bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula
Authors: Ellis Ryan J. , Brajcich Brian C. , Bertens Kimberly A. , Chan Carlos H.F. , Castillo Carlos Fernandez-del , Karanicolas Paul J. , Maithel Shishir K. , Reames Bradley N. , Weber Sharon M. , Vidri Roberto J. , Pitt Henry A. , Thompson Vanessa M. , Gonen Mithat , Seo Susan K. , Yopp Adam C. , Ko Clifford Y. , D’Angelica Michael I. 
Published: June 2023

Objective:
Establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis.

Background:
Patients undergoing pancreatoduodenectomy (PD) experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined.

Methods:
Intraoperative bile cultures (IOBC) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing PD. After complication of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent.

Results:
Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew one organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter or Enterococcus species, was associated with development of SSI in participants treated with cefoxitin (53.5% vs 25.0%; OR 3.44, 95%CI 1.50-7.91; P=0.004) but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR 0.42, 95%CI 0.14-1.29; P=0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR 3.45, 95%CI 1.22-9.74; P=0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR 0.92, 95%CI 0.30-2.80; P=0.888).

Conclusion:
Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp and Enterococcus spp.
Bradykinin release following trauma and hemorrhagic shock causes pulmonary alveolar leak in a rodent model
Authors: Eitel Andrew , Moore Ernest E. , Kelher Marguerite R. , Cohen Mitchell J. , Kissau Daniel , Hadley Jamie B. , Debot Margot , Banerjee Anirban , Silliman Christopher C. 
Published: June 2023

BACKGROUND
Hemorrhage accounts for 40% of the preventable death following severe injury. Activation of systemic coagulation produces bradykinin (BK), which may cause leak from the plasma to the extravascular space and to the tissues, which is part of the complex pathophysiology of trauma-induced end-organ injury. We hypothesize that BK, released during activation of coagulation in severe injury, induces pulmonary alveolar leak.

METHODS
Isolated neutrophils (PMNs) were pretreated with a specific BK receptor B2 antagonist HOE-140/icatibant and BK priming of the PMN oxidase was completed. Rats underwent tissue injury/hemorrhagic shock (TI/HS), TI/icatibant/HS, and controls (no injury). Evans blue dye was instilled, and the percentage leak from the plasma to the lung was calculated from the bronchoalveolar lavage fluid (BALF). CINC-1 and total protein were measured in the BALF, and myeloperoxidase was quantified in lung tissue.

RESULTS
The BK receptor B2 antagonist HOE140/icatibant inhibited (85.0 ± 5.3%) BK priming of the PMN oxidase (p < 0.05). The TI/HS model caused activation of coagulation by increasing plasma thrombin-antithrombin complexes (p < 0.05). Versus controls, the TI/HS rats had significant pulmonary alveolar leak: 1.46 ± 0.21% versus 0.36 ± 0.10% (p = 0.001) and increased total protein and CINC-1 in the BALF (p < 0.05). Icatibant given after the TI significantly inhibited lung leak and the increase in CINC-1 in the BALF from TI/icatibant/HS rats versus TI/HS (p < 0.002 and p < 0.05) but not the total protein. There was no PMN sequestration in the lungs. Conclusions: This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release.

CONCLUSION
This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release.

LEVEL OF EVIDENCE
Original Article, Basic Science
Early venous thromboembolism prophylaxis in patients with trauma intracranial hemorrhage: Analysis of the prospective multicenter Consortium of Leaders in Traumatic Thromboembolism study
Authors: Wu Yu-Tung , Chien Chih-Ying , Matsushima Kazuhide , Schellenberg Morgan , Inaba Kenji , Moore Ernest E. , Sauaia Angela , Knudson M. Margaret , Martin Matthew J. ,   the CLOTT Study Group
Published: June 2023

BACKGROUND
The optimal time to initiate venous thromboembolism prophylaxis (VTEp) for patients with intracranial hemorrhage (ICH) is controversial and must balance the risks of VTE with potential progression of ICH. We sought to evaluate the efficacy and safety of early VTEp initiation after traumatic ICH.

METHODS
This is a secondary analysis of the prospective multicenter Consortium of Leaders in the Study of Thromboembolism study. Patients with head Abbreviated Injury Scale score of > 2 and with immediate VTEp held because of ICH were included. Patients were divided into VTEp ≤ or >48 hours and compared. Outcome variables included overall VTE, deep vein thrombosis (DVT), pulmonary embolism, progression of intracranial hemorrhage (pICH), or other bleeding events. Univariate and multivariate logistic regressions were performed.

RESULTS
There were 881 patients in total; 378 (43%) started VTEp ≤48 hours (early). Patients starting VTEp >48 hours (late) had higher VTE (12.4% vs. 7.2%, p = 0.01) and DVT (11.0% vs. 6.1%, p = 0.01) rates than the early group. The incidence of pulmonary embolism (2.1% vs. 2.2%, p = 0.94), pICH (1.9% vs. 1.8%, p = 0.95), or any other bleeding event (1.9% vs. 3.0%, p = 0.28) was equivalent between early and late VTEp groups. On multivariate logistic regression analysis, VTEp >48 hours (odds ratio [OR], 1.86), ventilator days >3 (OR, 2.00), and risk assessment profile score of ≥5 (OR, 6.70) were independent risk factors for VTE (all p < 0.05), while VTEp with enoxaparin was associated with decreased VTE (OR, 0.54, p < 0.05). Importantly, VTEp ≤48 hours was not associated with pICH (OR, 0.75) or risk of other bleeding events (OR, 1.28) (both p = NS).

CONCLUSION
Early initiation of VTEp (≤48 hours) for patients with ICH was associated with decreased VTE/DVT rates without increased risk of pICH or other significant bleeding events. Enoxaparin is superior to unfractionated heparin as VTE prophylaxis in patients with severe TBI.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
American Association for the Surgery of Trauma/American College of Surgeons Committee on Trauma clinical protocol for management of acute respiratory distress syndrome and severe hypoxemia
Authors: Fawley Jason A. , Tignanelli Christopher J. , Werner Nicole L. , Kasotakis George , Mandell Samuel P. , Glass Nina E. , Dries David J. , Costantini Todd W. , Napolitano Lena M. 
Published: June 2023

LEVEL OF EVIDENCE
Therapeutic/Care Management: Level V.
Directing polymorph specific calcium carbonate formation with de novo protein templates
Authors: Davila-Hernandez Fatima A. , Jin Biao , Pyles Harley , Zhang Shuai , Wang Zheming , Huddy Timothy F. , Chen Chun-Long , De Yoreo James J. , Baker David 
Published: June 2023

AbstractBiomolecules modulate inorganic crystallization to generate hierarchically structured biominerals1–5, but the atomic structure of the organic-inorganic interfaces that regulate mineralization remain unknown6–8. We hypothesized that heterogeneous nucleation of calcium carbonate could be achieved by a structured flat molecular template that pre-organizes calcium ions on its surface. To test this hypothesis, we designed helical repeat proteins (DHRs) displaying regularly spaced carboxylate arrays on their surfaces and found that both protein monomers and protein-Ca2+assemblies directly nucleate nano-calcite with non-natural (110) or (202) faces while vaterite, which forms first absent the proteins, is bypassed. The nanocrystals then assemble by oriented attachment into calcite mesocrystals. We find further that nanocrystal size and polymorph can be tuned by varying the length and surface chemistry of the designed protein templates. Thus, bio-mineralization can be programmed using de novo protein design, providing a route to next-generation hybrid materials.One sentence summaryDe novo designed protein templates promote nucleation of nano-calcite and direct its growth by oriented particle attachment.
Single Cell Track and Trace: live cell labelling and temporal transcriptomics via nanobiopsy
Authors: Marcuccio Fabio , Chau Chalmers C. , Tanner Georgette , Elpidorou Marilena , Finetti Martina A. , Ajaib Shoaib , Taylor Morag , Lascelles Carolina , Carr Ian , Macaulay Iain , Stead Lucy F. , Actis Paolo 
Published: June 2023

ABSTRACTSingle-cell RNA sequencing has revolutionised our understanding of cellular heterogeneity, but whether using isolated cells or more recent spatial transcriptomics approaches, these methods require isolation and lysis of the cell under investigation. This provides a snapshot of the cell transcriptome from which dynamic trajectories, such as those that trigger cell state transitions, can only be inferred. Here, we present cellular nanobiopsy: a platform that enables simultaneous labelling and sampling from a single cell without killing it. The technique is based on scanning ion conductance microscopy (SICM) and uses a double-barrel nanopipette to inject a fluorescent dye and to extract femtolitre-volumes of cytosol. We used the nanobiopsy to longitudinally profile the transcriptome of single glioblastoma (GBM) brain tumour cells in vitro over 72hrs with and without standard treatment. Our results suggest that treatment either induces or selects for more transcriptionally stable cells. We envision the nanobiopsy will transform standard single-cell transcriptomics from a static analysis into a dynamic and temporal assay.
Homeostasis of a representational map in the neocortex
Authors: Noda Takahiro , Kienle Eike , Eppler Jens-Bastian , Aschauer Dominik F. , Kaschube Matthias , Loewenstein Yonatan , Rumpel Simon 
Published: June 2023

SummaryCortical function in general and the processing of sensory stimuli in particular are remarkably robust against the continuous loss of neurons during aging, and even the accelerated loss during prodromal stages of neurodegeneration1,2. Population activity of neurons in sensory cortices represents the environment in form of a map, which is structured in an informative way for guiding behavior. Here, we used the mouse auditory cortex as a model and tested in how far the structure of the representational map is protected by homeostatic network mechanisms against the removal of neurons. We combined longitudinal two-photon calcium imaging of population responses evoked by a diverse set of sound stimuli with a targeted microablation of functionally characterized neurons. Unilateral microablation of 30 - 40 selected highly sound-responsive neurons in layer 2/3 led to a temporary disturbance of the representational map in the spared population that, however, recovered in subsequent days. At the level of individual neurons, we observed that the recovery of the spared network was predominantly driven by neurons unresponsive to the sounds before microablation which strengthened the correlation structure of the local network after gaining responsiveness. In contrast, selective microablation of inhibitory neurons induced a prolonged disturbance of the representational map that was primarily characterized by a destabilization of sound responses across trials. Together, our findings provide a link between the tuning and plasticity of individual neurons and the structure of a representational map at the population level which reveals homeostatic network mechanisms safeguarding sensory processing in neocortical circuits.
Coordinated regulation of photosynthesis and translation via NIK1/RPL10/LIMYB signaling module in response to biotic and abiotic stresses
Authors: Teixeira Ruan M. , Ferreira Marco Aurélio , Brustolini Otávio J.B. , Saia Thainá F.F. , Jean-Baptiste James , Breves Samera S. , Soares Igor N. , Ribeiro Nathalia G.A. , Duarte Christiane E. M. , Lima Lucas L. , Oliveira Leandro Licursi , Ramos Humberto J.O. , Reis Pedro A.B. , Fontes Elizabeth P. B. 
Published: June 2023

ABSTRACTPhotosynthesis and translation are targets of metabolic control and development in plants, yet, how stress signals coordinately regulate these opposing energy-producing and consuming processes remains enigmatic. Here, we described a growth control circuit that ties the photosynthetic function to translational control in response to biotic and abiotic signals. We showed first that the downstream component of the NIK1/RPL10 antiviral signaling module, LIMYB, which represses translational machinery-related gene expression and translation, also suppresses photosynthetic apparatus-related genes leading to inhibition of the photosynthetic function. The repressing transcriptional activity of LIMYB, which was regulated by phosphorylation, was the primary determinant for the decrease in electron transport rate, exchange gas parameters, quantum efficiency, and water-use efficiency in the LIMYB-overexpressing lines. The decreased photosynthetic activity was linked to the NIK1 antiviral signaling and stunted growth. NIK1 activation by viral or bacterial PAMPs, or expressing a constitutively activated NIK1 mutant, T474D, repressed the photosynthesis-related marker genes and inhibited the photosynthetic function in control lines but not inlymyb. We also showed that heat and osmotic stress activate the NIK1/RPL10/LIMYB signaling circuit readouts in wild- type lines. Conversely, inlimyb-32knockout, heat and osmotic stress induced NIK1 phosphorylation but did not cause repression of the marker genes, indicating that LIMYB links NIK1 activation to the stress-mediated downregulation of translation- and photosynthesis-related genes. The coordinated repression of photosynthesis and translation via the stress-activated NIK1/RPL10/LIMYB signaling module may adjust the plant growth pattern in response to the changing environment.Short summaryThe receptor-like kinase NIK1 (NSP-Interacting Kinase 1) undergoes phosphorylation under multiple biotic and abiotic signals activating the NIK1/RPL10/LIMYB signaling circuit, which coordinately downregulates translation and photosynthesis in response to the changing environment.
Longitudinal characterization of the captive adult and tadpole Wyoming toad (Anaxyrus baxteri) microbiome
Authors: Scarberry Nicole , McAdams Zachary L. , Benson Derek , Herrick Jason , Moore Brandon , Ericsson Aaron C. 
Published: June 2023

AbstractAt one time thought to be extinct in the wild, the Wyoming toad (Anaxyrus baxteri) is one of the most critically endangered North American amphibian species. Despite approximately 20 years ofex situbreeding and reintroduction programs, these animals remain functionally extinct in the wild. There is concern among those working in these programs that individuals bred in captivity fail to develop the proper microbiome to withstand the stressors of their native habitat following release. In related species, the skin microbiome has been shown to have a defensive function against common pathogens affecting these animals. However, the early-life microbiome of developing tadpoles in this species remains unknown and therefore this defensive function is unexplored in the Wyoming toad. This study employed 16S rRNA amplicon sequencing to document the baseline microbiome of tadpoles bred for release and captive adult breeder populations. To characterize microbiome development, multiple rounds of skin mucosal and cloacal swabs were obtained concurrently from adult Wyoming toads bred at Omaha’s Henry Doorly Zoo and Aquarium. Our results revealed significant differences between tadpole and adult microbiomes, as well as significant sex-dependent differences within the adult Wyoming toads, in terms of richness and composition. Thus, these findings have identified the baseline microbiome of this endangered species, and variables significantly influencing its composition. Ongoing studies of the only extant wild population are expected to identify taxa not present in captive toads, and potentially help design husbandry modifications to maximize survivability following reintroduction to the wild.
Development of anin situcell-type specific proteome analysis method using antibody-mediated biotinylation
Authors: Ryu Taekyung , Kim Seok-Young , Thuraisamy Thujitha , Jang Yura , Na Chan Hyun 
Published: June 2023

ABSTRACTSince proteins are essential molecules exerting cellular functions, decoding proteome changes is the key to understanding the normal physiology and pathogenesis mechanism of various diseases. However, conventional proteomic studies are often conducted on tissue lumps, in which multiple cell types are entangled, presenting challenges in interpreting the biological dynamics among diverse cell types. While recent cell-specific proteome analysis techniques, like BONCAT, TurboID, and APEX, have emerged, their necessity for genetic modifications limits their usage. The alternative, laser capture microdissection (LCM), although it does not require genetic alterations, is labor-intensive, time-consuming, and requires specialized expertise, making it less suitable for large-scale studies. In this study, we develop the method forin situcell-type specific proteome analysis usingantibody-mediatedbiotinylation (iCAB), in which we combined immunohistochemistry (IHC) with the biotin-tyramide signal amplification approach. Poly-horseradish peroxidase (HRP) conjugated to the secondary antibody will be localized at a target cell type via a primary antibody specific to the target cell type and biotin-tyramide activated by HRP will biotinylate the nearby proteins. Therefore, the iCAB method can be applied to any tissues that can be used for IHC. As a proof-of-concept, we employed iCAB for mouse brain tissue enriching proteins for neuronal cell bodies, astrocytes, and microglia, followed by identifying the enriched proteins using 16-plex TMT-based proteomics. In total, we identified ∼8,400 and ∼6,200 proteins from enriched and non-enriched samples. Most proteins from the enriched samples showed differential expressions when we compared different cell type data, while there were no differentially expressed proteins from non-enriched samples. The cell type enrichment analysis with the increased proteins in respective cell types using Azimuth showed that neuronal cell bodies, astrocytes, and microglia data exhibited Glutamatergic Neuron, Astrocyte and Microglia/Perivascular Macrophage as the representative cell types, respectively. The proteome data of the enriched proteins showed similar subcellular distribution as non-enriched proteins, indicating that the iCAB-proteome is not biased toward any subcellular compartment. To our best knowledge, this study represents the first implementation of a cell-type-specific proteome analysis method using an antibody-mediated biotinylation approach. This development paves the way for the routine and widespread use of cell-type-specific proteome analysis. Ultimately, this could accelerate our understanding of biological and pathological phenomena.
Regional estimates of gross primary production applying the Process-Based Model 3D-CMCC-FEM vs. multiple Remote-Sensing datasets
Authors: Dalmonech D. , Vangi E. , Chiesi M. , Chirici G. , Fibbi L. , Giannetti F. , Marano G. , Massari C. , Nolè A. , Xiao J. , Collalti A. 
Published: June 2023

AbstractProcess-based Forest Models (PBFMs) offer the possibility to capture important spatial and temporal patterns of both carbon fluxes and stocks in forests, accounting for ecophysiological, climate and geographical variability. Yet, their predictive capacity should be demonstrated not only at the stand-level but also in the context of large spatial and temporal heterogeneity. For the first time, we apply a stand scale process-based model (3D-CMCC-FEM) in a spatially explicit manner at 1 km spatial resolution in a Mediterranean region in southern Italy. Specifically, we developed a methodology to initialize the model that comprehends the use of spatial information derived from the integration of remote sensing (RS) data, the national forest inventory data and regional forest maps to characterize structural features of the main forest species. Gross primary production (GPP) is simulated over the period 2005-2019 and the multiyear predictive capability of the model in simulating GPP is evaluated both aggregated as at species-level by means of independent multiple data sources based on different RS-based products. We show that the model is able to reproduce most of the spatial (∼2800 km2) and temporal (32 years in total) patterns of the observed GPP at both seasonal, annual and interannual time scales, even at the species-level. These new very promising results open the possibility of applying the 3D-CMCC- FEM confidently and robustly to investigate the forests’ behavior under climate and environmental variability over large areas across the highly variable ecological and bio- geographical heterogeneity of the Mediterranean region.Key PointsWe apply a process-based forest model on a regular grid at 1 km spatial resolution in a Mediterranean region.Initial forest state is estimated using spatially explicit input data derived from remote sensing and national forest inventory data.The 3D-CMCC-FEM shows comparably estimates in simulating both spatial and temporally the gross primary production, when compared to independent satellite-based products.
ontophylo: Reconstructing the evolutionary dynamics of phenomes using new ontology-informed phylogenetic methods
Authors: Porto Diego S. , Uyeda Josef , Mikó István , Tarasov Sergei 
Published: June 2023

1. Reconstructing ancestral states for discrete characters is essential for understanding trait evolution in organisms. However, most existing methods are limited to individual characters and often overlook the hierarchical and interactive nature of traits. Recent advances in phylogenetics now offer the possibility of integrating knowledge from anatomy ontologies to reconstruct multiple discrete character histories. However, practical applications that fully harness the potential of these new approaches are still lacking.2. This paper introducesontophylo, an R package that extends the PARAMO pipeline to address these limitations.Ontophyloenables the reconstruction of phenotypic entities composed of amalgamated characters, such as entire phenomes or anatomical regions. It offers three new applications: (1) reconstructing evolutionary rates of amalgamated characters using phylogenetic non-homogeneous Poisson process (pNHPP), allowing for rate variation and shifts over time and phylogeny; (2) explicit reconstruction of morphospace dynamics; and (3) direct visualization of evolutionary rates and statistics on vector images of organisms.Ontophyloincorporates ontological knowledge to facilitate these applications.3. Benchmarking confirms the accuracy of pNHPP in estimating character rates under different evolutionary scenarios, and example applications demonstrate the utility ofontophyloin studying morphological evolution in Hymenoptera using simulated data.4.Ontophylois easily integrated with other ontologyoriented and general-purpose R packages and offers new opportunities to examine morphological evolution on a phenomic level using new and legacy data.