bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholangioscopy with Spyglass DS using percutaneous transhepatic cholangiography access: a retrospective cohort study
Authors: Solstad Trygve Ulvund , Thorsteinsson Morten , Schultz Nicolai , Larsen Peter Nørgaard , Taudorf Mikkel , Achiam Michael 
Published: February 2024

Background:
Conventional peroral methods to visualize biliary strictures are not feasible in some patients with altered anatomy or biliary obstruction, and percutaneous transhepatic cholangioscopy can be used as an alternative procedure. This study aimed to retrospectively review the use of percutaneous transhepatic cholangiography using the SpyGlass DS technology (S-PTCS) during a 5-year period at a Danish tertiary referral center.

Materials and Methods:
All patients who underwent S-PTCS at a single Danish tertiary referral center between 2016 and 2021 were retrospectively analyzed. The visual, technical, and overall success rates of S-PTCS were analyzed, as well as the complication rate. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of S-PTCS were calculated.

Results:
Twenty-two patients were included in the study. Visual, technical, and overall success of S-PTCS was achieved in 17/22, 22/22, and 21/22 patients, respectively. S-PTCS yielded a sensitivity of 83.3%, a specificity of 100%, a PPV of 100%, a NPV of 94.1%, and an accuracy of 95.4%. Complications occurred in 1/22 patients.

Conclusion:
S-PTCS is a safe modality, with high success rates, high predictive values, and a low rate of complications. This study suggests that S-PTCS is an alternative to conventional methods in patients with indeterminate biliary strictures where conventional methods were unfeasible.
Prevalence of Low-Acuity Pediatric Emergency Medical Services (EMS) Transports to a Pediatric Emergency Department (ED) in an Urban Area
Authors: Ward Caleb E. , Badolato Gia M. , Taylor Michael F. , Brown Kathleen M. , Simpson Joelle N. , Chamberlain James M. 
Published: February 2024

Objectives
Many patients transported by Emergency Medical Services (EMS) do not have emergent resource needs. Estimates for the proportion of pediatric EMS calls for low-acuity complaints, and thus potential candidates for alternative dispositions, vary widely and are often based on physician judgment. A more accurate reference standard should include patient assessments, interventions, and dispositions. The objective of this study was to describe the prevalence and characteristics of low-acuity pediatric EMS calls in an urban area.

Methods
This is a prospective observational study of children transported by EMS to a tertiary care pediatric emergency department. Patient acuity was defined using a novel composite measure that included physiologic assessments, resources used, and disposition. Bivariable and multivariable logistic regression were conducted to assess for factors associated with low-acuity status.

Results
A total of 996 patients were enrolled, of whom 32.9% (95% confidence interval, 30.0–36.0) were low acuity. Most of the sample was Black, non-Hispanic with a mean age of 7 years. When compared with adolescents, children younger than 1 year were more likely to be low acuity (adjusted odds ratio, 3.1 [1.9–5.1]). Patients in a motor vehicle crash were also more likely to be low acuity (adjusted odds ratio, 2.4 [1.2–4.6]). All other variables, including race, insurance status, chief complaint, and dispatch time, were not associated with low-acuity status.

Conclusions
One third of pediatric patients transported to the pediatric emergency department by EMS in this urban area are for low-acuity complaints. Further research is needed to determine low-acuity rates in other jurisdictions and whether EMS providers can accurately identify low-acuity patients to develop alternative EMS disposition programs for children.
In Search of the Truth: Choice of Ground Truth for Predictive Modeling of Trauma Team Activation in Pediatric Trauma
Authors: Chacon Miranda , Liu Catherine W , Crawford Loralai , Polydore Hadassah , Ting Tiffany , Wakeman Derek , Wilson Nicole A 
Published: February 2024

BACKGROUND:
Assigning trauma team activation (TTA) levels for trauma patients is a classification task that machine learning models can help optimize. However, performance is dependent on the “ground-truth” labels used for training. Our purpose was to investigate 2 ground truths, the Cribari matrix and the Need for Trauma Intervention (NFTI), for labeling training data.

STUDY DESIGN:
Data were retrospectively collected from the institutional trauma registry and electronic medical record, including all pediatric patients (age <18 years) who triggered a TTA (January 2014 to December 2021). Three ground truths were used to label training data: (1) Cribari (Injury Severity Score >15 = full activation), (2) NFTI (positive for any of 6 criteria = full activation), and (3) the union of Cribari+NFTI (either positive = full activation).

RESULTS:
Of 1,366 patients triaged by trained staff, 143 (10.47%) were considered undertriaged using Cribari, 210 (15.37%) using NFTI, and 273 (19.99%) using Cribari+NFTI. NFTI and Cribari+NFTI were more sensitive to undertriage in patients with penetrating mechanisms of injury (p = 0.006), specifically stab wounds (p = 0.014), compared with Cribari, but Cribari indicated overtriage in more patients who required prehospital airway management (p < 0.001), CPR (p = 0.017), and who had mean lower Glasgow Coma Scale scores on presentation (p < 0.001). The mortality rate was higher in the Cribari overtriage group (7.14%, n = 9) compared with NFTI and Cribari+NFTI (0.00%, n = 0, p = 0.005).

CONCLUSIONS:
To prioritize patient safety, Cribari+NFTI appears best for training a machine learning algorithm to predict the TTA level.
DEEP LEARNING APPROACH FOR RENAL CELL CARCINOMA DETECTION, SUBTYPING, AND GRADING
Authors: Aziz Maroof Abdul , Javadian Fatemeh , Mathew Sherin Susheel , Gopal Avinash , Stegmaier Johannes , Jose Abin 
Published: February 2024

AbstractWe propose a comprehensive end-to-end pipeline designed for the detection, subtyping, and grading of tumors. Our proposed method-ology initiates the generation of a heat map, indicating the severity of the tumor. Subsequently, the identification of the most critical patches is conducted based on the probability scores. These identified patches are then directed to a grade prediction network. A distinctive aspect of our research lies in being the first to explore an end-to-end pipeline for both heat map generation and grading prediction. Our experiments were conducted leveraging the public, The Cancer Genome Atlas (TCGA) repository, focusing specifically on renal cancer. We introduced additional patch-level labels to improve the model performance. The generation of tumor heat maps targeted three primary cancer subtypes: clear cell, papillary, and chromophobe. To enhance our approach, we implemented center-loss and introduced a method aimed at refining the quality of patches. The experimental outcomes highlight superior performance compared to state-of-the-art method. This research contributes to the advancement of tumor detection and grading, emphasizing the significance of an integrated approach for heat map generation and grading pre-diction.
Evaluation of a novel Tc-24 recombinant antigen ELISA for serologic testing forTrypanosoma cruziin dogs
Authors: Mejia Rojelio , Verocai Guilherme G. , Mosley Ilana A. , Zhan Bin , Vongthavaravat Lindsey , Busselman Rachel E. , Hamer Sarah A. 
Published: February 2024

AbstractChagas disease is a parasitic infection caused byTrypanosoma cruzi. Diagnosis of chroni Chagas disease in dogs relies on limited serological test options. This study used a new Tc-24 recombinant antigen ELISA on an archival set of 70 dog serum samples from multi-dog kennel environments in Texas subjected to three existing Chagas serological tests. Tc-24 ELISA produced a quantitative result and could detect anti-T. cruziantibodies in dogs with high sensitivity and specificity. Comparing individual tests to Tc-24 ELISA resulted in strong associations and correlations, which suggest that Tc-24 ELISA is a reliable and accurate diagnostic tool for dogs with a single test.
Hyperactivity Induced By Vapor Inhalation of Nicotine in Male and Female Rats
Authors: Javadi-Paydar Mehrak , Kerr Tony M. , Taffe Michael A. 
Published: February 2024

AbstractRationalePreclinical models of electronic nicotine delivery system (ENDS; “e-cigarette”) use have been rare, so there is an urgent need to develop experimental approaches to evaluate their effects.ObjectiveTo contrast the impact of inhaled nicotine across sex.MethodsMale and female Wistar rats were exposed to vapor from a propylene glycol vehicle (PG), nicotine (NIC; 1-30 mg/mL in PG), or were injected with NIC (0.1-0.8 mg/kg, s.c.), and then assessed for changes in temperature and activity. The antagonist mecamylamine (2 mg/kg) was administered prior to NIC to verify pharmacological specificity. Plasma levels of nicotine and cotinine were determined after inhalation and injection.ResultsActivity increased in females for ∼60 minutes after nicotine inhalation, and this was blocked by mecamylamine. A similar magnitude of hyperlocomotion was observed after s.c. administration. Body temperature was reduced after nicotine inhalation by female rats but mecamylamine increased this hypothermia. Increased locomotor activity was observed in male rats if inhalation was extended to 40 minutes or when multiple inhalation epochs were used per session. The temperature of male rats was not altered by nicotine. Plasma nicotine concentrations were slightly lower in male rats than in female rats after 30-minute nicotine vapor inhalation and slightly higher after nicotine injection (1.0 mg/kg, s.c.).ConclusionsNicotine inhalation increases locomotor activity in male and female rats to a similar or greater extent than by subcutaneous injection. Sex differences were observed, which may be related to lower nicotine plasma levels, lower baseline activity and/or a higher vehicle response in males.
Development of a novelin silicoclassification model to assess reactive metabolite formation in the cysteine trapping assay and investigation of important substructures
Authors: Umemori Yuki , Handa Koichi , Yoshimura Saki , Kageyama Michiharu , Iijima Takeshi 
Published: February 2024

AbstractPredicting whether a compound can cause drug-induced liver injury (DILI) is difficult due to the complexity of its mechanism. The production of reactive metabolites is one of the major causes of DILI, particularly idiosyncratic DILI. The cysteine trapping assay is one of the methods to detect reactive metabolites which bind to microsomes covalently. However, it is cumbersome to use 35S isotope-labeled cysteine for this assay. Therefore, we constructed anin silicoclassification model for predicting a positive/negative outcome in the cysteine trapping assay to accelerate the drug discovery process. In this study, we collected 475 compounds (436 in-house compounds and 39 publicly available drugs). Using a Message Passing Neural Network (MPNN) and Random Forest (RF) with extended connectivity fingerprint (ECFP) 4, we built machine learning models to predict the covalent binding risk of compounds. The 5-fold cross-validation (CV) and hold-out test were evaluated in random- and time-split trials. Additionally, we investigated the substructures that contributed to positive results in the cysteine trapping assay through the framework of the MPNN model. In the random-split dataset, the AUC-ROC of MPNN and RF were 0.698 and 0.811 in the 5-fold CV, and 0.742 and 0.819 in the hold-out test, respectively. In the time-split dataset, AUC-ROC of MPNN and RF were 0.729 and 0.617 in the 5-fold CV, and 0.625 and 0.559 in the hold-out test, restrictively. This result suggests that the MPNN model has a higher predictivity than RF in the time-split dataset. Hence, we conclude that thein silicoMPNN classification model for the cysteine trapping assay have better predictive power. Furthermore, most of the substructures that contributed positively to the cysteine trapping assay were consistent with previous reports such as propranolol, verapamil, and imipramine. This is a new machine learning model that can determine the outcome of the cysteine trapping assay, namely accurately predicting the covalent binding risk as the one of factors of idiosyncratic DILI. We believe that this can contribute to mitigating DILI risk for reactive metabolites at the early stages of drug discovery.
Leaf abaxial and adaxial surfaces differentially affect plant-fungal pathogen interactions
Authors: Caseys Celine , Muhich Anna Jo , Vega Josue , Ahmed Maha , Hopper Aleshia , Kelly David , Kim Sydney , Madrone Matisse , Plaziak Taylor , Wang Melissa , Kliebenstein Daniel J. 
Published: February 2024

AbstractEudicot plant species have bifacial leaves with each surface varying in a diversity of components, resulting in potentially different microhabitats for pathogens. We tested howBotrytis cinerea,a necrotroph fungal pathogen, interacts with the two different leaf surfaces across 16 crop species and 20 Arabidopsis genotypes. This showed that the abaxial surface is generally more susceptible to the pathogen than the adaxial surface. In Arabidopsis, the differential lesion area between leaf surfaces was associated to jasmonic acid (JA) and salicylic acid (SA) signaling and differential induction of defense chemistry. When infecting the adaxial surface, leaves mounted stronger defenses by producing more glucosinolates and camalexin defense compounds, partially explaining the differential susceptibility across surfaces. Testing a collection of 96B. cinereastrains showed genetic heterogeneity of growth patterns, with a few strains preferring the adaxial surface while most are more virulent on the abaxial surface. Overall, we show that leaf-Botrytis interactions are complex with host-specific, surface-specific, and strain-specific behaviors. Within Arabidopsis, this mechanistically links to potential variation in JA/SA signaling across the two surfaces.
The interplay of trophic interactions and game dynamics gives rise to life-history trade-offs, consistent personalities, and predator-prey and aggression power laws
Authors: Salahshour Mohammad 
Published: February 2024

AbstractBy introducing a simple model of ecological interactions where individuals interact trophically, and through a game dynamic, I show that the dissipative flow of resources can derive evolution and lead to the emergence of a scale-invariant ecosystem exhibiting a wide range of mean and fluctuation scaling laws that govern trophic interactions and game dynamics. The eco-evolutionary approach suggests life history trade-offs are a natural consequence of ecological dynamics and, combined with the non-equilibrium dynamic, lead to the evolution of consistent personalities. Aggressiveness and personality consistency depend on trophic position, and predators evolve a higher aggressiveness and starker personality differences.Author summaryThroughout the history of life, the flow of energy across ecosystems has contributed to the evolution of complex forms of life and strikingly universal patterns on a large scale. However, it is not clear what factors lead to such universal patterns and how they relate to evolution. Simple mathematical models suggest that the dissipative flow of resources through ecosystems leads to self-organization in a critical state with scale-invariant avalanches of activity. The scale-invariant structure of ecosystems results in a complex set of scaling laws governing the structure and dynamics of populations. The same non-equilibrium ecological dynamics derive evolution and account for the evolution of individuals’ behavioral differences and consistent personalities.
Thyroid Hormone Suppresses Medulloblastoma Progression Through Promoting Terminal Differentiation of Tumor Cells
Authors: Yang Yijun , Valdés-Rives Silvia Anahi , Liu Qing , Li Yuzhe , Tan Jun , Tan Yinfei , Koch Christian A , Rong Yuan , Houser Steven R. , Wei Shuanzeng , Cai Kathy Q , Cheng Sheue-yann , Curran Tom , Wechsler-Reya Robert , Yang Zeng-jie 
Published: February 2024

SummaryHypothyroidism is commonly detected in patients with medulloblastoma (MB). A possible link between thyroid hormone (TH) signaling and MB pathogenicity has not been reported. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.
The atypical antipsychotic aripiprazole alters the outcome of disseminatedCandida albicansinfections
Authors: Reitler Parker , Regan Jessica , DeJarnette Christian , Srivastava Ashish , Carnahan Jen , Tucker Katie M. , Meibohm Bernd , Peters Brian M , Palmer Glen E. 
Published: February 2024

AbstractInvasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 approved medications that antagonize azole activity. While gain-of-function mutants resulting in antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impactC. albicansphysiology, fitness, or virulence. In this study, we examined how exposure to azole antagonists affectedC. albicansphenotype and capacity to cause disease. We discovered that most of the azole antagonists had little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact onC. albicanshyphal growth and increased cell wall chitin content. It also worsened the outcome of disseminated infections in mice at human equivalent concentrations. This effect was abrogated in immunosuppressed mice, indicating an additional impact of aripiprazole on host immunity. Collectively, these data provide proof-of-principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.ImportanceAs natural inhabitants of the gastrointestinal and reproductive tracts,Candidasp. are routinely exposed to medications consumed by their human host. This study provides new insight into how drugs can modulate the physiology, fitness, and pathogenicity ofCandida albicans- one of the most important human fungal pathogens. These results provide a proof of principle that co-administered medications consumed by at-risk patients may influence the initiation and/or outcome of life-threatening fungal disease.
Silencing of a raspberry homologue ofVRN1is associated with disruption of dormancy induction and misregulation of subsets of dormancy-associated genes
Authors: Mateos Brezo , Preedy Katharine , Milne Linda , Morris Jenny , Hedley Pete E. , Simpson Craig , Hancock Robert D. , Graham Julie 
Published: February 2024

ABSTRACTWinter dormancy is a key process in the phenology of temperate perennials. The changing climate is severely impacting its course leading to economic losses in agriculture. A better understanding of the underlying mechanisms, as well as the genetic basis of the different responses, are necessary for the development of climate-resilient cultivars. This study aims to provide an insight into winter dormancy in red raspberry (Rubus idaeusL).We report the transcriptomic profiles during dormancy in two raspberry cultivars with contrasting responses. The cultivar ‘Glen Ample’ showed a typical perennial phenology, whereas ‘Glen Dee’ registered consistent dormancy dysregulation, exhibiting active growth and flowering out of season. RNA-seq combined with weighted gene co-expression network analysis (WGCNA) highlighted gene clusters in both genotypes that exhibited time-dependent expression profiles, Functional analysis of ‘Glen Ample’ gene clusters highlighted the significance of the cell and structural development prior to dormancy entry as well the role of genetic and epigenetic processes such as RNAi and DNA methylation in regulating gene expression. On the contrary, dormancy release in ‘Glen Ample’ was associated with upregulation of transcripts associated with the resumption of metabolism, nucleic acid biogenesis and processing signal response pathways.Many of the processes occurring in ‘Glen Ample’ were dysregulated in ‘Glen Dee’ and twenty-eight transcripts exhibiting time-dependent expression in ‘Ample’ that also had an Arabidopsis homologue were not found in all samples from ‘Glen Dee’. These included a gene with homology to ArabidopsisVRN1(RiVRN1.1) that exhibited a sharp decline in expression following dormancy induction in Glen Ample. Characterisation of the gene region in the ‘Glen Dee’ genome revealed two large insertions upstream of the ATG start codon. We propose that non-expression of a specific VRN1 homologue in ‘Glen Dee’ causes dormancy misregulation as a result of inappropriate expression of a subset of genes that are directly or indirectly regulated byRiVRN1.1.HIGHLIGHTThe raspberry cultivar Glen Dee exhibits aberrant winter dormancy status associated with insertions in the upstream promoter region of aVRN1(RiVRN1.1) homologue that silence expression, allowing the identification of dormancy-associated genetic modules that are regulated byRiVRN1.1.
Potent pollen gene regulation by DNA glycosylases in maize
Authors: Zeng Yibing , Somers Julian , Bell Harrison S. , Vejlupkova Zuzana , Dawe R. Kelly , Fowler John E. , Nelms Brad , Gent Jonathan I. 
Published: February 2024

ABSTRACTAlthough DNA methylation primarily represses TEs, it also represses select genes that are methylated in plant body tissues but demethylated by DNA glycosylases (DNGs) in endosperm or pollen. Activity of either one of two DNGs, MDR1 or DNG102, is essential for pollen viability in maize. Using single-pollen mRNA sequencing on pollen segregating mutations in both genes, we identified 58 candidate DNG target genes that account for 11.1% of the wild-type transcriptome but are silent or barely detectable in the plant body (sporophyte). They are unusual in their tendency to lack introns but even more so in their having TE-like methylation in their CDS. The majority have predicted functions in cell wall modification, and they likely support the rapid tip growth characteristic of pollen tubes. These results suggest a critical role for DNA methylation and demethylation in regulating maize genes with potential for extremely high expression in pollen but constitutive silencing elsewhere.