bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia–reperfusion injury via mTOR/ULK1/FUNDC1 pathways
Authors: Deng Chao , Dong Kangkang , Liu Yongjun , Chen Ken , Min Chuwei , Cao Zheming , Wu Panfeng , Luo Gaojie , Cheng Gechang , Qing Liming , Tang Juyu 
Published: September 2023

AbstractFlap necrosis, the most prevalent postoperative complication of reconstructive surgery, is significantly associated with ischaemia–reperfusion injury. Recent research indicates that exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold potential therapeutic applications in several diseases. Traditionally, BMSCs are cultured under normoxic conditions, a setting that diverges from their physiological hypoxic environment in vivo. Consequently, we propose a method involving the hypoxic preconditioning of BMSCs, aimed at exploring the function and the specific mechanisms of their exosomes in ischaemia–reperfusion skin flaps. This study constructed a 3 × 6 cm2 caudal superficial epigastric skin flap model and subjected it to ischaemic conditions for 6 h. Our findings reveal that exosomes from hypoxia-pretreated BMSCs significantly promoted flap survival, decrease MCP-1, IL-1β, and IL-6 levels in ischaemia–reperfusion injured flap, and reduce oxidative stress injury and apoptosis. Moreover, results indicated that Hypo-Exo provides protection to vascular endothelial cells from ischaemia–reperfusion injury both in vivo and in vitro. Through high-throughput sequencing and bioinformatics analysis, we further compared the differential miRNA expression profiles between Hypo-Exo and normoxic exosomes. Results display the enrichment of several pathways, including autophagy and mTOR. We have also elucidated a mechanism wherein Hypo-Exo promotes the survival of ischaemia–reperfusion injured flaps. This mechanism involves carrying large amounts of miR-421-3p, which target and regulate mTOR, thereby upregulating the expression of phosphorylated ULK1 and FUNDC1, and subsequently further activating autophagy. In summary, hypoxic preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of BMSC-derived exosomes in the treatment of flap ischaemia–reperfusion injury.
The health and economic impact and cost effectiveness of interventions for the prevention and control of overweight and obesity in Kenya: a stakeholder engaged modelling study
Authors: Wanjau Mary Njeri , Kivuti-Bitok Lucy W. , Aminde Leopold N. , Veerman J. Lennert 
Published: September 2023

Abstract
Background
The global increase in mean body mass index has resulted in a substantial increase of non-communicable diseases (NCDs), including in many low- and middle-income countries such as Kenya. This paper assesses four interventions for the prevention and control of overweight and obesity in Kenya to determine their potential health and economic impact and cost effectiveness.

Methods
We reviewed the literature to identify evidence of effect, determine the intervention costs, disease costs and total healthcare costs. We used a proportional multistate life table model to quantify the potential impacts on health conditions and healthcare costs, modelling the 2019 Kenya population over their remaining lifetime. Considering a health system perspective, two interventions were assessed for cost-effectiveness. In addition, we used the Human Capital Approach to estimate productivity gains.

Results
Over the lifetime of the 2019 population, impacts were estimated at 203,266 health-adjusted life years (HALYs) (95% uncertainty interval [UI] 163,752 − 249,621) for a 20% tax on sugar-sweetened beverages, 151,718 HALYs (95% UI 55,257 − 250,412) for mandatory kilojoule menu labelling, 3.7 million HALYs (95% UI 2,661,365–4,789,915) for a change in consumption levels related to supermarket food purchase patterns and 13.1 million HALYs (95% UI 11,404,317 − 15,152,341) for a change in national consumption back to the 1975 average levels of energy intake. This translates to 4, 3, 73 and 261 HALYs per 1,000 persons. Lifetime healthcare cost savings were approximately United States Dollar (USD) 0.14 billion (USD 3 per capita), USD 0.08 billion (USD 2 per capita), USD 1.9 billion (USD 38 per capita) and USD 6.2 billion (USD 124 per capita), respectively. Lifetime productivity gains were approximately USD 1.8 billion, USD 1.2 billion, USD 28 billion and USD 92 billion. Both the 20% tax on sugar sweetened beverages and the mandatory kilojoule menu labelling were assessed for cost effectiveness and found dominant (health promoting and cost-saving).

Conclusion
All interventions evaluated yielded substantive health gains and economic benefits and should be considered for implementation in Kenya.
Extracellular vesicle-cell adhesion molecules in tumours: biofunctions and clinical applications
Authors: Lin Weikai , Fang Jianjun , Wei Shibo , He Guangpeng , Liu Jiaxing , Li Xian , Peng Xueqiang , Li Dai , Yang Shuo , Li Xinyu , Yang Liang , Li Hangyu 
Published: September 2023

AbstractCell adhesion molecule (CAM) is an umbrella term for several families of molecules, including the cadherin family, integrin family, selectin family, immunoglobulin superfamily, and some currently unclassified adhesion molecules. Extracellular vesicles (EVs) are important information mediators in cell-to-cell communication. Recent evidence has confirmed that CAMs transported by EVs interact with recipient cells to influence EV distribution in vivo and regulate multiple cellular processes. This review focuses on the loading of CAMs onto EVs, the roles of CAMs in regulating EV distribution, and the known and possible mechanisms of these actions. Moreover, herein, we summarize the impacts of CAMs transported by EVs to the tumour microenvironment (TME) on the malignant behaviour of tumour cells (proliferation, metastasis, immune escape, and so on). In addition, from the standpoint of clinical applications, the significance and challenges of using of EV-CAMs in the diagnosis and therapy of tumours are discussed. Finally, considering recent advances in the understanding of EV-CAMs, we outline significant challenges in this field that require urgent attention to advance research and promote the clinical applications of EV-CAMs.
Epigenetic meets metabolism: novel vulnerabilities to fight cancer
Authors: Scumaci Domenica , Zheng Qingfei 
Published: September 2023

AbstractHistones undergo a plethora of post-translational modifications (PTMs) that regulate nucleosome and chromatin dynamics and thus dictate cell fate. Several evidences suggest that the accumulation of epigenetic alterations is one of the key driving forces triggering aberrant cellular proliferation, invasion, metastasis and chemoresistance pathways. Recently a novel class of histone “non-enzymatic covalent modifications” (NECMs), correlating epigenome landscape and metabolic rewiring, have been described. These modifications are tightly related to cell metabolic fitness and are able to impair chromatin architecture. During metabolic reprogramming, the high metabolic flux induces the accumulation of metabolic intermediate and/or by-products able to react with histone tails altering epigenome homeostasis. The accumulation of histone NECMs is a damaging condition that cancer cells counteracts by overexpressing peculiar “eraser” enzymes capable of removing these modifications preserving histones architecture. In this review we explored the well-established NECMs, emphasizing the role of their corresponding eraser enzymes. Additionally, we provide a parterre of drugs aiming to target those eraser enzymes with the intent to propose novel routes of personalized medicine based on the identification of epi-biomarkers which might be selectively targeted for therapy.
Elucidating the molecular mechanisms underlying the induction of autophagy by antidepressant-like substances in C57BL/6J mouse testis model upon LPS challenge
Authors: Sołek Przemysław , Czechowska Ewelina , Sowa-Kućma Magdalena , Stachowicz Katarzyna , Kaczka Piotr , Tabęcka-Łonczyńska Anna 
Published: September 2023

AbstractThe treatment of depression with pharmaceuticals is associated with many adverse side effects, including male fertility problems. The precise mechanisms by which these agents affect testicular cells remain largely unknown, but they are believed to induce cellular stress, which is sensed by the endoplasmic reticulum (ER) and the Golgi apparatus. These organelles are responsible for maintaining cellular homeostasis and regulating signal pathways that lead to autophagy or apoptosis. Therefore, in this study, we aimed to investigate the autophagy, ER, and Golgi stress-related pathways in mouse testis following treatment with antidepressant-like substances (ALS) and ALS combined with lipopolysaccharide (LPS). We found that most ALS and activated proteins are associated with the induction of apoptosis. However, when imipramine (IMI) was combined with NS-398 (a cyclooxygenase-2 inhibitor) after LPS administration, we observed a marked increase in the BECLIN1, Bcl-2, ATG16L, and LC3 expression, which are marker proteins of autophagosome formation. The expression of the BECN1 and ATG16L genes was also high compared to the control, indicating the induction of autophagy processes that may potentially protect mouse testicular cells from death and regulate metabolism in the testis. Our findings may provide a better understanding of the stress-related effects of specific ALS on the testis.
Graphical Abstract
Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p
Authors: Shi Lei , Li Bowen , Zhang Yuhan , Chen Yuting , Tan Jiyu , Chen Yan , Li Jie , Xiang Meng , Xing H. Rosie , Wang Jianyu 
Published: September 2023

Abstract
Background
Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression.

Methods
The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed.

Results
This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability.

Conclusion
We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells.
Identification of memory B-cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma
Authors: Liu Ruquan , Huang Biaojie , Shao Yongzhao , Cai Yongming , Liu Xi , Ren Zhonglu 
Published: September 2023

Abstract
Background
Memory B cells and microRNAs (miRNAs) play important roles in the progression of gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD). However, few studies have investigated the use of memory B-cell-associated miRNAs in predicting the prognosis of STAD.

Methods
We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA‒miRNA coexpression network. Then, univariate Cox, random survival forest (RSF), and stepwise multiple Cox regression (StepCox) algorithms were used to identify memory B-cell-associated miRNAs that were significantly related to overall survival (OS). A prognostic risk model was constructed and validated using these miRNAs, and patients were divided into a low-risk group and a high-risk group. In addition, the differences in clinicopathological features, tumour microenvironment, immune blocking therapy, and sensitivity to anticancer drugs in the two groups were analysed.

Results
Four memory B-cell-associated miRNAs (hsa-mir-145, hsa-mir-125b-2, hsa-mir-100, hsa-mir-221) with significant correlations to OS were identified and used to construct a prognostic model. Time-dependent receiver operating characteristic (ROC) curve analysis confirmed the feasibility of the model. Kaplan‒Meier (K‒M) survival curve analysis showed that the prognosis was poor in the high-risk group. Comprehensive analysis showed that patients in the high-risk group had higher immune scores, matrix scores, and immune cell infiltration and a poor immune response. In terms of drug screening, we predicted eight drugs with higher sensitivity in the high-risk group, of which CGP-60474 was associated with the greatest sensitivity.

Conclusions
In summary, we identified memory B-cell-associated miRNA prognostic features and constructed a novel risk model for STAD based on scRNA-seq data and bulk RNA-seq data. Among patients in the high-risk group, STAD showed the highest sensitivity to CGP-60474. This study provides prognostic insights into individualized and precise treatment for STAD patients.
Characterization of tumor microenvironment and tumor immunology based on the double-stranded RNA-binding protein related genes in cervical cancer
Authors: Li Jin , Wan Chong , Li Xiaoqi , Quan Chenlian , Li Xiaoqiu , Wu Xiaohua 
Published: September 2023

Abstract
Background
Cervical cancer is one of the most common gynecological cancers threatening women’s health worldwide. Double-stranded RNA-binding proteins (dsRBPs) regulate innate immunity and are therefore believed to be involved in virus-related malignancies, however, their role in cervical cancer is not well known.

Methods
We performed RNA-seq of tumor samples from cervical cancer patients in local cohort and also assessed the RNA-seq and clinical data derived from public datasets. By using single sample Gene Set Enrichment Analysis (ssGSEA) and univariate Cox analysis, patients were stratified into distinct dsRBP clusters. Stepwise Cox and CoxBoost were performed to construct a risk model based on optimal dsRBPs clusters-related differentially expressed genes (DEGs), and GSE44001 and CGCI-HTMCP-CC were employed as two external validation cohorts. Single cell RNA sequencing data from GSE168652 and Scissor algorithm were applied to evaluated the signature-related cell population.

Results
The expression of dsRBP features was found to be associated with HPV infection and carcinogenesis in CESC. However, only Adenosine deaminases acting on RNA (ADAR) and Dicer, Drosha, and Argonautes (DDR) exhibited significant correlations with the overall survival (OS) of CESC patients. Based on these findings, CESC patients were divided into three dsRBP clusters. Cluster 3 showed superior OS but lower levels of ADAR and DDR. Additionally, Cluster 3 demonstrated enhanced innate immunity, with significantly higher activity in cancer immunity cycles, immune scores, and levels of tumor-infiltrating immune cells, particularly CD8+ T cells. Furthermore, a risk model based on nine dsRBP cluster-related DEGs was established. The accuracy of survival prediction for 1 to 5 years was consistently above 0.78, and this model’s robust predictive capacity was confirmed by two external validation sets. The low-risk group exhibited significantly higher levels of immune checkpoints, such as PDCD1 and CTLA4, as well as a higher abundance of CD8+ T cells. Analysis of single-cell sequencing data revealed a significant association between the dsRBP signature and glycolysis. Importantly, low-risk patients showed improved OS and a higher response rate to immunotherapy, along with enduring clinical benefits from concurrent chemoradiotherapy.

Conclusions
dsRBP played a crucial role in the regulation of prognosis and tumor immunology in cervical cancer, and its prognostic signature provides a strategy for risk stratification and immunotherapy evaluation.
Macrophage activation syndrome in juvenile dermatomyositis: a case report and a comprehensive review of the literature
Authors: Chang Yong , Shan Xueyan , Ge Yongpeng 
Published: September 2023

Abstract
Background
Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. The coexistence of MAS and juvenile dermatomyositis (JDM) is not well reported. This report describes a case of JDM with MAS and summarizes the clinical characteristics and prognosis of MAS in patients with JDM.

Case presentation
The patient was a 15-year-old female with JDM, presenting with heliotrope rash, muscle weakness, increased muscle enzyme, anti-nuclear matrix protein 2 (NXP2) antibody, and muscle biopsy consistent with JDM. The patient developed fever, cytopenia, and hyperferritinemia three months after the first manifestations. Hemophagocytosis was found in the bone marrow. The final diagnosis was JDM combined with MAS. Despite intensive treatment, the patient died of MAS. By reviewing the literature, we found 17 similar cases. Together with the present case, 18 patients were identified, the median age of disease onset was 13.5 years, and male to female ratio was 1.25: 1. Nine out of 16 (56.3%) patients were complicated with interstitial lung disease (ILD). The median time interval between JDM onset and MAS diagnosis was 9 weeks. At the onset of MAS, all (100%) patients had elevated levels of ferritin and serum liver enzymes. Among 18 patients, 14 (77.8%) had fever, 14/17 (82.4%) had cytopenia, 11/11 (100%) had hepatosplenomegaly, and 13/14 (92.9%) had hemophagocytosis. Five (27.8%) patients showed central nervous system (CNS) involvement. The mortality of MAS rate of in patients with JDM was 16.7%, despite various treatment methods.

Conclusion
. The coexistence of JDM and MAS is underestimated with increased mortality. Hepatosplenomegaly and increased serum levels of ferritin in patients with JDM should raise clinical suspicion for MAS.
The BE-UJI hand function activity set: a reduced set of activities for the evaluation of the healthy and pathological hand
Authors: Jarque-Bou Néstor J. , Gracia-Ibáñez Verónica , Vergara Margarita , Sancho-Bru Joaquín L. 
Published: September 2023

Abstract
Background
Hand kinematics during hand function tests based on the performance of activities of daily living (ADLs) can provide objective data to determine patients’ functional loss. However, they are rarely used during clinical assessments because of their long duration. Starting with the 20 Sollerman Hand Function Test (SHFT) tasks, we propose identifying a reduced set of ADLs that provides similar kinematic information to the original full set in terms of synergies, ranges of motion and velocities.

Methods
We followed an iterative method with the kinematics of 16 hand joints while performing the 20 ADLs of the SHFT. For each subject, ADLs were ordered according to their influence on the synergies obtained by means of a principal component analysis, the minimum number of ADLs that represented the original kinematic synergies (maximum angle of 30° between synergies), and the maintained ranges of joint movements (85% of the original ones) were selected for each subject. The set of the most frequently selected ADLs was verified to be representative of the SHFT ADLs in terms of motion strategies, ranges of motion and joint velocities when considering healthy subjects and Hand Osteoarthritis patients.

Results
A set of 10 tasks, the BE-UJI activity set, was identified by ensuring a certain (minimum) similarity in synergy (maximum mean angle between synergies of 25.5°), functional joint ranges (maximum differences of 10°) and joint velocities (maximum differences of 15°/s). The obtained tasks were: pick up coins from purses, lift wooden cubes, pick up nuts and turn them, write with a pen, cut with a knife, lift a telephone, unscrew jar lids and pour water from a cup, a jar and a Pure-Pak. These activities guarantee using the seven commonest handgrips in ADLs.

Conclusion
The BE-UJI activity set for the hand function assessment can be used to obtain quantitative data in clinics as an alternative to the SHFT. It reduces the test time and allows clinicians to obtain objective kinematic data of the motor strategies, ranges of motion and joint velocities used by patients.
A bidirectional fabric-based soft robotic glove for hand function assistance in patients with chronic stroke
Authors: Lim Daniel Yuan-Lee , Lai Hwa-Sen , Yeow Raye Chen-Hua 
Published: September 2023

Abstract
Background
Chronic stroke patients usually experience reduced hand functions, impeding their ability to perform activities of daily living (ADLs) independently. Additionally, improvements in hand functions by physical therapy beyond six months after the initial onset of stroke are much slower than in the earlier months. As such, chronic stroke patients could benefit from an assistive device to enhance their hand functions, allowing them to perform ADLs independently daily. In recent years, soft robotics has provided a novel approach to assistive devices for motor impaired individuals, offering more compliant and lightweight alternatives to traditional robotic devices. The scope of this study is to demonstrate the viability of a fabric-based soft robotic (SR) glove with bidirectional actuators in assisting chronic stroke study participants with hand impairments in performing ADLs.

Methods
Force and torque measurement tests were conducted to characterize the SR Glove, and hand functional tasks were given to eight chronic stroke patients to assess the efficacy of the SR Glove as an assistive device. The tasks involved object manipulation tasks that simulate ADLs, and the series of tasks was done by the participants once without assistance for baseline data, and once while using the SR Glove. A usability questionnaire was also given to each participant after the tasks were done to gain insight into how the SR Glove impacts their confidence and reliance on support while performing ADLs.

Results
The SR Glove improved the participants’ manipulation of objects in ADL tasks. The difference in mean scores between the unassisted and assisted conditions was significant across all participants. Additionally, the usability questionnaire showed the participants felt more confident and less reliant on support while using the SR Glove to perform ADLs than without the SR Glove.

Conclusions
The results from this study demonstrated that the SR Glove is a viable option to assist hand function in chronic stroke patients who suffer from hand motor impairments.