bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles in burn injury: roles, mechanisms, and applications
Authors: Wang Min , Zhao Xinyu , Cui Yuyu , Gui Hengshuo , Wang Shuai , Liu Zhuang , Wang Xianwen 
Published: January 2025

Abstract
Burn injuries are associated with high morbidity and mortality, and severe burns trigger many pathophysiological reactions, such as metabolic changes, distributive shock, and inflammatory responses, which are potentially devastating to patients. Burn wound management necessitates infection prevention, anti-inflammation, pain management, and growth factor management, but significant obstacles remain. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types, including mammalian cells, plant cells, and even prokaryotes, They are widely involved in various biological processes, such as cell survival, neovascularization, and immunomodulation. EVs are abundant in components that can play a significant role in different stages of wound repair and at different subcellular levels simultaneously by transporting various active contents, such as proteins and nucleic acids. Moreover, EVs are detectable in many biofluids of burn injury patients and are thus regarded as novel biomarkers for monitoring therapeutic response and predicting prognosis. This review summarizes the biological roles of EVs and their mechanisms of action in burn injury are summarized. The prospects and opportunities for the clinical application of EVs in burn wounds are also discussed. This review will stimulate and guide additional in-depth studies of EVs in burn wound repair, provide a new therapy for burn wounds, and provide a reference and guidance for applying EVs in clinical wound repair.
Reversible Mg2+ insertion/deinsertion of rutile TiO2 in noncorrosive electrolytes
Authors: Yamamoto Keito , Thanh Truc Nguyen Thi , Shimizu Masahiro 
Published: January 2025

Abstract
Single-crystal rutile TiO2 with a spindle morphology was investigated as a negative electrode material for Mg-ion batteries. In the electrolyte with ethylene carbonate and diethyl carbonate typically used for Li-ion batteries, the rutile TiO2 exhibited reversible capacities of 163 and 94 mA h g−1 at the first cycle and 50th cycle, respectively. The spindle structure developed in the c-axis direction should contribute easier Mg2+ diffusion inside the structure to improve utilization of the active material.
Impact of COVID-19 on hospitalization for heart failure: a perspective from Victoria, Australia
Authors: Nguyen Dieu , Kavanagh Shane , Bowe Steve , Tan Elise , Moodie Marj , Gao Lan 
Published: January 2025

Abstract

Aims
The COVID-19 pandemic disrupted healthcare systems and possibly impacted the management of heart failure (HF). This study examined the impact of the pandemic on HF hospitalization activities, outcomes, and costs in Victoria, Australia.

Methods and results
Data on HF hospitalizations were acquired from the Victorian Admitted Episodes Dataset. All consecutive patients hospitalized for HF in both public and private hospitals in Victoria between February 2019 and March 2021 were extracted using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification. Data were analysed using descriptive analysis and interrupted time series analysis. A total of 85 564 completed admissions were identified, of which 45 080 were hospitalized in the pre-COVID-19 period and 40 484 were hospitalized in the COVID-19 impacted period. A higher average cost per completed admission in the COVID-19 impacted period was observed, while average length of stay (LOS) was not different between the two periods. It was revealed that monthly total LOS and hospitalization activity cost across all HF admissions dropped at the beginning of the pandemic and continued to decrease until the end of the observation period. However, these changes were not statistically significant.

Conclusion
The impacts of COVID-19 on HF hospitalization activities and associated outcomes at the beginning of the pandemic appeared relatively small and were not sustained. Further studies using other data (i.e. linkage data) are required to understand if, or how, the pandemic impacted on HF management in Australia, especially in the long COVID-19 era.
ZW Sex Chromosome Differentiation in Palaeognathous Birds Is Associated with Mitochondrial Effective Population Size but Not Mitochondrial Genome Size or Mutation Rate
Authors: Weinstein Brooke , Wang Zongji , Zhou Qi , Roy Scott William 
Published: January 2025

Abstract
Eukaryotic genome size varies considerably, even among closely related species. The causes of this variation are unclear, but weak selection against supposedly costly “extra” genomic sequences has been central to the debate for over 50 years. The mutational hazard hypothesis, which focuses on the increased mutation rate to null alleles in superfluous sequences, is particularly influential, though challenging to test. This study examines the sex chromosomes and mitochondrial genomes of 15 flightless or semiflighted palaeognathous bird species. In this clade, the nonrecombining portion of the W chromosome has independently expanded stepwise in multiple lineages. Given the shared maternal inheritance of the W chromosome and mitochondria, theory predicts that mitochondrial effective population size (Ne) should decrease due to increased Hill–Robertson interference in lineages with expanded nonrecombining W regions. Our findings support the extent of the nonrecombining W region with three indicators of reduced selective efficiency: (i) the ratio of nonsynonymous to synonymous nucleotide changes in the mitochondrion, (ii) the probability of radical amino acid changes, and (iii) the number of ancient, W-linked genes lost through evolution. Next, we tested whether reduced Ne affects mitochondrial genome size, as predicted by weak selection against genome expansion. We find no support for a relationship between mitochondrial genome size and expanded nonrecombining W regions, nor with increased mitochondrial mutation rates (predicted to modulate selective costs). These results highlight the utility of nonrecombining regions and mitochondrial genomes for studying genome evolution and challenge the general idea of a negative relation between the efficacy of selection and genome size.
Associations between regional supply and integration of home and community-based service providers and risk of institutionalization: Evidence from South Korea
Authors: Yun Sunghun , Kim Hongsoo 
Published: January 2025

Abstract

Background and Objectives
To examine whether the regional density of integrated home and community-based services (HCBS) providers affects long-term care (LTC) service utilization pattern and institutionalization risk in South Korea.

Research Design and Methods
This observational study utilized data from the National Health Insurance Service (NHIS) on individuals aged 65 and older who became newly eligible for LTC insurance benefits in 2018. The final sample excluded individuals admitted to long-term care hospitals during the previous year or those living away from home, resulting in a total of 91,302 individuals included in the study. We analyzed the impact of regional HCBS and integrated care provider density on four outcomes: choice of HCBS over LTC facilities (LTCF) as first LTC service, intensity and comprehensiveness of HCBS use, and risk of institutionalization within a year.

Results
Higher regional densities of integrated care providers are associated with increased odds of using HCBS as the first LTC service (Odds Ratio 1.066, model 1, p&lt;0.01). Increased density was also associated with higher odds of using multiple HCBS (Odds Ratio 1.108, model 1, p&lt;0.01). Additionally, higher density of integrated care providers was associated to decreased risk of institutionalization into LTC facilities (Hazard Ratio 0.98, model 1, p&lt;0.01).

Discussion and Implications
The density integrated care providers significantly reduce institutionalization rates, by increasing the possibility of choosing HCBS over LTCF as their first LTC service and using a more comprehensive combination of HCBS services. Further investment in integrated care models may enhance the effectiveness of LTC systems.
Intact N-glycopeptide analysis of human platelets reveals a Glycostructure important for platelet function
Authors: Zhu Hui-Jun , Dong Hang-Yan , Qian Cheng-Rui , Ma Qin-Qin , Li Rui-Shu , Fu Min , He Ye , Lu Ping 
Published: January 2025

Abstract
Glycosylation is an important posttranslational modification in platelets, and the glycosylation pattern is critical for platelet function. To date, the exploration of the roles of various glycoforms in specific platelet functions is largely lacking. In this study, a global analysis of intact N-glycopeptides in human platelets was performed to map all the glycopeptides, glycosites and glycans of platelets. The glycopeptides were enriched by the ZIC- hydrophilic interaction chromatography method and then analyzed by Liquid Chromatography–Tandem Mass Spectrometry analysis. A total of 1,425 intact glycopeptides belonging to 190 N-glycoproteins from human platelets were identified. Moreover, 358 glycans modified 328 glycosites from those glycoproteins. Functional analysis revealed that these glycoproteins are involved mainly in processes and pathways related to platelet adhesion. Among the proteins in these adhesion-related annotations, von Willebrand factor, thrombospondin 1and glycoprotein V were found to contain a possible Lewis y structure, and this finding was further verified by immunoprecipitation assays. As a blood group-related antigen, Lewis y was previously reported to exist in human platelets, but its function remains unclear. Since the glycosylation of von Willebrand factor, thrombospondin 1 and glycoprotein V is involved in platelet–collagen adhesion, the importance of Lewis y on platelet function was evaluated by adhesion assays, which demonstrated that the blockade of Lewis y on platelets decreased the adhesion of platelets to collagen I under both static and flow conditions.
Extraction and characterization of gelatin from acoupa weakfish skins (Cynoscion acoupa) pretreated with EDTA
Authors: Barbosa Jhonatas Rodrigues , Santos Freitas Maurício Madson , Fátima Henriques Lourenço Lúcia 
Published: January 2025

Abstract
The growth of the fish production chain in the Amazon region brought large investments, generating jobs and income. However, accompanied by economic growth, there was an increase in the accumulation of organic waste without any management and use. Here, we present an elegant solution for efficient recovery of high Bloom gelatin from fish skin (Cynoscion acoupa). A new method has been employed using skin pretreatment with EDTA and reflux extraction with acidified water. The protocol was efficient in gelatin recovery, with a maximum yield of 82%. In addition, we reduce the extraction time to a maximum of 1 h, being able to produce high bloom gelatin, with excellent technological properties. Gelatin showed a high correlation between structural amino acids such as proline and hydroxyproline and pseudoplastic rheological behaviour, with high viscosity. The method is scalable and can be applied to expand socioeconomic opportunities in the Amazon.
P20 Evaluation of cefepime/enmetazobactam against MDR Enterobacterales
Authors: Richards J R , Wooton M , Ward J R 
Published: January 2025

Abstract

Background
Cefepime/enmetazobactam is a fourth generation cephalosporin in combination with a novel penicillanic acid sulfone ESBL inhibitor. Cefepime is stable to AmpC β-lactamases (class C) and OXA-48-like carbapenemases (class D) whilst enmetazobactam has activity against most class A β-lactamases (TEM, SHV, CTX-M). Limited activity has been reported against KPC carbapenemases and no activity seen against metallo-β-lactamases (class B). Cefepime/enmetazobactam is approved for use as treatment for complicated urinary tract infections (cUTI), pyelonephritis, hospital acquired pneumonia (HAP) and ventilator acquired pneumonia (VAP). The aim of this study was to understand the activity of cefepime/enmetazobactam against UK isolates of MDR Enterobacterales.

Materials and methods
Cefepime/enmetazobactam MICs were determined on 203 clinical Enterobacterales using broth micro dilution (BMD) according to International Standard 20776-1. All isolates were resistant third generation cephalosporin and/or carbapenems, due to native and plasmid-mediated AmpC β-lactamases, ESBLs, OXA-48-like carbapenemases and efflux mechanisms. Ceftazidime-avibactam was tested concomitantly. Clinically derived susceptibility testing data for carbapenems, cephalosporins and aminoglycosides was also collected. EUCAST v14 clinical breakpoints were used to interpret MICs.

Results
Overall cefepime/enmetazobactam susceptibility was 94.1% and resistance 5.9%. Cefepime/enmetazobactam susceptibility for third generation cephalosporin resistant Enterobacterales, harbouring either a CTX-M ESBL, hyper-expressed native (intrinsic) AmpC β-lactamase or plasmid-mediated AmpC β-lactamase was 96.1%, 92% and 100%, respectively. Overall ceftazidime/avibactam susceptibility was 99%. For those isolates harbouring an OXA-48-like carbapenemase (without CTX-M but possibly some native AmpC activity) the cefepime/enmetazobactam susceptibility was 100%. Whilst the percentage cefepime/enmetazobactam susceptibility in isolates containing OXA-48-like carbapenemase and a CTX-M enzymes was 89.1%. For Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae, cefepime/enmetazobactam susceptibility was 98.8%, 87.1% and 83.3%, respectively. For all other species susceptibility was 100%. Only 12 (5.9%) isolates exhibited cefepime/enmetazobactam resistance, with MICs ranging from 8 mg/L to &gt;128 mg/L. However, seven of these isolates had MICs just above the breakpoint (8 mg/L). Resistance mechanisms present were CTX-M ESBL or AmpC alongside efflux.

Conclusions
Cefepime/enmetazobactam has good activity against third generation cephalosporin and carbapenem resistant Enterobacterales. The agent has excellent activity against all third generation cephalosporin resistance mechanisms (native and plasmid-mediated AmpC and ESBL) as well as carbapenem resistance due to OXA-48 like carbapenemases and efflux.
The association between clinical trial participation, drug costs, and performance in the Oncology Care Model
Authors: Canavan Maureen E , Westvold Sarah , Csik Valerie , Franks Jeffrey , Rocque Gabrielle , Gross Cary P , Adelson Kerin B 
Published: January 2025

Abstract
It has long been assumed that academic oncology practices are disadvantaged in value-based payment programs because of patient complexity and research costs. This assumption has not been tested. The Oncology Care Model (OCM) was a Medicare alternative payment model, which sought to curb costs while improving care. We assessed the impact of clinical trial participation on 2 outcomes: (1) cost and (2) practice performance among 3 participating National Cancer Institute–designated cancer centers using a random effects meta-analysis. The mean total Medicare cost per episode was $42 225 for clinical trial episodes and $34 937 for nonclinical trial episodes. Despite higher total costs, clinical trial episodes were more likely to be under spending targets than non–clinical trial episodes (odds ratio = 0.37, 95% confidence interval = 0.25 to 0.48). Drug costs in clinical trial episodes were lower than in nonclinical trial episodes, although this was only statistically significant at the largest volume practice. In conclusion, clinical trials may offer an advantage in value-based programs.
Abdominal pseudohernia caused by thoracic disk herniation: case series and review of the literature
Authors: Massé G , Al Khaldi M , Schwenter F , Boudier-Revéret M , Sebajang H 
Published: January 2025

Abstract
Intervertebral thoracic disk herniation (TDH) is a rare occurrence and presents with a wide variety of symptoms. Errors in diagnosis are thought to be frequent due to the variable clinical presentations. We herein present two unusual cases of TDH presenting with abdominal pseudohernias, abdominal pain, and hypoesthesia along the T11-T12 dermatomes due to TDH at the same level. Both patients were managed conservatively, using a combination of analgesics and muscle relaxants. At 10 months of follow-up, the first patient reported complete resolution of abdominal bulge and no residual pain. The second patient reported residual paresthesia of T11-T12 dermatome, with non-limiting back pain and almost complete resolution of abdominal bulge. In conclusion, TDH may present with an abdominal wall bulge mimicking hernia, hypoesthesia, and radicular pain along the affected dermatome. Conservative management can be considered as first-line treatment.
Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence
Authors: Tang Weicheng , Wang Kaichen , Feng Yourong , Tsui Kuan-Hao , Singh Keshav K , Stout Michael B , Wang Shixuan , Wu Meng 
Published: January 2025

Abstract
The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility and dysfunction across multiple organs. Research has demonstrated that cellular senescence in various cell types within the ovary can trigger a decline in ovarian function through distinct stress responses, resulting in ovarian aging. This review explores how cellular senescence may contribute to ovarian aging and reproductive failure. Additionally, we discuss the factors that cause ovarian cellular senescence, including the accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, and exposure to chemotherapy. Furthermore, we discuss senescence in six distinct cell types, including oocytes, granulosa cells, ovarian theca cells, immune cells, ovarian surface epithelium and ovarian endothelial cells, inside the ovary and explore their contribution to the accelerated ovarian aging. Lastly, we describe potential senotherapeutics for the treatment of ovarian aging and offer novel strategies for ovarian longevity.
A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei
Authors: Jonsdottir Thorey K , Paoletta Martina S , Ishizaki Takahiro , Hernandez Sophia , Ivanova Maria , Herrera Curbelo Alicia , Saiki Paulina A , Selinger Martin , Das Debojyoti , Henriksson Johan , Bushell Ellen S C 
Published: January 2025

Abstract
Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses a single cloning step to generate targeting vectors with 100-bp homology arms physically linked to a guide RNA (gRNA) that effectively integrate into the target locus. We show that PbHiT coupled with gRNA sequencing robustly recapitulates known knockout mutant phenotypes in pooled transfections. Furthermore, we provide an online resource of knockout and tagging designs to target the entire P. berghei genome and scale-up vector production using a pooled ligation approach. This work presents for the first time a tool for high-throughput CRISPR screens in Plasmodium for studying the parasite’s biology at scale.
Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors
Authors: Bremer Juliane , Franco Pamela , Menstell Joelle Aline , Tey Shelisa , Zajt Kamil Kajetan , Popzhelyazkova Klimentina , Nolte Kay , Schlegel Jürgen , Pedro Maria Teresa , Osterloh Anja , Delev Daniel , Hohenhaus Marc , Scholz Christoph , Schnell Oliver , Beck Juergen , Weis Joachim , Heiland Dieter Henrik 
Published: January 2025

Abstract

Background
Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells. Here, we aimed at determining the spatial and biological heterogeneity of PNSTs.

Methods
We performed spatial transcriptomics on formalin-fixed paraffin-embedded diseased peripheral nerve tissue. We used spatial clustering and weighted correlation network analysis to construct niche-similarity networks and gene expression modules. We determined differential expression in primary pathologies, analysed pathways to investigate the biological significance of identified meta-signatures, integrated the transcriptional data with histological features and existing single cell data, and validated expression data by immunohistochemistry.

Results
We identified distinct transcriptional signatures differentiating PNSTs. Immune cell infiltration, APOD and perineurial fibroblast marker expression highlighted the neurofibroma component of hybrid PNSTs (HPNSTs). While APOD was evenly expressed in neurofibromatous tumor tissue in both, HPNST and pure neurofibromas, perineurial fibroblast markers were evenly expressed in HPNST, but restricted to the periphery in plexiform neurofibromas. Furthermore, we provide a spatial cellular differentiation map for MPNST, locating Schwann cell precursors, neural crest-like cells and those with mesenchymal transition.

Conclusions
This pilot study shows that applying spatial transcriptomics to PNSTs provides important insight into their biology. It helps establishing new markers and provides spatial information about cellular composition and distribution of cellular differentiation states. By integrating morphological and high-dimensional molecular data it can improve PNSTs classification in the future.
Big Data Bayesian Truths: No Vancomycin Trough Concentration Target is Sufficiently Precise for Safety or Efficacy
Authors: Shiau Justin , Roy Sharmeen , Sabourenkov Paul , Scheetz Marc H 
Published: January 2025

Abstract

Introduction
Therapeutic drug monitoring is standard of care for vancomycin because of the known efficacy and safety exposure window [i.e. area under the concentration-time curve (AUC) of 400-600 mg*24hours/L]. Despite guideline recommendations, AUCs are infrequently calculated because of the perceived adequacy of trough (Cmin) concentrations. Yet, the percentage of real-world patients with goal measured vancomycin trough concentrations that achieve target vancomycin AUC remains unknown.

Methods
A large cohort of internationally represented adult patients treated with vancomycin in 2021 and 2022 and therapeutic drug monitoring performed had data anonymized via an electronic clearinghouse at DoseMe. Unique patients, dosing events, and measured Cmin were identified. Patient individualized AUC was calculated using a Bayesian method with 4 validated models. For each dosing event, Cmin and AUC pairs were compared and categorized as “low”, “target”, and “high” using the therapeutic ranges for Cmin of 15-20 mg/L and AUC of 400-600 mg*24hours/L.

Results
In 2022, 17,711 adult patients from the European Union (4.9%), Australia (4.0%), and the United States (91.1%) with 26,769 measured trough levels obtained. Categorical disagreement between Cmin and AUC was 34.3%, with most disagreement (7,959 Cmin levels, 30%) occurring with low Cmin but target AUC. Only 23% of paired Cmin and AUC were within range. AUC was variable for all trough categories (i.e. low, target, and high).

Conclusion
These findings support AUC therapeutic drug monitoring and challenge Cmin as an adequate vancomycin AUC proxy. Since no trough concentration or range was sufficiently precise to ensure AUC targets, we suggest direct calculation of AUC.