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Imbalances in the gut microbiome have emerged as an important factor in endothelial dysfunction, a significant risk factor for cardiovascular disease. Thus, interventions targeting the microbiome may prove helpful in preventing or reversing this impairment. We previously reported that spore-forming Bacillus subtilis DE111 improved endothelial function in a cohort of healthy, non-obese humans after a four-week intervention. Building on these promising results, the present study sought to investigate whether administering B. subtilis DE111 could reverse endothelial dysfunction in mice with diet-induced obesity. Male C57BL/6J mice were fed a Western diet (WD; n = 24) or standard diet (SD; n = 24) for ten weeks to induce endothelial dysfunction, after which half of the animals in each group (n = 12) were allocated to receive B. subtilis DE111 (hereafter, PB) formulated into the diet for an additional eight weeks. Outcomes included endothelial-dependent arterial dilation, glucose tolerance, body weight changes, microbiota profiles, and assessments of intestinal permeability and mucosal immunity markers. Furthermore, a cell culture model of gut barrier function was used to assess the effects of PB on gut barrier integrity. PB treatment significantly attenuated WD-induced mesenteric endothelial-dependent arterial dilation, independent of changes in other cardiometabolic parameters or changes in gut barrier function. In vitro trans-epithelial electrical resistance of the Caco-2 cell culture confirmed that neither PB-conditioned media nor faecal waters from B. subtilis-treated human stool resulted in gut barrier improvements, nor did they protect against inflammation-associated barrier disruptions. Unsurprisingly, microbiota analysis revealed significant differences in Shannon's alpha diversity of WD-fed animals compared to SD. These data suggest that PB consumption significantly attenuated WD diet-induced endothelial dysfunction; however, the underlying mechanisms of this protection were not determined. Improvement in endothelial function was independent of PB-mediated changes to body weight or gut barrier function. Further studies should explore B. subtilis-mediated immune responses or metabolite production as mechanisms underlying these endothelial protective effects.

Importance: Recent research has demonstrated that domains of social determinants of health (SDOH) (e.g., air pollution and social context) are associated with psychosis. However, SDOHs have often been studied in isolation., Objective: To identify distinct exposure profiles, estimate their associations with persistent distressing psychotic-like experiences (PLE), and evaluate whether involvement with physical activities partially explains this association., Design Setting and Participants: This population-based study used data from the Adolescent Brain and Cognitive Development (ABCD) Study. Participants were recruited from 22 US sites between September 2016 and January 2022. Data from baseline and three follow-ups were included., Exposures: Area-level geocoded variables spanning various domains of SDOH, including socioeconomic status (SES), education, crime, built environment, social context, and crime, were clustered using a self-organizing map method to identify exposure profiles., Main Outcomes and Measures: Persistent distressing PLE was derived from the Prodromal Questionnaire-Brief Child Version across four years. Generalized linear mixed modeling tested the association between exposure profiles and persistent distressing PLE as well as physical activities (i.e., team and individual sports), adjusting for individual-level covariates including age, sex, race/ethnicity, highest level of parent education, family-relatedness, and study sites., Results: Among 8,145 participants (baseline mean [SD] age, 9.92 [0.63] years; 3,868 (47.5%) females; 5,566 (68.3%) White, 956 (11.7%) Black, 159 (2.0%) Asian, and 1,480 (18.4%) Hispanic participants), five exposure profiles were identified. Compared to the reference Profile 1 (suburban affluent areas, 2521 children, 30.9%), Profile 3 (rural areas with low walkability and high ozone; 1459 children, 17.9%; adjusted OR: 1.34, 95% CI: 1.09-1.64) and Profile 4 (urban areas with high SES deprivation, high crime, and high pollution; 715 children, 8.8%; adjusted OR: 1.40, 95% CI: 1.08-1.81), were associated with persistent distressing PLE. Team sports mediated 6.14% of the association for Profile 3., Conclusion and Relevance: This study found that neighborhoods characterized by rural areas with low walkability and urban areas with high socioeconomic deprivation, air pollutants, and crime were associated with persistent distressing PLE. Further research is needed to explore the pathways through which different environmental factors may impact the development of psychosis.

Purpose: To identify differences in mortality or length of hospital stay for mothers treated with uterine artery embolization (UAE) or hysterectomy for severe postpartum hemorrhage (PPH), as well as to analyze whether geographic or clinical determinants affected the type of therapy received., Materials and Methods: This National Inpatient Sample study from 2005 to 2017 included all patients with live-birth deliveries. Severe PPH was defined as PPH that required transfusion, hysterectomy, or UAE. Propensity score weighting-adjusted demographic, maternal, and delivery risk factors were used to assess mortality and prolonged hospital stay., Results: Of 9.8 million identified live births, PPH occurred in 31.0 per 1,000 cases. The most common intervention for PPH was transfusion (116.4 per 1,000 cases of PPH). Hysterectomy was used more frequently than UAE (20.4 vs 12.9 per 1,000 cases). The following factors predicted that hysterectomy would be used more commonly than UAE: previous cesarean delivery, breech fetal position, placenta previa, transient hypertension during pregnancy without pre-eclampsia, pre-existing hypertension without pre-eclampsia, pre-existing hypertension with pre-eclampsia, unspecified maternal hypertension, and gestational diabetes (all P < .001). Delivery risk factors associated with greater utilization of hysterectomy over UAE included postterm pregnancy, premature rupture of membranes, cervical laceration, forceps vaginal delivery, and shock (all P < .001). There was no difference in mortality between hysterectomy and UAE. After balancing demographic, maternal, and delivery risk factors, the odds of prolonged hospital stay were 0.38 times lower with UAE than hysterectomy (P < .001)., Conclusions: Despite similar mortality and shorter hospital stays, UAE is used far less than hysterectomy in the management of severe PPH., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the utilization and efficacy of various treatments for management of adult patients with splenic trauma, highlighting the evolving role of splenic artery embolization., Materials and Methods: The National Trauma Data Bank (NTDB) was queried for patients who sustained splenic trauma between 2007 and 2015, excluding those with death on arrival and selected nonsplenic high-grade injuries. Patients were categorized into (1) nonoperative management (NOM), (2) embolization, (3) splenectomy, (4) splenic repair, and (5) combined treatment groups. Evaluated outcomes included hospital length of stay (LOS), intensive care unit LOS, mortality, and NOM and embolization failures., Results: Overall, 117,743 patients with splenic predominant trauma were included in this study. Over the 9-year study period, 85,793 (72.9%) were treated with NOM, 21,999 (18.9%) with splenectomy, 3895 (3.3%) with embolization, and 2131 (1.8%) with splenic repair. From 2007 to 2015, mortality rates declined from 7.6% to 4.7%. The rate of NOM did not significantly change over time, while embolization increased 369% (1.3%-4.8%). Failure of NOM was 4.4% in 2007 and decreased to 3.4% in 2015. Across all injury grades, NOM had the shortest LOS (8.3 days), followed by splenic repair (12.3), embolization (12.6), and splenectomy (13.8) (p < 0.001). When adjusted for various clinical factors including severity of splenic injury, mortality rates were 7.1% for splenectomy, 3.2% for embolization, and 2.5% for NOM., Conclusion: Most patients with splenic-dominant blunt trauma are managed with NOM. Over time, the use of embolization has increased while open surgery has declined, and mortality has improved for all treatment methods. Compared to splenectomy, embolization is associated with shorter hospital LOS but is still used relatively infrequently., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To compare logistic regression to elastic net for identifying and ranking clinical risk factors for blunt cerebrovascular injury (BCVI)., Materials and Methods: Consecutive trauma patients undergoing screening CTA at a level 1 trauma center over a 2-year period. Each internal carotid artery (ICA) and vertebral artery (VA) was independently graded by 2 neuroradiologists using the Denver grading scale. Unadjusted odds ratios were calculated by univariate and adjusted odds ratios by multiple logistic regression with FDR correction. We applied logistic regression with the elastic net penalty and tenfold cross-validation., Results: Total of 467 patients; 73 patients with BCVI. Maxillofacial fracture, basilar skull fracture, and GCS had significant unadjusted odds ratios (OR) for ICA injury and C-spine fracture, spinal ligamentous injury, and age for VA injury. Only transverse foramen fracture had significant adjusted OR for VA injury, with none for ICA injury, after FDR correction. Using elastic net, ICA injury variables included maxillofacial fracture, basilar skull fracture, GCS, and carotid canal fracture. For VA injury, these included cervical spine transverse foramen fracture, ligamentous injury, C1-C3 fractures, posterior element fracture, and vertebral body fracture., Conclusion: Elastic net statistical learning methods identified additional risk factors and outperformed multiple logistic regression for BCVI. Elastic net allows the study of a large number of variables, and is useful when covariates are correlated., (© 2021. American Society of Emergency Radiology.)

There has been increasing interest in jointly studying structural connectivity (SC) and functional connectivity (FC) derived from diffusion and functional MRI. Previous connectome integration studies almost exclusively required predefined atlases. However, there are many potential atlases to choose from and this choice heavily affects all subsequent analyses. To avoid such an arbitrary choice, we propose a novel atlas-free approach, named Surface-Based Connectivity Integration (SBCI), to more accurately study the relationships between SC and FC throughout the intra-cortical gray matter. SBCI represents both SC and FC in a continuous manner on the white surface, avoiding the need for prespecified atlases. The continuous SC is represented as a probability density function and is smoothed for better facilitation of its integration with FC. To infer the relationship between SC and FC, three novel sets of SC-FC coupling (SFC) measures are derived. Using data from the Human Connectome Project, we introduce the high-quality SFC measures produced by SBCI and demonstrate the use of these measures to study sex differences in a cohort of young adults. Compared with atlas-based methods, this atlas-free framework produces more reproducible SFC features and shows greater predictive power in distinguishing biological sex. This opens promising new directions for all connectomics studies., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Purpose: To quantify changes in the management of pediatric patients with isolated splenic injury from 2007 to 2015., Materials and Methods: Patients under 18 years old with registered splenic injury in the National Trauma Data Bank (2007-2015) were identified. Splenic injuries were categorized into 5 management types: nonoperative management (NOM), embolization, splenic repair, splenectomy, or a combination therapy. Linear mixed models accounting for confounding variables were used to examine the direct impact of management on length of stay (LOS), intensive care unit (ICU) days, and ventilator days., Results: Of included patients (n = 24,128), 90.3% (n = 21,789), 5.6% (n = 1,361), and 2.7% (n = 640) had NOM, splenectomy, and embolization, respectively. From 2007 to 2015, the rate of embolization increased from 1.5% to 3.5%, and the rate of splenectomy decreased from 6.9% to 4.4%. Combining injury grades, NOM was associated with the shortest LOS (5.1 days), ICU days (1.9 days), and ventilator days (0.5 day). Moreover, splenectomy was associated with longer LOS (10.1 days), ICU days (4.5 days), and ventilator days (2.1 days) than NOM. The average failure rate of NOM was 1.5% (180 failures/12,378 cases). Average embolization failure was 1.3% (6 failures/456 cases). Splenic artery embolization was associated with lower mortality than splenectomy (OR: 0.10, P <.001). No statistically significant difference was observed in mortality between embolization and NOM (OR: 0.96, P = 1.0)., Conclusions: In pediatric splenic injury, NOM is the most utilized and associated with favorable outcomes, most notably in grades III to V pediatric splenic injury. If intervention is needed, embolization is effective and increasingly utilized most significantly in lower grade injuries., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose To evaluate the interrater reliability among radiologists examining posttreatment head and neck squamous cell carcinoma (HNSCC) fluorodeoxyglucose PET/contrast-enhanced CT (CECT) scans using Neck Imaging Reporting and Data System (NI-RADS). Materials and Methods In this retrospective study, images in 80 patients with HNSCC who underwent posttreatment surveillance PET/CECT and immediate prior comparison CECT or PET/CECT (from June 2014 to July 2016) were uploaded to the American College of Radiology's cloud-based website, Cortex. Eight radiologists from seven institutions with variable NI-RADS experience independently evaluated each case and assigned an appropriate prose description and NI-RADS category for the primary site and the neck site. Five of these individuals were experienced readers (> 5 years of experience), and three were novices (< 5 years of experience). In total, 640 lexicon-based and NI-RADS categories were assigned to lesions among the 80 included patients by the eight radiologists. Light generalization of Cohen κ for interrater reliability was performed. Results Of the 80 included patients (mean age, 63 years ± 10 [standard deviation]), there were 58 men (73%); 60 patients had stage IV HNSCC (75%), and the most common tumor location was oropharynx ( n = 32; 40%). Light κ for lexicon was 0.30 (95% CI: 0.23, 0.36) at the primary site and 0.31 (95% CI: 0.24, 0.37) at the neck site. Light κ for NI-RADS category was 0.55 (95% CI: 0.46, 0.63) at the primary site and 0.60 (95% CI: 0.48, 0.69) at the neck site. Percent agreement between lexicon and correlative NI-RADS category was 84.4% (540 of 640) at the primary site and 92.6% (593 of 640) at the neck site. There was no significant difference in interobserver agreement among the experienced versus novice raters. Conclusion Moderate agreement was achieved among eight radiologists using NI-RADS at posttreatment HNSCC surveillance imaging. Keywords: CT, PET/CT, Head/Neck, Neck, Neoplasms-Primary, Observer Performance Supplemental material is available for this article. © RSNA, 2021.

Purpose: (1) Evaluate radiology resident perception of emergency radiology (ER). (2) Identify potential barriers to pursuing fellowship training or a career in ER among radiology residents., Materials and Methods: A 9-question digital survey was designed using Qualtrics Experience Management software (Qualtrics Inc., Provo, UT) and distributed to all US radiology residents via a multi-pronged distribution approach., Results: Four hundred fifty-one residents responded out of an estimated national total of 4432 residents (10.2%). Gender proportion was nationally representative (female = 24.5%; p = 0.57), with a slight R1 predominance (p = 0.034). Of the residents, 88.8% were aware that an ER subspecialty exists, 82.0% were aware that ER fellowships exist, but only 51.7% were aware that the American Society of Emergency Radiology (ASER) exists. Nearly a quarter reported no ER division or ER resident rotation. Residents in a program without an ER division or rotation were nearly twice as likely to be unaware of the existence of ER subspecialty, ER fellowships, and ASER compared to others (p = 0.017). The presence of an ER division and rotation significantly increases the knowledge of ASER (65.5% vs. 40.7%, p < 0.001) and increases residents' ratings of their ER training (p < 0.001). The following factors were ranked as the most important for fellowship choice: (1) personal interest, (2) intellectually stimulating, and (3) work hours. When asked if ER had an appealing work schedule, the mean response was 56 out of 100 (0 = disagree, 100 = agree)., Conclusion: US radiology residents with the greatest exposure to ER during residency are more familiar with ER training, ER career opportunities, and ASER and had a more favorable perception of the field. Subspecialty leaders should focus on ER's inherent intellectual appeal and reframe its nontraditional schedule as positive (flexible).

Objective: Various models of peer support may be implemented in mental health settings. This randomized trial assessed the effectiveness of a telephone-delivered mutual peer support intervention., Methods: A total of 443 patients receiving ongoing depression treatment from the U.S. Department of Veterans Affairs were enrolled in either enhanced usual care (N=243) or the peer support intervention (N=200). Intent-to-treat analyses assessed outcomes at six months postenrollment, excluding 56 patients who experienced an unplanned telephone platform shutdown., Results: At baseline, patients had substantial depressive symptoms, functional limitations, and low quality of life. Both groups showed significant clinical improvements at six months, with no significant differences by group., Conclusions: Telephone-delivered mutual peer support for patients with depression did not improve outcomes beyond those observed with enhanced usual care. Other peer support models, with more "professionalized" peers delivering a structured curriculum, may be more effective.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human genome loci classified as long noncoding RNAs (lncRNAs), yet only ~100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these RNAs, we jointly analyzed two recent data sets produced in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in long polyA+ and polyA- fractions in the cell lines K562 and GM12878. We used the machine-learning algorithm RuleFit3 to regress the peptide data against RNA expression data. The most important covariate for predicting translation was, surprisingly, the Cytosol polyA- fraction in both cell lines. LncRNAs are ~13-fold less likely to produce detectable peptides than similar mRNAs, indicating that ~92% of GENCODE v7 lncRNAs are not translated in these two ENCODE cell lines. Intersecting 9640 lncRNA loci with 79,333 peptides yielded 85 unique peptides matching 69 lncRNAs. Most cases were due to a coding transcript misannotated as lncRNA. Two exceptions were an unprocessed pseudogene and a bona fide lncRNA gene, both with open reading frames (ORFs) compromised by upstream stop codons. All potentially translatable lncRNA ORFs had only a single peptide match, indicating low protein abundance and/or false-positive peptide matches. We conclude that with very few exceptions, ribosomes are able to distinguish coding from noncoding transcripts and, hence, that ectopic translation and cryptic mRNAs are rare in the human lncRNAome.