bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo direct cell-penetrating peptide mediated protein transduction system in Acyrthosiphon pisum
Authors: Takenaka Aya , Konno Harutomo , Kikuta Shingo 
Published: September 2023

Abstract
Objective
The principal delivery method for CRISPR-based genome editing in insects is now based on microinjection into single cells or embryos. The direct protein transduction systems cannot be employed in aphids because oogenesis occurs without apparent vitellogenesis. Given the limited timing of injection into the embryonic stage in oviparous aphids, a protein delivery system from the hemolymph to the germline and embryos would be a useful tool for genome editing. This study reports a newly developed direct protein delivery system for aphids using cell-penetrating peptides (CPPs). CPPs are short peptides that translocate across the plasma membrane when bound to cargo proteins.

Results
Penetratin (PEN), a widely conserved CPP among insects, was identified in this study. We used mVenus, a recombinant fluorescent protein, as a visual marker for CPP availability assessments, and fused it with PEN by bacterial protein expression. The mVenus-PEN recombinant proteins were introduced into the hemolymph of adult unwinged Acyrthosiphon pisum females using a nanoinjector. Fluorescence emitted by mVenus-PEN was observed in various tissues, such as the gut, trachea, bacteriocytes, and their progeny. This study shows that PEN can deliver exogenously expressed proteins into tissues in vivo, indicating that CPPs are powerful tools for protein transduction.
Cost-effectiveness of physical activity interventions for prevention and management of cognitive decline and dementia—a systematic review
Authors: Li Weixin , Kim Kun-Woo Rafael , Zhang Donglan , Liu Bian , Dengler-Crish Christine M. , Wen Ming , Shi Lu , Pan Xi , Gu Yian , Li Yan 
Published: September 2023

Abstract
Background
Although increasing physical activity (PA) has been suggested to prevent and manage cognitive decline and dementia, its economic impact on healthcare systems and society is largely unknown. This study aimed to summarize evidence on the cost-effectiveness of PA interventions to prevent and manage cognitive decline and dementia.

Methods
Electronic databases, including PubMed/MEDLINE, Embase, and ScienceDirect, were searched from January 2000 to July 2023. The search strategy was driven by a combination of subject-heading terms related to physical activity, cognitive function, dementia, and cost-effectiveness. Selected studies were included in narrative synthesis, and extracted data were presented in narrative and tabular forms. The risk of bias in each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list.

Results
Five of the 11 identified studies focused on individuals with existing dementia. Six of the 11 identified studies focused on individuals with no existing dementia, including 3 on those with mild cognitive impairment (MCI), and 3 on those with no existing MCI or dementia. PA interventions focused on individuals with no existing dementia were found to be cost-effective compared to the control group. Findings were mixed for PA interventions implemented in individuals with existing dementia.

Conclusions
PA interventions implemented before or during the early stage of cognitive impairment may be cost-effective in reducing the burden of dementia. More research is needed to investigate the cost-effectiveness of PA interventions in managing dementia. Most existing studies used short-term outcomes in evaluating the cost-effectiveness of PA interventions in the prevention and management of dementia; future research should consider adding long-term outcomes to strengthen the study design.
Subspecialisation in radiology in Europe, a survey of the accreditation council of imaging
Authors: Rupreht Mitja , Ricci Paolo , Prosch Helmut , Adriaensen Miraude E. A. P. M. 
Published: September 2023

Abstract
Background
To provide an overview of existing Subspecialty Exams and Diplomas in Radiology and their endorsement as well as to providing an insight into the status of subspecialisation in radiology in Europe. The European Training Curriculum for Subspecialisation in Radiology mentions thirteen fields of subspecialisation within radiology. The websites of the corresponding subspecialty societies were checked for Subspecialty Exams and Diplomas. In addition, we performed a survey among European radiologists regarding subspecialisation in radiology.

Results
Ten out of 13 European subspecialty societies offer a European subspecialty diploma. At least 7 out of the 10 European subspecialties societies in radiology offering a European subspecialty diploma obtained European Society of Radiology (ESR) endorsement. Two out of 10 obtained European Union of Medical Specialists—Council of European Specialist Medical Assessment endorsement. Survey among European radiologists who were ESR full members in March 2021 demonstrated that almost 20% of respondents indicated that they have no subspecialisation. Another 15% indicated that their area of subspecialisation is not recognised in their country of work. Eighty-four percent of respondents would like their area of subspecialisation in radiology to be officially recognised. According to the respondents, the major benefit of having their subspecialisation in radiology officially recognised is personal interest (45%).

Conclusions
There is a desire for more subspecialty recognition in radiology among European radiologists. Therefore, European subspecialty diplomas in radiology fulfil a need. Furthermore, there is room for further harmonisation and implementation on a European level regarding subspecialty training and recognition in radiology.

Critical relevance statement
As there is a desire for more subspecialty recognition in radiology among European radiologists, European subspecialty diplomas in radiology fulfil a need and there is still room for further harmonisation and implementation on a European level regarding subspecialty training in radiology.

Key points
• Radiology has 13 subspecialties as per the European Training Curriculum for Subspecialisation.
• Currently, 15 subspecialty diplomas are offered by European subspecialty societies in radiology
• Members of the European Society of Radiology seek greater recognition of radiology subspecialties.

Graphical Abstract
Label-set impact on deep learning-based prostate segmentation on MRI
Authors: Meglič Jakob , Sunoqrot Mohammed R. S. , Bathen Tone Frost , Elschot Mattijs 
Published: September 2023

Abstract
Background
Prostate segmentation is an essential step in computer-aided detection and diagnosis systems for prostate cancer. Deep learning (DL)-based methods provide good performance for prostate gland and zones segmentation, but little is known about the impact of manual segmentation (that is, label) selection on their performance. In this work, we investigated these effects by obtaining two different expert label-sets for the PROSTATEx I challenge training dataset (n = 198) and using them, in addition to an in-house dataset (n = 233), to assess the effect on segmentation performance. The automatic segmentation method we used was nnU-Net.

Results
The selection of training/testing label-set had a significant (p < 0.001) impact on model performance. Furthermore, it was found that model performance was significantly (p < 0.001) higher when the model was trained and tested with the same label-set. Moreover, the results showed that agreement between automatic segmentations was significantly (p < 0.0001) higher than agreement between manual segmentations and that the models were able to outperform the human label-sets used to train them.

Conclusions
We investigated the impact of label-set selection on the performance of a DL-based prostate segmentation model. We found that the use of different sets of manual prostate gland and zone segmentations has a measurable impact on model performance. Nevertheless, DL-based segmentation appeared to have a greater inter-reader agreement than manual segmentation. More thought should be given to the label-set, with a focus on multicenter manual segmentation and agreement on common procedures.

Critical relevance statement
Label-set selection significantly impacts the performance of a deep learning-based prostate segmentation model. Models using different label-set showed higher agreement than manual segmentations.

Key points
• Label-set selection has a significant impact on the performance of automatic segmentation models.
• Deep learning-based models demonstrated true learning rather than simply mimicking the label-set.
• Automatic segmentation appears to have a greater inter-reader agreement than manual segmentation.

Graphical Abstract
Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis
Authors: Liu Airu , Liang Xiaonan , Wang Wenxin , Wang Chen , Song Jia , Guo Jinbo , Sun Donglei , Wang Dong , Song Mei , Qian Jiaming , Zhang Xiaolan 
Published: September 2023

Abstract
Background
Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.

Methods
Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4+T homeostasis.

Results
Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.

Conclusion
The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.
Meta-analysis on last ten years of clinical injection of bone marrow-derived and umbilical cord MSC to reverse cirrhosis or rescue patients with acute-on-chronic liver failure
Authors: Wang Huimin , Yao Weiqi , Wang Yuyan , Dong Haibo , Dong Tengyun , Zhou Wangyi , Cui Lingling , Zhao Lulu , Zhang Yu , Shi Lei , Jiang Yingan 
Published: September 2023

Abstract
Background
Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on the efficacy and safety of MSCs has not been reached.

Methods
A systemic literature review was conducted by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of MSC therapy on the outcomes among patients with end-stage liver disease. Various parameters, including pre- and post-treatment model of end-stage liver disease (MELD) score, serum albumin (ALB), total bilirubin (TB), coagulation function, aminotransferase, and survival rate, were evaluated.

Results
This meta-analysis included a final total of 13 studies and 854 patients. The results indicated improved liver parameters following MSC therapy at different time points, including in terms of MELD score, TB level, and ALB level, compared with conventional treatment. Furthermore, the MSC treatment increased the overall survival rate among patients with liver cirrhosis and acute-on-chronic liver failure (ACLF). The changes in transaminase level and coagulation function differed between the different therapies at various post-treatment time points, indicating that MSC therapy provided no significant benefits in this regard. The further subgroup analysis stratified by liver background revealed that patients with ACLF benefit more from MSC therapy at most time points with improved liver function, including in terms of MELD score, TB level, and ALB level. In addition, no serious side effects or adverse events were reported following MSC therapy.

Conclusions
The meta-analysis results suggest that MSC therapy is safe and results in improved liver function and survival rates among patients with end-stage liver disease. The subgroup analysis stratified by liver background indicated that patients with ACLF benefit more from MSC therapy than patients with liver cirrhosis at most time points.
Inflammation-inducible promoters to overexpress immune inhibitory factors by MSCs
Authors: Selich Anton , Fleischauer Jenni , Roepke Tina , Weisskoeppel Luisa , Galla Melanie , von Kaisenberg Constantin , Maus Ulrich A. , Schambach Axel , Rothe Michael 
Published: September 2023

Abstract
Background
Mesenchymal stromal cells (MSCs) are excessively investigated in the context of inflammation-driven diseases, but the clinical results are often moderate. MSCs are naturally activated by inflammatory signals, which lead to the secretion of immune inhibitory factors in inflamed tissues. Many work groups try to improve the therapeutic outcome of MSCs by genetic modification and the constitutive overexpression of immune modulatory transgenes. However, the ectopic secretion of immune inhibitory transgenes increases the chances of infections, and constitutive transgene expression is not necessary for chronic diseases undergoing different inflammatory stages.

Methods
We designed and tested inflammation-induced promoters to control transgene expression from integrating lentiviral vectors in human umbilical cord MSCs. Therefore, we investigated different combinations of general transcription factor elements to achieve a minimal promoter with low basal activity. The best candidates were combined with interferon-induced GAS or ISRE DNA motifs. The constructs with the highest transgene expression upon addition of pro-inflammatory cytokines were compared to vectorized promoters from inflammation-induced genes (CD317, CXCL9, CXCL10, CXCL11 and IDO1). Finally, we investigated IL10 as a potential immune inhibitory transgene by transcriptome analyses, ELISA and in an acute lung injury mouse model.

Results
The synthetic promoters achieved a high and specific transgene expression upon IFN-γ addition. However, the CXCL11 promoter showed synergistic activity upon IFN-γ, TNF-α and IL1-β treatment and surpassed the transgene expression height of all tested promoters in the study. We observed in transcriptome analyses that IL10 has no effect on MSCs and in ELISA that IL10 is only secreted by our genetically modified and activated CXCL11-IL10-MSCs. Finally, transplanted CXCL11-IL10-MSCs increased CD19+ and CD4+ lymphoid cells, and decreased CD11b+ Ly6g myeloid cells in an ALI mouse model.

Conclusion
These results provide new insights into MSC inflammatory activation and the subsequent translation into a tool for a tailored expression of transgenes in inflammatory microenvironments. The newly developed promoter elements are potentially interesting for other inflamed tissues, and can be combined with other elements or used in other cell types.
Probabilistic generative transformer language models for generative design of molecules
Authors: Wei Lai , Fu Nihang , Song Yuqi , Wang Qian , Hu Jianjun 
Published: September 2023

AbstractSelf-supervised neural language models have recently found wide applications in the generative design of organic molecules and protein sequences as well as representation learning for downstream structure classification and functional prediction. However, most of the existing deep learning models for molecule design usually require a big dataset and have a black-box architecture, which makes it difficult to interpret their design logic. Here we propose the Generative Molecular Transformer (GMTransformer), a probabilistic neural network model for generative design of molecules. Our model is built on the blank filling language model originally developed for text processing, which has demonstrated unique advantages in learning the “molecules grammars” with high-quality generation, interpretability, and data efficiency. Benchmarked on the MOSES datasets, our models achieve high novelty and Scaf compared to other baselines. The probabilistic generation steps have the potential in tinkering with molecule design due to their capability of recommending how to modify existing molecules with explanation, guided by the learned implicit molecule chemistry. The source code and datasets can be accessed freely at https://github.com/usccolumbia/GMTransformer
The optimization of the number of deployed antennas in large-scale CL-DAS for energy efficiency
Authors: Han Yonggue , Sim Dongkyu 
Published: September 2023

AbstractWe consider the deployment of a large-scale circular layout-distributed antenna system. To maximize energy efficiency, we define the optimization problem with the approximated analysis and find the number of deployed antennas as a closed-form solution. In simulation results, we verify that the analysis based on approximation is accurate and the closed-form solution can achieve near-optimal energy efficiency without an exhaustive search method.
The association of body mass index and weight waist adjustment index with serum ferritin in a national study of US adults
Authors: Han Hao , Ni Ping , Zhang Siqi , Ji Xiaojuan , Zhu Mingli , Ma Wanyu , Ge Hongfeng , Chu Hailiang 
Published: September 2023

Abstract
Background
Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described.

Objective
This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults.

Methods
Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed.

Results
A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (β = 0.68, 95% CI: 0.17–1.19) when BMI was the independent variable and (β = 8.62, 95% CI: 3.53–13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend < 0.001). In subgroup analyses, the positive association between the independent variables and serum ferritin was more pronounced in participants who were male, 40–59 years old, white, and had diabetes and hypertension. In addition, smoothed curve fitting and threshold effects analysis demonstrated a linear positive association of BMI and WWI with serum ferritin.

Conclusions
In the US adult population, while there was a linear positive association of WWI and BMI with serum ferritin, the effect values between WWI and serum ferritin were more significant. Male, 40–59 years old, white, participants with diabetes and hypertension should be cautious that higher WWI might entail a risk of higher serum ferritin levels.
The PTX3/TLR4 autocrine loop as a novel therapeutic target in triple negative breast cancer
Authors: Giacomini Arianna , Turati Marta , Grillo Elisabetta , Rezzola Sara , Ghedini Gaia Cristina , Schuind Ander Churruca , Foglio Eleonora , Maccarinelli Federica , Faletti Jessica , Filiberti Serena , Chambery Angela , Valletta Mariangela , Melocchi Laura , Gofflot Stephanie , Chiavarina Barbara , Turtoi Andrei , Presta Marco , Ronca Roberto 
Published: September 2023

Abstract
Background
The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. Thus, the characterization of new molecular pathways and/or alternative druggable targets is of great interest in TNBC.

Methods
The expression of PTX3 in BC tumor samples and in BC cell lines has been analyzed using the Gene Expression-Based Outcome for Breast Cancer Online (GOBO), qPCR, Western blot and ELISA assay. The contribution of tumor and stromal cells to PTX3 production in TNBC was assessed by analyzing single cell RNA sequencing data and RNAscope performed on TNBC tumor samples. In order to investigate the effects of PTX3 in TNBC, different cell lines were engineered to knock-down (MDA-MB-231 and BT549 cells) or overexpress (MDA-MB-468 and E0771 cells) PTX3. Finally, using these engineered cells, in vitro (including gene expression profiling and gene set enrichment analyses) and in vivo (orthotopic tumor models in immune-compromised and immune competent mice) analyses were performed to assess the role and the molecular mechanism(s) exerted by PTX3 in TNBC.

Results
In silico and experimental data indicate that PTX3 is mainly produced by tumor cells in TNBC and that its expression levels correlate with tumor stage. Accordingly, gene expression and in vitro results demonstrate that PTX3 overexpression confers a high aggressive/proliferative phenotype and fosters stem-like features in TNBC cells. Also, PTX3 expression induces a more tumorigenic potential when TNBC cells are grafted orthotopically in vivo. Conversely, PTX3 downregulation results in a less aggressive behavior of TNBC cells. Mechanistically, our data reveal that PTX3 drives the activation of the pro-tumorigenic Toll-like receptor 4 (TLR4) signaling pathway in TNBC, demonstrating for the first time that the PTX3/TLR4 autocrine stimulation loop contributes to TNBC aggressiveness and that TLR4 inhibition significantly impacts the growth of PTX3-producing TNBC cells.

Conclusion
Altogether, these data shed light on the role of tumor-produced PTX3 in TNBC and uncover the importance of the PTX3/TLR4 axis for therapeutic and prognostic exploitation in TNBC.

Graphical abstract