bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes
Authors: de Mestral Charles , Abdel-Qadir Husam M , Austin Peter C , Chong Alice S , McAlister Finlay A , Lindsay Thomas F , Ross Heather J , Oreopoulos George , Wijeysundera Duminda N , Lee Douglas S 
Published: May 2024

Objective:
To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery.

Background:
Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care.

Methods:
This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication.

Results:
Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes.

Conclusions:
Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.
A Method for Continuous Surgeon Improvement in Rectal Cancer
Authors: Ferrari Davide , Violante Tommaso , Merchea Amit , Dozois Eric , Vierkant Robert A. , Larson David W. 
Published: May 2024

Objective:
To develop and analyze a risk-adjusted cumulative sum (RA-CUSUM) chart as a potential method to monitor individual surgeon performance in robotic total mesorectal excision (TME) for rectal cancer.

Summary Background Data:
Currently, surgeons lack real-time tools to monitor and enhance their performance beyond residency completion. While national quality programs exist, granular, individual-level data is crucial for continuous improvement. Previous studies suggest CUSUM charts hold promise in identifying performance trends and outliers.

Methods:
This retrospective study analyzed data from 640 robotic TME cases performed by 12 surgeons at two institutions. RA-CUSUM charts were generated for three outcomes: complications, operative time, and length of stay.

Results:
The overall RA-CUSUM curves for operative time and complications showed an initial learning phase followed by a plateau or downward slope, indicating proficiency or improvement. However, individual surgeon curves revealed significant heterogeneity. Three surgeons consistently excelled in operative time, while five minimized complications most effectively. Potential quality improvement could be implemented to drive performance toward positive outliers. No differences were found in unadjusted outcomes, including conversion, number of lymph nodes harvested, and positive circumferential margins.

Conclusions:
The RA-CUSUM chart is a promising method for identifying individual surgeon performance in robotic TME. It could help surgeons, teams, and leaders identify improvement areas and benchmark themselves against positive outliers. Further studies are needed to explore the potential of RA-CUSUM for implementing interventions to improve surgical quality.
Postoperative Activity Restrictions After Slings: A Randomized Controlled Trial
Authors: Lai Erica , McDonald Katherine , Chopra Vini , Robinson Lindsay , Alvarez Alejandro , O’Shaughnessy Danielle , Pillalamarri Nirmala , Polland Allison , Shalom Dara , Winkler Harvey 
Published: May 2024

Importance
Restricting activity after midurethral slings is an unproven practice.

Objective
The objective of this study was to evaluate the effect of postoperative activity restriction on satisfaction and outcomes after slings.

Study Design
This was a multicenter, 2-arm, noninferiority randomized controlled trial. Patients aged 18–85 years undergoing treatment with a midurethral sling were randomized 1:1 to postoperative activity restriction or liberal activity. Restrictions included avoidance of strenuous exercise and heavy lifting. The liberal group was allowed to resume activity at their discretion. Our primary outcome was satisfaction with postoperative instruction at 2 weeks. Secondary outcomes included surgical failure, mesh exposure rates, and other adverse events.

Results
In total, 158 patients were randomized with 80 to the liberal group and 78 to the restricted group. At 2 weeks, 54 (80.6%) of patients in the liberal group and 48 (73.9%) of patients in the restricted group were satisfied. We found statistical evidence supporting the hypothesis that postoperative liberal activity instruction is noninferior to activity restriction with regard to patient satisfaction (P = 0.0281). There was no significant difference in strenuous activity at 2 weeks (P = 0.0824). The liberal group reported significantly more moderate activity at 2 weeks (P = 0.0384) and more strenuous activity at 6 weeks and 6 months (P = 0.0171, P = 0.0118, respectively). The rate of recurrent or persistent stress incontinence for liberal versus restricted groups was 18.52% versus 23.53% (P = 0.635). There were no statistically significant differences in complication rates.

Conclusions
Postoperative liberal activity was noninferior to activity restriction with regard to patients’ satisfaction. There was no evidence supporting a statistically significant association between postoperative instruction and negative surgical outcomes.
A phylogeny of extant coleoid cephalopods with brain data
Authors: Basava Kiran , Bendixen Theiss , Birk Sørensen Alexander Leonhard , George Nicole , Vanhersecke Zoé , Omotosho Joshua , Mather Jennifer , Muthukrishna Michael 
Published: May 2024

AbstractExtant coleoid cephalopods include over 800 species of octopuses, squid, and cuttlefish, which have drawn scientific and public interest for their complex behavior and cognition. Of these, approximately 10% (79) species have adult specimens with recorded measures of central nervous system size distributed across various sources. Here, we use a combination of topological placements from previous phylogenetic studies, along with mitochondrial and nuclear gene sequences obtained from GenBank, to build a composite phylogenetic tree with estimated branch lengths of all species with available brain measurements. This phylogeny is used for analyses in a forthcoming paper on cephalopod brain evolution, and ideally will be of use to other researchers interested in conducting comparative studies of coleoid cephalopod brains.
Non Parametric Differential Network Analysis: A Tool for Unveiling Specific Molecular Signatures
Authors: Guzzi Pietro Hiram , Arkaprava Roy , Milano Marianna , Veltri Pierangelo 
Published: May 2024

AbstractThe rewiring of molecular interactions in various conditions leads to distinct phenotypic outcomes. Differential Network Analysis (DNA) is dedicated to exploring these rewirings within gene and protein networks. Leveraging statistical learning and graph theory, DNA algorithms scrutinize alterations in interaction patterns derived from experimental data. Introducing a novel approach to differential network analysis, we incorporate differential gene expression based on sex and gender attributes. We hypothesize that gene expression can be accurately represented through non-Gaussian processes. Our methodology involves quantifying changes in non-parametric correlations among gene pairs and expression levels of individual genes. Applying our method to public expression datasets concerning diabetes mellitus and atherosclerosis in liver tissue, we identify gender-specific differential networks. Results underscore the biological relevance of our approach in uncovering meaningful molecular distinctions.Author summaryThis paper explores a novel technique for Differential Network Analysis (DNA) that considers sex-based variations. DNA compares biological networks under different conditions, like healthy vs. diseased states. Our method tackles the limitations of traditional DNA approaches, which often assume specific data distributions. We propose a non-parametric DNA methodology that integrates sex differences and identifies differential edges between networks. This approach utilizes data on gene expression levels and sex to construct a more accurate picture of the molecular mechanisms underlying diseases, particularly those exhibiting sex-dependent variations. Our method paves the way for a deeper understanding of how sex and age influence disease processes at the molecular level.
SMC complex unidirectionally translocates DNA by coupling segment capture with an asymmetric kleisin path
Authors: Yamauchi Masataka , Brandani Giovanni B. , Terakawa Tsuyoshi , Takada Shoji 
Published: May 2024

ABSTRACTSMC (structural maintenance of chromosomes) protein complexes are ring-shaped molecular motors essential for genome folding. Despite recent progress, the detailed molecular mechanism of DNA translocation in concert with the ATP-driven conformational changes of the complex remains to be clarified. In this study, we elucidated the mechanisms of SMC action on DNA using multiscale molecular dynamics simulations. We first created a near-atomic full-length model of prokaryotic SMC-kleisin complex that implemented protein-DNA hydrogen bond interactions derived from fully atomistic simulations and emulated ATP-dependent conformational changes. Extensive simulations of the SMC complex with 800 base pairs of duplex DNA over the ATP cycle revealed unidirectional DNA translocation via the DNA segment capture mechanism. The process exhibited a step size of ∼200 base pairs, wherein the complex captured a DNA segment of about the same size within the SMC ring in the engaged state, followed by its pumping into the kleisin ring as ATP was hydrolyzed. We found that the hinge-DNA interaction is not critical for the DNA translocation. On the other hand, analysis of trajectories identified the asymmetric path of the kleisin as a critical factor for the observed unidirectionality.SIGNIFICANCE STATEMENTRing-shaped SMC (structural maintenance of chromosomes) protein complexes, which are highly conserved across all three domains of life, play an essential role in chromosome organization through a process called DNA loop extrusion. However, the molecular mechanism underlying the ATP-dependent motor activity of SMC complexes remains unclear. Using all-atom and residue-resolution coarse-grained molecular dynamics simulations, we revealed that prokaryotic SMC complexes translocate unidirectionally along DNA via a segment capture mechanism. We found that the unidirectionality arises from the kleisin subunit breaking the symmetry of the ring-shaped SMC complex structure. Our findings provide insights into the molecular motor mechanisms shared by SMC complexes.
Mechanical characterization of soft biomaterials: which time and spatial scale to choose?
Authors: Krivega E.S. , Kotova S.L. , Timashev P.S. , Efremov Y.M. 
Published: May 2024

AbstractThe mechanical properties of soft gels hold significant relevance in biomedicine and biomaterial design, including the development of tissue engineering constructs and bioequivalents. It is important to adequately characterize the gel’s mechanical properties since they play a role both in the overall structural properties of the construct and in cells’ physiological responses. The question remains which approach for mechanical characterization is most suitable for specific biomaterials. Our investigation is centered on the comparison of three types of gels and four distinct mechanical testing techniques: shear rheology, compression, microindentation, and nanoindentation by atomic force microscopy. While analyzing an elastic homogeneous synthetic hydrogel (polyacrylamide gel), we observed close mechanical results across the different testing techniques. However, our findings revealed more distinct outcomes when assessing a highly viscoelastic gel (Ecoflex) and a heterogeneous biopolymer hydrogel (enzymatically crosslinked gelatin). To ensure the precise data interpretation, we introduced correction factors to account for the boundary conditions inherent in many of the testing methods. The results of the study underscore the critical significance of considering both the temporal and spatial scales in mechanical measurements of biomaterials. Furthermore, they encourage the employment of a combination of diverse testing techniques, particularly in the characterization of heterogeneous viscoelastic materials such as biological samples. The obtained results will contribute to refining mechanical testing protocols and advance the development of soft gels for tissue engineering.
Myoglobin Inhibits Breast Cancer Cell Fatty Acid Oxidation and Migration via Heme-dependent Oxidant Production and Not Fatty Acid Binding
Authors: Johnson Aaron R. , Rao Krithika , Zhang Bob B. , Mullet Steven , Goetzman Eric , Gelhaus Stacy , Tejero Jesus , Shiva uti 
Published: May 2024

AbstractThe monomeric heme protein myoglobin (Mb), traditionally thought to be expressed exclusively in cardiac and skeletal muscle, is now known to be expressed in approximately 40% of breast tumors. While Mb expression is associated with better patient prognosis, the molecular mechanisms by which Mb limits cancer progression are unclear. In muscle, Mb’s predominant function is oxygen storage and delivery, which is dependent on the protein’s heme moiety. However, prior studies demonstrate that the low levels of Mb expressed in cancer cells preclude this function. Recent studies propose a novel fatty acid binding function for Mb via a lysine residue (K46) in the heme pocket. Given that cancer cells can upregulate fatty acid oxidation (FAO) to maintain energy production for cytoskeletal remodeling during cell migration, we tested whether Mb-mediated fatty acid binding modulates FAO to decrease breast cancer cell migration. We demonstrate that the stable expression of human Mb in MDA-MB-231 breast cancer cells decreases cell migration and FAO. Site-directed mutagenesis of Mb to disrupt Mb fatty acid binding did not reverse Mb-mediated attenuation of FAO or cell migration in these cells. In contrast, cells expressing Apo-Mb, in which heme incorporation was disrupted, showed a reversal of Mb-mediated attenuation of FAO and cell migration, suggesting that Mb attenuates FAO and migration via a heme-dependent mechanism rather than through fatty acid binding. To this end, we show that Mb’s heme-dependent oxidant generation propagates dysregulated gene expression of migratory genes, and this is reversed by catalase treatment. Collectively, these data demonstrate that Mb decreases breast cancer cell migration, and this effect is due to heme-mediated oxidant production rather than fatty acid binding. The implication of these results will be discussed in the context of therapeutic strategies to modulate oxidant production and Mb in tumors.Graphical AbstractGraphical Abstract:Mb-dependent oxidant generation (but not fatty acid binding) dysregulates mitochondrial respiration and migratory gene expression, leading to decreased cell migration. Created with BioRender.HighlightsMyoglobin (Mb) expression in MDA-MB-231 breast cancer cells slows migration.Mb expression decreases mitochondrial respiration and fatty acid oxidation.Mb-dependent fatty acid binding does not regulate cell migration or respiration.Mb-dependent oxidant generation decreases mitochondrial metabolism and migration.Mb-derived oxidants dysregulate migratory gene expression.
RegulaTome: a corpus of typed, directed, and signed relations between biomedical entities in the scientific literature
Authors: Nastou Katerina , Mehryary Farrokh , Ohta Tomoko , Luoma Jouni , Pyysalo Sampo , Jensen Lars Juhl 
Published: May 2024

AbstractMotivationIn the field of biomedical text mining, the ability to extract relations from literature is crucial for advancing both theoretical research and practical applications. There is a notable shortage of corpora designed to enhance the extraction of multiple types of relations, particularly focusing on proteins and protein-containing entities such as complexes and families, as well as chemicals.ResultsIn this work we present RegulaTome, a corpus that overcomes the limitations of several existing biomedical relation extraction (RE) corpora, many of which concentrate on single-type relations at the sentence level. RegulaTome stands out by offering 16,962 relations annotated in over 2,500 documents, making it the most extensive dataset of its kind to date. This corpus is specifically designed to cover a broader spectrum of over 40 relation types beyond those traditionally explored, setting a new benchmark in the complexity and depth of biomedical RE tasks. Our corpus both broadens the scope of detected relations and allows for achieving noteworthy accuracy in RE. A Transformer-based model trained on this corpus has demonstrated a promising F1-score (66.6%) for a task of this complexity, underscoring the effectiveness of our approach in accurately identifying and categorizing a wide array of biological relations. This achievement highlights RegulaTome’s potential to significantly contribute to the development of more sophisticated, efficient, and accurate RE systems to tackle biomedical tasks. Finally, a run of the trained relation extraction system on all PubMed abstracts and PMC Open Access full-text documents resulted in over 18 million relations, extracted from the entire biomedical literature.AvailabilityThe corpus and all introduced resources are openly accessible via Zenodo (https://zenodo.org/doi/10.5281/zenodo.10808330) and GitHub (https://github.com/farmeh/RegulaTome_extraction).
Trazodone, dibenzoylmethane and tauroursodeoxycholic acid do not prevent motor dysfunction and neurodegeneration in Marinesco-Sjögren syndrome mice
Authors: Lavigna Giada , Grasso Anna , Pasini Chiara , Grande Valentina , Mignogna Laura , Restelli Elena , Masone Antonio , Fracasso Claudia , Lucchetti Jacopo , Gobbi Marco , Chiesa Roberto 
Published: May 2024

AbstractThere is no cure for Marinesco-Sjögren syndrome (MSS), a genetic multisystem disease linked to loss-of-function mutations in theSIL1gene, encoding a BiP co-chaperone. We previously found that the PERK kinase inhibitor GSK2606414 delayed cerebellar Purkinje cell (PC) degeneration and the onset of ataxia in the woozy mouse model of MSS. However, GSK2606414 is toxic to the pancreas and does not completely rescue the woozy phenotype. The present study tested trazodone and dibenzoylmethane (DBM), which partially inhibit PERK signaling with neuroprotective effects and no pancreatic toxicity. We also tested the chemical chaperone tauroursodeoxycholic acid (TUDCA), which can protect MSS patients’ cells from stress-induced apoptosis. Mice were chronically treated for five weeks, starting from a presymptomatic stage. Trazodone was given 40 mg/kg daily by intraperitoneal (ip) injection. DBM was given 0.5% in the diet ad libitum. TUDCA was given either 0.4% in the diet, or 500 mg/kg ip every three days. None of the treatments prevented motor dysfunction in woozy mice, assessed by the beam walking and rotarod tests. Only trazodone slightly boosted beam walking performance. However, immunohistochemistry found no reduction in the number of CHOP-positive PCs, or increased PC survival, indicating no neuroprotective inhibition of PERK signaling. Pharmacokinetic studies excluded that the lack of effect was due to altered drug metabolism in woozy mice. These results indicate that trazodone, DBM and TUDCA, at dosing regimens active in other neurodegenerative disease mouse models, have no disease-modifying effect in a preclinical model of MSS.
Forest edge landscape context affects mosquito community composition and risk of pathogen emergence
Authors: Hendy Adam , Fé Nelson Ferreira , Pedrosa Igor , Girão André , Figueira dos Santos Taly Nayandra , Mendonça Claudia Reis , Andes Júnior José Tenaçol , Assunção Flamarion Prado , Costa Edson Rodrigues , Sluydts Vincent , Gordo Marcelo , Scarpassa Vera Margarete , Buenemann Michaela , Lacerda Marcus Vinícius Guimarães de , Mourão Maria Paula Gomes , Vasilakis Nikos , Hanley Kathryn A. 
Published: May 2024

AbstractForest edges, where humans, mosquitoes, and wildlife interact, may serve as a nexus for zoonotic arbovirus exchange. Although often treated as uniform interfaces, the landscape context of edge habitats can greatly impact ecological interactions. Here, we investigated how the landscape context of forest edges shapes mosquito community structure in an Amazon rainforest reserve near the city of Manaus, Brazil, using hand-nets to sample mosquitoes at three distinct forest edge types. Sampling sites were situated at edges bordering urban land cover, rural land cover, and natural treefall gaps, while sites in continuous forest served as controls. Community composition differed substantially among edge types, with rural edges supporting the highest species diversity. Rural edges also provided suitable habitat for forest specialists, including key sylvatic vectors, of whichHaemagogus janthinomyswas the most abundant species sampled overall. Our findings emphasize the importance of landscape context in assessing pathogen emergence risk at forest edges.
UNG-RPA interaction governs the choice between high-fidelity and mutagenic uracil repair
Authors: Mu Yunxiang , Chen Zaowen , Plummer Joshua B. , Zelazowska Monika A. , Dong Qiwen , Krug Laurie T. , McBride Kevin M. 
Published: May 2024

AbstractMammalian Uracil DNA glycosylase (UNG) removes uracils and initiates high-fidelity base excision repair to maintain genomic stability. During B cell development, activation-induced cytidine deaminase (AID) creates uracils that UNG processes in an error-prone fashion to accomplish immunoglobulin (Ig) somatic hypermutation (SHM) or class switch recombination (CSR). The mechanism that governs high-fidelity versus mutagenic uracil repair is not understood. The B cell tropic gammaherpesvirus (GHV) encodes a functional homolog of UNG that can process AID induced genomic uracils. GHVUNG does not support hypermutation, suggesting intrinsic properties of UNG influence repair outcome. Noting the structural divergence between the UNGs, we define the RPA interacting motif as the determinant of mutation outcome. UNG or RPA mutants unable to interact with each other, only support high-fidelity repair. In B cells, transversions at the Ig variable region are abated while CSR is supported. Thus UNG-RPA governs the generation of mutations and has implications for locus specific mutagenesis in B cells and deamination associated mutational signatures in cancer.