bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone healing study of alendronate combined with enoxaparin sodium bone cement in rabbits with bone defects
Authors: Xiao Zhihang , Fu Dehao , Zhang Li , Fan Weiye , Shen Xiaoyu , Qi Xiangbei 
Published: September 2022

Abstract
Background
To observe the effect of enoxaparin sodium-polymethyl methacrylate (ES-PMMA) bone cement supplemented with alendronate (AN) on bone repair of bone defects in New Zealand rabbits.

Methods
Twenty-seven New Zealand rabbits were randomly divided into ES/AN, ES-PMMA and PMMA groups, with a total of 27 New Zealand rabbits. The drugs loaded in 40 g bone cement powder were as follows: ES/AN group 8000 AxaIU enoxaparin (ES) and 200 mg alendronate (AN), ES-PMMA group 8000 AxaIU enoxaparin (ES), PMMA group without drugs. A bone defect model with a length of 10 mm and a diameter of 5 mm was made from the left tibia of rabbits, and the prepared bone cement was placed in the tibia defect. At 4 weeks, 8 weeks and 12 weeks after the operation, 3 rabbits in each group were sacrificed, and left tibia samples were collected for histological scoring, HE staining and Masson staining. Bone mineral density and new bone volume were measured by imaging, and the related data were processed by one-way ANOVA and least significance difference (LSD) post hoc test.

Results
(1) Bone mineral density (BMD, mg/mm3) around the bone defect: at the 4th week, BMD in the ES/AN group was higher than that in the PMMA group; at the 8th week, the BMD in the ES/AN group was significantly higher than that in the other two groups; and at the 12th week, the BMD in the ES/AN group was significantly higher than that in the other two groups. (2) New bone volume (BV, mm3): at the 4th week, BV in the ES/AN group was significantly higher than that in the other two groups, BV in the ES/AN group was significantly higher than that in the other two groups at the 8th and 12th weeks, and BV in the ES-PMMA group was higher than that in the PMMA group. (3) Histological score: at the 4th and 8th weeks, the histological score of the ES/AN group was higher than that of the PMMA group, and at the 12th week, the histological score of the ES/AN group was higher than that of the other two groups. (4) Cortical bone thickness (μm): at the 4th, 8th and 12th weeks, the cortical bone thickness in the ES/AN group was higher than that in the other two groups, and the cortical bone thickness in the ES-PMMA group was higher than that in the PMMA group. (5) The percentage of mature area of new bone in the ES/AN group was higher than that in the other two groups at the 4th week, and at the 8th and 12th weeks, the percentage of mature area of new bone in the ES/AN group and ES-PMMA group was significantly higher than that in the PMMA group.

Conclusion
(1) Enoxaparin sodium bone cement supplemented with alendronate was superior to enoxaparin sodium bone cement and PMMA bone cement in promoting bone repair of tibial bone defects in New Zealand rabbits. (2) Enoxaparin sodium bone cement is superior to PMMA bone cement in promoting bone repair, showing a certain osteogenic potential.
Impact of hyperbilirubinemia associated acute kidney injury on chronic kidney disease after aortic arch surgery: a retrospective study with follow-up of 1-year
Authors: Lyu Lin , Song Haicheng , Gao Guodong , Dong He , Liao Pingping , Shen Ziying , Liu Hui , Chu Haichen , Yuan Li 
Published: September 2022

Abstract
Background
Hyperbilirubinemia (HB) is a serious complication in aortic arch surgery, which is associated with acute kidney injury (AKI). The association between HB and chronic kidney disease (CKD) is unknown. The aim of this study was to investigate the impact of HB associated AKI on CKD after aortic arch surgery.

Methods
We reviewed 284 patients who underwent aortic arch surgery from 2016 to 2020 in our hospital. AKI was defined as a 50% increase in sCr from baseline value within the first 7 postoperative days. HB was defined as total bilirubin > 51.3 μmol/L. Patients were divided into 3 groups based on AKI and HB: HB associated AKI (HB-AKI) group (AKI patients suffered HB within the first 7 postoperative days); AKI without HB group and Non-AKI group.

Results
Follow-up for 204 patients ranged from 3 to 12 months. Kaplan–Meier analysis showed that the 1-year cumulative incidence of CKD was highest in HB-AKI (32.6%) than AKI without HB (17.8%) and Non-AKI (7.4%, log-rank test, p < 0.001), and the incidence of CKD was higher in HB group than that in Non-HB group (26.7% vs. 13.9%, log-rank test, p = 0.015). Preoperative sCr (HR 1.010, 95% CI 1.004–1.016, p = 0.001), AKI without HB (HR 2.887, 95% CI 1.133–7.354, p = 0.026) and HB-AKI (HR 4.490, 95% CI 1.59–12.933, p = 0.005) were associated with CKD during 1-year follow-up.

Conclusions
Patients suffering HB associated AKI were at more increased odds of CKD than patients suffering AKI without HB after aortic arch surgery.
Polygenic risk modeling of tumor stage and survival in bladder cancer
Authors: Nascimben Mauro , Rimondini Lia , Corà Davide , Venturin Manolo 
Published: September 2022

Abstract
Introduction
Bladder cancer assessment with non-invasive gene expression signatures facilitates the detection of patients at risk and surveillance of their status, bypassing the discomforts given by cystoscopy. To achieve accurate cancer estimation, analysis pipelines for gene expression data (GED) may integrate a sequence of several machine learning and bio-statistical techniques to model complex characteristics of pathological patterns.

Methods
Numerical experiments tested the combination of GED preprocessing by discretization with tree ensemble embeddings and nonlinear dimensionality reductions to categorize oncological patients comprehensively. Modeling aimed to identify tumor stage and distinguish survival outcomes in two situations: complete and partial data embedding. This latter experimental condition simulates the addition of new patients to an existing model for rapid monitoring of disease progression. Machine learning procedures were employed to identify the most relevant genes involved in patient prognosis and test the performance of preprocessed GED compared to untransformed data in predicting patient conditions.

Results
Data embedding paired with dimensionality reduction produced prognostic maps with well-defined clusters of patients, suitable for medical decision support. A second experiment simulated the addition of new patients to an existing model (partial data embedding): Uniform Manifold Approximation and Projection (UMAP) methodology with uniform data discretization led to better outcomes than other analyzed pipelines. Further exploration of parameter space for UMAP and t-distributed stochastic neighbor embedding (t-SNE) underlined the importance of tuning a higher number of parameters for UMAP rather than t-SNE. Moreover, two different machine learning experiments identified a group of genes valuable for partitioning patients (gene relevance analysis) and showed the higher precision obtained by preprocessed data in predicting tumor outcomes for cancer stage and survival rate (six classes prediction).

Conclusions
The present investigation proposed new analysis pipelines for disease outcome modeling from bladder cancer-related biomarkers. Complete and partial data embedding experiments suggested that pipelines employing UMAP had a more accurate predictive ability, supporting the recent literature trends on this methodology. However, it was also found that several UMAP parameters influence experimental results, therefore deriving a recommendation for researchers to pay attention to this aspect of the UMAP technique. Machine learning procedures further demonstrated the effectiveness of the proposed preprocessing in predicting patients’ conditions and determined a sub-group of biomarkers significant for forecasting bladder cancer prognosis.
Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression
Authors: Wang Kun , Dai Xiaoyong , Yu Albert , Feng Chunyan , Liu Kewei , Huang Laiqiang 
Published: September 2022

Abstract
Background
Peptide proteolysis-targeting chimeras (p-PROTACs) with advantages of high specificity and low toxicity have emerged as a powerful technology of targeted protein degradation for biomedical applications. FOXM1, a proliferation-associated transcription factor, is overexpressed in a variety of human tumors as a key driver of tumorigenesis and cancer progression, and is a potential anticancer therapeutic target. However, FOXM1-targeting p-PROTACs has not been researched.

Methods
Here, we first analyzed the expression of FOXM1, GLUT1 and PD-L1 in liver cancer through database and clinical samples of patients. FOXM1-targeting peptides, selected by screening phage display library, are verified its targeting effect by immunofluorescence and CCK-8 test. The novel p-PROTAC degrader of FOXM1 is chemically synthesis, named FOXM1-PROTAC, by linking a FOXM1-binding antagonistic peptide, with the E3 ubiquitin ligase recruitment ligand Pomalidomide and with the cell membrane penetrating peptide TAT. Its degradation effect on FOXM1 was detected by Western blotting, qPCR, and we verified its effect on the behavior of cancer cells by flow cytometry, scratch assay, and Transwell in vitro. The tumor xenografted mice model was used for evaluating FOXM1-PROTAC therapeutic response in vivo. Finally, we detected the expression of GLUT1 and PD-L1 after FOXM1-PROTAC degraded FOXM1 by using Western Blotting and hippocampal detectors and dual immunofluorescence.

Results
We found that the novel FOXM1-PROTAC efficiently entered cells and induced degradation of FOXM1 protein, which strongly inhibits viability as well as migration and invasion in various cancer cell lines, and suppressed tumor growth in HepG2 and MDA-MB-231 cells xenograft mouse models, without detected toxicity in normal tissues. Meanwhile, FOXM1-PROTAC decreased the cancer cells glucose metabolism via downregulating the protein expression levels of glucose transporter GLUT1 and the immune checkpoint PD-L1, which suggests involvement of FOXM1 in cancer cell metabolism and immune regulation.

Conclusions
Our results indicate that biologically targeted degradation of FOXM1 is an attractive therapeutic strategy, and antagonist peptide-containing FOXM1-PROTACs as both degrader and inhibitor of FOXM1 could be developed as a safe and promising drug for FOXM1-overexpressed cancer therapy.
LncRNA FAM83H-AS1 promotes the malignant progression of pancreatic ductal adenocarcinoma by stabilizing FAM83H mRNA to protect β-catenin from degradation
Authors: Zhou Min , Pan Shutao , Qin Tingting , Zhao Chunle , Yin Taoyuan , Gao Yang , Liu Yuhui , Zhang Zhenxiong , Shi Yongkang , Bai Yu , Gong Jun , Guo Xingjun , Wang Min , Qin Renyi 
Published: September 2022

Abstract
Background
Pancreatic ductal adenocarcinoma is prone to metastasis, resulting in short survival and low quality of life. LncRNAs are pivotal orchestrators that participate in various tumor progress. The underlying role and mechanism of lncRNA FAM83H-AS1 is still unknown in PDAC progression.

Methods
To address this issue, firstly, we profiled and analyzed the aberrant lncRNA expression in TCGA database and identified FAM83H-AS1 as the most effective one in promoting the migration of pancreatic cancer cells. Then, the expression levels of FAM83H-AS1 in patient’s serum, tumor tissues and PDAC cells were detected using RT-qPCR, and FAM83H-AS1 distribution in PDAC cells was determined by performing FISH and RT-qPCR. Next, a series of in vivo and in vitro functional assays were conducted to elucidate the role of FAM83H-AS1 in cell growth and metastasis in PDAC. The regulatory relationship between FAM83H-AS1 and FAM83H (the homologous gene of FAM83H-AS1) was verified by performing protein and RNA degradation assays respectively. Co-IP assays were performed to explore the potential regulatory mechanism of FAM83H to β-catenin. Rescue assays were performed to validate the regulation of the FAM83H-AS1/FAM83H/β-catenin axis in PDAC progression.

Results
FAM83H-AS1 was highly expressed in the tumor tissues and serum of patients with PDAC, and was correlated with shorter survival. FAM83H-AS1 significantly promoted the proliferation, invasion and metastasis of PDAC cells, by protecting FAM83H mRNA from degradation. Importantly, FAM83H protein manifested the similar malignant functions as that of FAM83H-AS1 in PDAC cells, and could bind to β-catenin. Specifically, FAM83H could decrease the ubiquitylation of β-catenin, and accordingly activated the effector genes of Wnt/β-catenin signaling.

Conclusions
Collectively, FAM83H-AS1 could promote FAM83H expression by stabilizing its mRNA, allowing FAM83H to decrease the ubiquitylation of β-catenin, thus resulted in an amplified FAM83H-AS1/FAM83H/β-catenin signal axis to promote PDAC progression. FAM83H-AS1 might be a novel prognostic and therapeutic target for combating PDAC.
Integrated mental health care and vocational rehabilitation intervention to improve return to work rates for people on sick leave due to common mental and functional disorders (IBBIS-II)—a study protocol for a randomized clinical trial
Authors: Christensen Thomas Nordahl , Poulsen Chalotte Heinsvig , Ebersbach Bea Kolbe , Eplov Lene Falgaard 
Published: September 2022

Abstract
Background
Mental illness has an estimated financial burden on the Danish economy of 3.4% of the gross national product every year due to lost productivity, social benefits, and healthcare costs, and approximately 50% of people receiving long-term sickness benefits have a common mental illness. Furthermore, a significant treatment gap exists where less than 30% are treated for their mental illness. The primary objective of the randomized trial is to examine whether people on sick leave with a diagnosis of anxiety, depression, stress, personality disorders, or functional disorders return to work faster and have higher job retention if they receive an integrated and optimized vocational rehabilitation and mental health care intervention, compared to people who receive the standard mental health care and vocational rehabilitation service.

Methods
The trial is designed as an investigator-initiated, randomized, two-group parallel, assessor-blinded, superior trial. A total of 900 participants with a common mental illness will randomly be assigned into two groups: (1) IBBIS-II, consisting of integrated mental health care and vocational rehabilitation, or (2) service as usual (SAU), at two sites in Denmark. The primary outcome is the difference between the two groups in time to return to work (RTW) at 12 months using data from the Danish Register for Evaluation of Marginalization (DREAM) database.

Discussion
This study will contribute with new knowledge on vocational recovery and integrated vocational and health care interventions in a Scandinavian context.

Trial registration
ClinicalTrials.govNCT04432129. Registered on June 16, 2020
Effectiveness of the Unified Barlow Protocol (UP) and neuropsychological treatment in cancer survivors for cognitive impairments: study protocol for a randomized controlled trial
Authors: García-Torres Francisco , Tejero-Perea Adrián , Gómez-Solís Ángel , Castillo-Mayén Rosario , Jaén-Moreno Maria José , Luque Bárbara , Gálvez-Lara Mario , Sánchez-Raya Araceli , Jablonski Marcin , Rodríguez-Alonso Beatriz , Aranda Enrique 
Published: September 2022

Abstract
Background
Cancer survivors frequently develop cognitive impairment, which negatively affects their quality of life and emotional well-being. This study compares the effectiveness of a well-established treatment (neuropsychological treatment) with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) to reduce these cognitive deficits and evaluate the effect of both treatments on anxiety-depressive symptoms and the quality of life of cancer survivors.

Methods
A three-arm, randomized superiority clinical trial with a pre-post and repeated follow-up measures intergroup design using a 1:1:1 allocation ratio will be performed. One hundred and twenty-three cancer survivors with mild to moderate cognitive impairment will be randomly assigned to one of the study interventions: a cognitive rehabilitation intervention group, an intervention group with UP intervention, or a control group on the waiting list. The primary outcome is to observe a significant improvement in cognitive function in both intervention groups and a significant decrease in emotional impairments in comparison with the waitlist group. Improvements in anxiety, depression, and quality of life are also expected as secondary outcomes. These results will be maintained at 6 months of follow-up.

Discussion
The aim of this trial is to test the efficacy of the UP intervention in reducing cognitive deficits in breast cancer survivors. The results of this trial may be useful in reducing the presence of cognitive problems in cancer survivors and improving their emotional state and quality of life.

Trial registration
ClinicalTrials.gov NCT05289258. Registered 12 March 2022, v01.
Observation on the effectiveness and safety of sodium bicarbonate Ringer’s solution in the early resuscitation of traumatic hemorrhagic shock: a clinical single-center prospective randomized controlled trial
Authors: Zhang Jizhe , Han Dong , Zhang Kun , Guan Weiqiang , Li Li , Gu Zhengtao 
Published: September 2022

Abstract
Background
Traumatic hemorrhagic shock (THS) is the main cause of death in trauma patients with high mortality. Rapid control of the source of bleeding and early resuscitation are crucial to clinical treatment. Guidelines recommend isotonic crystal resuscitation when blood products are not immediately available. However, the selection of isotonic crystals has been controversial. Sodium bicarbonate Ringer solutions (BRS), containing sodium bicarbonate, electrolyte levels, and osmotic pressures closer to plasma, are ideal. Therefore, in this study, we will focus on the effects of BRS on the first 6 h of resuscitation, complications, and 7-day survival in patients with THS.

Methods
/design.
This single-center, prospective, randomized controlled trial will focus on the efficacy and safety of BRS in early THS resuscitation. A total of 400 adults THS patients will be enrolled in this study. In addition to providing standard care, enrolled patients will be randomized in a 1:1 ratio to receive resuscitation with BRS (test group) or sodium lactate Ringer’s solution (control group) until successful resuscitation from THS. Lactate clearance at different time points (0.5, 1, 1.5, 3, and 6 h) and shock duration after drug administration will be compared between the two groups as primary end points. Secondary end points will compare coagulation function, temperature, acidosis, inflammatory mediator levels, recurrence of shock, complications, medication use, and 7-day mortality between the two groups. Patients will be followed up until discharge or 7 days after discharge.

Discussion
At present, there are still great differences in the selection of resuscitation fluids, and there is a lack of systematic and detailed studies to compare and observe the effects of various resuscitation fluids on the effectiveness and safety of early resuscitation in THS patients. This trial will provide important clinical data for resuscitation fluid selection and exploration of safe dose of BRS in THS patients.
Trial registration.
Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100045044. Registered on 4 April 2021.
Fusarium proliferatum-induced chronic lip ulcer: successful treatment with itraconazole: a case report
Authors: Mohaghegh Fatemeh , Abtahi-Naeini Bahareh , Nasri Elahe , Badiee Parisa , Morovati Hamid , Fakhim Hamed , Farmani Aida , Meidani Mohsen , Ranjbar-Mobarake Maryam , Mohammadi Rasoul 
Published: September 2022

Abstract
Background
Fusarium species are saprophytic fungi with a worldwide distribution. These fungi cause various infections among immunocompromised patients; however, they can also involve immunocompetent individuals.

Case presentation
We report a case of a 41-year-old Iranian woman who presented with ulcerative lesions on her lips 10 months ago. She had a long history of anxiety but had no history of classical risk factors such as trauma, cosmetic lip tattoo, burning in her lips, smoking or use of alcohol and opium. A skin biopsy from the lower lip was performed and sent for microbiological examinations. Hyaline septate hyphae were seen on direct microscopy with potassium hydroxide. The clinical specimen was subcultured on sabouraud dextrose agar with chloramphenicol and prepared for antifungal susceptibility testing and molecular identification. Considering the minimum inhibitory concentrations (MIC) for antifungals, itraconazole (100 mg orally twice a day) was started for her, and after 2 months, the lesions were treated. She followed up for 3 months, and no signs of disease recurrence were observed.

Conclusions
Selecting an appropriate treatment strategy according to the laboratory assessments is essential in clinical practice and the management of rare infections to prevent related mortality and morbidity of opportunistic fungal infections.
Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption
Authors: Zeng Li , He Hong , Sun Mingjie , Gong Xinyi , Zhou Mengqi , Hong Yaya , Wu Yongjia , Chen Xuepeng , Chen Qianming 
Published: September 2022

AbstractDental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt‐related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.