bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation and sustainment of virtual reality stroke workflow training for physician trainees at comprehensive stroke centres: a quantitative and qualitative study
Authors: Maltby Steven , Mahadevan Joshua J. , Spratt Neil J. , Garcia-Esperon Carlos , Kluge Murielle G. , Paul Christine L. , Kleinig Timothy J. , Levi Christopher R. , Walker Frederick R. 
Published: December 2024

Abstract
Background
Variation in stroke treatment metrics highlight a need for approaches to improve clinical processes. Training interventions can improve outcomes, but Australian physician trainees do not currently receive formal process-directed stroke training. Virtual reality (VR) stroke workflow training has proven acceptable, usable, useful and feasible in trial contexts, but how to integrate VR training into physician training remains unclear. The current study sought to document stroke staff perceptions of existing training and assess implementation of routine VR training at comprehensive stroke centres, outside of a trial context.

Methods
Training was delivered to physician trainees via individual sessions or facilitated group workshops depending on the hospital site. VR usage data was captured automatically via Wi-Fi. Survey responses from both trainees and training staff were collected, with statistical comparisons performed for matching questions in pre- and post-training surveys. Themes identified in open-ended survey responses were enumerated and reported.

Results
Forty-two TACTICS VR training sessions were logged at 2 hospitals between May 2022 and October 2023. Trainees reported receiving low amounts of prior formal stroke training; both trainees and training staff identified unmet needs and barriers to existing training. VR users (n = 30) provided positive feedback on VR hardware, software design, user experience, content, educational value and delivery approach (mean scores 3.9 to 4.7; 1 = strongly disagree, 5 = strongly agree). VR training improved confidence in: knowledge of acute stroke assessment / treatment (post-training vs. pre-training = 4.0±0.7 vs. 2.9±1.0; P < .0001), ability to effectively assess / treat stroke (4.0±0.6 vs. 3.1±1.0; P < .0001), ability to optimally communicate with colleagues (4.1±0.6 vs. 3.3±1.0; P < .001), understanding of workflow practices (4.3±0.6 vs. 3.2±1.2; P < .0001), ability to make improvements (4.1±0.8 vs. 3.0±1.2; P < .0001) and awareness of local stroke management criteria / processes (4.1±0.8 vs. 3.6±1.1; P < .01). Respondents suggested enhancements in funding, access, awareness, training populations and delivery modality to improve training sustainment.

Conclusions
VR stroke workflow training was perceived by trainees and training staff as feasible, acceptable, usable, useful and positively impacted stroke training. Respondents endorsed future use of VR training to support training at comprehensive stroke centres and identified aspects for improved future integration.
In vitro and in vivo studies of selenium nanoparticles coated bacterial polysaccharide as anti-lung cancer agents
Authors: Shehata Nourhan S. , Elwakil Bassma H. , Elshewemi Salma S. , Ghareeb Doaa A. , Olama Zakia A. 
Published: December 2024

AbstractMicrobial exopolysaccharides (EPSs) possess valuable biological functions and fascinating physicochemical properties. On the other hand, lung cancer is the primary contributor to global cancer-related deaths. However, health and safety concerns have prevented the identification and approval of any medications, including chemotherapeutic agents, for lung cancer treatment to date. The current study aims to enhance the production of bacterial EPS as a coating agent for the synthesis of selenium nanoparticles (AZEPS-SeNPs), to enhance their biological activity against pathogenic microbes, human lung adenocarcinoma cells (A549) in vitro, and diethyl nitrosamine (DEN)-induced lung cancer in vivo. The synthesized AZEPS-SeNPs exhibited a significant antifungal effect reaching 49.3 mm against Candida albicans. SeNPs and EPSs demonstrated a concentration-dependent synergistic antioxidant effect of 96.8%. Moreover, the synthesized nanoparticles showed a highly potent cytotoxic effect against A549 cells (1.724 ± 0.08 µg/mL) with a therapeutic index of 7.18 ± 0.21 that leads to increased reactive oxygen species (ROS) production. AZEPS-SeNPs demonstrated a proapoptotic effect on the lung adenocarcinoma A549 cell line by stimulating caspase 3 and Bax (7.08-fold and 6.505-fold, respectively), inhibiting the anti-apoptotic gene Bcl2, and arresting the cell cycle in the S phase. In vivo study revealed that the AZEPS-SeNPs-treated group showed improved histopathological examination of lung tissue sections. The present study concluded the efficiency of the synthesized bacterial EPS-SeNPs as multi-functional antimicrobial, anticancer and antioxidant agent.
Development of a prognostic model based on lysosome-related genes for ovarian cancer: insights into tumor microenvironment, mutation patterns, and personalized treatment strategies
Authors: Sun Ran , Li Siyi , Ye Wanlu , Lu Yanming 
Published: December 2024

Abstract
Background
Ovarian cancer (OC) is often associated with an unfavorable prognosis. Given the crucial involvement of lysosomes in tumor advancement, lysosome-related genes (LRGs) hold promise as potential therapeutic targets.

Methods
To identify differentially expressed lysosome-related genes (DE-LRGs), we performed a matching analysis between differentially expressed genes (DEGs) in OC and the pool of LRGs. Genes with prognostic significance were analyzed using multiple regression analyses to construct a prognostic risk signature. The model's efficacy was validated through survival analysis in various cohorts. We further explored the model's correlation with clinical attributes, tumor microenvironment (TME), mutational patterns, and drug sensitivity. The quantitative real-time polymerase chain reaction (qRT-PCR) validated gene expression in OC cells.

Results
A 10-gene prognostic risk signature was established. Survival analysis confirmed its predictive accuracy across cohorts. The signature served as an independent prognostic element for OC. The high-risk and low-risk groups demonstrated notable disparities in terms of immune infiltration patterns, mutational characteristics, and sensitivity to therapeutic agents. The qRT-PCR results corroborated and validated the findings obtained from the bioinformatic analyses.

Conclusions
We devised a 10-LRG prognostic model linked to TME, offering insights for tailored OC treatments.
Mechanical stability of the proximal tibia with different bone formations after plate removal in medial opening-wedge high tibial osteotomy: a finite element analysis
Authors: Jang Chul-Young , Kang Kyoung-Tak , Hong Hyongtaek , Jung Min , Kim Sungjun , Yoo Je-Hyun , Kim Sung-Hwan 
Published: December 2024

Abstract
Background
No clear agreement exists on the degree of bone formation required to remove a metal plate without correction loss after medial opening-wedge high tibial osteotomy (MOWHTO). We aimed to investigate the mechanical stability of the proximal tibia with different bone formations after plate removal in MOWHTO using finite element models and determine the extent of bone formation when the plate can be removed without correction loss.

Methods
The MOWHTO models with 5, 10, and 15 mm opening gaps were generated. The mechanical stability of proximal tibial models with different extents of bone formation (from the lateral cortex of the osteotomy wedge to 20% (zone 1), 40% (zone 2), 50% (zone 2.5), 60% (zone 3), 70% (zone 3.5), 80% (zone 4), and 100% bone formation medially) after plate removal was analyzed using finite element analysis. Bone stress and strain and micromotion were evaluated to investigate fracture risk and bone stability, respectively, in various types of tibial models.

Results
Peak von Mises stress was lower than yield strength when bone formation reached zone 3.5 (70%) or more in 5- and 10-mm osteotomy gap models, and zone 4 (80%) or more in a 15-mm gap model. Maximal principal strains were lower than 6,130 microstrain when bone formation reaches zone 3.5 (70%) or more in models with osteotomy gaps of 5, 10, and 15 mm.

Conclusions
This indicates that plate removal without correction loss after MOWHTO may be possible when bone formation reaches zone 3.5 (> 70%) or more during 5- and 10-mm osteotomy gap corrections, and zone 4 (> 80%) or more during 15-mm gap correction. The present study results suggest that it would be safer to perform plate removal after obtaining sufficient bone formation rather than performing it near the osteotomy gap center (50%) to avoid correction loss considering both coronal and sagittal plane aspects.
Microscopy observations reveal a new glandular morphology in four Pinguicula L. species
Authors: Natale Sara , Canella Marco , Moschin Silvia , Baldan Barbara , Alboresi Alessandro , La Rocca Nicoletta , Dal Grande Francesco 
Published: December 2024

AbstractThe adaxial leaf surface of butterworts (Pinguicula L.) presents specialized structures for carnivory, such as trichomes and sessile glands. The micromorphology of abaxial leaf surfaces has rarely been investigated; therefore, this study aimed to compare the micromorphology of adaxial and abaxial surfaces through electron scanning microscopy (SEM) and light microscopy (LM). We selected four species occurring in the Eastern Alps. All the species showed the same pattern: trichomes and sessile glands occurring only on the adaxial surface; stomata occurring on both surfaces with significant differences in density and size; and four-cells glands occurring only on the abaxial surface. The four-cells gland is a micromorphological structure that has never been described before, and its eco-physiological function needs to be investigated.
Response to Schmidt et al.: Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis
Authors: Anderson Emma L 
Published: December 2024

AbstractA recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson’s dementia. Alzheimer’s disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer’s risk and may even potentially modestly increase risk. There is also little evidence to support an effect of CETP inhibition on all-cause or vascular dementia. Thus, CETP inhibition is unlikely to be a viable target to treat the most prevalent causes of dementia.
Unmasking culprits: novel analysis identifies complement factors as potential therapeutic targets to mitigate inflammation during children's heart surgery
Authors: Bierer Joel , Stanzel Roger , Henderson Mark , Sapp John , Andreou Pantelis , Marshall Jean S. , Horne David 
Published: December 2024

Abstract
Background
Cardiopulmonary bypass (CPB) causes systemic inflammation during pediatric cardiac surgery, which can contribute to post-operative organ dysfunction and prolonged recovery. This study aims to identify key inflammatory mediators related to this clinically significant immunologic response.

Methods
Pediatric patients were enrolled in a single-arm prospective clinical study (NCT05154864) and received standard cardiac operation, CPB and subzero-balance ultrafiltration. Arterial samples were taken before CPB initiation and immediately after weaning, and concentrations of 33 inflammatory mediators were assayed. A principal component analysis with hierarchical clustering (PCA-HCPC) included inflammatory mediator concentrations measured at the end of CPB, validated peak post-operative clinical scores, ventilation time and intensive care length of stay. Mahalanobis distance assessed statistical differences between clusters. Spearman’s correlation described the linear relationship between mediator concentrations at the end of CPB and intensive care length of stay. Results are median (IQR).

Results
Forty consecutive patients were enrolled; the majority were male (58%), age of 7.3 (1.7–39.0) months and weight of 6.7 (4.6–14.9) kg. The PCA-HCPC revealed activated complement factors along with all peak clinical scores and prolonged intensive care requirements in the same cluster. Cytokine, chemokine, and leukocyte adhesion molecule concentrations were found in two other distinct clusters (Mahalanobis distance = 16.5; p = 0.004 and Mahalanobis distance = 17.4; p = 5.8 × 10–4). Mediator concentrations of C2 (Rho = 0.50; p = 0.001), C3 (Rho = 0.58; p = 1.1 × 10–4), C3b (Rho = 0.47; p = 0.002), C5 (Rho = 0.48; p = 0.002) and C5a (Rho = 0.63; 1.7 × 10–5) showed linear correlations with intensive care unit length of stay.

Conclusions
Activated complement factors, but not pro-inflammatory cytokines or chemokines, were most related to cardiopulmonary dysfunction and prolonged recovery in this novel analysis. Investigation of therapies that inhibit complement to dampen CPB-associated inflammation and enhance recovery after pediatric cardiac surgery is warranted.
Trial Registration ClinicalTrials.gov, NCT05154864
CD2AP deficiency aggravates Alzheimer’s disease phenotypes and pathology through p38 MAPK activation
Authors: Xue Yan-Yan , Zhang Zhe-Sheng , Lin Rong-Rong , Huang Hui-Fen , Zhu Ke-Qing , Chen Dian-Fu , Wu Zhi-Ying , Tao Qing-Qing 
Published: December 2024

Abstract

Background
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder, which is characterized by a decline in cognitive abilities. Genome-wide association and clinicopathological studies have demonstrated that the CD2-associated protein (CD2AP) gene is one of the most important genetic risk factors for AD. However, the precise mechanisms by which CD2AP is linked to AD pathogenesis remain unclear.

Methods
The spatiotemporal expression pattern of CD2AP was determined. Then, we generated and characterized an APP/PS1 mouse model with neuron-specific Cd2ap deletion, using immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay, electrophysiology and behavioral tests. Additionally, we established a stable CD2AP-knockdown SH-SY5Y cell line to further elucidate the specific molecular mechanisms by which CD2AP contributes to AD pathogenesis. Finally, the APP/PS1 mice with neuron-specific Cd2ap deletion were treated with an inhibitor targeting the pathway identified above to further validate our findings.

Results
CD2AP is widely expressed in various regions of the mouse brain, with predominant expression in neurons and vascular endothelial cells. In APP/PS1 mice, neuronal knockout of Cd2ap significantly aggravated tau pathology, synaptic impairments and cognitive deficits. Mechanistically, the knockout of Cd2ap activated p38 mitogen-activated protein kinase (MAPK) signaling, which contributed to increased tau phosphorylation, synaptic injury, neuronal apoptosis and cognitive impairment. Furthermore, the phenotypes of neuronal Cd2ap knockout were ameliorated by a p38 MAPK inhibitor.

Conclusion
Our study presents the first in vivo evidence that CD2AP deficiency exacerbates the phenotypes and pathology of AD through the p38 MAPK pathway, identifying CD2AP/p38 MAPK as promising therapeutic targets for AD.
A schedule for phasing-out knife crime
Authors: Farrell Graham , Davies Toby 
Published: December 2024

AbstractKnife crime has become a prominent and seemingly intractable problem in England & Wales. Theory and evidence indicate that reducing crime opportunities is an effective means of crime control, including restrictions on lethal weapons. While public debate has centred on zombie and other ‘status’ knives, the most prevalent homicide weapon is a kitchen knife. Here we argue that replacing lethal pointed-tip kitchen knives with safer round-tip knives would reduce knife crime with little or no displacement. Drawing on the approach to remove fossil-fuel vehicles from roads, we propose a phased removal of lethal kitchen knives that we estimate will cut knife-related homicide in half, reduce other knife crime and criminality, and prevent thousands of non-criminal knife-related injuries.
Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses
Authors: Kim Myung Sup , Kang Hyeokgu , Baek Jung-Hwan , Cho Moon-Gyu , Chung Eun Joo , Kim Seok-Jun , Chung Joon-Yong , Chun Kyung-Hee 
Published: December 2024

Abstract
Background
Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Methods
In this work, we constructed conditional Hes1 knockout mice to selectively delete Hes1 in TAMs. We further analyzed the TME composition, T cell infiltration and activation, and anti-tumor effects in these mice, both alone and in combination with PD-1 checkpoint blockade.

Results
Our study showed that expression levels of Notch target Hes1 were increase in TAMs and mice with conditional knockout of Hes1 gene in TAMs exhibited decreased tumor growth, with increased infiltration and activation of cytotoxic T cells in tumors. Expression of tumor promoting factors was critically altered in Hes1-conditional KO TAMs, leading to the improved tumor microenvironment. Notably, arginase-1 expression was decreased in Hes1-conditional KO mice. Arg1 is known to deplete arginine and deactivate T cells in the TME. Administration of anti-PD-1 monoclonal antibody inhibited tumor growth to a greater extent in Hes1-conditional KO mice than in WT mice.

Conclusions
We identified a pivotal role for the Notch signaling pathway in shaping TAM function, suggesting that T-cell dysfunction in the TME is caused when the Notch target, HES1, in TAMs is upregulated by tumor-associated factors (TAFs), which, in turn, increases the expression of arginase-1. Targeting HES1 in TAMs appears to be a promising strategy for cancer immunotherapy.
Recent advancements in traditional Chinese medicine for COVID-19 with comorbidities across various systems: a scoping review
Authors: Shang Xiyu , Cao Yuqing , Guo Yang , Zhang Lei , Li Jiajia , Zhang Huifang , Fan Yipin , Huang Yuxuan , Li Jiantao , Wang Yanping , Xiong Yibai , Cai Qiujie , Zhang Huamin , Ma Yan 
Published: December 2024

Abstract
Background
Traditional Chinese medicine (TCM) has developed a rich theoretical system and practical experience in fighting to infectious diseases over the past thousands of years, and has played an important role in controlling the spread owing to its unique advantages. In particular, its significant contribution to the prevention and control of Corona Virus Disease 2019 (COVID-19) is widely recognized. COVID-19 infection is mainly non-severe with a favorable overall outcome, but patients with comorbidities tend to have a poor prognosis. However, a comprehensive review of TCM for preventing and treating COVID-19 with comorbidities across various systems is still lacking. Hence, this scoping review aims to conduct a comprehensive investigation on treatment outcome of TCM for treating COVID-19 with comorbidities across various systems.

Methods
The scoping review was conducted by searching English databases including PubMed and Web of Science, and Chinese databases including China National Knowledge Infrastructure and Wanfang between January 2020 and January 2024. We followed the inclusion and exclusion criteria to identify relevant literature. Information for inclusion in the literature were subsequently extracted and consolidated.

Results
We enrolled 13 literature that met the inclusion criteria in the review finally. Our analysis revealed that research on COVID-19 with comorbidities was mostly focused on circulatory diseases, including hypertension, heart failure, and cerebrovascular diseases, most common comorbidities were hypertension. Followed by endocrine and metabolic diseases such as diabetes, respiratory diseases including pulmonary tuberculosis and chronic obstructive pulmonary disease have been also addressed. However, there were few studies on co-infectious urogenital system disease, and no studies on the rheumatic, immune, hematological, nervous, reproductive, and skin systems diseases. Based on existing studies, TCM has significantly improved the clinical symptoms of COVID-19 with comorbidities such as fever, fatigue, dry cough, anorexia and asthma, the absorption of lung lesions, shortened the duration of viral shedding and the course of disease.

Conclusions
TCM has great application prospects in treating COVID-19 with comorbidities. These findings could provide important evidence for clinicians to treat COVID-19 with comorbidities. Multi-center studies are required to confirm our results in the future.

Graphical Abstract
Material hardship and secure firearm storage: findings from the 2022 behavioral risk factor Surveillance System
Authors: Testa Alexander , Henson-Garcia Mike , Jackson Dylan B. , Fu Karyn , Ganson Kyle T. , Nagata Jason M. 
Published: December 2024

Abstract
Background
Firearm secure storage is an important public health practice due to its potential impact on reducing the incidence of accidental injuries, suicides, and thefts. Yet, there is limited research on how economic conditions might shape firearm storage patterns.

Methods
This study explores the relationship between material hardship and firearm secure storage among firearm-owning households. Data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed, including responses from 7,197 firearm-owning adults in California, Minnesota, Nevada, and New Mexico. Multinomial logistic regression models assessed the relationship between levels of material hardship and storage practices, adjusting for demographic and socioeconomic factors.

Results
Among respondents, 14.3% reported firearms were stored, loaded and unlocked. Compared to respondents experiencing no hardships, those experiencing three or more material hardships incurred a 183% higher risk of storing firearms in an unsecured manner (Relative Risk Ratio = 2.828, 95% CI = 1.286, 6.220).

Conclusion
This study highlights an association between greater material hardship and unsecured firearm storage. These findings emphasize the need for public health interventions that address economic barriers to safe firearm storage, potentially reducing firearm-related injuries and deaths among individuals experiencing material hardship.