bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing challenges in radiomics research: systematic review and repository of open-access cancer imaging datasets
Authors: Woznicki Piotr , Laqua Fabian Christopher , Al-Haj Adam , Bley Thorsten , Baeßler Bettina 
Published: December 2023

Abstract
Objectives
Open-access cancer imaging datasets have become integral for evaluating novel AI approaches in radiology. However, their use in quantitative analysis with radiomics features presents unique challenges, such as incomplete documentation, low visibility, non-uniform data formats, data inhomogeneity, and complex preprocessing. These issues may cause problems with reproducibility and standardization in radiomics studies.

Methods
We systematically reviewed imaging datasets with public copyright licenses, published up to March 2023 across four large online cancer imaging archives. We included only datasets with tomographic images (CT, MRI, or PET), segmentations, and clinical annotations, specifically identifying those suitable for radiomics research. Reproducible preprocessing and feature extraction were performed for each dataset to enable their easy reuse.

Results
We discovered 29 datasets with corresponding segmentations and labels in the form of health outcomes, tumor pathology, staging, imaging-based scores, genetic markers, or repeated imaging. We compiled a repository encompassing 10,354 patients and 49,515 scans. Of the 29 datasets, 15 were licensed under Creative Commons licenses, allowing both non-commercial and commercial usage and redistribution, while others featured custom or restricted licenses. Studies spanned from the early 1990s to 2021, with the majority concluding after 2013. Seven different formats were used for the imaging data. Preprocessing and feature extraction were successfully performed for each dataset.

Conclusion
RadiomicsHub is a comprehensive public repository with radiomics features derived from a systematic review of public cancer imaging datasets. By converting all datasets to a standardized format and ensuring reproducible and traceable processing, RadiomicsHub addresses key reproducibility and standardization challenges in radiomics.

Critical relevance statement
This study critically addresses the challenges associated with locating, preprocessing, and extracting quantitative features from open-access datasets, to facilitate more robust and reliable evaluations of radiomics models.

Key points
- Through a systematic review, we identified 29 cancer imaging datasets suitable for radiomics research.
- A public repository with collection overview and radiomics features, encompassing 10,354 patients and 49,515 scans, was compiled.
- Most datasets can be shared, used, and built upon freely under a Creative Commons license.
- All 29 identified datasets have been converted into a common format to enable reproducible radiomics feature extraction.

Graphical Abstract
Media matters: culture medium-dependent hypervariable phenotype of mesenchymal stromal cells
Authors: Fitzgerald Joan C. , Shaw Georgina , Murphy J. Mary , Barry Frank 
Published: December 2023

Abstract
Background
Despite a long history of investigation and sustained efforts in clinical testing, the number of market authorisations for mesenchymal stromal cell (MSC) therapies remains limited, with none approved by the United States Food and Drug Administration. Several barriers are impeding the clinical progression of MSC therapies, to the forefront of these is a lack of standardised manufacturing protocols which is further compounded by an absence of biologically meaningful characterisation and release assays. A look at clinical trial registries demonstrates the diversity of MSC expansion protocols with variabilities in cell source, isolation method and expansion medium, among other culture variables, making it extraordinarily difficult to compare study outcomes. Current identification and characterisation standards are insufficient; they are not specific to MSCs and do not indicate cell function or therapeutic action.

Methods
This work analysed the influence of five widely used culture media formulations on the colony-forming potential, proliferation kinetics, trilineage differentiation potential and immunomodulatory potential of human bone marrow-derived MSCs (BM-MSCs). The surface marker expression profiles were also characterised using a high-content flow cytometry screening panel of 243 markers.

Results
Significant differences in the biological attributes of BM-MSCs including clonogenicity, proliferation, differentiation propensity and immunomodulatory capacity were revealed in response to the composition of the culture medium. Despite their biological differences, all cell preparations uniformly and strongly expressed the standard positive markers proposed for BM-MSCs: CD73, CD90 and CD105. Immunophenotypic profiling revealed that the culture medium also had a significant influence on the surface proteome, with one-third of tested markers exhibiting variable expression profiles. Principal component analysis demonstrated that BM-MSCs isolated and expanded in a proprietary xeno- and serum-free medium displayed the most consistent cell phenotypes with little variability between donors compared to platelet lysate and foetal bovine serum-containing media.

Conclusions
These data suggest that media composition has a highly significant impact on the biological attributes of MSCs, but standard surface marker tests conceal these differences. The results indicate a need for (1) standardised approaches to manufacturing, with an essential focus on defined media and (2) new biologically relevant tests for MSC characterisation and product release.
Maintenance of the synergistic effects of cord blood cells and erythropoietin combination therapy after additional cord blood infusion in children with cerebral palsy: 1-year open-label extension study of randomized placebo-controlled trial
Authors: Suh Mi Ri , Min Kyunghoon , Cho Kye Hee , Kim Jongwook , Lim Ikhyun , Park Mijin , Noh Eun-Min , Kim Min Young 
Published: December 2023

Abstract
Background
This 1-year open-label extension study aimed to identify the persistent synergistic effects of allogeneic umbilical cord blood (UCB) cells and erythropoietin (EPO) in children with cerebral palsy (CP) for up to 2 years.

Methods
This open-label extension study followed children with CP who were enrolled in the previous randomized, double blind, placebo-controlled trial. The following groups from the first trial were maintained: (A) UCB + EPO, (B) UCB, (C) EPO, and (D) only placebo, and all the participants had continued active rehabilitation. This extended study started 3 months after termination of the first trial, which had a 1-year follow-up duration. All subjects received single additional UCB intravenous infusion at the extension baseline regardless of their initial allocation. Outcome measures were the gross motor performance measure (GMPM), gross motor function measure-66 (GMFM-66), and Bayley scales of infant development-II (BSID-II), which were followed at 3, 6, and 12 months after the extension baseline. Changes in the outcome scores from the baseline values of the previous trial and this study were analysed.

Results
Sixty-nine children (4.29 ± 1.28 years, M:F = 34:35) were included in this study. Each group showed improvements in the outcome measures at 12 months after additional UCB infusion compared to the baseline scores, except for GMFM and GMPM in Group C which were elevated at 3 and 6 months post-therapy. Total subject analyses did not show significant differences in the outcome measures between the four different groups at 3, 6 and 12 months after additional UCB therapy. However, patients with severe dysfunction, whose GMFCS levels were IV and V, revealed a larger improvement of the GMPM score in Group A than in Group D (Ps < 0.05) from the baseline value of the previous trial. The changes in BSID-II mental scale scores were positively correlated with the number of administered total nucleated cells per unit body weight during this one-year extension study period (r = 0.536, P = 0.001).

Conclusions
These results suggest that when administering UCB to treat patients with CP, combination therapy with EPO is more effective, and the effect might last as long as 2 years, especially in patients with severe impairments.
Trial registration: CHA Bundang Medical Center IRB, No. 2015–06-093, approved on July 29, 2015, (https://www.e-irb.com:3443/devlpg/nlpgS200.jsp), ClinicalTrials.gov, NCT03130816, retrospectively registered on April 27, 2017 (https://clinicaltrials.gov/ct2/show/NCT03130816?term=NCT03130816&draw=2&rank=1).
Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile
Authors: Wu Xiaoyun , Ma Zhijie , Yang Yuxiao , Mu Yongxu , Wu Daocheng 
Published: December 2023

Abstract
Background
Safety evaluations in preclinical studies are needed to confirm before translating a cell-based product into clinical application. We previously developed a serum-free, xeno-free, and chemically defined media (S&XFM–CD) for the derivation of clinical-grade umbilical cord-derived MSCs (UCMSCs), and demonstrated that intraperitoneal administration of UCMSCs in S&XFM–CD (UCMSCS&XFM−CD) exhibited better therapeutic effects than UCMSCs in serum-containing media (SCM, UCMSCSCM). However, a comprehensive investigation of the safety of intraperitoneal UCMSCS&XFM−CD treatment should be performed before clinical applications.

Methods
In this study, the toxicity, immunogenicity and biodistribution of intraperitoneally transplanted UCMSCS&XFM−CD were compared with UCMSCSCM in rats via general vital signs, blood routine, blood biochemistry, subsets of T cells, serum cytokines, pathology of vital organs, antibody production and the expression of human-specific gene. The tumorigenicity and tumor-promoting effect of UCMSCS&XFM−CD were compared with UCMSCSCM in nude mice.

Results
We confirmed that intraperitoneally transplanted UCMSCS&XFM−CD or UCMSCSCM did not cause significant changes in body weight, temperature, systolic blood pressure, diastolic blood pressure, heart rate, blood routine, T lymphocyte subsets, and serum cytokines, and had no obvious histopathology change on experimental rats. UCMSCS&XFM−CD did not produce antibodies, while UCMSCSCM had very high chance of antibody production to bovine serum albumin (80%) and apolipoprotein B-100 (60%). Furthermore, intraperitoneally injected UCMSCS&XFM−CD were less likely to be blocked by the lungs and migrated more easily to the kidneys and colon tissue than UCMSCSCM. In addition, UCMSCS&XFM−CD or UCMSCSCM showed no obvious tumorigenic activity. Finally, UCMSCS&XFM−CD extended the time of tumor formation of KM12SM cells, and decreased tumor incidence than that of UCMSCSCM.

Conclusions
Taken together, our data indicate that UCMSCS&XFM−CD display an improved safety performance and are encouraged to use in future clinical trials.
Advancements in the pathogenesis of hepatic osteodystrophy and the potential therapeutic of mesenchymal stromal cells
Authors: Xia Senzhe , Qin Xueqian , Wang Jinglin , Ren Haozhen 
Published: December 2023

AbstractHepatic osteodystrophy (HOD) is a metabolically associated bone disease mainly manifested as osteoporosis with the characteristic of bone loss induced by chronic liver disease (CLD). Due to its high incidence in CLD patients and increased risk of fracture, the research on HOD has received considerable interest. The specific pathogenesis of HOD has not been fully revealed. While it is widely believed that disturbance of hormone level, abnormal secretion of cytokines and damage of intestinal barrier caused by CLD might jointly affect the bone metabolic balance of bone formation and bone absorption. At present, the treatment of HOD is mainly to alleviate the bone loss by drug treatment, but the efficacy and safety are not satisfactory. Mesenchymal stromal cells (MSCs) are cells with multidirectional differentiation potential, cell transplantation therapy based on MSCs is an emerging therapeutic approach. This review mainly summarized the pathogenesis and treatment of HOD, reviewed the research progress of MSCs therapy and the combination of MSCs and scaffolds in the application of osteoporotic bone defects, and discussed the potential and limitations of MSCs therapy, providing theoretical basis for subsequent studies.
2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified
Authors: Neto Nuno G. B. , Suku Meenakshi , Hoey David A. , Monaghan Michael G. 
Published: December 2023

Abstract
Background
Human mesenchymal stem cells (hMSCs) utilize discrete biosynthetic pathways to self-renew and differentiate into specific cell lineages, with undifferentiated hMSCs harbouring reliance on glycolysis and hMSCs differentiating towards an osteogenic phenotype relying on oxidative phosphorylation as an energy source.

Methods
In this study, the osteogenic differentiation of hMSCs was assessed and classified over 14 days using a non-invasive live-cell imaging modality—two-photon fluorescence lifetime imaging microscopy (2P-FLIM). This technique images and measures NADH fluorescence from which cellular metabolism is inferred.

Results
During osteogenesis, we observe a higher dependence on oxidative phosphorylation (OxPhos) for cellular energy, concomitant with an increased reliance on anabolic pathways. Guided by these non-invasive observations, we validated this metabolic profile using qPCR and extracellular metabolite analysis and observed a higher reliance on glutaminolysis in the earlier time points of osteogenic differentiation. Based on the results obtained, we sought to promote glutaminolysis further by using lactate, to improve the osteogenic potential of hMSCs. Higher levels of mineral deposition and osteogenic gene expression were achieved when treating hMSCs with lactate, in addition to an upregulation of lactate metabolism and transmembrane cellular lactate transporters. To further clarify the interplay between glutaminolysis and lactate metabolism in osteogenic differentiation, we blocked these pathways using BPTES and α-CHC respectively. A reduction in mineralization was found after treatment with BPTES and α-CHC, demonstrating the reliance of hMSC osteogenesis on glutaminolysis and lactate metabolism.

Conclusion
In summary, we demonstrate that the osteogenic differentiation of hMSCs has a temporal metabolic profile and shift that is observed as early as day 3 of cell culture using 2P-FLIM. Furthermore, extracellular lactate is shown as an essential metabolite and metabolic fuel to ensure efficient osteogenic differentiation and as a signalling molecule to promote glutaminolysis. These findings have significant impact in the use of 2P-FLIM to discover potent approaches towards bone tissue engineering in vitro and in vivo by engaging directly with metabolite-driven osteogenesis.

Graphical Abstract
Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows
Authors: Wu Deyuan , Xiong Wenyu , Ma Shuo , Luo Jinxi , Ye Hongxuan , Huang Shuangbo , Li Fuyong , Xiang Xi’en , Chen Qiling , Gao Binghui , Deng Jinping , Yin Yulong , Tan Chengquan 
Published: December 2023

AbstractOur previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.
Estimation of estuarine habitat degradation and its influence on the reproduction process of the crab Eriocheir sinensis in the Yangtze River Estuary
Authors: Zhang Tingting , Du Nan , Geng Zhi , Wang Sikai , Gao Yu , Yang Gang , Huang Xiaorong , Zhang Tao , Zhuang Ping , Zhao Feng 
Published: December 2023

Abstract
Background
The provision of habitat for fishery species in estuaries is highly valued and represents one of the most challenging ecosystem service values to quantify. However, quantifying this value is challenging due to complex relationships between habitat change, ecological processes, and environmental variations. This study aims to estimate estuarine habitat degradation and its impact on the reproduction process of the crab Eriocheir sinensis by characterizing the changes in breeding habitat and investigating relationships between the species and its habitat in the Yangtze River Estuary.

Methods
A species distribution model recently developed was applied to estimate the extent and quality of breeding habitat changes from 2014–2021. The intrinsic (physiological) and external (structural) reproductive attributes of the breeding process were measured to assess the effects of habitat change. The relationships among habitat change, reproductive attributes and environmental factors were analyzed to understand the underlying driving forces of habitat degradation for breeding process by multivariate statistical analysis.

Results
About 34.24% of essential habitat was lost, mainly in highly suitable areas due to reclamation and waterway construction. Habitat degradation significantly affects female distribution and their reproductive processes, particularly gonad development during the pre-reproductive period and fecundity during the reproductive period, without altering population structure. These results indicated that the main ecological function served by the highly suitable breeding ground was the provision for development of gonad and improvement of fecundity. Increases of salinity and turbidity, caused by hydrodynamic changes from large-scale waterway construction, were identified as the environmental determinants contributing to cumulative habitat degradation. These influences ultimately led to a decrease in the fecundity of E. sinensis.

Conclusions
Our research sheds light on the quantification of habitat degradation in the Yangtze River Estuary and its implications for the reproduction process of E. sinensis, which can serve as a foundation for assessing and quantifying the ecosystem service values provided by these breeding grounds. This information is valuable for policymakers and resource managers in making informed decisions regarding habitat conservation and the sustainable utilization of fishery resources.
Cortical microvascular raspberries and ageing: an independent but not exclusive relationship
Authors: Ek Olofsson Henric , Österling Delshammar Thea , Englund Elisabet 
Published: December 2023

Abstract
Introduction
Raspberries are cerebral microvascular formations of unknown origin, defined as three or more transversally sectioned vascular lumina surrounded by a common perivascular space. We have previously demonstrated an increased raspberry density in the cortex of patients with vascular dementia and cerebral atherosclerosis, while studies by other authors on overlapping and synonymously defined vascular entities mainly associate them with advancing age. The aim of the present study was to examine the relationship between raspberries and age in a large study sample while including multiple potential confounding factors in the analysis.

Materials and methods
Our study sample consisted of 263 individuals aged 20–97 years who had undergone a clinical autopsy including a neuropathological examination. The cortical raspberry density had either been quantified as part of a previous study or was examined de novo in a uniform manner on haematoxylin- and eosin-stained tissue sections from the frontal lobe. The medical records and autopsy reports were assessed regarding neurodegeneration, cerebral infarcts, cerebral atherosclerosis and small vessel disease, cardiac hypertrophy, nephrosclerosis, hypertension, and diabetes mellitus. With the patients grouped according to 10-year age interval, non-parametric tests (the Kruskal–Wallis test, followed by pairwise testing with Bonferroni-corrected P values) and multiple linear regression models (not corrected for multiple tests) were performed.

Results
The average raspberry density increased with advancing age. The non-parametric tests demonstrated statistically significant differences in raspberry density when comparing the groups aged 60–99 years and 70–99 years to those aged 20–29 years (P < 0.012) and 30–59 years (P < 0.011), respectively. The multiple linear regression models demonstrated positive associations with age interval (P < 0.001), cerebral atherosclerosis (P = 0.024), cardiac hypertrophy (P = 0.021), hypertension subgrouped for organ damage (P = 0.006), and female sex (P = 0.004), and a tendency towards a negative association with Alzheimer’s disease neuropathologic change (P = 0.048).

Conclusion
The raspberry density of the frontal cortex increases with advancing age, but our results also indicate associations with acquired pathologies. Awareness of the biological and pathological context where raspberries occur can guide further research on their origin.