bluuebunny/crossref_metadata_2025 huggingface dataset:
Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders
Authors: Ye Junping , Huang Zhanwang , Li Qiyang , Li Zhongwei , Lan Yuting , Wang Zhongju , Ni Chaoying , Wu Xiaohui , Jiang Tingyun , Li Yujing , Yang Qiong , Lim Junghwa , Ren Cun-Yan , Jiang Meijun , Li Shufen , Jin Peng , Chen Jian-Huan , Zhao Cunyou
Published: December 2023

Background

Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored.

Methods

We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells.

Results

We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking.

Conclusion

Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.
Comparison of plugin and redundant marker sets to analyze gait kinematics between different populations
Authors: Ji Run , Lee Wayne Yuk-wai , Guan Xinyu , Yan Bin , Yang Lei , Yang Jiemeng , Wang Ling , Tao Chunjing , Kuai Shengzheng , Fan Yubo
Published: December 2023

Background

Gait model consists of a marker set and a segment pose estimation algorithm. Plugin marker set and inverse kinematic algorithm (IK.) are prevalent in gait analysis, especially musculoskeletal motion analysis. Adding extra markers for the plugin marker set could increase the robustness to marker misplacement, motion artifacts, and even markers occlusion. However, how the different marker sets affect the gait analysis's kinematic output is unclear. Therefore, this study aims to investigate the effect of marker sets on the kinematic output during level walking in different populations.

Results

In all three planes, there are significant differences (P < 0.05) between marker sets in some kinematic variables at the hip, knee, and ankle. In different populations, the kinematic variables that show significant differences varied. When comparing the kinematic differences between populations using the two marker sets separately, the range of motion (ROM) of hip flexion was only found to be a significant difference using the redundant marker set, while the peak internal rotation at the knee was only found a significant difference using plugin marker set. In addition, the redundant marker set shows less intra-subject variation than the plugin marker set.

Conclusion

The findings in this study demonstrate the importance of marker set selection since it could change the result when comparing the kinematic differences between populations. Therefore, it is essential to increase the caution in explaining the result when using different marker sets. It is crucial to use the same marker set, and the redundant marker set might be a better choice for gait analysis.
QALYs and rare diseases: exploring the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing for childhood and adult-onset rare genetic conditions in Australia
Authors: Pan Tianxin , Wu You , Buchanan James , Goranitis Ilias
Published: December 2023

Background

Genomic testing transforms the diagnosis and management of rare conditions. However, uncertainty exists on how to best measure genomic outcomes for informing healthcare priorities. Using the HTA-preferred method should be the starting point to improve the evidence-base. This study explores the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing across childhood and adult-onset genetic conditions.

Method

Self-reported patient-reported outcomes (PRO) were obtained from: primary caregivers of children with suspected neurodevelopmental disorders (NDs) or genetic kidney diseases (GKDs) (carers’ own PRO), adults with suspected GKDs using SF-12v2; adults with suspected complex neurological disorders (CNDs) using EQ-5D-5L; and adults with dilated cardiomyopathy (DCM) using AQol-8D. Responsiveness was assessed using the standardised response mean effect-size based on diagnostic (having a confirmed genomic diagnosis), personal (usefulness of genomic information to individuals or families), and clinical (clinical usefulness of genomic information) utility anchors.

Results

In total, 254 people completed PRO measures before genomic testing and after receiving results. For diagnostic utility, a nearly moderate positive effect size was identified by the AQoL-8D in adult DCM patients. Declines in physical health domains masked any improvements in mental or psychosocial domains in parents of children affected by NDs and adult CNDs and DCM patients with confirmed diagnosis. However, the magnitude of the changes was small and we did not find statistically significant evidence of these changes. No other responsiveness evidence related to diagnostic, clinical, and personal utility of genomic testing was identified.

Conclusion

Generic PRO measures may lack responsiveness to the diagnostic, clinical and personal outcomes of genomics, but further research is needed to establish their measurement properties and relevant evaluative space in the context of rare conditions. Expected declines in the physical health of people experiencing rare conditions may further challenge the conventional application of quality of life assessments.
Cirsiliol induces autophagy and mitochondrial apoptosis through the AKT/FOXO1 axis and influences methotrexate resistance in osteosarcoma
Authors: Luo Mengliang , Su Zexin , Gao Haotian , Tan Jianye , Liao Rongdong , Yang Jiancheng , Lin Lijun
Published: December 2023

Background

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown.

Methods

The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS.

Results

Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo.

Conclusions

Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.
Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019
Authors: Li Sangzi , Zhang Xuan , Cai Yilu , Zheng Leilei , Pang Hu , Lou Lixia
Published: December 2023

Background

Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019).

Methods

Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence.

Results

Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705–1.706)) and 2019 (RR: 1.602 (1.619–1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910–1.915)) was observed in the age group of 10–14. Relative sex difference had a significant positive relationship with SDI (standardized β = 0.267, P < 0.001).

Conclusions

Despite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.
Selective aortic arch perfusion: a first-in-human observational cadaveric study
Authors: Marsden Max , Barratt Jon , Donald-Simpson Helen , Wilkinson Tracey , Manning Jim , Rees Paul
Published: December 2023

Background

Selective aortic arch perfusion (SAAP) is a novel endovascular technique that combines thoracic aortic occlusion with extracorporeal perfusion of the brain and heart. SAAP may have a role in both haemorrhagic shock and in cardiac arrest due to coronary ischaemia. Despite promising animal studies, no data is available that describes SAAP in humans. The primary aim of this study was to assess the feasibility of selective aortic arch perfusion in humans. The secondary aim of the study was to assess the feasibility of achieving direct coronary artery access via the SAAP catheter as a potential conduit for salvage percutaneous coronary intervention.

Methods

Using perfused human cadavers, a prototype SAAP catheter was inserted into the descending aorta under fluoroscopic guidance via a standard femoral percutaneous access device. The catheter balloon was inflated and the aortic arch perfused with radio-opaque contrast. The coronary arteries were cannulated through the SAAP catheter.

Results

The procedure was conducted four times. During the first two trials the SAAP catheter was passed rapidly and without incident to the intended descending aortic landing zone and aortic arch perfusion was successfully delivered via the device. The SAAP catheter balloon failed on the third trial. On the fourth trial the left coronary system was cannulated using a 5Fr coronary guiding catheter through the central SAAP catheter lumen.

Conclusions

For the first time using a perfused cadaveric model we have demonstrated that a SAAP catheter can be easily and safely inserted and SAAP can be achieved using conventional endovascular techniques. The SAAP catheter allowed successful access to the proximal aorta and permitted retrograde perfusion of the coronary and cerebral circulation.
Utility of ultrasound in managing acute medical conditions in space: a scoping review
Authors: Asachi Parsa , Ghanem Ghadi , Burton Jason , Aintablian Haig , Chiem Alan
Published: December 2023

Background

In long-distance spaceflight, the challenges of communication delays and the impracticality of rapid evacuation necessitate the management of medical emergencies by onboard physicians. Consequently, these physicians must be proficient in tools, such as ultrasound, which has proven itself a strong diagnostic imaging tool in space. Yet, there remains a notable gap in the discourse surrounding its efficacy in handling acute medical scenarios. This scoping review aims to present an updated analysis of the evidence supporting the role of ultrasound in diagnosing acute conditions within microgravity environments.

Methods

A systematic search was executed across three bibliographic databases: PubMed, EMBASE (Embase.com), and the Web of Science Core Collection. We considered articles published up to February 25, 2023, that highlighted the application of ultrasound in diagnosing acute medical conditions in either microgravity or microgravity-simulated settings. Exclusions were made for review papers, abstracts, and in-vitro studies.

Results

After removing duplicates, and filtering papers by pre-determined criteria, a total of 15 articles were identified that discuss the potential use of ultrasound in managing acute medical conditions in space. The publication date of these studies ranged from 1999 to 2020. A relatively similar proportion of these studies were conducted either on the International Space Station or in parabolic flight, with one performed in supine positioning to simulate weightlessness. The included studies discuss acute pathologies, such as abdominal emergencies, decompression sickness, deep venous thrombosis, acute lung pathologies, sinusitis, musculoskeletal trauma, genitourinary emergencies, and ocular emergencies.

Conclusions

While ultrasound has shown promise in addressing various acute conditions, significant knowledge gaps remain, especially in gastrointestinal, cardiac, vascular, and reproductive emergencies. As we venture further into space, expanding our medical expertise becomes vital to ensure astronaut safety and mission success.
The sixth Japanese meeting on biological function and evolution through interactions between hosts and transposable elements
Authors: Ichiyanagi Kenji , Ikeda Yoko , Saito Kuniaki
Published: December 2023

The sixth Japanese meeting on host–transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on August 24th and 25th, 2023, at the National Institute of Genetics as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of TEs in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, yeast, protozoa, and bacteria. Here, we have presented the highlights of the discussion.

Organizers: Kenji Ichiyanagi, Yoko Ikeda, and Kuniaki Saito.
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

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

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

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

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

Hepatic 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

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

Our 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

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

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.
Temporal and spatial patterns of traditional village distribution evolution in Xiangxi, China: identifying multidimensional influential factors and conservation significance
Authors: Zhu Jiaji , Xu Wenzhuo , Xiao Yuhong , Shi Jianyu , Hu Xijun , Yan Bingwen
Published: December 2023

This study systematically investigates the spatio-temporal distribution, influential factors, and conservation significance of 413 traditional villages in Xiangxi, China. Employing methods such as ArcGIS spatial analysis, geographic statistical analysis, and historical literature review, this work meticulously delineates the intricate interplay of natural, societal, and cultural elements in shaping the evolution of village distributions. As pillars of China's rich traditional culture, these villages encapsulate profound historical, folkloric, and architectural values. Their spatial and temporal transformations are instrumental in unraveling Xiangxi’s historical and cultural tapestry, thereby informing strategic conservation efforts. The research findings are as follows: (1) from a spatial perspective, traditional villages in Xiangxi, China, exhibit an overall clustering tendency, characterized by a distribution pattern of "more in the core, fewer on the periphery, with small clusters and significant dispersion." These villages are distributed in multiple bands along ancient postal routes, the Wuling Mountains, the Xuefeng Mountains, and river basins. (2) Traditional villages in Xiangxi primarily originated prior to the Yuan Dynasty, with a predominant north–south spatial orientation. Over successive dynasties, the distribution center gradually shifted northeastward, resulting in an expansion of the spatial distribution range and a decrease in directional bias. (3) The formation and distribution evolution of traditional villages are influenced by a combination of natural factors, socio-economic factors, and historical-cultural factors. Natural factors and cultural elements influence the selection and layout of traditional village sites, while socio-economic and historical-cultural factors impact their development and evolution. In conclusion, the distribution evolution of traditional villages in Xiangxi, China, underscores the intricate interplay of diverse factors, spanning the realms of nature, society, and culture. Recognizing this complexity is essential in comprehending the historical and cultural tapestry of Xiangxi and in formulating strategies for the preservation of these invaluable cultural and historical assets. The preservation of traditional villages transcends mere heritage conservation; it represents a pivotal step towards safeguarding the multifaceted heritage of Xiangxi.
Factors related to students’ psychological distress during COVID-19 disruption across countries
Authors: Rožman Mojca , Liaw Yuan-Ling , Chen Minge
Published: December 2023

Background

The global outbreak of the novel COVID-19 virus presented a significant threat to students’ well-being across the globe. In this paper, we construct a measure of student psychological distress related to COVID-19 disruption. We then examine the variation in students’ psychological distress as a function of student demographic characteristics, home, school and student factors and compare the results across countries.

Methods

We use item response theory to construct a comparable scale for students’ psychological distress across participating countries. Furthermore, we employ linear regression to explore the association of student characteristics and other student and school factors.

Results

An internationally comparable scale for students’ psychological distress was constructed using the model assuming equal item parameters across countries. This enables us to compare the levels of students’ psychological distress and its relationships with the construct across countries. The most important factors contributing to students’ psychological distress were school support, school belonging, disrupted sleep, difficulties in learning after the disruption and preparedness for future disruptions. In some countries, we find suggestive evidence that boys exhibited lower psychological distress than girls. We do not find any meaningful relationship between home resources and the students’ psychological distress scale.

Conclusions

Students across participating countries expressed negative feelings about schooling and events happening during the disruption and their effects on their future. We find indication that some school and student factors had a significant relationship with students’ psychological distress in many countries. This was especially the case in countries where remote learning took place during the disruption. In addition, differences across countries are found. The key finding is that high psychological distress is present in all countries studied around the world. However, it is important to note that the factors contributing to this distress are not the same everywhere. Therefore potential interventions must consider country specific factors.
A plethora of choices: an anatomists’ practical perspectives for the selection of digital anatomy resources
Authors: Aland R. Claire , Hugo Honor J. , Battle Andrew , Donkin Rebecca , McDonald Aaron , McGowan Heath , Nealon Jessica R. , Ritchie Helen , Stirling Allan , Tentrisanna Melby , Valter Krisztina , Xiao Junhua
Published: December 2023

The use of digital resources in the new learning environment has drastically influenced how human topographic anatomy is taught and assessed. An array of digital technologies for anatomy teaching have been recently adopted in medical and health science schools in both undergraduate and postgraduate courses. This resulted from a surging demand for digital anatomy technologies in the wake of the coronavirus disease 2019 (COVID-19) pandemic and required rapid digital up-skilling of anatomists. Despite the wide adoption of digital technologies in anatomy teaching, there is little comprehensive information on the selection and implementation of these digital resources from a practical perspective. Based on the authors’ experience and supported by literature, this article describes their implementation of digital anatomy resources for teaching gross anatomy in eleven Australian universities. This paper highlights the advantages and limitations that the authors encountered and their recommendations for using these current digital technologies in anatomy teaching.
Drowning is fast, silent, and preventable: a Texas example of research in action
Authors: Williams Stewart R. , Dow Emily A. , Johnson Molly B.
Published: December 2023

Drowning is a major public health issue internationally. In August 2022, a report was released by members of the Central Texas Drowning Prevention Action Team that provided data on drowning fatalities in Texas between 2006 and 2020 and offered recommendations for drowning prevention actions. The information in the Texas drowning report is an important contribution to the field of injury prevention. The aim of this editorial is to allow the information in the report to be available to a wider audience and potentially used as a model for other states.