis accompanied by chronic hepatocyte adaptations to reduce liver injury. We noticed that TAZ, a paralog of YAP1, was significantly upregulated in hepatocytes of YAP1 KO mice and bound to TEAD transcription factors, suggesting compensatory activity in hepatocytes.We next queried the relationship between YAP1 and TAZ by deleting both genes during early liver development using the Foxa3‐Cre promoter, similar to the YAP1 KO mice, resulting in multiple allele combinations. Interestingly, we show that YAP1/TAZ double knock‐out (DKO) mice are embryonic lethal and stillborn, the embryos surviving almost until birth with no grossly visible abnormalities. The liver morphology during development does not show gross abnormalities, suggesting an extrahepatic source of lethality. This suggests that while YAP1 loss has profound impact on biliary development, YAP1 and TAZ together play a co‐dependent critical role in foregut endoderm development yet to be determined.Next, when we examined TAZ heterozygosity in YAP1 KO mice, we found significant embryonic lethality among males, with insufficient samples to analyze a potential cause at this time. However, among females, loss of one copy of TAZ from YAP1 KO mice resulted in a similar gross phenotype to YAP1 KO, with a complete lack of intrahepatic bile ducts resulting in severe chronic cholestatic disease. While serum bilirubin levels were comparable after TAZ heterozygosity, liver transaminases were more elevated than in YAP1 KO alone, suggesting worsening hepatocyte injury. Hepatocyte proliferation levels were not affected by TAZ heterozygosity. Global gene expression patterns as detected by RNA‐sequencing were grossly similar as compared to YAP1 KO mice, although subtle alterations were identified in pathways related to apoptosis, cell division, inflammatory signaling, and metabolism, and we also show that TAZ is needed to regulate canonical YAP1 targets in YAP1 KO hepatocytes such as CTGF and CYR61. We also found significant elevation in serum cholesterol compared to YAP1 KO alone, and xanthomas were observed at later stages on these mice, suggesting worsening metabolic derangements caused by TAZ heterozygosity beyond what was observed in YAP1 KO alone. Interestingly, bile acid profiles in both liver and serum as detected by mass spectrometry showed no difference in YAP1 KO with or without TAZ heterozygosity. Ongoing work aims to further identify the role of TAZ in metabolic adaptations to chronic cholestasis with potential implications for clinical regulation of hypercholesterolemia and long‐term liver metabolic health.
Human CD99L2 Regulates a Step in TEM Independent of PECAM and CD99 Regulated Steps
Authors: Rutledge Nakisha S. , Ogungbe Faith T. , Watson Richard L. , Sullivan David P. , Muller William A. 
Published: May 2022

CD99‐like 2 (CD99L2; L2) is a highly glycosylated 52 kDa type‐1 membrane protein that is important for leukocyte transendothelial migration (TEM) in mice. Inhibiting L2 using function blocking antibody or genetic ablation significantly reduces the recruitment of leukocytes to sites of inflammation in vivo. Similarly, endothelial L2 knockout mice have an inherent defect in leukocyte transmigration into sites of inflammation, but not the preceding steps in inflammation. The position of neutrophil arrest suggests L2 regulates a step in TEM independent of platelet endothelial cell adhesion molecule (PECAM). However, the role of L2 in inflammation has only been studied in mice and the mechanism by which it regulates TEM is not known.In order to study the relevance to human inflammation, we studied the role of L2 on primary human cells in vitro. Using immunofluorescence and flow cytometry, our data show that human L2 is constitutively expressed at the borders of endothelial cells and on the surfaces of leukocytes. Inhibiting L2 using antibody blockade, L2‐Fc chimera decoy molecules, or genetic knockdown in endothelial cells significantly reduced transmigration of human neutrophils and monocytes across endothelial cells. Furthermore, our data also show that L2 regulates a specific, sequential step of TEM between PECAM and CD99, rather than operating in parallel or redundantly with these molecules. Similar to PECAM and CD99, L2 promotes transmigration by recruiting the lateral border recycling compartment (LBRC) to sites of TEM, specifically downstream of PECAM initiation. Collectively, our data identify a novel functional role for human L2 in TEM and elucidate a mechanism that is distinct from PECAM and CD99.
Fever and Systemic Inflammatory Response Syndrome After Wide Resection of Pediatric Bone Sarcomas
Authors: Gallaway Kathryn E. , Atadja Louise A. , Callan Alexandra K. 
Published: May 2022

Background:
While postoperative fever is common and thought to be physiological, data is limited in pediatric patients with bone sarcomas. Understanding the predictive value of postoperative fever and systemic inflammatory response syndrome (SIRS) in this population is essential to guide further workup and avoid delays in adjuvant therapy. The aim of this study is to characterize the prevalence of postoperative fever and SIRS in pediatric patients undergoing wide resection of bone sarcomas and to determine whether these signs are associated with wound or infectious complications.

Methods:
A retrospective chart review of cases performed by a single surgeon between January 2018 and December 2020 was performed.

Results:
Twenty-two patients were identified. All patients had pathology-confirmed diagnoses of osteosarcoma (77.3%) or Ewing sarcoma (22.7%). Before discharge, 68.2% developed a fever >38°C and 90.9% met SIRS criteria. The rate of wound and infectious complications during the first 6 weeks after surgery was 27.3%. The positive predictive values (PPV) of fever and SIRS were low at 26.7% and 31.0% respectively. No association between complications and fever [dds ratio (OR): 0.91, 95% confidence interval (CI): 0.12-6.72] or SIRS (OR: 2.24, 95% CI: 0.78-46.14) was identified. High fever >39°C had a better PPV of 50.0%. However, the association between high fever and complications did not reach significance (OR: 6.00, 95% CI: 0.78-46.14). Age, tumor size, days from chemo to surgery, duration of surgery, estimated blood loss, number of packed red blood cells units transfused, and length of stay were not associated with the development of postoperative fever or complications.

Conclusion:
Pediatric patients undergoing wide resection of bone sarcomas frequently mount a robust SIRS response after surgery. However, fever and SIRS are both poor predictors of infection and wound complications. Patients with postoperative fever or SIRS should not undergo an extensive infectious workup unless there are clear signs or symptoms to suggest an infectious etiology.

Level of Evidence:
Level II—prognostic retrospective study.
The Impact of Students Studying Abroad on the Subsequent Career of the Professional Nurse
Authors: Johanson Linda , Priode Kimberly 
Published: May 2022

ABSTRACT:
A study abroad course adds to the academic experience of nursing students by offering exposure to other cultures, service opportunities, and an introduction to international healthcare systems. The purpose of this study was to explore the perceived impact of a student study abroad experience on the subsequent career of the professional nurse. The phenomenological qualitative study approach revealed three themes: changed personal perspectives in practice, appreciation and service orientation, and insights on the healthcare system. Nurses reported that the study abroad experience helped to shape their views as professional nurses.
An Ounce of Prediction is Worth a Pound of Cure: Risk Calculators in Breast Reconstruction
Authors: Oleck Nicholas C. , Biswas Sonali , Shammas Ronnie L. , Naga Hani I. , Phillips Brett T. 
Published: May 2022

Background:
Preoperative risk calculators provide individualized risk assessment and stratification for surgical patients. Recently, several general surgery–derived models have been applied to the plastic surgery patient population, and several plastic surgery–specific calculators have been developed. In this scoping review, the authors aimed to identify and critically appraise risk calculators implemented in postmastectomy breast reconstruction.

Methods:
A systematic review of the literature was conducted. Included studies described the development of a novel risk calculator, or validation of an existing calculator, in postmastectomy breast reconstruction.

Results:
In total, 4641 studies met criteria for title and abstract screening. Forty-seven were eligible for full-text review, and 28 met final inclusion criteria. The most common risk calculators included the Breast Reconstruction Risk Assessment score (n = 6 studies), modified frailty index (n = 3), Caprini score (n = 3), and ACS NSQIP calculator (n = 2). Calculators were applied to institutional data (n = 17), NSQIP (n = 6), and Tracking Outcomes in Plastic Surgery (n = 1) databases. Predicted outcomes included general postoperative complications (n = 17), venous thromboembolism/pulmonary embolism (n = 4), infection (n = 2), and patient reported outcomes (n = 2). Model accuracy was reported in 18 studies, and it varied significantly (accurate risk calculator 0.49–0.85).

Conclusions:
This is the first study to provide a systematic review of available risk calculators for breast reconstruction. Models vary significantly in their statistical basis, predicted outcomes, and overall accuracy. Risk calculators are valuable tools that may aid in individualized risk assessments, preoperative counseling, and expectation management in breast reconstruction.
An Integrated Neuroimaging Approach to Inform Transcranial Electrical Stimulation Targeting in Visual Hallucinations
Authors: Raymond Nicolas , Reinhart Robert M. G. , Keshavan Matcheri , Lizano Paulo 
Published: May 2022

Abstract
For decades, noninvasive brain stimulation (NIBS), such as transcranial electrical stimulation (tES), has been used to directly modulate human brain mechanisms of visual perception, setting the groundwork for the development of novel circuit-based therapies. While the field of NIBS has grown considerably over recent years, few studies have used these technologies to treat visual hallucinations (VH). Here, we review the NIBS-VH literature and find mixed results due to shortcomings that may potentially be addressed with a unique multimodal neuroimaging–NIBS approach. We highlight methodological advances in NIBS research that have provided researchers with more precise anatomical measurements that may improve our ability to influence brain activity. Specifically, we propose a methodology that combines neuroimaging advances, clinical neuroscience developments such as the identification of brain regions causally involved in VH, and personalized NIBS approaches that improve anatomical targeting. This methodology may enable us to reconcile existing discrepancies in tES-VH research and pave the way for more effective, VH-specific protocols for treating a number of neuropsychiatric disorders with VH as a core symptom.
The effect of Epstein–Barr virus viremia on the progression to severe COVID-19
Authors: Im Jae Hyoung , Nahm Chung Hyun , Je Young Soo , Lee Jin-Soo , Baek Ji Hyeon , Kwon Hea Yoon , Chung Moon-Hyun , Jang Ji-Hun , Kim Jung Soo , Lim Jun Hyeok , Park Mi Hwa 
Published: May 2022

Abstract
Epstein–Barr virus (EBV) is frequently reactivated by coronavirus 2019 (COVID-19), and a high incidence of EBV viremia has been reported in patients with severe COVID-19. However, the impact of EBV viremia on progression to severe COVID-19 is unclear. Therefore, we conducted a study to evaluate the effect of EBV on COVID-19 progression.
We investigated EBV viremia at the time of admission in COVID-19 patients hospitalized between February 1, 2020, and April 11, 2021. A cross-sectional study was performed to compare the severity of COVID-19 according to the presence or absence of EBV viremia. However, since it is difficult to analyze the influence of EBV viremia on COVID-19 progression with cross-sectional studies, a retrospective cohort study, limited to patients with mild COVID-19, was additionally conducted to observe progression to severe COVID-19 according to the presence or absence of EBV viremia.
Two hundred sixty-nine COVID-19 patients were tested for EBV viremia. In a cross-sectional study that included patients with both mild and severe COVID-19, the EBV viremia group had more severe pneumonia than the EBV-negative group. However, in the cohort study limited to mild cases (N = 213), EBV viremia was not associated with COVID-19 progression.
COVID-19 severity may affect EBV viremia; however, there was no evidence that EBV viremia was a factor in exacerbating pneumonia in patients with mild COVID-19.