bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of ultrasound enhancing agents on clinical management
Authors: Fraiche Ariane M. , Strom Jordan B. 
Published: August 2022

Purpose of review
Ultrasound enhancing agents (UEAs), microbubbles which are composed of lipid or albumin shells containing high molecular weight gases with nonlinear acoustic properties in the ultrasound field, are important components of the diagnostic armamentarium in echocardiography. This review highlights the substantial value of UEAs in delineating endocardial border definition and influencing downstream decision-making in cardiovascular ultrasound.

Recent findings
In this article, we review recent updates to the clinical applications of UEAs, special circumstances regarding use, the impact of use on downstream testing and cost-effectiveness, and recommended approaches for optimizing workflow in the echocardiography laboratory with UEAs.

Summary
In multiple studies, UEAs have been identified as a useful tool in echocardiography, improving study accuracy and reader confidence, while reducing downstream testing and procedures and resulting in significant changes in clinical management. Despite their proven efficacy and cost-effectiveness, recent studies have suggested utilization remains low, in part due to perceived concerns and workflow issues that impair uptake. With an increasingly broader list of indications for echocardiography, UEAs will continue to play an important role in the diagnosis and management of patients with cardiovascular and noncardiovascular diseases.
Predictive factors of inhospital mortality for ICU patients with acute-on-chronic liver failure undergoing liver transplantation
Authors: Laici Cristiana , Guizzardi Chiara , Morelli Maria Cristina , Vitale Giovanni , Caraceni Paolo , Cescon Matteo , Ravaioli Matteo , Bacchi Reggiani Maria Letizia , Baldassarre Maurizio , Siniscalchi Antonio 
Published: August 2022

Introduction
Liver transplantation (LT) is the only effective treatment for acute-on-chronic liver failure (ACLF), but it is limited by organ availability. This study aims to identify predictive factors of mortality for LT candidates based on parameters measured at the admission into the ICU.

Methods
Sixty-four patients diagnosed with ACLF, admitted consecutively into ICU between 2015 and 2019, were retrospectively enrolled in the study. Data were assessed using univariate and multivariate regression analyses to identify risk factors for inhospital mortality and 1-year mortality.

Results
A total of 67% of patients were diagnosed with ACLF grade 3, and 25 and 8% with grades 2 and 1. Thirty percent received LT with a 1-year mortality rate of 16%, whereas for nontransplanted patients it reached 90%. Clinical features were compared according to transplant eligibility. In the univariate analysis model, lung failure (HR, 3.01; 95% CI, 1.48–6.09; P = 0.002), high lactate levels (HR, 1.03; 95% CI, 1.02–1.04; P < 0.001) and CLIF-ACLF score (HR, 1.04; 95% CI, 1.01–1.09; P = 0.026) were independently correlated to increased inhospital mortality. LT reduced mortality risk (HR, 0.16; 95% CI, 0.04–0.72; P = 0.016).

Conclusion
Lung failure, CLIF-ACLF score and blood lactate levels at admission were the only statistically significant independent predictors of inhospital mortality, more accurate in determining transplant success than ACLF grade.
Gastrointestinal sequalae months after severe acute respiratory syndrome corona virus 2 infection: a prospective, observational study
Authors: Liptak Peter , Duricek Martin , Rosolanka Robert , Ziacikova Ivana , Kocan Ivan , Uhrik Peter , Grendar Marian , Hrnciarova Martina , Bucova Patricia , Galo David , Banovcin Peter 
Published: August 2022

Introduction
Post-coronavirus disease (post-COVID) symptoms arise mostly from impaired function of respiratory tract although in many patients, the dysfunction of gastrointestinal tract and liver among other organ systems may persist.

Methods
Primary data collection was based on a short gastrointestinal symptom questionnaire at the initial screening. A brief telephone survey within the patient and control group was performed 5–8 months after the initial screening. R ver. 4.0.5 and imbalanced RandomForest (RF) machine-learning algorithm were used for data explorations and analyses.

Results
A total of 590 patients were included in the study. The general presence of gastrointestinal symptoms 208.2 days (153–230 days) after the initial acute severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection was 19% in patients with moderate-to-serious course of the disease and 7.3% in patients with mild course compared with 3.0% in SARS-CoV-2 negative controls (P < 0.001). Diarrhea and abdominal pain are the most prevalent post-COVID gastrointestinal symptoms. RF machine-learning algorithm identified acute diarrhea and antibiotics administration as the strongest predictors for gastrointestinal sequelae with area under curve of 0.68. Variable importance for acute diarrhea is 0.066 and 0.058 for antibiotics administration.

Conclusion
The presence of gastrointestinal sequelae 7 months after the initial SARS-CoV-2 infection is significantly higher in patients with moderate-to-severe course of the acute COVID-19 compared with asymptomatic patients or those with mild course of the disease. The most prevalent post-COVID gastrointestinal symptoms are diarrhea and abdominal pain. The strongest predictors for persistence of these symptoms are antibiotics administration and acute diarrhea during the initial infection.
Under-triage: A New Trigger to Drive Quality Improvement in the Emergency Department
Authors: Berkowitz Deena , Morrison Sephora , Shaukat Haroon , Button Katherine , Stevenson Michele , LaViolette Debbie , Meisler Yael , Gallagher Kerri A. , Chamberlain James 
Published: August 2022

Introduction:
The emergency department (ED) is a care setting with a high risk for medical error. In collaboration with our nursing colleagues, we identified a new trigger, under-triage, and demonstrated how its implementation could detect and reduce medical errors in the ED.

Methods:
We defined under-triage as patient visits with an Emergency Severity Index (ESI) score of 4 or 5 (ie, low acuity), and the patient was admitted to the hospital during the same visit. We defined mistriage, or medical error, when nurse-physician dyad reviewers determined that a different ESI level should have been assigned based on the information available at triage. A multidisciplinary team used nominal group technique to build consensus on key drivers and outcome metrics for this new trigger. We randomly selected 267 charts for review utilizing the under-triage trigger.

Results:
Of the 125,457 patients triaged as level 4 or 5 in 2019 and 2020, 1.1% (n = 1,423) were under-triaged. Of the 267 charts reviewed, 127 were categorized as mistriage, making the under-triage’s positive predictive value trigger 48%. Reviews took 2–10 minutes per chart. We identified 10 categories of under-triage. Nine themes emerged, with four specific and measurable action items mapped to process and outcome metrics.

Conclusions:
We identify a new, feasible ED trigger, under-triage, that identifies medical error with a high positive predictive value. We identify process and outcome metrics and interventions to improve triage for future patients.
Splenic Vessels as a Rescue for Pediatric Kidney Retransplantation in Children With Iliac-caval Agenesis or Thrombosis
Authors: Tandoi Francesco , Peruzzi Licia , Lonardi Pietro , Cussa Davide , Catalano Silvia , Verri Aldo , Merlo Maurizio , Sedigh Omidreza , Gerocarni Nappo Simona , Melloni Claudia , Patrono Damiano , Gianoglio Bruno , Romagnoli Renato 
Published: August 2022

Background.
Unavailability of the iliac-caval system due to thrombosis or aberrant anatomy may preclude kidney transplantation (KT) in small infants, exposing them to the complications of long-term dialysis. A tailored approach may enable KT also in these difficult patients.

Methods.
We report the cases of 2 pediatric patients with a history of long-term hemodialysis, a previously failed KT, pending exhaustion of vascular accesses for dialysis, and unsuitability of the iliac-caval axis as a site for KT. Both patients were successfully managed by using splenic vessels as a source of arterial inflow or venous drainage during KT. Notably, one patient also had a previous liver transplant.

Results.
Both kidney grafts showed primary function. Posttransplant courses were uneventful, and no rejection episode was observed. At 64- and 10-mo follow-ups, both children had optimal renal function and excellent quality of life.

Conclusions.
When the iliac-caval system is unavailable, kidney graft implantation on splenic vessels represents a safe and effective option for pediatric KT.
An Assessment of the Value of Donor-derived Cell-free DNA Surveillance in Patients With Preserved Kidney Allograft Function
Authors: Huang Edmund , Haas Mark , Gillespie Matt , Sethi Supreet , Peng Alice , Najjar Reiad , Vo Ashley , Jordan Stanley C. 
Published: August 2022

Background.
Donor-derived cell-free DNA (dd-cfDNA) is a biomarker validated to detect rejection when measured to assess kidney allograft dysfunction. However, it remains unclear whether routine surveillance with dd-cfDNA provides additional information over standard monitoring of kidney allografts with creatinine and donor-specific antibodies (DSAs), particularly among those with little suspicion of rejection or injury. We investigated the value of measuring dd-cfDNA in patients with preserved allograft function and describe its association with future events.

Methods.
Three-hundred seventeen kidney transplant recipients with a creatinine ≤1.5 mg/dL, no current DSA, and no prior rejection were assessed with dd-cfDNA and categorized into low (dd-cfDNA <0.5%; n = 239), moderate (dd-cfDNA 0.5% to <1.0%; n = 43), and high (dd-cfDNA ≥1.0%; n = 35) groups. The occurrence of rejection, DSA, graft loss, and change in estimated glomerular filtration rate over time after dd-cfDNA assessment was compared.

Results.
Over follow-up, rejections were more commonly found among patients with high vs low dd-cfDNA (17% versus 5%; P = 0.01); a similar nonsignificant trend was observed among patients with moderate compared to low dd-cfDNA (12% versus 5%; P = 0.13). DSA development was uncommon and not different between groups (low: 4%; moderate: 3%; high: 0%; P = 0.52). There was only 1 graft loss in a patient with low dd-cfDNA, and dd-cfDNA was not associated with graft dysfunction over time.

Conclusions.
Most patients with elevated dd-cfDNA in conjunction with preserved allograft function remained stable over follow-up without deterioration in function or graft loss. Studies are needed to differentiate patients with elevated dd-cfDNA who will develop adverse outcomes from those who will remain clinically stable.
Short Report: Evaluating the Effects of Automated Donor Referral Technology on Deceased Donor Referrals
Authors: Levan Macey L. , Trahan Chad , Klitenic Samantha B. , Hewlett Jonathan , Strout Tyler , Levan Michael A. , Vanterpool Karen B. , Segev Dorry L. , Adams Bradley L. , Massie Allan B. , Niles Patricia 
Published: August 2022

Background.
Automation of deceased donor referrals with standardized clinical triggers allows organ procurement organizations to be rapidly aware of medically eligible potential donors without the need for manual reporting and subjective decision-making of otherwise very busy hospital staff. In October 2018, 3 Texas hospitals (pilot hospitals) began using an automated referral system; our goal was to evaluate the impact of this system on eligible donor referral.

Methods.
We studied ventilated referrals (n = 28 034) in a single organ procurement organization from January 2015 to March 2021. We estimated the change in referral rate in the 3 pilot hospitals due to the automated referral system using a difference-in-differences analysis with Poisson regression.

Results.
Ventilated referrals from the pilot hospitals increased from mean 11.7 per month pre-October 2018 to 26.7 per month post-October 2018. The difference-in-differences analysis estimated that automated referral was associated with a 45% increase in referrals (adjusted incidence rate ratio [aIRR] = 1.30 1.45 1.62), an 83% increase in approaches for authorization (aIRR = 1.34 1.83 2.48), a 73% increase in authorizations (aIRR = 1.18 1.73 2.55), and a 92% increase in organ donors (aIRR = 1.13 1.92 3.09).

Conclusions.
Following deployment of an automated referral system that did not require any actions by the referring hospital, referrals, authorizations, and organ donors increased substantially in the 3 pilot hospitals. Broader deployment of automated referral systems may lead to increases in the deceased donor pool.
Integrated transcriptome analysis of Huntington’s disease iPSC-derived and mouse astrocytes implicates dysregulated synaptogenesis, actin, and astrocyte maturation
Authors: Reyes-Ortiz Andrea M. , Abud Edsel M. , Burns Mara S. , Wu Jie , Hernandez Sarah J. , Geller Nicolette , Wang Keona Q. , Schulz Corey , Miramontes Ricardo , Lau Alice , Michael Neethu , Miyoshi Emily , Blurton-Jones Mathew , Van Vactor David , Reidling John C. , Swarup Vivek , Poon Wayne W. , Lim Ryan G. , Thompson Leslie M. 
Published: August 2022

SummaryHuntington’s disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat within the Huntingtin (HTT) gene having dysregulated cellular homeostasis in the central nervous system, particularly in the striatum and cortex. Astrocytes establish and maintain neuronal functions through the secretion of soluble factors and physical interactions with other neurovascular unit cell types. Under pathological conditions, astrocytes can become reactive, causing cell state transitions that affect brain function. To investigate transitions between cellular states in unaffected and HD astrocytes at high resolution, single-nuclei RNA-sequencing (snRNA-seq) was performed on human HD patient induced pluripotent stem cell (iPSC)-derived astrocytes and on striatal and cortical tissue from a rapidly progressing HD mouse model (R6/2). Analysis of HD human and mouse astrocytes revealed both models have alterations in morphology, glutamate uptake, and dysregulation of astrocyte identity and maturation, whereas dysregulated actin-mediated signaling was unique to human iPSC-derived astrocytes. Representative proteins showed altered levels by Western. In both species, HD transcriptional changes reveal potential astrocyte maturation deficits that were potentially driven by astrogliogenesis transcription factors, including ATF3 and NFIA. When perturbed in a drosophila model of HD, knockdown of NFIA in glia rescued the climbing deficit. These data further support the hypothesis that mutant HTT induces dysregulated astrocyte cell states resulting in dysfunctional astrocytic properties, suggests that some of these states are cell autonomous and maybe unique to human HD, and implicate ATF3 and maturation deficits in HD pathogenesis.
Sensbio: An online server for biosensor design
Authors: Tellechea-Luzardo Jonathan , Moreno López Raul , Carbonell Pablo 
Published: August 2022

AbstractAllosteric transcription factor (aTF) based biosensors can be used to engineer genetic circuits for a wide range of applications. The literature and online databases contain hundreds of experimentally validated molecule-TF pairs, however the knowledge is scattered and often incomplete. Additionally, compared to the number of compounds that can potentially be produced using living systems, the number of those discovered with TF-based interactions is low. For these reasons, new tools that help researchers find new possible TF-ligand pairs are called for. In this work we present Sensbio (https://bit.ly/3OF4msH), an online web server that through similarity comparison against a TF-ligand reference database, is able to identify putative transcription factors that may be activated by a given input molecule. As a complement to the application, a predictive model has been developed to find new possible matches based on machine learning.
TraceTrack, an Open-Source Software for Batch Processing, Alignment and Visualization of Sanger Sequencing Chromatograms
Authors: Brazdilova Kveta , Prihoda David , Ton Quynh , Klock Heath , Bitton Danny A. 
Published: August 2022

AbstractBackgroundDespite the advent of Next Generation Sequencing technology and its widespread applications, Sanger sequencing remains instrumental for molecular biology subcloning work in biological and medical research and indispensable for drug discovery campaigns. Although Sanger sequencing technology has been long established, existing software for processing and visualization of trace file chromatograms are limited in terms of functionality, scalability, and availability for commercial use.ResultsTo fill this gap, we developed TraceTrack, an open-source web application tool for batch alignment, analysis and visualization of Sanger trace files. TraceTrack offers high throughput matching of trace files to reference sequences, rapid identification of mutations and an intuitive chromatogram analysis. Comparative analysis between TraceTrack and existing software tools highlights the advantages of TraceTrack with regards to batch processing, visualization and export functionalities. TraceTrack is available at https://github.com/Merck/TraceTrack and also at https://tracetrack.dichlab.org as a web application.ConclusionTraceTrack is a web application for batch processing and visualization of Sanger trace file chromatograms that meets the increasing demand of industrial sequence validation workflows in pharmaceutical settings.
Distance estimation in the Goldfish (Carassius auratus)
Authors: Sibeaux Adelaide , Karlsson Cecilia , Newport Cait , de Perera Theresa Burt 
Published: August 2022

AbstractNeurophysiological advances have given us exciting insights into the systems responsible for spatial mapping in mammals. However, we are still lacking information on the evolution of these systems and whether the underlying mechanisms identified are universal across phyla, or specific to the species studied. Here we address these questions by exploring whether a species that is evolutionarily distant from mammals can perform a task central to mammalian spatial mapping – distance estimation. We developed a behavioural paradigm allowing us to test whether goldfish (Carassius auratus) can estimate distance and explored the behavioural mechanisms that underpin this ability. Fish were trained to swim a set distance within a narrow tank covered with striped pattern. After changing the background pattern, we found that goldfish use the spatial frequency of their visual environment to estimate distance; doubling the spatial frequency of optic flow pattern resulted in a large overestimation of the swimming distance. These results provide robust evidence that goldfish can accurately estimate distance, and show that they use optic flow to do so. These results provide a compelling basis to utilise goldfish as a model system to interrogate the evolution of the mechanisms that underpin spatial cognition, from brain to behaviour.
Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
Authors: Weber Rebecca Z , Mulders Geertje , Perron Patrick , Tackenberg Christian , Rust Ruslan 
Published: August 2022

AbstractBackgroundStroke remains a leading cause of disability and death worldwide. It has become apparent that inflammation and immune mediators have a pre-dominant role in initial tissue damage and long-term recovery following the injury. Still, different immunosuppressed mouse models are necessary in stroke research e.g., to evaluate therapies using human cell grafts. Despite mounting evidence delineating the importance of inflammation in the stroke pathology, it is poorly described to what extent partial immune deficiency influences the overall stroke outcome.MethodsHere, we assessed the stroke pathology of popular genetic immunodeficient mouse models, i.e., NOD scid gamma (NSG) and recombination activating gene 2 (Rag2-/-) mice as well as pharmacologically immunosuppressed mice and compared them to immune competent, wildtype (WT) C57BL/6J mice up to three weeks after injury. We performed histology, gene expression profiling, serum analysis and functional behavioural tests to identify the impact of immunosuppression on the stroke progression.ResultsWe detected distinct changes in microglia infiltration, scar-forming and vascular repair in immune-suppressed mice three weeks after injury. Gene expression analysis of stroked tissue revealed the strongest deviation from immune competent mice was observed in NSG mice, for instance, affecting immunological and angiogenic pathways. Pharmacological immunosuppression resulted in the least variation in gene expression compared with the WT. Major differences have been further identified in the systemic inflammatory response following stroke acutely and three weeks following injury. These anatomical, genetic, and systemic changes did not affect functional deficits and recovery in a time course of three weeks. To determine whether the timing of immunosuppression after stroke is critical, we compared mice with acute and delayed pharmacological immunosuppression after stroke. Mice with a delayed immunosuppression (7d) after stroke showed increased inflammatory and scarring responses compared to animals acutely treated with tacrolimus, thus more closely resembling WT pathology. Transplantation of human cells in the brains of immunosuppressed mouse models led to prolonged cell survival in all immunosuppressed mouse models, which was most consistent in NSG and Rag2-/-mice.ConclusionsIn sum, we detected distinct anatomical and molecular changes in the stroke pathology between the individual immunosuppressed mouse models that should be carefully considered when selecting an appropriate mouse model for stroke research.