bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Outcomes Following Elective Repair of Intact Abdominal Aortic Aneurysms
Authors: Garland Sarah K. , Falster Michael O. , Beiles C. Barry , Freeman Anthony J. , Jorm Louisa R. , Sedrakyan Art , Sotade Oluwadamisola , Varcoe Ramon L. 
Published: October 2021

Objective:
Compare long-term mortality, secondary intervention and secondary rupture following elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR).

Background:
EVAR has surpassed OSR as the most common procedure used to repair abdominal aortic aneurysm (AAA), but evidence regarding long-term outcomes is inconclusive.

Methods:
We included patients in linked clinical registry and administrative data undergoing EVAR or OSR for intact AAA between January 2010 and June 2019. We used an inverse probability of treatment-weighted survival analysis to compare all-cause mortality, cause-specific mortality, secondary interventions and secondary rupture, and evaluate the impact of secondary interventions and secondary rupture on all-cause mortality.

Results:
The study included 3460 EVAR and 427 OSR patients. Compared to OSR, the EVAR all-cause mortality rate was lower in the first 30 days [adjusted hazard ratio (HR) = 0.22, 95% confidence interval (CI) 0.140.33], but higher between 1 and 4 years (HR = 1.29, 95% CI 1.12–1.48) and after 4years (HR = 1.41, 95% CI 1.23–1.63). Secondary intervention rates were higher over the first 30 days (HR = 2.26, 95% CI 1.11–4.59), but lower between 1 and 4years (HR = 0.59, 95% CI 0.48–0.74). Secondary aortic intervention rates were higher across the entire follow-up period (HR = 2.52, 95% CI 2.06–3.07). Secondary rupture rates did not differ significantly (HR = 1.06, 95% CI 0.73–1.55). All-cause mortality beyond 1 year remained significantly higher for EVAR after adjusting for any secondary interventions, or secendary rupture

Conclusions:
EVAR has an early survival benefit compared to OSR. However, elevated long-term mortality and higher rates of secondary aortic interventions and subsequent aneurysm repair suggest that EVAR may be a less durable method of aortic aneurysm exclusion.
Electronic health record machine learning model predicts trauma inpatient mortality in real time: A validation study
Authors: Mou Zongyang , Godat Laura N. , El-Kareh Robert , Berndtson Allison E. , Doucet Jay J. , Costantini Todd W. 
Published: October 2021

INTRODUCTION
Patient outcome prediction models are underused in clinical practice because of lack of integration with real-time patient data. The electronic health record (EHR) has the ability to use machine learning (ML) to develop predictive models. While an EHR ML model has been developed to predict clinical deterioration, it has yet to be validated for use in trauma. We hypothesized that the Epic Deterioration Index (EDI) would predict mortality and unplanned intensive care unit (ICU) admission in trauma patients.

METHODS
A retrospective analysis of a trauma registry was used to identify patients admitted to a level 1 trauma center for >24 hours from October 2019 to July 2020. We evaluated the performance of the EDI, which is constructed from 125 objective patient measures within the EHR, in predicting mortality and unplanned ICU admissions. We performed a 5 to 1 match on age because it is a major component of EDI, then examined the area under the receiver operating characteristic curve (AUROC), and benchmarked it against Injury Severity Score (ISS) and new injury severity score (NISS).

RESULTS
The study cohort consisted of 1,325 patients admitted with a mean age of 52.5 years and 91% following blunt injury. The in-hospital mortality rate was 2%, and unplanned ICU admission rate was 2.6%. In predicting mortality, the maximum EDI within 24 hours of admission had an AUROC of 0.98 compared with 0.89 of ISS and 0.91 of NISS. For unplanned ICU admission, the EDI slope within 24 hours of ICU admission had a modest performance with an AUROC of 0.66.

CONCLUSION
Epic Deterioration Index appears to perform strongly in predicting in-patient mortality similarly to ISS and NISS. In addition, it can be used to predict unplanned ICU admissions. This study helps validate the use of this real-time EHR ML-based tool, suggesting that EDI should be incorporated into the daily care of trauma patients.

LEVEL OF EVIDENCE
Prognostic, level III.
Improved identification of severely injured pediatric trauma patients using reverse shock index multiplied by Glasgow Coma Scale
Authors: Reppucci Marina L. , Acker Shannon N. , Cooper Emily , Meier Maxene , Stevens Jenny , Phillips Ryan , Moulton Steven L. , Bensard Denis D. 
Published: October 2021

BACKGROUND
The shock index pediatric age-adjusted (SIPA) predicts the need for increased resources and mortality among pediatric trauma patients without incorporating neurological status. A new scoring tool, rSIG, which is the reverse shock index (rSI) multiplied by the Glasgow Coma Scale (GCS), has been proven superior at predicting outcomes in adult trauma patients and mortality in pediatric patients compared with traditional scoring systems. We sought to compare the accuracy of rSIG to Shock Index (SI) and SIPA in predicting the need for early interventions in civilian pediatric trauma patients.

METHODS
Patients (aged 1–18 years) in the 2014 to 2018 Pediatric Trauma Quality Improvement Program database with complete heart rate, systolic blood pressure, and total GCS were included. Optimal cut points of rSIG were calculated for predicting blood transfusion within 4 hours, intubation, intracranial pressure monitoring, and intensive care unit admission. From the optimal thresholds, sensitivity, specificity, and area under the curve were calculated from receiver operating characteristics analyses to predict each outcome and compared with SI and SIPA.

RESULTS
A total of 604,931 patients with a mean age of 11.1 years old were included. A minority of patients had a penetrating injury mechanism (5.6%) and the mean Injury Severity Score was 7.6. The mean SI and rSIG scores were 0.85 and 18.6, respectively. Reverse shock index multiplied by Glasgow Coma Scale performed better than SI and SIPA at predicting early trauma outcomes for the overall population, regardless of age.

CONCLUSION
Reverse shock index multiplied by Glasgow Coma Scale outperformed SI and SIPA in the early identification of traumatically injured children at risk for early interventions, such as blood transfusion within 4 hours, intubation, intracranial pressure monitoring, and intensive care unit admission. Reverse shock index multiplied by Glasgow Coma Scale adds neurological status in initial patient assessment and may be used as a bedside triage tool to rapidly identify pediatric patients who will likely require early intervention and higher levels of care.

LEVEL OF EVIDENCE
Prognostic, level III.
An estrogen (17α-ethinyl estradiol-3-sulfate) reduces mortality in a swine model of multiple injuries and hemorrhagic shock
Authors: Abdou Hossam , Morrison Jonathan J. , Edwards Joseph , Patel Neerav , Lang Eric , Richmond Michael J. , Elansary Noha , Gopalakrishnan Mathangi , Berman Jonathan , Hubbard William J. , Scalea Thomas M. , Chaudry Irshad H. 
Published: October 2021

BACKGROUND
Although 17α-ethinyl estradiol-3-sulfate (EES) reduces mortality in animal models of controlled hemorrhage, its role in a clinically relevant injury model is unknown. We assessed the impact of EES in a swine model of multiple injuries and hemorrhage.

METHODS
The study was performed under Good Laboratory Practice, with 30 male uncastrated swine (25–50 kg) subjected to tibial fracture, pulmonary contusion, and 30% controlled hemorrhage for an hour. Animals were randomized to one of five EES doses: 0 (control), 0.3, 1, 3, and 5 mg/kg, administered postinjury. Subjects received no resuscitation and were observed for 6 hours or until death. Survival data were analyzed using Cox-proportional hazard regression. Left ventricular pressure-volume loops were used to derive preload recruitable stroke work as a measure of cardiac inotropy. Immediate postinjury preload recruitable stroke work values were compared with values at 1 hour post–drug administration.

RESULTS
Six-hour survival for the 0, 0.3, 1, 3, and 5 mg/kg groups was 0%, 50%, 33.3%, 16.7%, and 0%, respectively. Following Cox regression, the hazard (95% confidence interval) of death was significantly reduced in the 0.3 (0.22 [0.05–0.93]) and 1 (0.24 [0.06–0.89]) mg/kg groups but not the 3 (0.49 [0.15–1.64]) and 5 (0.46 [0.14–1.47]) mg/kg groups. Mean survival time was significantly extended in the 1 mg/kg group (246 minutes) versus the 0 mg/kg group (96 minutes) (p = 0.04, t test). At 1 hour post–drug administration, inotropy was significantly higher than postinjury values in the 0.3 and 1 mg/kg groups (p = 0.003 and p < 0.001, respectively). Inotropy was unchanged in the 3 and 5 mg/kg groups but significantly depressed in the control (p = 0.022).

CONCLUSION
Administration of EES even in the absence of fluid resuscitation reduces mortality and improves cardiac inotropy in a clinically relevant swine model of multiple injuries and hemorrhage. These findings support the need for a clinical trial in human trauma patients.
Molecular pathology of a cystic fibrosis mutation is explained by loss of a hydrogen bond
Authors: Simon Márton A. , Csanády László 
Published: October 2021

AbstractThe phosphorylation-activated anion channel CFTR is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived “flickery” nor in the long-lived “interburst” closed state. Loss of this H-bond explains the entire gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design.
Global and context-specific transcriptional consequences of oncogenic Fbw7 mutations
Authors: Thirimanne H. Nayanga , Wu Feinan , Janssens Derek H , Swanger Jherek , Feldman Heather M , Amezquita Robert A , Gottardo Raphael , Paddison Patrick J , Henikoff Steven , Clurman Bruce E 
Published: October 2021

AbstractFbw7 is a ubiquitin ligase substrate receptor that targets proteins for proteasomal degradation. Most known Fbw7 substrates are transcription factors (TFs) and many are also oncoproteins (e.g., c-Myc, c-Jun, Notch). Fbw7 is an important tumor suppressor andFBXW7mutations drive tumorigenesis through activation of oncogenic Fbw7 substrates. Defining the mechanisms of Fbw7-associated tumorigenesis is critical for developing targeted therapies. We thus determined the transcriptional consequences of oncogenic Fbw7 mutations by studying isogenic colorectal cancer cell lines with engineeredFBXW7null and heterozygous missense mutations. We used an integrated approach employing RNA-Seq and high-resolution mapping (CUT&RUN) of histone modifications and TF occupancy (c-Jun and c-Myc) to examine the combinatorial effects of mis-regulated Fbw7 substrates. Fbw7 mutations caused widespread transcriptional changes associated with active chromatin and altered TF occupancy at distal regulatory regions. Some regulatory changes were common to bothFBXW7-mutant cell lines whereas others wereFBXW7mutation-specific. By comparing c-Jun and c-Myc binding sites, we also identified co-regulated elements, suggesting that Fbw7 substrates may have synergistic effects. One co-regulated gene was CIITA, a master regulator of MHC Class II gene expression, and Fbw7 loss increased CIITA and MHC Class II gene expression in colorectal cancer cells. Fbw7 mutations were also correlated with increased CIITA expression in TCGA colorectal tumors and cell lines, which may have immunologic implications for progression and treatment of Fbw7-associated cancers. This integrative analysis provides a framework for understanding normal and neoplastic context-specific Fbw7 functions.
Coral settlement and recruitment are negatively related to reef fish trait diversity
Authors: Chow Cher F Y , Bolton Caitlin , Boutros Nader , Brambilla Viviana , Fontoura Luisa , Hoey Andrew S , Madin Joshua S , Pizarro Oscar , Torres-Pulliza Damaris , Woods Rachael M , Zawada Kyle J A , Barbosa Miguel , Dornelas Maria 
Published: October 2021

AbstractThe process of coral recruitment is crucial to the functioning of coral reef ecosystems, as well as recovery of coral assemblages following disturbances. Fishes can be key mediators of this process by removing benthic competitors like algae, but their foraging impacts are capable of being facilitative or harmful to coral recruits depending on species traits. Reef fish assemblages are highly diverse in foraging strategies and the relationship between this diversity with coral settlement and recruitment success remains poorly understood. Here, we investigate how foraging trait diversity of reef fish assemblages covaries with coral settlement and recruitment success across multiple sites at Lizard Island, Great Barrier Reef. Using a multi-model inference approach incorporating six metrics of fish assemblage foraging diversity (foraging rates, trait richness, trait evenness, trait divergence, herbivore abundance, and sessile invertivore abundance), we found that herbivore abundance was positively related to both coral settlement and recruitment success. However, the correlation with herbivore abundance was not as strong in comparison with foraging trait diversity metrics. Coral settlement and recruitment exhibited a negative relationship with foraging trait diversity, especially with trait divergence and richness in settlement. Our findings provide further evidence that fish play a role in making benthic habitats more conducive for coral settlement and recruitment. Because of their ability to shape the reef benthos, the variation of fish biodiversity is likely to contribute to spatially uneven patterns of coral recruitment and reef recovery.
Immortalization and Functional Screening of Natively Paired Human T Cell Receptor Repertoires
Authors: Fahad Ahmed S. , Chung Cheng Yu , Lopez Acevedo Sheila N. , Boyle Nicoleen , Madan Bharat , Gutiérrez-González Matias F. , Matus-Nicodemos Rodrigo , Laflin Amy D. , Ladi Rukmini R. , Zhou John , Wolfe Jacy , Llewellyn-Lacey Sian , Douek Daniel C. , Balfour Henry H. , Price David A. , DeKosky Brandon J. 
Published: October 2021

AbstractFunctional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. Here we developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale. To exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of human TCRs against diverse antigen targets associated with health, vaccination, or disease.
Phospho-regulation accommodates Type III secretion and assembly of a tether of ER-Chlamydia inclusion membrane contact sites
Authors: Murray Rebecca L. , Ende Rachel J. , D’Spain Samantha K. , Derré Isabelle 
Published: October 2021

AbstractMembrane contact sites (MCS) are crucial for non-vesicular trafficking-based inter-organelle communication. ER-organelle tethering occurs in part through the interaction of the ER resident protein VAP with FFAT-motif containing proteins. FFAT motifs are characterized by a seven amino acidic core surrounded by acid tracks. We have previously shown that the human intracellular bacterial pathogen Chlamydia trachomatis establishes MCS between its vacuole (the inclusion) and the ER through expression of a bacterial tether, IncV, displaying molecular mimicry of eukaryotic FFAT motif cores. Here, we show that multiple layers of host cell kinase-mediated phosphorylation events govern the assembly of the IncV-VAP tethering complex. CK2-mediated phosphorylation of a C-terminal region of IncV enables IncV hyperphosphorylation of a phospho- FFAT motif core and serine-rich tracts immediately upstream of IncV FFAT motif cores. Phosphorylatable serine tracts, rather than genetically-encoded acidic tracts, accommodate Type III-mediated translocation of IncV to the inclusion membrane, while achieving full mimicry of FFAT motifs. Thus, regulatory components and post-translational modifications are integral to MCS biology, and intracellular pathogens such as C. trachomatis have evolved complex molecular mimicry of these eukaryotic features.
Multireader Evaluation of Radiologist Performance for COVID-19 Detection on Emergency Department Chest Radiographs
Authors: Gichoya Judy W. , Sinha Priyanshu , Davis Melissa , Dunkle Jeffrey W. , Hamlin Scott A. , Herr Keith D. , Hoff Carrie N. , Letter Haley P. , McAdams Christopher R. , Puthoff Gregory D. , Smith Kevin L. , Steenburg Scott D. , Banerjee Imon , Trivedi Hari 
Published: October 2021

AbstractBackgroundChest radiographs (CXR) are frequently used as a screening tool for patients with suspected COVID-19 infection pending reverse transcriptase polymerase chain reaction (RT-PCR) results, despite recommendations against this. We evaluated radiologist performance for COVID-19 diagnosis on CXR at the time of patient presentation in the Emergency Department (ED).Materials and MethodsWe extracted RT-PCR results, clinical history, and CXRs of all patients from a single institution between March and June 2020. 984 RT-PCR positive and 1043 RT-PCR negative radiographs were reviewed by 10 emergency radiologists from 4 academic centers. 100 cases were read by all radiologists and 1927 cases by 2 radiologists. Each radiologist chose the single best label per case: Normal, COVID-19, Other – Infectious, Other – Noninfectious, Non-diagnostic, and Endotracheal Tube. Cases labeled with endotracheal tube or non-diagnostic were excluded. Remaining cases were analyzed for label distribution, clinical history, and inter-reader agreement.Results1727 radiographs (732 RT-PCR positive, 995 RT-PCR negative) were included from 1,594 patients (51.2% male, 48.8% female, age 59 ± 19 years). For 89 cases read by all readers, there was poor agreement for RT-PCR positive (Fleiss Score 0.36) and negative (Fleiss Score 0.46) exams. Agreement between two readers on 1,638 cases was 54.2% (373/688) for RT-PCR positive cases and 71.4% (679/950) for negative cases. Agreement was highest for RT-PCR negative cases labeled as Normal (50.4%, n= 479). Reader performance did not improve with clinical history or time between CXR and RT-PCR result.ConclusionAt the time of presentation to the emergency department, emergency radiologist performance is non-specific for diagnosing COVID-19.
Food Security Impacts of the COVID-19 Pandemic: Following a Cohort of Vermonters During the First Year
Authors: McCarthy Ashley C. , Belarmino Emily H. , Bertmann Farryl , Niles Meredith T. 
Published: October 2021

AbstractObjectiveThis study assessed changes in household food insecurity throughout the first year of the COVID-19 pandemic in a cohort of Vermonters and examined the socio-demographic characteristics associated with increased odds of experiencing food insecurity during the pandemic.DesignWe conducted three online surveys with a cohort of Vermonters between March 2020 and March 2021 to collect longitudinal data on food security, food access, and job disruptions during the COVID-19 pandemic. Food security was measured using the USDA six-item module. We used t-tests and chi-square tests to determine statistically significant differences between groups and multivariate logistic regression models to determine the factors correlated with food insecurity.Participants441 adults (18 years and older)SettingVermont, United StatesResultsFood insecurity rates increased significantly during the pandemic and remained above pre-pandemic levels a year after the start of the pandemic. Nearly a third (31.6%) of respondents experienced food insecurity at some point during the first year of the pandemic. Certain demographic groups were at significantly higher odds of experiencing food insecurity during the first year of the COVID-19 pandemic including households with children (OR 5.1, p < 0.01), women (OR 7.3, p < 0.05), BIPOC/Hispanic respondents (OR 10.4, p < 0.05), and households experiencing a job disruption (OR 4.6, p <0.01).ConclusionThe prevalence of food insecurity increased during the first year of the COVID-19 pandemic and remained higher than pre-pandemic levels a year after the pandemic began. Odds of experiencing food insecurity during the pandemic vary based on socio-demographic factors.
Combinatorial tumor suppressor inactivation efficiently initiates lung adenocarcinoma with therapeutic vulnerabilities
Authors: Yousefi Maryam , Boross Gábor , Weiss Carly , Murray Christopher W. , Hebert Jess D. , Cai Hongchen , Ashkin Emily L. , Karmakar Saswati , Andrejka Laura , Chen Leo , Wang Minwei , Tsai Min K. , Lin Wen-Yang , Li Chuan , Yakhchalian Pegah , Colón Caterina I. , Chew Su- Kit , Chu Pauline , Swanton Charles , Kunder Christian A. , Petrov Dmitri A. , Winslow Monte M. 
Published: October 2021

ABSTRACTLung cancer is the leading cause of cancer death worldwide, with lung adenocarcinoma being the most common subtype. Many oncogenes and tumor suppressor genes are altered in this cancer type and the discovery of oncogene mutations has led to the development of targeted therapies that have improved clinical outcomes. However, a large fraction of lung adenocarcinomas lacks mutations in known oncogenes, and the genesis and treatment of these oncogene-negative tumors remain enigmatic. Here, we perform iterative in vivo functional screens using quantitative autochthonous mouse model systems to uncover the genetic and biochemical changes that enable efficient lung tumor initiation in the absence of oncogene alterations. Through the generation of hundreds of diverse combinations of tumor suppressor alterations, we demonstrate that the inactivation of suppressors of the RAS and PI3K pathways drive the development of oncogene-negative lung adenocarcinoma. Human genomic data and histology identified RAS/MAPK and PI3K pathway activation as a common event in oncogene- negative human lung adenocarcinomas. We demonstrate that these Onc-negativeRAS/PI3K tumors and related cell lines are vulnerable to pharmacological inhibition of these signaling axes. These results transform our understanding of this prevalent yet understudied subtype of lung adenocarcinoma.