bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining rib fracture age from CT scans with a radiomics-based combined model: a multicenter retrospective study
Authors: Tang Yilin , Jin Liang , Ji Wenbin , Ma Zhuangxuan , Li Dechun , Hong Wei , Li Ming 
Published: December 2023

Abstract
Objectives
We aimed to develop a combined model based on clinical and radiomic features to classify fracture age.

Methods
We included 1219 rib fractures from 239 patients from our center between March 2016 and September 2022. We created an external dataset using 120 rib fractures from 32 patients from another center between October 2019 and August 2023. According to tasks (fracture age between < 3 and ≥ 3 weeks, 3–12, and > 12 weeks), the internal dataset was randomly divided into training and internal test sets. A radiomic model was built using radiomic features. A combined model was constructed using clinical features and radiomic signatures by multivariate logistic regression, visualized as a nomogram. Internal and external test sets were used to validate model performance.

Results
For classifying fracture age between < 3 and ≥ 3 weeks, the combined model had higher areas under the curve (AUCs) than the radiomic model in the training set (0.915 vs 0.900, p = 0.009), internal test (0.897 vs 0.854, p < 0.001), and external test sets (0.881 vs 0.811, p = 0.003). For classifying fracture age between 3–12 and > 12 weeks, the combined model had higher AUCs than the radiomic model in the training model (0.848 vs 0.837, p = 0.12) and internal test sets (0.818 vs 0.793, p < 0.003). In the external test set, the AUC of the nomogram-assisted radiologist was 0.966.

Conclusion
The combined radiomic and clinical model showed good performance and has the potential to assist in the classification of rib fracture age. This will be beneficial for clinical practice and forensic decision-making.

Critical relevance statement
This study describes the development of a combined radiomic and clinical model with good performance in the classification of the age of rib fractures, with potential clinical and forensic applications.

Key points
• Complex factors make it difficult to determine the age of a fracture.
• Our model based on radiomic features performed well in classifying fracture age.
• Associating the radiomic features with clinical features improved the model’s performance.

Graphical Abstract
Quantification and significance of extraprostatic findings on prostate MRI: a retrospective analysis and three-tier classification
Authors: Wagnerova Monika , Macova Iva , Hanus Petr , Jurka Martin , Capoun Otakar , Lambert Lukas , Burgetova Andrea 
Published: December 2023

Abstract
Objectives
To quantify extraprostatic findings (EPFs) on prostate MRI, estimate the proportion of reported and unreported EPFs, assess their clinical importance, and propose standardized reporting of EPFs.

Materials and methods
Prostate 3-T MRI studies, reports, and clinical data from 623 patients (age 67.9 ± 8.2 years) were retrospectively analyzed and re-evaluated for the presence of EPFs and their clinical significance: E1—no finding or findings that have no clinical significance; E2—potentially significant findings; and E3—significant findings.

Results
Secondary reading identified 1236 EPFs in 593 patients (1.98 ± 1.13 EPFs per patient, no EPFs in 30 patients), from which 468 (37.8%) were mentioned in the original report. The most common findings included diverticulosis (44% of patients), hydrocele (34%), inguinal fat hernia (16%), and bladder wall trabecular hypertrophy (15%). There were 80 (6.5%) E2 EPFs and 30 (2.4%) E3 EPFs. From E3 EPFs, 10 (33%) were not originally reported. A workup was suggested in 35 (52%) of the 67 originally reported E2 and E3 findings with follow-up and performed in 20 (30%). Fourteen (21%) EPFs in 11 patients influenced their management. Four experienced radiologists originally reported 1.8 to 2.5 findings per patient (p < 0.0001).

Conclusions
EPFs on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. Only 30% of E2 and E3 findings are further explored, and 21% influence patient management. We suggest that an “E” category should be attached to the PI-RADS system to identify the presence of EPFs that require further workup.

Critical relevance statement
Extraprostatic findings on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. We advocate standardized reporting of extraprostatic findings indicating their clinical significance.

Key points
• Extraprostatic findings on prostate MRI are frequent with an average of two findings per patient.
• 2.4% of extraprostatic findings are significant, and 33% of these are not reported.
• There is a significant variability among experienced radiologists in reporting extraprostatic findings.

Graphical Abstract
Successful full-term pregnancy after preterm event in a liver transplant patient: a case report
Authors: Galsone Ramona , Vītiņa Sandra , Jansone Maira , Staka Aiga , Mohammadian Reza 
Published: December 2023

Abstract
Background
Pregnancy after liver transplantation poses a significant challenge to both the patient and the transplant team.

Case presentation
We present the case of a 19-year-old European patient who underwent liver transplantation 5 years previously owing to autoimmune hepatitis. Poor compliance with immunosuppressive therapy and missed follow-up visits during the patient’s first pregnancy likely contributed to her liver function deterioration, hospitalization, and failed pregnancy. Owing to the patient’s complex medical history, combined immunosuppressive treatment, and risks to the fetus, her second pregnancy was high risk. However, close outpatient monitoring and adherence to treatment led to a successful, uneventful, full-term pregnancy and healthy delivery.

Conclusion
Liver transplant recipients who desire to become pregnant require careful planning and management to ensure optimal outcomes for both the mother and the fetus. A personalized strategy is necessary to balance the potential benefits of childbirth with the risks involved in pregnancy after liver transplantation.
Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury
Authors: Faria João , Calcat-i-Cervera Sandra , Skovronova Renata , Broeksma Bonnie C. , Berends Alinda J. , Zaal Esther A. , Bussolati Benedetta , O’Brien Timothy , Mihăilă Silvia M. , Masereeuw Rosalinde 
Published: December 2023

Abstract
Background
Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown.

Methods
In this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-d-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics.

Results
Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40–50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.

Conclusion
Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.
A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment
Authors: Hoseinzadeh Akram , Mahmoudi Mahmoud , Rafatpanah Houshang , Rezaieyazdi Zahra , Tavakol Afshari Jalil , Hosseini Sara , Esmaeili Seyed-Alireza 
Published: December 2023

Abstract
Background
Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease.

Methods
Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons.

Results
Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation.

Conclusions
Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties.

Graphical abstract
Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells
Authors: Rifes Pedro , Isaksson Marc , Rusimbi Charlotte , Ramón Santonja Adrián , Nelander Jenny , Laurell Thomas , Kirkeby Agnete 
Published: December 2023

AbstractBackgroundVentral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic (DA) neurons with functionality relevant for cell replacement in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing.MethodsWe performed shotgun proteomics on cell culture supernatants from rostral and caudal VM progenitor cells to search for novel secreted biomarkers specific to DA progenitors from the caudal VM. Key hits were validated by qRT-PCR and ELISA.ResultsWe identified and validated novel secreted markers enriched in caudal VM progenitor cultures (CPE, LGI1 and PDGFC), and found these markers to correlate strongly with the expression ofEN1, which is a predictive marker for successful graft outcome in DA cell transplantation products. Other markers (CNTN2 and CORIN) were found to conversely be enriched in the non-dopaminergic rostral VM cultures. Key novel ELISA markers were further validated on supernatant samples from GMP-manufactured caudal VM batches.ConclusionAs a non-invasive in-process quality control test for predicting correctly patterned batches of caudal VM DA cells during clinical manufacturing, we propose a dual ELISA panel measuring LGI1/CORIN ratios around day 16 of differentiation.
A 3D “sandwich” co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro
Authors: Xu Junjun , Zhang Linye , Ye Zihui , Chang Binwen , Tu Zheng , Du Xuguang , Wen Xi , Teng Yili 
Published: December 2023

Abstract
Background
Various methods for ex utero culture systems have been explored. However, limitations remain regarding the in vitro culture platforms used before implanting mouse embryos and the normal development of mouse blastocysts in vitro. Furthermore, vascular niche support during mouse embryo development from embryonic day (E) 3.5 to E7.5 is unknown in vitro.

Methods
This study established a three-dimensional (3D) “sandwich” vascular niche culture system with in vitro culture medium (IVCM) using human placenta perivascular stem cells (hPPSCs) and human umbilical vein endothelial cells (hUVECs) as supportive cells (which were seeded into the bottom layer of Matrigel) to test mouse embryos from E3.5 to E7.5 in vitro. The development rates and greatest diameters of mouse embryos from E3.5 to E7.5 were quantitatively determined using SPSS software statistics. Pluripotent markers and embryo transplantation were used to monitor mouse embryo quality and function in vivo.

Results
Embryos in the IVCM + Cells (hPPSCs + hUVECs) group showed higher development rates and greater diameters at each stage than those in the IVCM group. Embryos in the IVCM + Cells group cultured to E5.5 morphologically resembled natural egg cylinders and expressed specific embryonic cell markers, including Oct4 and Nanog. These features were similar to those of embryos developed in vivo. After transplantation, the embryos were re-implanted in the internal uterus and continued to develop to a particular stage.

Conclusions
The 3D in vitro culture system enabled embryo development from E3.5 to E7.5, and the vascularization microenvironment constructed by Matrigel, hPPSCs, and hUVECs significantly promoted the development of implanted embryos. This system allowed us to further study the physical and molecular mechanisms of embryo implantation in vitro.
The application of nanoparticles in theranostic systems targeting breast cancer stem cells: current progress and future challenges
Authors: Lin Xinyu , Wang Ying , Fang Kai , Guo Zijian , Lin Nan , Li Lihua 
Published: December 2023

AbstractBreast cancer (BC) is one of the diseases with the highest female mortality rates in the world and is closely related to breast cancer stem cells (BCSCs). Conventional breast cancer chemotherapy drugs target noncancer stem cells (non-CSCs), while cancer stem cells (CSCs) can still survive, which is an important reason for breast cancer drug resistance and local recurrence or distant metastasis. How to eradicate BCSCs while killing BCs is the key factor to improve the effect, and it is also an important scientific problem to be solved urgently. Therefore, targeted BCSC therapy has become a research hotspot. Interestingly, the emergence of nanotechnology provides a new idea for targeting BCSCs. This study summarizes the current application status of nanomaterials in targeting BCSCs, and attempts to construct a new type of lipid nanoparticle (LNP) that can target BCSCs through mRNA, providing a new idea for the treatment of BC.
COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes
Authors: Jiang Mengqi , Song Yuanxiu , Chen Xi , Lu Wenjing , Zhu Min , Wei Mingyu , Lan Feng , Cui Ming , Bai Yun 
Published: December 2023

AbstractBackgroundCardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism.MethodsA human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes.ResultsCOX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model.ConclusionsWe have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.
Healthcare workers’ compliance with the catheter associated urinary tract infection prevention guidelines: an observational study in Yemen
Authors: Al-Sayaghi Khaled Mohammed , Alqalah Talal Ali Hussein , Alkubati Sameer Abdulmalik , Alshoabi Sultan Abdulwadoud , Alsabri Mohammed , Alrubaiee Gamil Ghaleb , Almoliky Mokhtar Abdo , Saleh Khalil A. , Al-Sayaghi Anas Khaled , Elshatarat Rami A. , Saleh Zyad T. , Saleh Ahmad Mahmoud , Abdel-Aziz Hassanat Ramadan 
Published: December 2023

Abstract
Background
Catheter-associated urinary tract infection is a global problem but it can be prevented with the appropriate implementation of evidence-based guidelines. This study was conducted to assess the level of compliance of healthcare workers with the catheter-associated urinary tract infection prevention guidelines during the insertion of a urinary catheter.

Methods
An observational study using a descriptive cross-sectional design was conducted at Sana’a City hospitals, Yemen. All the nurses and physicians from the governmental, teaching, and private hospitals were eligible to participate in the study. The data collection was performed through convenience sampling from March 2020 to December 2020, using a structured observational checklist prepared specifically for this study.

Results
The majority of the urinary catheter insertions were performed by nurses. There were no written policy or procedures for an urinary catheter insertion and no in-service education or training departments in the majority of the hospitals. The overall mean score of compliance was 7.31 of 10. About 71% of the healthcare workers had a high or acceptable level of compliance and 29% had an unsafe level of compliance. Compliance was low for maintaining aseptic technique throughout the insertion procedure, using a single use packet of lubricant jelly, performing hand hygiene immediately before insertion, and securing the urinary catheter once inserted. Factors affecting the healthcare workers compliance were gender, the working ward/unit of the healthcare workers, the availability of a written policy/procedure and a department or unit for in-service education.

Conclusion
Yemeni healthcare workers’ overall compliance was acceptable but it was unsafe in several critical measures. There is an urgent need for developing, implementing, and monitoring national guidelines and institutional policy and procedures for catheter-associated urinary tract infection prevention. Periodical in-service education and training programs and adequate access to the necessary materials and supplies are paramount.
Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization
Authors: Zhang Haitao , Xu Chuanglong , Yuan Chunchun , Shi Binhao , Zhu Wenhao , Wang Hongyu , Fu Furui , Tang Dezhi , Wang Yongjun 
Published: December 2023

Abstract
Background
The causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR).

Methods
The genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries.

Results
UVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01–1.04, p = 8.03E−03) and MDD (OR 1.15, 95% CI 1.08–1.22, p = 1.38E−05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E−03) on risk of falls.

Conclusions
This study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.