bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic exercise training improves learning and memory performance in hypoxic-exposed rats by activating the hippocampal PKA–CREB–BDNF signaling pathway
Authors: Luo Shichen , Shi Lei , Liu Tong , Jin Qiguan 
Published: February 2025

Abstract

Background
This study aims to investigate the effects of aerobic exercise training on learning and memory (L&M) performance in rats exposed to altitude hypoxia and its relationship with hippocampal plasticity and the PKA–CREB–BDNF signaling pathway.

Methods
Male Sprague–Dawley rats were exposed to 14.2% hypoxia with or without 60 min of non-weight-bearing swimming training for 8 weeks. The L&M performance was evaluated using the Morris water maze, and the mRNA expression of PSD95, SYP, PKA, CREB, CBP, and BDNF in the hippocampus was detected.

Results
Chronic hypoxia exposure significantly impaired L&M performance and reduced the mRNA expression of hippocampal PSD95, SYP, PKA, CREB, CBP, and BDNF. Aerobic exercise training effectively reversed these changes by enhancing hippocampal synaptic plasticity through the activation of the PKA–CREB–BDNF signaling pathway.

Conclusion
Aerobic exercise training can alleviate the decline in L&M performance caused by altitude hypoxia exposure, possibly through the activation of the hippocampal PKA–CREB–BDNF signaling pathway.
Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes
Authors: Le Goff Wilfried , Bourron Olivier , Materne Clément , Galier Sophie , Phan Franck , Tan-Chen Sophie , Guillas Isabelle , Hartemann Agnès , Salem Joe-Elie , Redheuil Alban , Foufelle Fabienne , Le Stunff Hervé , Hajduch Eric , Guerin Maryse 
Published: February 2025

Abstract

Background
Sphingosine 1-phosphate (S1P) is a key mediator of lipid signaling with strong immunomodulatory and anti-inflammatory effects. Circulating S1P levels including S1P in high-density lipoproteins (HDL) were demonstrated to be inversely associated with cardiovascular diseases (CVD). However, no studies are available regarding a potential implication of S1P on the risk of CVD in type 2 diabetes (T2D). The objective of this study is to determine if the increased CVD risk in T2D may involve an alteration of circulating S1P species as well as their precursors.

Methods
A total of 168 and 31 patients with T2D (154 men and 45 women) with available Coronary artery calcification (CAC) score from the DIACART and CERABIAB cohorts, respectively, were included in the study. Quantification of S1P species and their precursors was carried out by LC–MS/MS in plasma and isolated HDL. CAC score was modeled as a binary variable (0/1 below or equal/above 100) using CAC < 100 for reference. S1P species or precursors were modeled as binary variables dichotomized at the median (0/1: below or equal/above the median). The relationships between S1P species and CAC score modeled as a binary variable (below or equal/above 100) was evaluated by linear regression analyses. In vitro experiments were conducted to evaluate the contribution of HDL-S1P content on anti-inflammatory properties of HDL particles.

Results
Multivariate analysis revealed that plasma S1P levels, especially d18:1-S1P, and sphingosine in HDL were inversely associated with the high risk of CVD (CAC > 100) in patients with T2D. Clustering of HDL according to their concentration in S1P species and their precursors revealed that S1P-impoverished HDL is a major feature of patients with a CAC > 100. In vitro analysis of monocyte adhesion and inflammation in human umbilical vein endothelial cells as well as inflammatory phenotype of human macrophages demonstrated that low HDL-S1P exhibited impaired anti-inflammatory properties in comparison to high HDL-S1P.

Conclusion
This study unraveled that circulating S1P and their precursors are biomarkers of coronary atherosclerosis in T2D, which may underlie the lower abundance of S1P and anti-inflammatory activities of HDL.

Trial registration ClinicalTrials.gov number, NCT02431234.

Graphical abstract
Association of Kawasaki disease with intellectual disability, attention deficit hyperactivity disorder, and autism spectrum disorder: a systematic review and meta-analysis
Authors: Hsu Chih-Wei , Lin Yu-Wei , Chen Yang-Chieh Brian , Wang Liang-Jen , Kuo Ho-Chang 
Published: February 2025

Abstract

Background
The relationship between Kawasaki disease (KD) and neurodevelopmental disorders (NDDs) remains unclear. This study aims to explore the association between them.

Method
A systematic review was conducted using PubMed and Embase databases from inception to May 1, 2024 (INPLASY202450017). We included case-control or cohort studies comparing KD patients to healthy controls in assessing attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). The meta-analysis employed a random-effects model to calculate effect sizes using hazard ratios (HRs) with 95% confidence intervals (CIs) for the disease occurrence. Moreover, mean differences (MDs) were used to calculate intelligence quotient (IQ).

Results
Four eligible studies, including 1,454,499 participants, were analyzed for ADHD, ASD, and ID. The risk of ADHD in KD patients was higher than in healthy controls (HR[95%CI] = 1.76[1.21–2.57]). However, the risks of ASD (HR[95%CI] = 1.68[0.47–5.94]) and ID (HR[95%CI] = 1.39[0.52–2.63]) were not significantly different between KD and controls. Additionally, three studies with 365 participants were analyzed for IQ. IQ comparisons showed no significant differences in full IQ (MD[95%CI]=-0.01[-2.44–2.42]), verbal IQ (MD[95%CI]=-1.05[-4.42–2.33]), and performance IQ (MD[95%CI]=-0.08[-2.75–2.59]).

Conclusion
This study indicates that individuals with KD have a higher risk for ADHD but not for ASD or ID.

Trial registration
INPLASY, INPLASY202450017. Registered 05 May 2024, https://inplasy.com/inplasy-2024-5-0017/.
Gene-activation of surface-modified 3D printed calcium phosphate scaffolds
Authors: Laird Noah Z. , Phruttiwanichakun Pornpoj , Mohamed Esraa , Acri Timothy M. , Jaidev Leela R. , Salem Aliasger K. 
Published: February 2025

Abstract
Large volume bone defects that do not spontaneously heal despite surgical stabilization (“critical-sized” defects) remain a challenge to treat clinically. Recent research investigating bone regenerative implants made from 3D printed materials have shown promise as a potential alternative to current treatment methods, such as autografting, allografting, and multi-step surgical interventions. Recent work has shown that implanting 3D printed calcium phosphate cement (CPC) scaffolds loaded with bone morphogenetic protein-2 (BMP-2) can provide a one-step surgical intervention that has similar bone healing outcomes to a popular two-step intervention: the Masquelet technique. The aim of this study was to investigate whether a 3D printed CPC scaffold loaded with a lyophilized polyplex gene-delivery formulation could serve as an alternative to loading BMP-2 protein onto such scaffolds. We 3D printed CPC scaffolds, hardened them with multiple methods, and explored the impact of these hardening methods on surface texture, mechanical strength, osteogenic differentiation, and ion flux. We then gene-activated these materials with cationic polyplexes containing plasmid DNA encoding reporter genes to investigate transfection from the gene-activated scaffolds. We found that incubating CPC scaffolds in aqueous solutions after initial hardening in a humid environment could enhance scaffold mechanical strength (compressive strength of 21.28 MPa vs. 6.54 MPa) and osteogenic differentiation. We also found that when we increased the total surface area of the CPC material exposed to polyplex solutions, there was a reduction in transfection via adsorption of polyplexes to the CPC surface. This study shows that 3D printed, gene-activated CPC scaffolds are a promising avenue for future exploration in the field of bone regeneration, though the level of gene expression induced by the scaffolds must be improved.
Novel 5,6-dichlorobenzimidazole derivatives as dual BRAFWT and BRAFV600E inhibitors: design, synthesis, anti-cancer activity and molecular dynamics simulations
Authors: Temirak Ahmed , El Kerdawy Ahmed M. , Nageeb Amira M. , Abdel-Mohsen Heba T. 
Published: February 2025

Abstract
A new series of 1-substiuted-5,6-dichloro-2-(4-methoxyphenyl)-1H-benzo[d]imidazoles 10a–p was designed and synthesized to target both BRAFWT and BRAFV600E. The design strategy ensures that these derivatives would effectively occupy the ATP binding pocket of BRAFWT/V600E kinase domains and extend over the gate area interacting through hydrogen bonding with the surrounding key amino acids Glu500 and Asp593 and to finally occupy the allosteric hydrophobic back pocket. Some synthesized derivatives demonstrated impressive potency against BRAFWT with % inhibition approaching 91% at a concentration of 10 µM. The most potent candidate 10h demonstrated IC50 values of 1.72 and 2.76 µM on BRAFWT and BRAFV600E, respectively. At the same time, the synthesized benzimidazoles 10a–p were examined for their growth inhibitory activity on NCI-60 cancer cell lines. Again, compound 10h revealed a potent GI50 across a range of cancer cell lines. Moreover, it arrested cell cycle progression in HT29 colon cancer cell line at G2/M phase and induced apoptosis in the same cell line. Molecular dynamics simulations supported the validity of the design assumption, simultaneously, ADME prediction study displayed that the designed benzimidazoles exhibit promising physiochemical and drug-likeness properties as anticancer agents.

Graphical Abstract
Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics
Authors: Witz Andréa , Dardare Julie , Betz Margaux , Michel Cassandra , Husson Marie , Gilson Pauline , Merlin Jean-Louis , Harlé Alexandre 
Published: February 2025

Abstract
The use of poly(ADP-ribose) polymerase inhibitors (PARPi) revolutionized the treatment of BRCA-mutated cancers. Identifying patients exhibiting homologous recombination deficiency (HRD) has been proved useful to predict PARPi efficacy. However, obtaining HRD status remains an arduous task due to its evolution over the time. This causes HRD status to become obsolete when obtained from genomic scars, rendering PARPi ineffective for these patients. Only two HRD tests are currently FDA-approved, both based on genomic scars detection and BRCA mutations testing. Nevertheless, new technologies for obtaining an increasingly reliable HRD status continue to evolve. Application of these tests in clinical practice is an additional challenge due to the need for lower costs and shorter time to results delay.
In this review, we describe the currently available methods for HRD testing, including the methodologies and corresponding tests for assessing HRD status, and discuss the clinical routine application of these tests and their technical validation.
Vancomycin dosing design method considering risk factors for nephrotoxicity
Authors: Matsuki Yoshihiko , Kozima Yutaro , Yanagi Megumi , Sako Ken-ichi , Watanabe Tamaki , Yasuno Nobuhiro , Watanabe Shigekazu 
Published: February 2025

Abstract

Background
Vancomycin (VCM) induces nephrotoxicity in a dose-dependent manner, and patients with risk factors for nephrotoxicity have been reported to develop nephrotoxicity even within the effective concentration range. In the present study, we investigated measures to set an appropriate AUCss for each case by assessing the risk of developing nephrotoxicity using logistic regression curves, separating patients into a High-risk group with risk factors associated with nephrotoxicity when VCM is used and a Low-risk group without risk factors.

Methods
A multivariate logistic regression analysis was used to identify risk factors for nephrotoxicity. The AUCss threshold was selected by a CART analysis and ROC curves, and a logistic regression analysis was used to examine the relationship between AUCss and the probability of developing nephrotoxicity.

Results and discussion
The incidence of nephrotoxicity was 31.7% (33/104) in the High-risk group and 13.0% (14/108) in the Low-risk group, and was significantly higher in the former (p = 0.001). The AUCss threshold was set at 575 mg·h/L for the High-risk group and 650 mg·h/L for the Low-risk group. The probability of developing nephrotoxicity in the High-risk group (104 patients) was high: AUCss 400 mg·h/L (16.8%), 500 mg·h/L (23.3%), and 575 mg·h/L (29.3%). The target concentration range was newly set at 400 ≤ AUCss < 500, suggesting that the target AUCss needs to be considered for each patient based on the balance between therapeutic efficacy and the prevention of adverse effects. The probability of developing nephrotoxicity in the Low-risk group (108 patients) was AUCss 500 mg·h/L (4.7%), 575 mg·h/L (8.4%), and 650 mg·h/L (14.6%). Since the Low-risk group has a high safety profile, the target concentration range was newly set at 400 ≤ AUCss < 650, suggesting the safe administration of the drug up to AUCss 650 mg·h/L while aiming for AUCss 600 mg·h/L from the initial dose design.

Conclusion
In the present study, the risk of nephrotoxicity for each AUCss was quantitatively analyzed using logistic regression curves for the High- and Low-risk groups. This allowed for the proposal of strategic individual target concentrations based on the balance between risk and benefit.
Neurosurgical Approach to Neurocysticercosis in Adults: A Comprehensive Systematic Review of Clinical and Imaging Insights
Authors: Knott Maxon V. , Berke Chandler N. , Shah Khushi Hemendra , Gurses Muhammet Enes , Bashti Malek , Lu Victor M. , Ivan Michael E. , Castro Jose G. , Komotar Ricardo J. , Shah Ashish H. 
Published: February 2025

BACKGROUND AND OBJECTIVES:
Neurocysticercosis (NCC), caused by larval cysts of Taenia solium, presents a significant health challenge worldwide with diverse clinical presentations and varying management approaches. Untreated NCC can lead to increased intracranial pressure and/or hydrocephalus, with possible death. This review provides comprehensive neurosurgical insight into the heterogeneity of NCC. As there is currently no treatment algorithm for NCC, we propose a framework based on the management strategies most prevalent in the literature.

METHODS:
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted searching PubMed, Scopus, and Embase from November 1993 to August 2023. Included articles had individual patient data on the treatments and outcomes of adult patients treated for confirmed symptomatic NCC. Relevant patient data on patient presentations, management, and outcomes and disease characteristics were collected.

RESULTS:
Our analysis included 90 studies with 205 patients. Neuroimaging was diagnostic for all, with MRI being predominant (74%). Cysts were intraparenchymal (n = 69), extraparenchymal (n = 68), spinal (n = 24), and mixed distribution (n = 16). Common symptoms included seizures (39%), headache (39%), and motor weakness/paresis (28%). 67 patients presented with hydrocephalus, 30 (45%) of which received a ventriculoperitoneal shunt. NCC was most commonly treated medically with corticosteroids (56%) and albendazole (55%). Neurosurgical intervention was most commonly performed for surgical extraction of cysts (33%). Combination of medical and surgical treatment (98%, 44/45) or surgical intervention alone (98%, 40/41) was the most successful at resolving symptoms after first treatment. Resolution of symptoms with added radiographic resolution of the cyst was common with maximal treatment (n = 137, 70%).

CONCLUSION:
NCC's diverse presentations and outcomes emphasize the importance of tailored therapeutic strategies. Limitations of this study include its retrospective nature and low sample sizes of individual studies. The prominence of corticosteroids, albendazole, and surgical procedures highlights their central role in NCC management, as well as the indispensable role of neurosurgeons.
How Good is Neurosurgical Training? Validation of a Perfused Microsurgical Aneurysm Training Simulator Using a Modified Objective Structured Assessment of Aneurysm Clipping Skills Score and Indocyanine Green Angiography
Authors: Reiser Julius , Amini Amir , Swiatek Vanessa M. , Taskaya Firat , Al-Hamid Sifian , Stein Klaus-Peter , Rashidi Ali , Sandalcioglu I. Erol , Neyazi Belal 
Published: February 2025

BACKGROUND AND OBJECTIVES:
The training of cerebrovascular neurosurgeons faces significant challenges, particularly due to the decreasing volume of aneurysm clipping procedures. Traditional training methods rely heavily on clinical case availability, which limits skill development. This study aimed to implement and validate a Microsurgical Aneurysm Training Simulator (MATS) that offers a comprehensive, realistic, and cost-effective solution for neurosurgical training.

METHODS:
MATS was designed using semiautomated algorithms and additive manufacturing to replicate a bifurcation aneurysm of the middle cerebral artery. The simulator includes a pulsatile perfusion system and is compatible with indocyanine-green angiography. The simulation was evaluated by medical students, residents, and experienced neurosurgeons through face, content, and construct validity assessments. Performance was measured using a modified Objective Structured Assessment of Aneurysm Clipping Skills.

RESULTS:
MATS demonstrated high face and content validity, particularly in replicating the visual and procedural aspects of aneurysm clipping. Participants across all experience levels showed significant improvements in modified Objective Structured Assessment of Aneurysm Clipping Skills scores, with medical students displaying the most pronounced learning curve. The simulators compatibility with indocyanine green angiography was confirmed, though limitations were noted in replicating physiological perfusion pressures and the visual impact of subarachnoid hemorrhage during aneurysm rupture simulations.

CONCLUSION:
MATS is a validated, cost-effective, and reproducible tool that significantly enhances neurosurgical training by improving technical skills, especially in inexperienced participants. While the simulator effectively mimics key aspects of aneurysm surgery, further research is needed to assess its predictive validity and its potential impact on actual surgical outcomes.
Focusing on the Future: Making the Reinstatement Process More Effective for Vulnerable Students
Authors: Bowlus Angela 
Published: February 2025

Abstract
Reinstatement from suspension is a complex process. Students hoping to be reinstated must demonstrate, usually through a written appeal, that previous issues are resolved and that they have a plan for academic success. Writing reinstatement appeals requires students to be vulnerable and share intimate details of their lives with complete strangers to persuade them that they are ready for and capable of returning. That complexity and vulnerability could discourage students from returning to complete their degrees. This study used a narrative theory framework to understand the importance of student narratives and identify whether focus can be placed on the characteristics of success rather than invoking past trauma placing students in a vulnerable position.
Isolation and characterization of bacteriophage against clinical isolates of AmpC beta lactamase–Producing Klebsiella pneumoniae from hospital wastewater
Authors: Abusalah Manal Abdel Haleem A. , Abusalah Mai Abdel Haleem A. , Yean Yean Chan , Aziah Ismail , Zaidah Abdul Rahman 
Published: February 2025

Background
The increasing incidence of AmpC β-lactamase producing by K. pneumoniae has raised global alarm. Consequently, there is a crucial need for effective methods to inactivate pathogenic bacteria and mitigate the associated risks. Bacteriophage therapy has been demonstrated to be an effective and alternative approach for targeting and inactivating K. pneumoniae that produces AmpC.
This study aimed to isolate and characterize the Klebsiella pneumoniae AmpC-specific phages from hospital wastewater.

Methods
The hospital wastewater samples were collected from the sewage water effluent of a tertiary hospital at Universiti Sains Malaysia, located on the east coast of Malaysia. These samples underwent serial filtration and centrifugation processes for phage recovery. The phage solutions were undergoing a screening test by spot assay using clinical isolates of Klebsiella pneumoniae AmpC strain as amplification hosts. The isolated AmpC-phages were further studied and characterised to determine the phage’s host range, temperature, pH, and chloroform stabilities. High-Resolution Transmission Electron Microscopy (HRTEM) was performed to determine the phage type.

Results
Thirty HWW samples were analyzed using four K. pneumoniae AmpC strains resulting in a total of 120 screening plates. The AmpC—Klebsiella pneumoniae (AmpC-KP) phages were detected in 31.70% (38/120) of the plates. The AmpC-KP phages had lytic diameters ranging from 1–3 mm, and a phage titer ranged from4×103–3.2×107 PFU/ml. The phages had a narrow–host range stable at a temperature range from -20–50˚C. The phages were also stable at pH ranging from 4 to 9 and at different concentrations of chloroform (5%,10%). Based on HRTEM, Siphoviridea was identified.

Conclusions
The AmpC-phages were abundant in hospital wastewater, and HWW was a good source for AmpC-KP phages. The isolated AmpC phages had a high effectivity and specificity for AmpC-KP with a narrow host range and could survive under harsh conditions such as (temperature, pH, and chloroform).
Comparison of ultrasound and dynamic MRI for the measurement of diaphragmatic excursion: A prospective single-center study
Authors: Delplancke Clara , Charpentier Etienne , Grolleau François , Hernigou Anne , Nougué Hélène , Le Pimpec-Barthes Françoise , Cholley Bernard , Daniel Matthieu 
Published: February 2025

Objectives
Ultrasound (US) measurements of diaphragmatic excursion (DE) are widely used to provide a non-invasive assessment of the diaphragmatic function at the bedside, especially in intensive care. However, this measurement has never been validated against a less operator-dependent technique such as MRI. Dynamic MRI is the only imaging modality that creates a four-dimensional reconstruction of the diaphragm. The primary objective of this study was to assess the agreement between DE obtained using dynamic MRI with those obtained using ultrasound. The secondary objectives were to define DE thresholds for the diagnosis of DD using MRI and to compare the performance of US and MRI to diagnose DD.

Methods
Prospective single-center study in which consecutive outpatients referred for a dynamic thoracic MRI were included. This study was conducted at a university hospital in Paris, where there was daily access to ultrasound (US) and extensive expertise in diaphragmatic MRI The DE of each hemi-diaphragm was measured sequentially using ultrasound and MRI in random order, during spontaneous breathing (SB) and forced inspiration (FI) by independent observers blinded to each other. We analyzed the agreement between DE obtained using US and MRI for each hemi-diaphragm.

Results
We enrolled forty-five patients, aged 58 ± 36 years, of which twenty-eight (68%) had a confirmed DD. During SB, the mean bias for DE measurement was −3.8 mm, 95% CI [−7.1; −0.6] for the left hemi-diaphragm, and 1.0 mm, 95% CI [−3.5; 5.5] for the right hemi-diaphragm. Limits of agreement (millimeters) were [−25; 17] on the left side, and [−28; 30] on the right side. MRI threshold values for DE defining dysfunction were 11 mm for quiet SB, and 38 mm for FI. These thresholds had a sensitivity of 77.7% and a specificity of 77.4% during SB, with an AUC of 0.86.

Conclusion
US and MRI provide different values for DE, probably because the measurements were not obtained exactly at the same localization. Nevertheless, diagnostic performances of MRI and US to recognize DD appeared comparable.