bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highlights From the 2023 Revision of Pediatric Tactical Emergency Casualty Care Guidelines
Authors: Garrett Andrew L. , Elsherbiny Amina , Shapiro Geoffrey L. 
Published: October 2024

Abstract
In 2023 the Committee for Tactical Emergency Casualty Care (C-TECC) issued updated Pediatric Tactical Emergency Casualty Care (TECC) Guidelines (Guidelines) that focus on the delivery of stabilizing care of children who are the victims of high-threat incidents such as an active shooter event. The Guidelines provide evidence-based and best practice recommendations to those individuals and departments that specifically provide operational medical support to law enforcement agencies caring for children in this uniquely dangerous environment where traditional resources may not be available. This article highlights key takeaway points from the Guidelines, including several updates since the first version was released in 2013.
The evidence base for the care of children in this environment is lacking, and medical care delivered in the high-threat environment is inconsistent and often not optimized for the care of infants and children. The Guidelines are supported from the existing literature base where possible, and where it is not, by consensus as to the current best practices as determined by iterative deliberations among the diverse and experienced group of stakeholders who are members of C-TECC. The Guidelines provide patient assessment and management information specific to the care of children in the following 3 dynamic phases of the high-threat environment: Direct Threat, Indirect Threat, and Evacuation. The phases represent a continuum of risk to the patient and the responder ranging from extreme (such as ongoing gunfire) to minimal (during movement toward definitive medical care).
The high-threat environment is dynamic and there is competing safety, tactical/operational, and patient care priorities for responders when infants and children are injured. The Guidelines provide recommendations on the type of medical and psychological care that should be considered under each phase of threat and establishes the context for how and why to deliver (or potentially defer) certain interventions under some circumstances in order the maximize the opportunity for a good outcome for an injured pediatric patient. The Guidelines also emphasize the importance of synergizing hospital-based pediatric trauma care with those law enforcement and fire/emergency medical services that may provide field care to children under high-threat circumstances.
Does Early Continuous Passive Motion Improves Effectiveness of Physical Therapy After Arthroscopic Release of Elbow Contracture: A Prospective Randomized Trial
Authors: Lihua Huang M.M. , Wang Yanmao , Ma Yanhong , Ding Jian , Lu Shengdi 
Published: October 2024

Abstract:

Objective
To investigate the effectiveness of early continuous passive motion combined with physical therapy compared to physical therapy alone as the rehabilitation protocol after the release of elbow contracture.

Design
In this randomized controlled trial, 61 patients were randomly assigned to two groups (31 in the early continuous passive motion with physical therapy group vs. 30 in the physical therapy group). The patients received rehabilitation with or without early continuous passive motion for 4 weeks and were followed up for 6 months. The outcome measures were the range of motion and Mayo Elbow Performance Score.

Results
The early continuous passive motion with physical therapy group demonstrated statistically significant improvements in range of motion and the Mayo Elbow Performance Score compared with the physical therapy group at 6 weeks, 3 months, and 6 months postoperatively. These differences were not observed in the stability subscale of the Mayo Elbow Performance Score at any of the assessed time points, nor in its pain subscale at 6 months.

Conclusion
Compared with physical therapy alone, early continuous passive motion combined with physical therapy enabled a quicker recovery of functional elbow motion and early pain control within the 6-month follow-up after arthroscopic release of elbow contracture.
Characteristics, Impact, and Trends of Healthcare Simulation in Latin America and the Caribbean
Authors: Velásquez-Rimachi Victor , Cabanillas-Lazo Miguel , Prialé-Zevallos Alvaro , Dubreuil-Wakeham Solange , Samaniego-Lara Daniela , Runzer-Colmenares Fernando M. , Mayta-Tristán Percy 
Published: October 2024

Summary Statement
This study highlights the growing significance of healthcare simulation in enhancing the quality and safety of patient care across Latin America and the Caribbean, by analyzing bibliometric trends and the impact of publications on simulation-based clinical training between 2012 and 2022. Leveraging the Scopus database and VOSviewer software for thesaurus interaction analysis, the research identified 610 documents, accumulating 4681 citations, thereby indicating a burgeoning interest in this field with notable publication spikes in 2017 and 2020. Brazil and the United States emerged as leading contributors, with a primary focus on “simulation training,” “clinical competence,” “medical education,” and “education.” The study observed an uptick in international collaboration, mirroring the increase in document count and citations. This bibliometric review underscores the emphasis on evaluating technical skills and clinical practices as prevailing areas of interest, highlighting Brazil's significant academic contributions, and suggesting a promising future for the implementation of clinical simulation in the region. The study advocates for continued scholarly output to align with global advancements in medical simulation, aiming to optimize patient outcomes.
Functional study ofPhaeodactylum tricornutumSeipin homolog highlights unique features of lipid droplets biogenesis in diatoms
Authors: Moigne Damien Le , Richard Fabien , Albrieux Catherine , Mahieu Mégane , Arrighi Matteo , Si-Larbi Grégory , Jouneau Pierre-Henri , Gros Valérie , Louwagie Mathilde , Roy Sylvaine , Amari Chems , Carletti Marta , Bonnarde Rachel , Gong Yangmin , Pan Yufang , Hu Hanhua , Bastien Olivier , Jouhet Juliette , Amato Alberto , Maréchal Eric , Salvaing Juliette 
Published: October 2024

AbstractDiatoms are a major phylum of microalgae, playing crucial ecological roles. They derive from secondary endosymbiosis of a red alga by an unknown heterotrophic eukaryote, leading to a complex intracellular organization. In response to unfavorable conditions (stress), diatoms store oil in lipid droplets (LD), raising interest for applications, in particular biofuels. In spite of numerous investigations aiming to increase their oil content, LD biogenesis mechanisms in these organisms remain poorly understood. In this study, we functionally characterized the homolog of Seipin, a major actor of LD biogenesis, in the diatomPhaeodactylum tricornutum.PtSeipin shares conserved structural features with other Seipins, yet presents unique characteristics, that appear common to diatoms and more broadly Stramenopiles. We provide evidence that Stramenopiles Seipins were inherited from the host during secondary endosymbiosis. The localization of PtSeipin highlights that LD biogenesis can arise simultaneously from the endoplasmic reticulum (ER) and the plastid’s most external membrane. Finally, the knock-out of PtSeipin leads to a strong increase of TAG accumulation, a feature that is not observed in other organisms and is greatly enhanced following high light exposure. Our results suggest a redirection of lipid fluxes towards TAG synthesis, reduced TAG recycling or a combination of both.
Three cytochrome P450 enzymes catalyse the formation of furanoclerodane precursors in Salvia spp
Authors: Lin Ruoxi , Li Haixiu , Xiao Yiren , Wang Zhuo , Liu Licheng , Saalbach Gerhard , Martins Carlo , Martin Cathie , Tatsis Evangelos C. 
Published: October 2024

AbstractSalvia species native to the Americas are rich in valuable bioactive furanoclerodanes, like the psychoactive salvinorin A found inSalvia divinorum, which is used in treatment of opioid addiction. However, there is relatively little known about their biosynthesis. To address this, we investigated the biosynthesis of salviarin, the simplest furanoclerodane structure in the ornamental sageSalvia splendens. Using a self-organizing map and mutual rank analysis of RNA-seq co-expression data, we identified three cytochrome P450 enzymes responsible for converting kolavenol into salviarin precursors, consecutively: annonene, hardwickiic acid and hautriwaic acid. As annonene and hardwickiic acid have also been proposed as intermediates in the biosynthesis of salvinorin A, and to examine our hypothesis for common evolutionary origin of the furanoclerodane pathway between the two Salvia species, we searched for homologous genes in available data forS. divinorum. The enzymes encoded by orthologous genes fromS. divinorumdisplayed kolavenol synthase (SdKLS), annonene synthase (SdANS), and hardwickiic acid synthase (SdHDAS) activity respectively, supporting the view that these are intermediate steps in the biosynthesis of salvinorin A. We investigated the origin of annonene synthase and the role of gene duplication in the evolution of this specific activity. Our work shows howS. splendenscan serve as a model species for studying furanoclerodanes biosynthesis in Salvia species, contributes to understanding the evolution of specialized metabolism in plants, and provides new tools to produce salvinorin A in biotechnological chassis.
Analysis of exome sequencing data implicates rare coding variants inSTAG1andZNF136in schizophrenia
Authors: Chick Sophie L , Holmans Peter , Grozeva Detelina , Sims Rebecca , Williams Julie , Owen Michael J , O’Donovan Michael C , Walters James T R , Rees Elliott 
Published: October 2024

AbstractRare coding variants across many genes contribute to schizophrenia liability, but they have only been implicated in 12 genes at exome-wide levels of significance. To increase power for gene discovery, we analysed exome-sequencing data for rare coding variants in a new sample of 4,650 schizophrenia cases and 5,719 controls, and combined these with published sequencing data for a total of 28,898 cases, 103,041 controls and 3,444 proband-parent trios. Novel associations were identified forSTAG1andZNF136at exome-wide significance and for six additional genes at a false discovery rate of 5%. Among these genes,SLC6A1andKLC1are associated with damaging missense variants alone. Four of the eight novel genes are also enriched for rare coding variants in other developmental and psychiatric disorders. Moreover,STAG1andKLC1have fine-mapped common variant signals in schizophrenia. These findings provide novel insights into the neurobiology of schizophrenia, including an aetiological role for disrupted chromatin organisation.
Expanding and improving analyses of nucleotide recoding RNA-seq experiments with the EZbakR suite
Authors: Vock Isaac W. , Mabin Justin W. , Machyna Martin , Zhang Alexandra , Hogg J. Robert , Simon Matthew D. 
Published: October 2024

AbstractNucleotide recoding RNA sequencing methods (NR-seq; TimeLapse-seq, SLAM-seq, TUC-seq, etc.) are powerful approaches for assaying transcript population dynamics. In addition, these methods have been extended to probe a host of regulated steps in the RNA life cycle. Current bioinformatic tools significantly constrain analyses of NR-seq data. To address this limitation, we developed EZbakR, an R package to facilitate a more comprehensive set of NR-seq analyses, and fastq2EZbakR, a Snakemake pipeline for flexible preprocessing of NR-seq datasets, collectively referred to as the EZbakR suite. Together, these tools generalize many aspects of the NR-seq analysis workflow. The fastq2EZbakR pipeline can assign reads to a diverse set of genomic features (e.g., genes, exons, splice junctions, etc.), and EZbakR can perform analyses on any combination of these features. EZbakR extends standard NR-seq mutational modeling to support multi-label analyses (e.g., s4U and s6G dual labeling), and implements an improved hierarchical model to better account for transcript-to-transcript variance in metabolic label incorporation. EZbakR also generalizes dynamical systems modeling of NR-seq data to support analyses of premature mRNA processing and flow between subcellular compartments. Finally, EZbakR implements flexible and well-powered comparative analyses of all estimated parameters via design matrix-specified generalized linear modeling. The EZbakR suite will thus allow researchers to make full, effective use of NR-seq data.
Bayesian Inference of Pathogen Phylogeography using the Structured Coalescent Model
Authors: Roberts Ian , Everitt Richard G. , Koskela Jere , Didelot Xavier 
Published: October 2024

ABSTRACTOver the past decade, pathogen genome sequencing has become well established as a powerful approach to study infectious disease epidemiology. In particular, when multiple genomes are available from several geographical locations, comparing them is informative about the relative size of the local pathogen populations as well as past migration rates and events between locations. The structured coalescent model has a long history of being used as the underlying process for such phylogeographic analysis. However, the computational cost of using this model does not scale well to the large number of genomes frequently analysed in pathogen genomic epidemiology studies. Several approximations of the structured coalescent model have been proposed, but their effects are difficult to predict. Here we show how the exact structured coalescent model can be used to analyse a precomputed dated phylogeny, in order to perform Bayesian inference on the past migration history, the effective population sizes in each location, and the directed migration rates from any location to another. We describe an efficient reversible jump Markov Chain Monte Carlo scheme which is implemented in a new R package. We use simulations to demonstrate the scalability and correctness of our method and to compare it with existing comparable software. We also applied our new method to several state-of-the-art datasets on the population structure of real pathogens to showcase the relevance of our method to current data scales and research questions.
Synthesis and characterization of chloroquine-modified albumin-binding siRNA-lipid conjugates for improved intracellular delivery and gene silencing in cancer cells
Authors: Lo Justin H. , Gbur Eva F. , Francini Nora , Ma Jinqi , Sorets Alexander G. , Fletcher R. Brock , Yu Fang , D’Arcy Richard , Oltman Connor G. , Uddin Md. Jashim , Duvall Craig L. 
Published: October 2024

AbstractsiRNA therapeutics have considerable potential as molecularly-targeted therapeutics in malignant disease, but identification of effective delivery strategies that mediate rapid intracellular delivery while minimizing toxicity has been challenging. Our group recently developed and optimized an siRNA conjugate platform termed “siRNA-L2,” which harnesses non-covalent association with endogenous circulating albumin to extend circulation half-life and achieve tumor-selective delivery without the use of traditional cationic lipids or polymers for transfection. To improve intracellular delivery and particularly the endosomal escape properties of siRNA-L2towards more efficient gene silencing, we report synthesis of siRNA-CQ-L2conjugates, in which chloroquine (CQ), an endosomolytic quinoline alkaloid, is covalently incorporated into the branching lipid tail structure. We accomplished this via synthesis of a novel CQ phosphoramidite, which can be incorporated into a modular siRNA-L2backbone using on-column solid-phase synthesis through use of asymmetric branchers with levulinyl-protected hydroxide groups that allow covalent addition of pendant CQ repeats. We demonstrate that siRNA-CQ-L2maintains the ability to non-covalently bind albumin, and with multiple copies of CQ, siRNA-CQ-L2mediates higher endosomal disruption, cellular uptake/retention, and reporter gene knockdown in cancer cells. Further, in mice, the addition of CQ did not significantly affect circulation kinetics nor organ biodistribution and did not produce hematologic or organ-level toxicity. Thus, controlled, multivalent conjugation of albumin-binding siRNA-L2to endosomolytic small molecule compounds holds promise in improving siRNA-L2knockdown potency while maintaining albumin-binding properties and overall safety.
Biochemical and Phytochemical Efficacy of DefattedMoringa oleiferaSeeds in Alleviating Protein-Energy Malnutrition
Authors: Jegede Raphael Eneji , Ayeni Gideon , Abaniwo Rose Mafo , Audu Godwin Amoka , Haruna Abdullahi 
Published: October 2024

AbstractProtein-energy malnutrition (PEM) is a severe health condition affecting millions, especially in developing regions. This study investigates the potential ofMoringa oleiferaseeds as a low-cost protein source to address protein energy malnutrition.Moringa oleiferaseeds were defatted using different solvents (n-hexane, acetone, and a mixture of n-hexane and acetone) and used in formulating diets for PEM-induced Wistar rats. The study analyzed the seeds’ phytochemical constituents, proximate composition, amino acid profiles, and bioactive compounds through Gas Chromatograph-Mass Spectroscopy (GC-MS). Twenty (2) wistar Rats were randomly assigned to four groups: Group A, control group, B= PEM-induced group, Group C, malnourished rats treated with 15% soya bean based-diet and group D, malnourished rats treated with 15% defattedMoringa oleiferaseed-based diet. The results show that defatting increased protein content and reduced anti-nutritional factors like oxalates, saponins, and tannins, enhancing nutrient bioavailability. DefattedMoringa oleiferaseed-based diets improved liver and kidney functions, lipid profiles, and protein digestibility in protein energy malnutrition-induced rats. Additionally, the seeds contained essential bioactive compounds with potential antioxidant, antimicrobial, and anti-inflammatory properties. These findings suggest thatMoringa oleiferaseeds could be a promising alternative protein source for combating protein energy malnutrition.
Depleting trafficking regulator CASK promotes intercalated disc organization and ventricular function
Authors: Blandin Camille , Dilanian Gilles , Fontaine Vincent , Mougenot Nathalie , Gravez Basile , Bobin Pierre , Duboscq-Bidot Laetitia , Farhi Dounia , Chardonnet Solenne , Nadaud Sophie , Sanchez-Alonzo Jose L. , Shevchuk Andriy , Gorelik Julia , Gandjbakhch Estelle , Hatem Stéphane , Villard Eric , Balse Elise 
Published: October 2024

ABSTRACTBackgroundThe intercalated disc (ID) electromechanically couples adjacent cardiomyocytes. Alteration of this structure plays a central role in cardiac arrhythmias, notably arrhythmogenic cardiomyopathy (ACM), an inherited genetic disorder of desmosomes. Calcium/Calmodulin-Dependent Serine Protein Kinase (CASK), a costameric component of the lateral membrane, regulates cardiomyocyte protein trafficking. Here, we investigated CASK regulation of the organization of ID components in normal and pathological contexts. Here, we investigated CASK regulation of the organization of ID components in normal and pathological contexts.MethodsWe studied the outcomes of CASK depletion in neonatal rat hearts using a cardiac-specific adeno-associated virus strategy. We used conventional and strain echocardiography, hemodynamics, electrocardiography, histology, and gene and protein expression studies to characterize adult rat hearts. We also studied the effects of CASK depletion in neonatal rat ventricular cardiomyocytes (NRVM), and control and ACM (PKP2+/-) IPS cell-derived CM (hIPS-CM) using proteomics, electron microscopy, high-resolution imaging, mechano-scanning ion conductance microscopy (mechano-SICM), and stress resistance tests. We studied cardiac CASK expression and localization in human ACM and non-transplantable control hearts.ResultsDepletion of CASK in our multiple experimental models revealed that CASK regulates cardiomyocyte IDs. In rats, CASK depletion improved contractile reserve and compliance. In cultured rat cardiomyocytes, CASK knockdown increased localization of connexin 43 (Cx43) and PKP2 at IDs, resulting in increased contact stiffness. InPKP2+/-hIPS-CMs, CASK expression was increased. CASK depletion in these cells promoted PKP2 accumulation at cell contacts, formation of desmosome-like structures, and stress resistance. In the right ventricles of ACM patients, CASK protein level was also increased and CASK abnormally localized at the ID.ConclusionCASK functions as a repressor of ID organization and tissue cohesion, suggesting novel mechanisms for regulating ID structure and function. These observations, along with CASK upregulation and mislocalization in ACM, open up new perspectives on understanding the pathophysiology of ACM and suggest innovative strategies for its treatment.
Circulation ofKlebsiella pneumoniaestrains between the termites, chimpanzees and humans
Authors: Houmenou Cheikh Tidiane , Sarr Habibou , Diene Seydina M. , Kacel Idir , Sokhna Cheikh , Fenollar Florence , Mediannikov Oleg 
Published: October 2024

ABSTRACTThe emergence and multiplication of multi-resistant microbes is becoming a major concern in medicine and scientific research, requiring an integrated, global approach to prevent their spread and develop new therapeutic solutions. Klebsiella pneumoniaecan cause a variety of infections. It has several distinctive features, such as extended-spectrum beta-lactamase (ESBL) production and frequency in hospital-acquired infections, which set it apart from other bacteria asPseudomonas aeruginosaor staphylococci and make it of particular concern in the clinical setting. In this study, we worked on four strains of multidrug-resistantK. pneumoniaeisolated from different patients at Fann Hospital in Dakar, Senegal. Whole genomes were compared them with those of nineK. pneumoniaeisolates from chimpanzees (CHZ) and six from termites (T_NSC) from our previous study. The comparison revealed two major genetic groups: three human strains were virtually identical to those found in three chimpanzees and four genomes extracted from termites regularly consumed by chimpanzees were identical to fiveK. pneumoniaestrains from chimpanzees. In silico, we identified the resistance genes and their corresponding families from each isolate, then genotyped them before comparing them with other isolates stored in the Institute Pasteur database. These strains have never been previously identified in Senegal.It has been shown here that multiresistantK. pneumoniaestrains circulate between chimpanzees and termites and between chimpanzees and humans. Furthermore, these strains, often associated with nosocomial infections, have been identified and genotyped outside Senegal. Although similar strains have been already identified in tropical countries and in different intensive care units throughout the world, we hypothesize that they may originate from termite-chimpanzee ecosystem.