bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma β2-microglobulin and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact older adults: the CABLE study
Authors: Huang Yi-Ming , Ma Ya-Hui , Gao Pei-Yang , Wang Zhi-Bo , Huang Liang-Yu , Hou Jia-Hui , Tan Lan , Yu Jin-Tai 
Published: April 2023

Abstract
Background
Previous studies have suggested a correlation between elevated levels of β2-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers and cognition.

Methods
To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M’s relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition.

Results
We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aβ1–42 (P < 0.001) and Aβ1–42/Aβ1–40 (P = 0.015) as well as increases in T-tau/Aβ1–42 (P < 0.001) and P-tau/Aβ1–42 (P < 0.001). The subgroup analysis found B2M correlated with Aβ1–42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aβ pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect.

Conclusions
This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aβ pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.
CT appearances and classification of hepatic epithelioid hemangioendothelioma
Authors: Tan Haidong , Zhou Ruiquan , Yu Hongwei , Teng Feng , Si Shuang , Liu Liguo , Yang Shiwei , Han Dongdong , Liu Xiaolei 
Published: April 2023

Abstract
Background
Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, and CT features have never been analyzed in a large group of patients.

Methods
A retrospective study was designed to review the contrast-enhanced CT images of HEH patients. Intrahepatic lesions were categorized into three types: nodular, locally coalescent (coalescent lesion contained in one segment) or diffusely coalescent (coalescent lesion occupied more than one segment). CT features were compared among lesions of different sizes and patients with different lesion types.

Results
A total of 93 HEH patients were included in this study, and 740 lesions were analyzed. The results of per-lesion analysis showed that medium lesions (2–5 cm) had the highest rate of lollipop sign (16.8%) and target-like enhancement (43.1%), while lesions in large group (> 5 cm) had the highest rate of capsular retraction (38.8%) and vascular invasion (38.8%). The differences on enhancement pattern and the rates of lollipop sign and capsular retraction were significant among lesions of different sizes (p < 0.001, respectively). The results of per-patient analysis showed that patients in locally coalescent group had the highest rates of lollipop sign (74.3%) and target sign (94.3%). All patients in diffusely coalescent group had capsular retraction and vascular invasion. CT appearances of capsular retraction, lollipop sign, target sign and vascular invasion differed significantly among patients with different lesion types (p < 0.001, p = 0.005, p = 0.006 and p < 0.001, respectively).

Conclusion
CT features variated among HEH patients with different lesion types, and radiological appearances of HEH should be classified into nodular type, locally coalescent type and diffusely coalescent type.
Development and validation of a glioma-associated mesenchymal stem cell-related gene prognostic index for predicting prognosis and guiding individualized therapy in glioma
Authors: Peng Zesheng , Wu Yuxi , Wang Jiajing , Gu Sujie , Wang Yihao , Xue Bingzhou , Fu Peng , Xiang Wei 
Published: April 2023

Abstract
Background
Recent studies have demonstrated that glioma-associated mesenchymal stem cells (GA-MSCs) are implicated in the regulation of glioma malignant progression. However, the prognostic value of GA-MSCs has not been comprehensively explored in glioma.

Methods
We extracted GA-MSCs from glioma tissues, established intracranial xenograft models in nude mice, and obtained GA-MSC-related genes (GA-MSCRGs) by using microarrays. The transcriptome data and clinical information of glioma patients were obtained from the CGGA and TCGA databases. We screened 8 prognostic GA-MSCRGs to construct a prognostic index by using the multivariate Cox regression method. The validity of the GA-MSCRGPI was verified in the training (CGGA693) and validation (TCGA and CGGA325) cohorts. The expression patterns of these 8 GA-MSCRGs were validated in 78 glioma tissue specimens by using a qRT‒PCR assay.

Results
GA-MSCs were successfully isolated from glioma tissues. Based on intracranial xenograft models and transcriptome microarray screening, 8 genes (MCM7, CDK6, ORC1, CCL20, TNFRSF12A, POLA1, TRAF1 and TIAM1) were selected for the construction of a GA-MSC-related gene prognostic index (GA-MSCRGPI). In both the training and validation cohorts, high GA-MSCRGPI patients showed an inferior survival outcome compared with low GA-MSCRGPI patients. A nomogram was established based on independent prognostic indicators (age, WHO grade and GA-MSCRGPI) and exhibited a strong forecasting ability for overall survival (OS). Moreover, we found that the GA-MSCRGPI could evaluate the prognosis of glioma patients undergoing chemoradiotherapy. The high GA-MSCRGPI group exhibited higher immune, stromal and ESTIMATE scores; lower tumor purity; higher infiltration of Tregs and M2-type macrophages; fewer activated NK cells; and higher expression of immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) showed that the high GA-MSCRGPI group had more responders to ICI therapy. The results of the genetic mutation profile and tumor mutation burden (TMB) in different GA-MSCRGPI subgroups further supplement GA-MSCRGPI-related mechanisms. Finally, the expression patterns of 8 selected GA-MSCRGs in GA-MSCRGPI were correlated with glioma WHO grades to a certain extent.

Conclusion
The constructed GA-MSCRGPI could predict prognosis and guide individualized therapy in glioma patients.
COVID-19 patient and personal safety – lessons learnt for pandemic preparedness and the way to the next normal
Authors: Füszl Astrid , Ebner Julia , Van den Nest Miriam , Bouvier-Azula Lukas , Diab-El Schahawi Magda , Presterl Elisabeth 
Published: April 2023

Abstract
Background
The COVID-19 pandemic has profoundly challenged societies and healthcare systems in particular. To prevent the spread of SARS-CoV-2, infection prevention and control (IPC) strategies had to be developed on the local, national and international level. The aim of this study is to provide details of the COVID-19 experience at the Vienna General Hospital (VGH) in the context of the national and international COVID-19 response for learning and improvement.

Methods
This is a retrospective report, outlining the evolution of IPC measures and challenges encountered at the health facility (VGH), the national (Austria) and global level between February 2020 and October 2022.

Results
The IPC strategy at the VGH has been continuously adapted to changes in the epidemiological setting, new legal directives and Austrian by-laws. The current strategy, nationally and internationally, focuses on endemicity rather than maximum transmission risk reduction. For the VGH, this has recently resulted in an increase in COVID-19 clusters. To protect our particularly vulnerable patients, many COVID-19 precautions have been maintained. Barriers to adequate IPC implementation at the VGH and other hospitals include a lack of sufficient isolation options and non-adherence with universal face mask regulations. Globally, misinformation on COVID-19 hampered an effective response.

Conclusions
This retrospective analysis of the COVID-19 response at the VGH and international reports underline the need for pandemic preparedness, readiness and response by improving future hospital design and infrastructure, conducting regular trainings for protective attire and increasing health literacy as now recently published in a concise document by WHO.
Effects of regorafenib on the mononuclear/phagocyte system and how these contribute to the inhibition of colorectal tumors in mice
Authors: Grünewald Sylvia , Stecklum Maria , Rizzo Manuel , Rathjens Jonathan , Fiebig Lukas , Zopf Dieter 
Published: April 2023

Abstract
Background
Regorafenib was previously shown to reduce tumor-associated macrophages and potently inhibit colony-stimulating factor 1 receptor (CSF1R), also known as CD115, in biochemical assays. The CSF1R signaling pathway is essential in the biology of the mononuclear/phagocyte system, which can promote the development of cancer.

Methods
A deeper investigation of regorafenib’s effects on CSF1R signaling was performed using preclinical in vitro and in vivo studies with syngeneic CT26 and MC38 mouse models of colorectal cancer. Peripheral blood and tumor tissue were analyzed mechanistically by flow cytometry using antibodies against CD115/CSF1R and F4/80 and by ELISA for chemokine (C–C motif) ligand 2 (CCL2) levels. These read-outs were correlated with drug levels for the detection of pharmacokinetic/pharmacodynamic relationships.

Results
Potent inhibition of CSF1R by regorafenib and its metabolites M-2, M-4, and M-5 was confirmed in vitro in RAW264.7 macrophages. The dose-dependent growth inhibition of subcutaneous CT26 tumors by regorafenib was associated with a significant reduction in both the number of CD115hi monocytes in peripheral blood and the number of selective subpopulations of intratumoral F4/80hi tumor-associated macrophages. CCL2 levels were not affected by regorafenib in blood but increased in tumor tissue, which may contribute to drug resistance and prevent complete tumor remission. An inverse relationship between regorafenib concentration and the number of CD115hi monocytes and CCL2 levels was observed in peripheral blood, supporting the mechanistic involvement of regorafenib.

Conclusions
These findings may be clinically useful in optimizing drug dosing using blood-based pharmacodynamic markers and in identifying resistance mechanisms and ways to overcome them by appropriate drug combinations.
Numerical Investigation of the Progressive Collapse of the Reinforced Concrete Wall-Frame Structures Considering the Soil–Structure Interaction
Authors: Ekrami Kakhki Seyed Ali , Kheyroddin Ali , Mortezaei Alireza 
Published: April 2023

AbstractIn this essay, the progressive collapse resistance of the reinforced concrete wall-frame structures was evaluated with and without considering the soil–structure interaction. The vulnerability of the frames against progressive collapse was investigated with the middle column removal scenario from the first story, based on the sensitivity index. To evaluate the effects of soil–structure interaction, the wall-frame structures along with the soil (hard soil) and foundation were simultaneously modeled in FLAC software and compared with the frames in Seismostruct software. The results showed that the sensitivity index decreased by considering the soil–structure interaction in the wall-frame structures. Afterward, a parametric study of the structures (foundation thickness) and substructures (soil types, soil densities, soil saturation conditions and soil layers) was performed. The results showed that with an increase in thickness of the foundation, the sensitivity index increased, and therefore, the condition of the structure would be more critical against progressive collapse. It was found that high groundwater levels in the subsoil can reduce its bearing capacity and lead to the damage to the structure. In addition, it was determined that by changing the substructure soil type from type 4 (Clay-MC) to type 1 (Rock), the use of layer 1 (SM) and layer 2 (SM-CL/ML (Very hard clay)-SM), and the soils with high density, the condition of the structures is better to prevent progressive collapse.
Self-regulation as a resource for coping with developmental challenges during middle childhood and adolescence: the prospective longitudinal PIERYOUTH-study
Authors: Warschburger P. , Gmeiner M. S. , Bondü R. , Klein A. M. , Busching R. , Elsner B. 
Published: April 2023

AbstractBackgroundSelf-regulation (SR) as the ability to regulate one’s own physical state, emotions, cognitions, and behavior, is considered to play a pivotal role in the concurrent and subsequent mental and physical health of an individual. Although SR skills encompass numerous sub-facets, previous research has often focused on only one or a few of these sub-facets, and only rarely on adolescence. Therefore, little is known about the development of the sub-facets, their interplay, and their specific contributions to future developmental outcomes, particularly in adolescence. To fill these research gaps, this study aims to prospectively examine (1) the development of SR and (2) their influence on adolescent-specific developmental outcomes in a large community sample.Methods/designBased on previously collected data from the Potsdam Intrapersonal Developmental Risk (PIER) study with three measurement points, the present prospective, longitudinal study aims to add a fourth measurement point (PIERYOUTH). We aim to retain at least 1074 participants now between 16 and 23 years of the initially 1657 participants (6–11 years of age at the first measurement point in 2012/2013; 52.2% female). The study will continue to follow a multi-method (questionnaires, physiological assessments, performance-based computer tasks), multi-facet (assessing various domains of SR), and multi-rater (self-, parent-, and teacher-report) approach. In addition, a broad range of adolescent-specific developmental outcomes is considered. In doing so, we will cover the development of SR and relevant outcomes over the period of 10 years. In addition, we intend to conduct a fifth measurement point (given prolonged funding) to investigate development up to young adulthood.DiscussionWith its broad and multimethodological approach, PIERYOUTHaims to contribute to a deeper understanding of the development and role of various SR sub-facets from middle childhood to adolescence. The large sample size and low drop-out rates in the first three measurements points form a sound database for our present prospective research.Trial registrationGerman Clinical Trials Register, registration number DRKS00030847.
Effectiveness of clear aligners in achieving proclination and intrusion of incisors among Class II division 2 patients: a multivariate analysis
Authors: Yan Xinyu , Zhang Xiaoqi , Ren Linghuan , Yang Yi , Wang Qingxuan , Gao Yanzi , Jiang Qingsong , Jian Fan , Long Hu , Lai Wenli 
Published: April 2023

Abstract
Background
The predictability of incisor movement achieved by clear aligners among Class II division 2 patients is poorly understood. The aim of this retrospective study was to determine the effectiveness of clear aligners in proclining and intruding upper incisors and its influencing factors.

Methods
Eligible patients with Class II division 2 malocclusion were included. For clear aligner therapy, three types of incisor movements were designed: proclination, intrusion and labial movement. Pre-treatment and post-treatment dental models were superimposed. The differences between predicted and actual (DPA) tooth movement of incisors were analyzed. Univariate and multivariate linear regression were used to analyze the potential influencing factors.

Results
A total of 51 patients and their 173 upper incisors were included. Actual incisor proclination and intrusion were less than predicted ones (both P < 0.001), while actual labial movement was greater than predicted one (P < 0.001). Predictability of incisor proclination and intrusion was 69.8% and 53.3%, respectively. Multivariate linear regression revealed that DPA of proclination was significantly positively associated with predicted proclination (B = 0.174, P < 0.001), ipsilateral premolar extraction (B = 2.773, P < 0.001) and ipsilateral canine proclination (B = 1.811, P < 0.05), while negatively associated with molar distalization (B = − 2.085, P < 0.05). The DPA of intrusion was significantly positively correlated with predicted intrusion (B = 0.556, P < 0.001) while negatively associated with labial mini-implants (B = − 1.466, P < 0.001). The DPA of labial movement was significantly positively associated with predicted labial movement (B = 0.481, P < 0.001), while negatively correlated with molar distalization (B = − 1.004, P < 0.001), labial mini-implants (B = − 0.738, P < 0.001) and age (B = − 0.486, P < 0.05).

Conclusions
For Class II division 2 patients, predicted incisor proclination (69.8%) and intrusion (53.3%) are partially achieved with clear aligner therapy. Excessive labial movement (0.7 mm) of incisors may be achieved. Incisor movement is influenced by predicted movement amount, premolar extraction, canine proclination, molar distalization, mini-implants and age.
The Wakayama earthquake swarm in Japan
Authors: Nakajima Junichi 
Published: April 2023

AbstractAn earthquake swarm in the Wakayama prefecture, Japan, is known as the most active and persistent swarm, with > 95,000 earthquakes (M ≥ –1.3) occurring during the 2003–2020 period. However, no systematic studies have highlighted the source of this intriguing non-volcanic earthquake swarm to date. This study systematically investigates the temporal and spatial evolution of the Wakayama earthquake swarm and estimates the seismic velocity structure around the Kii peninsula, where we observe series of anomalous geophysical and geochemical signatures, such as high 3He/4He ratios, deep low-frequency earthquakes, and hot springs with high salinity and solute concentrations. We reveal that seismicity associated with the Wakayama earthquake swarm occurs almost evenly in both time and space, and that the majority of the earthquakes in the northern part of the swarm activity occur along well-defined planes that dip to the west at 30–45°. The seismic tomography results reveal that a northwestward-dipping low-velocity zone exists beneath the Wakayama swarm and the low-velocity zone is sandwiched by high-velocity anomalies in the continental crust interpreted as impermeable and rigid materials on both sides in the subduction direction. This unique tectonic setting controls a pathway of the upward migration of slab-derived fluids to the surface, with the high fluid concentration in the dipping low-velocity zone. Therefore, we infer that the location of the Wakayama swarm is controlled by deep crustal heterogeneities rather than by the major structures of geological accretionary complexes. This study suggests that the anomalous geophysical and geochemical signatures observed across the Kii peninsula are different manifestations of the frictional and hydrological processes during the upward migration of the slab-derived fluids. We further propose that the valley-shaped geometry of the Philippine Sea slab beneath the Kii peninsula is caused by the rigid materials in the continental crust.
Graphical Abstract
In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects
Authors: Bowers Kristin M. , Wright Ellis M. , Terrones Lori D. , Sun Xiaocun , Rifkin Rebecca , Grzeskowiak Remi , Croy Elizabeth , Seddighi Reza , Kleine Stephanie , Hampton Chiara , Hecht Silke , Adair Henry S. , Anderson David E. , Mulon Pierre‐Yves 
Published: April 2023

AbstractPurposeLocking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long‐term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon‐selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture.MethodsIn vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months.ResultsIn vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability.ConclusionsThis study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate‐to‐tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.