bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a droplet digital PCR method for detection of porcine circovirus 4
Authors: Liu Yangkun , Zhang Xinru , Han Xueying , Liu Jiaxing , Yao Lunguang 
Published: August 2023

Abstract
Background
Porcine circovirus 4 (PCV4), a newly emerging virus that was first discovered in 2019, may pose a potential threat to the pig industry. Droplet digital PCR (ddPCR) is an absolute quantitative method that has high sensitivity and accuracy. In this study, we developed a novel ddPCR assay to detect PCV4. Furthermore, we evaluated the detection limit, sensitivity, specificity and reproducibility of the ddPCR and TaqMan real-time quantitative PCR (qPCR) and tested 160 clinical samples to compare the detection rate of the two methods.

Results
The detection limit for ddPCR was 0.54 copies/µL, 10.6 times greater sensitivity than qPCR. Both ddPCR and qPCR assays exhibited good linearity and repeatability, and the established ddPCR method was highly specific for PCV4. The results of clinical sample testing showed that the positivity rate of ddPCR (5.6%) was higher than that of qPCR (4.4%).

Conclusions
This study successfully developed a sensitive, specific and repeatable ddPCR assay for PCV4 detection, which can be widely used in clinical diagnosis of PCV4 infections.
ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification
Authors: Wang Chia-Wen , Chuang Huai-Chia , Tan Tse-Hua 
Published: August 2023

AbstractAngiotensin-converting enzyme 2 (ACE2), a counter regulator of the renin-angiotensin system, provides protection against several chronic diseases. Besides chronic diseases, ACE2 is the host receptor for SARS-CoV or SARS-CoV-2 virus, mediating the first step of virus infection. ACE2 levels are regulated by transcriptional, post-transcriptional, and post-translational regulation or modification. ACE2 transcription is enhanced by transcription factors including Ikaros, HNFs, GATA6, STAT3 or SIRT1, whereas ACE2 transcription is reduced by the transcription factor Brg1-FoxM1 complex or ERRα. ACE2 levels are also regulated by histone modification or miRNA-induced destabilization. The protein kinase AMPK, CK1α, or MAP4K3 phosphorylates ACE2 protein and induces ACE2 protein levels by decreasing its ubiquitination. The ubiquitination of ACE2 is induced by the E3 ubiquitin ligase MDM2 or UBR4 and decreased by the deubiquitinase UCHL1 or USP50. ACE2 protein levels are also increased by the E3 ligase PIAS4-mediated SUMOylation or the methyltransferase PRMT5-mediated ACE2 methylation, whereas ACE2 protein levels are decreased by AP2-mediated lysosomal degradation. ACE2 is downregulated in several human chronic diseases like diabetes, hypertension, or lung injury. In contrast, SARS-CoV-2 upregulates ACE2 levels, enhancing host cell susceptibility to virus infection. Moreover, soluble ACE2 protein and exosomal ACE2 protein facilitate SARS-CoV-2 infection into host cells. In this review, we summarize the gene regulation and post-translational modification of ACE2 in chronic disease and COVID-19. Understanding the regulation and modification of ACE2 may help to develop prevention or treatment strategies for ACE2-mediated diseases.
Docetaxel-loaded pH/ROS dual-responsive nanoparticles with self-supplied ROS for inhibiting metastasis and enhancing immunotherapy of breast cancer
Authors: Wang Yu , Wang Qianmei , Wang Xiaowen , Yao Pu , Dai Qing , Qi Xiaowei , Yang Ming , Zhang Xiao , Huang Rong , Yang Jing , Wang Qian , Xia Peiyuan , Zhang Dinglin , Sun Fengjun 
Published: August 2023

Abstract
Background
Although stimuli-responsive nanoplatforms were developed to deliver immunogenic cell death (ICD) inducers to enhance cancer immunotherapy, the complete release of ICD inducers into the tumor microenvironment (TME) was limited by the inadequate supplementation of endogenous stimulus (e.g., reactive oxygen species (ROS)). To address this issue, we synthesized a self-responsive nanomaterial with self-supplied ROS, which mainly consists of a ROS responsive moiety HPAP and cinnamaldehyde (CA) as the ROS-generating agent. The endogenous ROS can accelerate the degradation of HPAP in materials to release docetaxel (DTX, an ICD inducer). In intracellular acidic environment, the pH-sensitive acetal was cleaved to release CA. The released CA in turn induces the generation of more ROS through mitochondrial damage, resulting in amplified DTX release. Using this self-cycling and self-responsive nanomaterial as a carrier, DTX-loaded pH/ROS dual-responsive nanoparticles (DTX/FA-CA-Oxi-αCD NPs) were fabricated and evaluated in vitro and in vivo.

Results
In vitro experiments validated that the NPs could be effectively internalized by FA-overexpressed cells and completely release DTX in acidic and ROS microenvironments to induce ICD effect. These NPs significantly blocked 4T1 cell migration and decreased cell invasion. In vivo experiments demonstrated that the tumor-targeted NPs significantly inhibited tumor growth and blocked tumor metastasis. More importantly, these NPs significantly improved immunotherapy through triggering effector T-cell activation and relieving the immunosuppressive state of the TME.

Conclusions
Our results demonstrated that DTX/FA-CA-Oxi-αCD NPs displayed great potential in preventing tumor metastasis, inhibiting tumor growth, and improving the efficacy of anti-PD-1antibody.

Graphical Abstract
The influence of SYRIZA-ANEL Greek health policies on hospital efficiency
Authors: Farantos Georgios I. , Koutsoukis Nikitas-Spiros 
Published: August 2023

Abstract
Background
We analyse the impact of the three following categories of Health Policies (HP) carried out by the Greek SYRIZA-ANEL governments on the efficiency of Greek public general hospitals. These governments have implemented policies intended to change the rate of contributions to publicly funded healthcare (PCnH), policies to affect the volume and quality of publicly funded health care (PVQH) and those intended to affect the costs of publicly funded healthcare (PCH). A literary review of the PCnH. PVQH and PCH policies of the Greek SYRIZA-ANEL governments was carried out and an efficiency window-DEA study was executed using data from the Ministry of Health (MoH) and the Greek Statistical Authority (ELSTAT).

Methods
The study was designed to assess the impact of PCnH. PVQH and PCH policies by the Greek SYRIZA-ANEL governments on the efficiency of Greek general hospitals. The data was collected from HEAL-Link scientific journals. Information on HPs was extracted from the work collected. The values of inputs and outputs used for the efficiency study were obtained from ELSTAT and Greek MoH databases.

Results
HPs of the Greek SYRIZA-ANEL governments extend to all three HP categories of the sample used. These policies have a dual effect on both the inputs and outputs used in efficiency. Efficiency values exhibit fluctuations with good and bad years. The SYRIZA-ANEL governments seek to ensure more equality in access to health services. Some of the policies reduce costs and have a positive impact on efficiency, while others have the opposite effect. The increase in outputs achieved as a result of health policies is counter balanced by an increase in inputs.

Conclusions
The PCnH, PVQH and PCH policies of the SYRIZA-ANEL governance seem to have a dual orientation: some policies reduce the cost of a category and contain the total cost, thus positively contributing to an increase in efficiency. Certain policies are aimed more at fulfilling the criterion of equality in the provision of health services and thus the cost inevitably increases. From the window-DEA study, three relatively “good” years emerge (2015, 2016, 2018) and two “bad years” (2017, 2019). This analysis will be useful for further research on the effect of health policies on hospital efficiency in other countries and periods.
Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma
Authors: Dall’Olmo Luigi , Papa Nicole , Surdo Nicoletta Concetta , Marigo Ilaria , Mocellin Simone 
Published: August 2023

AbstractAlpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their tissue specific expression and involvement in melanocyte homeostasis. However, their role in prevention and treatment of melanoma is still debated and controversial. Although a large body of evidence supports α-MSH in preventing melanoma development, some preclinical findings suggest that the α-MSH downstream signalling may promote immune escape and cancer resistance to therapy. Additionally, in metastatic melanoma both MC1R and α-MSH have been reported to be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition in BRAFV600E mutant tumours) has been shown to enhance this phenomenon. Collectively, these data suggest that targeting MC1R could serve as an approach in the treatment of metastatic melanoma. In this review, we explore the molecular biology of α-MSH with particular emphasis into its tumor-related properties, whilst elaborating the experimental evidence currently available regarding the interplay between α-MSH/MC1R axis, melanoma and antitumor strategies.
Primate TRIM34 is a broadly-acting, TRIM5-dependent lentiviral restriction factor
Authors: Twentyman Joy , Khalifeh Anthony , Felton Abby L. , Emerman Michael , Ohainle Molly 
Published: August 2023

AbstractHuman immunodeficiency virus (HIV) and other lentiviruses adapt to new hosts by evolving to evade host-specific innate immune proteins that differ in sequence and often viral recognition between host species. Understanding how these host antiviral proteins, called restriction factors, constrain lentivirus replication and transmission is key to understanding the emergence of pandemic viruses like HIV-1. Human TRIM34, a paralogue of the well-characterized lentiviral restriction factor TRIM5α, was previously identified by our lab via CRISPR-Cas9 screening as a restriction factor of certain HIV and SIV capsids. Here, we show that diverse primate TRIM34 orthologues from non-human primates can restrict a range of Simian Immunodeficiency Virus (SIV) capsids including SIVAGM−SAB, SIVAGM−TAN and SIVMAC capsids, which infect sabaeus monkeys, tantalus monkeys, and rhesus macaques, respectively. All primate TRIM34 orthologues tested, regardless of species of origin, were able to restrict this same subset of viral capsids. However, in all cases, this restriction also required the presence of TRIM5α. We demonstrate that TRIM5α is necessary, but not sufficient, for restriction of these capsids, and that human TRIM5α functionally interacts with TRIM34 from different species. Finally, we find that both the TRIM5α SPRY v1 loop and the TRIM34 SPRY domain are essential for TRIM34-mediated restriction. These data support a model in which TRIM34 is a broadly-conserved primate lentiviral restriction factor that acts in tandem with TRIM5α, such that together, these proteins can restrict capsids that neither can restrict alone.
Nasal cavity perforation by implant fixtures: case series with emphasis on panoramic imaging of nasal cavity extending posteriorly
Authors: Yeom Han-Gyeol , Huh Kyung-Hoe , Yi Won-Jin , Heo Min-Suk , Lee Sam-Sun , Choi Soon-Chul , Kim Jo-Eun 
Published: August 2023

AbstractThe nasal cavity is an important landmark when considering implant insertion into the anterior region of the maxillary arch. The perforation of implants into the nasal cavity may cause complications, such as implant migration, inflammation, or changes in nasal airflow; thus, precise assessment of the nasal cavity is mandatory.Three cases of nasal cavity perforation by dental implants are presented, including one case of implant fixture migration into the nasal cavity. On panoramic radiographs of the patients, the following common features were observed: the horizontal radiopaque line of the hard palate was observed to be inferior to or similar to that of the antral floor and the bone between the lateral wall of the nasal cavity and the medial wall of the maxillary sinus was emphasized in a triangular shape.When the maxillary sinus is small and alveolar bone resorption is severe, panoramic evaluation may cause overestimation of the available residual bone, particularly in the maxillary canine/premolar region. Therefore, the residual bone should be reevaluated three-dimensionally to measure the exact bony shape and volume.
Focused extracorporeal shockwave therapy for youth sports-related apophyseal injuries: case series
Authors: Shafshak Tarek , Amer Marwa Abdullah 
Published: August 2023

Abstract
Background
Apophyseal overuse injuries are self-limited with skeletal maturity; however, they may be a source of significant pain and time lost from training. There is a lack of consensus for its management with the current available treatment, which might lag behind the ongoing development of regenerative medicine. The current retrospective case study aimed to assess the potential effectiveness and short-term safety of extracorporeal shockwave therapy (ESWT) in apophyseal injuries.

Methods
Data from 22 growing athletes [15 patients with Osgood-Schlatter disease and seven patients with Sever’s disease] who received ESWT at a sports medicine unit in a university hospital were reviewed. All patients received low energy (= 0.1 mJ/mm2) level-focused ESWT using electrohydraulic generation technology. The clinical focusing technique was used upon applying ESWT.

Results
The number of sessions received to achieve full recovery ranged from 1 to 3 sessions. The time from treatment initiation to previous activity level was 2 weeks in 14 patients (63.3%), 4 weeks in seven patients (31.8%) and 11 weeks in one patient (4.5%). No adverse events were reported. No recurrence occurred up to 3 months after the last session.

Conclusion
ESWT is a potentially safe and effective treatment for apophyseal injuries. It may facilitate an early return to sport activities.
A risk prediction model for postoperative recovery of closed calcaneal fracture: a retrospective study
Authors: Li Wenjing , Wang Yan , Zhang Zenglei , Chen Wei , Lv Hongzhi , Zhang Yingze 
Published: August 2023

Abstract
Objective
To explore the risk factors for postoperative recovery of closed calcaneal fracture and develop a prediction model.

Methods
We retrospectively enrolled patients with closed calcaneal fracture from January 1, 2017 to December 31, 2020. Patients treated from 2017 to 2019 were selected as a training cohort and those in 2020 as a validation cohort. The outcome variable was the postoperative recovery evaluated by the Creighton-Nebraska calcaneal fracture scoring system. Multivariate logistic regression analysis was used to screen the risk factors of postoperative recovery. A risk prediction model was constructed in the training cohort and the corresponding nomogram was drawn. The model was validated internally using bootstrapping and externally by calculating the performance in the validation cohort.

Results
A total of 659 patients with closed calcaneal fracture met the inclusion and exclusion criteria, which were divided into the training cohort (n = 509) and the validation cohort (n = 150). 540 cases (81.9%) patients recovered well after calcaneal fracture surgery. According to multivariate logistic regression analysis, female (OR = 2.525, 95% CI 1.283–4.969), > 60 years (OR = 6.644, 95% CI 1.243–35.522), surgery within 8–14 days after fracture (OR = 2.172, 95% CI 1.259–3.745), postoperative infection (OR = 4.613, 95% CI 1.382–15.393), and weight-bearing time longer than 3 months after surgery (4–6 months, OR = 2.885, 95% CI 1.696–4.907; 7–12 months, OR = 3.030, 95% CI 1.212–7.578; > 12 months, OR = 15.589, 95% CI 3.244–74.912) were independent risk factors for postoperative recovery of calcaneal fractures. The C-indices were 0.750(95% CI 0.692–0.808) in the training cohort and 0.688(95% CI 0.571–0.804) in the external validation cohort, and the C-index of internal validation was 0.715. The Hosmer–Lemeshow test showed good fitting of the model (all P > 0.05), which was consistent with the results of the calibration plots. Decision Curve Analysis indicated that the clinical effectiveness was the best when the threshold probability was between 0.10 and 0.45.

Conclusions
Patients with female, > 60 years, surgery within 8–14 days after fracture, postoperative infection, and weight-bearing time longer than 3 months after surgery are more likely to have poor postoperative recovery. The risk prediction of fracture patients through this model might be translated into clinical guidance and application.
Trial registration This study was registered on the Chinese Clinical Trial Registry (Registration number: ChiCTR-EPR-15005878).
A biomechanical comparison of three fixation methods for unstable femoral neck fractures with medial calcar defect
Authors: Koraman Emre , Iyetin Yusuf , Ozyaman Oguzhan , Akyurek Muhlik 
Published: August 2023

Abstract
Background
Unstable femoral neck fractures with medial calcar defects are difficult to manage. The optimal fixation methods for these fractures have been a subject of ongoing debate among orthopedic surgeons. In this study, three different fixation techniques for vertical, medial defected femoral neck fractures were compared.

Methods
In this study, a biomechanical analysis was conducted to compare three fixation methods: cannulated screws (Group 1), cannulated screws combined with a medial buttress plate (Group 2), and intramedullary nails (Group 3). Synthetic composite bone models representing vertical collum femoris fractures with medial calcar defects were used. Each group consisted of seven specimens, and, to maintain consistency, a single surgeon performed the surgical procedure. Biomechanical testing involved subjecting the specimens to axial loading until failure, and the load to failure, stiffness, and displacement values were recorded. Normality was tested using the Shapiro–Wilk test. One-way ANOVA and Tukey’s HSD post hoc test were used for comparisons.

Results
The difference in the load to failure values was statistically significant among the groups, with Group 2 exhibiting the highest load to failure value, followed by Group 3 and Group 1. Stiffness values were significantly higher in Group 2 than in the other groups. Displacement values were not significantly different between the groups. Fracture and displacement patterns at the point of failure varied across the groups.

Conclusion
The results of this study indicate that fixation with a medial buttress plate in combination with cannulated screws provides additional biomechanical stability for vertical femoral neck fractures with medial calcar defects. Intramedullary nail fixation also demonstrated durable stability in these fractures. These findings can be used to better understand current management strategies for these challenging fractures to promote the identification of better evidence-based recommendations.
Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank
Authors: Cao Zhi , Min Jiahao , Tan Qilong , Si Keyi , Yang Hongxi , Xu Chenjie 
Published: August 2023

Abstract
Background
The effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features.

Methods
This prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest — dementia, stroke, and Parkinson’s disease (PD) — at enrollment (2006–2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014.

Results
During a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose–response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (β = 2.98 × 10–4, P < 0.001) and hippocampus (β = 3.37 × 10–4, P = 0.002) and smaller white matter hyperintensity (β = -3.12 × 10–3, P < 0.001).

Conclusions
Apart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.
Efficient delivery of mesenchymal stem/stromal cells to injured liver by surface PEGylation
Authors: Takayama Yukiya , Kusamori Kosuke , Katsurada Yuri , Obana Shu , Itakura Shoko , Nishikawa Makiya 
Published: August 2023

Abstract
Background
Mesenchymal stem/stromal cells (MSCs) have been used in clinical trials for various diseases. These have certain notable functions such as homing to inflammation sites, tissue repair, and immune regulation. In many pre-clinical studies, MSCs administered into peripheral veins demonstrated effective therapeutic outcomes. However, most of the intravenously administered MSCs were entrapped in the lung, and homing to target sites was less than 1%. This occurred mainly because of the adhesion of MSCs to vascular endothelial cells in the lung. To prevent this adhesion, we modified the surface of MSCs with polyethylene glycol (PEG; a biocompatible polymer) using the avidin–biotin complex (ABC) method.

Methods
The surface of MSCs was modified with PEG using the ABC method. Then, the cell adhesion to mouse aortic endothelial cells and the tissue distribution of PEG-modified MSCs were evaluated. Moreover, the homing to the injured liver and therapeutic effect of PEG-modified MSCs were evaluated using carbon tetrachloride-induced acute liver failure model mice.

Results
The PEG modification significantly suppressed the adhesion of MSCs to cultured mouse aortic endothelial cells as well as the entrapment of MSCs in the lungs after intravenous injection in mice. PEG-modified MSCs efficiently homed to the injured liver of carbon tetrachloride-induced acute liver failure model mice. More importantly, the cells significantly suppressed serum transaminase levels and leukocyte infiltration into the injured liver.

Conclusion
These results indicate that PEG modification to the surface of MSCs can suppress the lung entrapment of intravenously administered MSCs and improve their homing to the injured liver.

Graphical Abstract