bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Buerger’s rabbit model: a closer step to unravelling thromboangiitis obliterans?
Authors: Li Jia-Long , Kwan Kristine J. S. , Lin Xue-Guang , Wang Jie , Chen Bo , Lu Yi-Jie , Wang Bo , Xie Shi-Shuai , Zhou Jiong , Yu Bo , Deng Ying , Jiang Shuai , Tang Jing-Dong 
Published: July 2024

Abstract
Objective
Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO.

Methods
Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic).

Results
The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group.

Conclusion
The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.
Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma
Authors: Sun Yifang , Wu Jian , Zhang Qian , Wang Pengzhen , Zhang Jinglin , Yuan Yonggang 
Published: July 2024

Abstract
Background
Although there has been some progress in the treatment of primary uveal melanoma (UVM), distant metastasis remains the leading cause of death in patients. Monitoring, staging, and treatment of metastatic disease have not yet reached consensus. Although more than half of metastatic tumors (62%) are diagnosed within five years after primary tumor treatment, the remainder are only detected in the following 25 years. The mechanisms of UVM metastasis and its impact on prognosis are not yet fully understood.

Methods
scRNA-seq data of UVM samples were obtained and processed, followed by cell type identification and characterization of macrophage subpopulations. High-dimensional weighted gene co-expression network analysis (HdWGCNA) was performed to identify key gene modules associated with metastatic protective macrophages (MPMφ) in primary samples, and functional analyses were conducted. Non-negative matrix factorization (NMF) clustering and immune cell infiltration analyses were performed using the MPMφ gene signatures. Machine learning models were developed using the identified metastatic protective macrophages related genes (MPMRGs) to distinguish primary from metastatic patients. A deep learning convolutional neural network (CNN) model was constructed based on MPMRGs and cell type associations. Lastly, a prognostic model was established using the MPMRGs and validated in independent cohorts.

Results
Single-cell RNA-seq analysis revealed a unique immune microenvironment landscape in primary samples compared to metastatic samples, with an enrichment of macrophage cells. Using HdWGCNA, MPMφ and marker genes were identified. Functional analysis showed an enrichment of genes related to antigen processing progress and immune response. Machine learning and deep learning models based on key genes showed significant effectiveness in distinguishing between primary and metastatic patients. The prognostic model based on key genes demonstrated substantial predictive value for the survival of UVM patients.

Conclusion
Our study identified key macrophage subpopulations related to metastatic samples, which have a profound impact on shaping the tumor immune microenvironment. A prognostic model based on macrophage cell genes can be used to predict the prognosis of UVM patients.
Cross-talk between circRNAs and m6A modifications in solid tumors
Authors: Liu Fenfang , Gu Wendong , Shao Yingjie 
Published: July 2024

AbstractCircular RNAs (circRNAs) possess unique biological properties and distribution characteristics that enable a variety of biological functions. N6-methyladenosine (m6A), a prevalent epigenetic modification in organisms, is regulated by factors including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). These factors play critical roles in various pathophysiological processes. There is growing evidence that m6A modifications are common within circRNAs, affecting their synthesis, translation, translocation, degradation, and stability. Additionally, circRNAs regulate biological processes that influence m6A modifications. This review explores the metabolism and functions of m6A modifications and circRNAs, their interactions, and their specific regulatory mechanisms in different tumors, offering insights into m6A-circRNA interaction in cancer.
Current landscape and comprehensive management of glycemic variability in diabetic retinopathy
Authors: Chen Bo , Shen Chaozan , Sun Bao 
Published: July 2024

AbstractDiabetic retinopathy (DR), a well-known microvascular complication of diabetes mellitus, remains the main cause of vision loss in working-age adults worldwide. Up to now, there is a shortage of information in the study regarding the contributing factors of DR in diabetes. Accumulating evidence has identified glycemic variability (GV), referred to fluctuations of blood glucose levels, as a risk factor for diabetes-related complications. Recent reports demonstrate that GV plays an important role in accounting for the susceptibility to DR development. However, its exact role in the pathogenesis of DR is still not fully understood. In this review, we highlight the current landscape and relevant mechanisms of GV in DR, as well as address the mechanism-based therapeutic strategies, aiming at better improving the quality of DR management in clinical practice.
New insights into metabolism dysregulation after TBI
Authors: Oft Helena C. , Simon Dennis W. , Sun Dandan 
Published: July 2024

AbstractTraumatic brain injury (TBI) remains a leading cause of death and disability that places a great physical, social, and financial burden on individuals and the health system. In this review, we summarize new research into the metabolic changes described in clinical TBI trials, some of which have already shown promise for informing injury classification and staging. We focus our discussion on derangements in glucose metabolism, cell respiration/mitochondrial function and changes to ketone and lipid metabolism/oxidation to emphasize potentially novel biomarkers for clinical outcome prediction and intervention and offer new insights into possible underlying mechanisms from preclinical research of TBI pathology. Finally, we discuss nutrition supplementation studies that aim to harness the gut/microbiome-brain connection and manipulate systemic/cellular metabolism to improve post-TBI recovery. Taken together, this narrative review summarizes published TBI-associated changes in glucose and lipid metabolism, highlighting potential metabolite biomarkers for clinical use, the cellular processes linking these markers to TBI pathology as well as the limitations and future considerations for TBI “omics” work.
Surgical intervention for lung cancer in patients aged 75 and above: potential associations with increased mortality rates—a single-center observational study
Authors: Kaprin Andrey , Pikin Oleg , Ryabov Andrey , Aleksandrov Oleg , Larionov Denis , Garifullin Airat 
Published: July 2024

Abstract
Background
Lung cancer, which is diagnosed two to three times more frequently in patients over the age of 70, is a leading cause of cancer-specific mortality. Given the elevated risk of morbidity and mortality, surgical intervention may not always be the most appropriate primary treatment option. This study aims to evaluate specific risk factors associated with postoperative morbidity and mortality in elderly patients and to optimize patient selection therefore improving surgical outcomes.

Patients and methods
The study encompassed a cohort of 73 patients aged 75 and above who underwent surgical treatment for non-small cell lung cancer (NSCLC) at the Department of Thoracic Surgery of the P. Hertsen Moscow Oncological Research Institute between 2015 and 2021. All patients underwent preoperative evaluation, including PET/CT staging and functional assessment, carried out by a multidisciplinary team comprising thoracic surgeons, anesthesiologists, and other medical specialists.

Results
The investigation revealed a postoperative mortality rate of 5.5% and a postoperative morbidity incidence of 16.4%, with occurrences of atrial fibrillation in 41.6%, persistent air leak in 33.3%, and pneumonia in 25% of complicated cases. At the one-year follow-up, 88% of patients remained free from relapse, whereas at three years, this rate stood at 66%. During the follow-up period, 16 patients (22%) passed away, with a median survival duration of 44 months. Survival rates at one year, three years, and five years were 71%, 66%, and 35%, respectively. Multivariate analysis disclosed several significant factors predicting a complex postoperative period, including stage IIIb (p = 0.023), pN1 (p = 0.049), pN2 (p = 0.030), and central location (p = 0.007). Additionally, overall survival was primarily influenced by a Charlson comorbidity index of 6 (p = 0.044), stage Ia2 (p = 0.033), and the necessity for thoracotomy (p = 0.045).

Conclusion
Each case of lung cancer in patients aged 75 and older necessitates an individualized approach. Given the higher mortality rate relative to younger patients, comprehensive risk assessment and preoperative management of underlying comorbidities are imperative, with the involvement of anesthesiologists, intensive care physicians, cardiologists, and other relevant specialists as needed.
Clinical characteristics and prognosis of paediatric respiratory syncytial virus-related encephalopathy
Authors: He Yushan , Liu Gang , Zhuo Xiuwei , Tian Xiaojuan , Liu Jun , Xu Xiaomeng , Qian Suyun 
Published: July 2024

Abstract
Background
To understand the clinical characteristics and prognosis of respiratory syncytial virus (RSV)-related encephalopathy in children.

Methods
A retrospective analysis of the data of children who were diagnosed with RSV-related encephalopathy and admitted to the paediatric intensive care unit (PICU) of Beijing Children’s Hospital between November 2016 and November 2023 was performed.

Results
Four hundred and sixty-four children with RSV infection were treated in the PICU, and eight of these patients (1.7%) were diagnosed with RSV-related encephalopathy. The mean age of the patients was 24.89 (5.92 ∼ 36.86) months. Two patients had underlying diseases. The time from the onset of illness to impaired consciousness was 3 (1.88–3.75) days. Five patients had convulsions, and three patients had an epileptic status. The serum procalcitonin (PCT) level was 1.63 (0.24, 39.85) ng/ml for the eight patients, and the cerebrospinal fluid (CSF) protein level was 232 (163 ∼ 848) g/L. Among the 8 patients, four patients underwent electroencephalogram (EEG) monitoring or examination. One patient showed continuous low-voltage, nonresponsive activity, and another patient displayed persistent slow waves, the remaining two patients had negative results. One patient had a combination of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Additionally, one patient had ANE, and another had acute brain swelling (ABS). One patient died in the hospital, and the other seven patients were discharged with improvement. Routine follow-up was conducted for 4.58(0.5 ∼ 6.50) years, and all patients fully recovered.

Conclusions
RSV-related encephalopathy could have varying clinical manifestations, and some types, such as ANE and ABS, are dangerous and can lead to death.
Human leukocyte antigen HLA-B*57:01 status in HIV-1 patients developing hypersensitivity reactions in Benin: a pilot study
Authors: Adechina Adefounke Prudencia , Assogba Yaou Pierrot , Tchiakpe Edmond , Yessoufou Akadiri 
Published: July 2024

Abstract
Background
Antiretroviral drugs in people living with HIV-1 (PLHIV-1) often trigger side effects which may lead to discontinuation or failure of treatment. Human Leukocyte Antigen B*57:01 (HLA-B*57:01) allele is known to predict hypersensitivity reactions to Abacavir. Very few data are available on the prevalence of HLA-B*57:01 allele in PLHIV-1 in African countries. This study aimed to screen for HLA-B*57:01 allele in PLHIV-1 in Benin.

Methods
This pilot study was carried out on one hundred ten PLHIV-1 enrolled in two health facilities in Benin. Socio-demographic and clinical data were collected. Biological data were determined and HLA-B*57:01 allele was genotyped, using Single Specific Primer-Polymerase Chain Reaction in blood samples.

Results
70% of participants were female. PLHIV-1 were under TDF + 3TC + DTG (47.2%) or TDF + 3TC + EFV (57.3%). Their median age was 41 [36-48.75] years and the average CD4 + T cell count was 249 [130-381.25] cells/µl. The average viral load in treatment failure PLHIV-1 was 4.7 [3.9–5.2] Log10. At the inclusion date, twenty-nine (26.4%) PLHIV-1 under TDF + 3TC + EFV have developed hypersensitivity reactions. None of 110 patients had shown HLA-B*5701 allele.

Conclusion
Our study revealed that HLA-B*57:01 allele was very rare in PLHIV-1 in Benin, suggesting that its screening before starting the Abacavir regimen did not seem necessary.
Community overview on the differential prevalence of Hepatitis E in two sub-counties in Kitgum District, Uganda: a mixed study design
Authors: Aloyo Judith , Kiguli Juliet , Orach Christopher Garimoi , Kitara David Lagoro 
Published: July 2024

Abstract
Background
An epidemic of Hepatitis E infection occurred in Kitgum district, northern Uganda in 2009. In that epidemic, more than 10,422 people were infected, and over 166 deaths were registered. Kitgum District Health Management Information Systems (HMIS) showed that Hepatitis E cases continued to occur in Mucwini more than in Kitgum Matidi sub-county despite instituting similar epidemic control measures in the two communities. The tenacity of the virus in Mucwini sub-county had remained unclear. This study aimed to assess communities’ views and perspectives on the differential prevalence of Hepatitis E in the two sub-counties of Kitgum Matidi and Mucwini in northern Uganda.

Methods
A mixed study using qualitative and quantitative methods was used. Four Focus group discussions and six key informant interviews were conducted with the village health teams, local council chairpersons, health workers, and community members. These participants were chosen purposively because of their expertise and experience in community health services. Face-to-face interview guides were administered to obtain detailed information on factors associated with the differential occurrence of Hepatitis E in the two sub-counties. This study was approved by a local IRB and the Uganda National Council of Science and Technology (UNCS&T).

Results
The most substantial findings were the differences in prevention and control practices in the two communities. Residents of Mucwini were less compliant with infection, prevention, and control guidelines, and disagreements between local councilors and village health teams in Mucwini over allowances led to poor implementation and non-adherence to guidelines on community control of the epidemic.

Conclusion
A differentially higher prevalence of Hepatitis E in Mucwini than in Kitgum Matidi resulted from poor personal and community hygiene and non-adherence to behavior change communication among residents of Mucwini than their counterparts in Kitgum Matidi. The authors recommend a more proactive approach to managing an epidemic by securing the willingness of the affected community to adopt appropriate infection prevention and control guidelines. In addition, disagreements among stakeholders should be resolved quickly so that all community members adhere to control measures.
Umbilical cord blood derived cell expansion: a potential neuroprotective therapy
Authors: Penny Tayla R. , Jenkin Graham , Miller Suzanne L. , McDonald Courtney A. 
Published: July 2024

AbstractUmbilical cord blood (UCB) is a rich source of beneficial stem and progenitor cells with known angiogenic, neuroregenerative and immune-modulatory properties. Preclinical studies have highlighted the benefit of UCB for a broad range of conditions including haematological conditions, metabolic disorders and neurological conditions, however clinical translation of UCB therapies is lacking. One barrier for clinical translation is inadequate cell numbers in some samples meaning that often a therapeutic dose cannot be achieved. This is particularly important when treating adults or when administering repeat doses of cells. To overcome this, UCB cell expansion is being explored to increase cell numbers. The current focus of UCB cell expansion is CD34+ haematopoietic stem cells (HSCs) for which the main application is treatment of haematological conditions. Currently there are 36 registered clinical trials that are examining the efficacy of expanded UCB cells with 31 of these being for haematological malignancies. Early data from these trials suggest that expanded UCB cells are a safe and feasible treatment option and show greater engraftment potential than unexpanded UCB. Outside of the haematology research space, expanded UCB has been trialled as a therapy in only two preclinical studies, one for spinal cord injury and one for hind limb ischemia. Proteomic analysis of expanded UCB cells in these studies showed that the cells were neuroprotective, anti-inflammatory and angiogenic. These findings are also supported by in vitro studies where expanded UCB CD34+ cells showed increased gene expression of neurotrophic and angiogenic factors compared to unexpanded CD34+ cells. Preclinical evidence demonstrates that unexpanded CD34+ cells are a promising therapy for neurological conditions where they have been shown to improve multiple indices of injury in rodent models of stroke, Parkinson’s disease and neonatal hypoxic ischemic brain injury. This review will highlight the current application of expanded UCB derived HSCs in transplant medicine, and also explore the potential use of expanded HSCs as a therapy for neurological conditions. It is proposed that expanded UCB derived CD34+ cells are an appropriate cellular therapy for a range of neurological conditions in children and adults.
miR-340-3p-modified bone marrow mesenchymal stem cell-derived exosomes inhibit ferroptosis through METTL3-mediated m6A modification of HMOX1 to promote recovery of injured rat uterus
Authors: Xiao Bang , Zhu Yiqing , Liu Meng , Chen Meiting , Huang Chao , Xu Dabing , Wang Fang , Sun Shuhan , Huang Jinfeng , Sun Ningxia , Yang Fu 
Published: July 2024

Abstract
Background
Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia–reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive.

Methods
The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs.

Results
We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3′-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury.

Conclusions
Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.