bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotrophin-3 promotes peripheral nerve regeneration by maintaining a repair state of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway
Authors: Xu Xiong , Song Lili , Li Yueying , Guo Jin , Huang Shuo , Du Shuang , Li Weizhen , Cao Rangjuan , Cui Shusen 
Published: October 2023

Abstract
Background
Maintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms.

Methods
Western blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation.

Results
After peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway.

Conclusion
NT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation.
Evaluating a scalable ARCHES (Addressing Reproductive Coercion in Health Settings) model in government health facilities in Uasin Gishu county, Kenya: study protocol for a cluster-randomized controlled trial
Authors: Pearson Erin , Uysal Jasmine , Menzel Jamie , Undie Chi-Chi , Odwe George , Liambila Wilson , Silverman Jay G. 
Published: October 2023

Abstract
Background
Since 2013, the World Health Organization has recommended that reproductive coercion (RC) and intimate partner violence (IPV) be addressed within reproductive health services and, in 2018, the Lancet Commission on Sexual and Reproductive Health and Rights found that RC and IPV were significant contributors to unmet need for family planning (FP) and unintended pregnancy. In Kenya, the Ministry of Health (MOH) has made reduction of unintended pregnancy and gender-based violence a primary objective. Despite this need and guidance, no clinic-based intervention models outside of the U.S. (apart from the one described here) have demonstrated efficacy to improve FP use and reduce IPV or RC thereby reducing unintended pregnancy. ARCHES (Addressing Reproductive Coercion in Health Settings) is a brief, clinic-based intervention delivered by existing FP providers aiming to: (1) Increase women’s ability to use FP without interference, (2) Provide a safe and supportive environment for IPV disclosure and referral to support services, and (3) Improve quality of FP counseling, including addressing RC and IPV. The objective of this study is to generate evidence on scaling integrated FP services (including FP, RC, and IPV) in public sector health facilities in Uasin Gishu county, Kenya via adaptation and implementation of ARCHES in partnership with the Kenya MOH.

Methods
A cluster-randomized controlled trial paired with concurrent implementation science assessments will test effectiveness of the ARCHES model, adapted for scale by the Kenya MOH, in reducing unintended pregnancy. Female FP clients aged 15–49 years at selected sites will complete baseline surveys (immediately prior to receiving care), immediately post-visit exit surveys, and 6-month follow-up surveys. Provider surveys will assess changes in gender-equitable attitudes and self-efficacy to address violence reported by their clients. Costs associated with scaling ARCHES will be tracked and utilized in combination with results of the effectiveness trial to assess costs and cost-effectiveness relative to the standard of care.

Discussion
This study will provide evidence of the effectiveness of a facility-based intervention to address RC and IPV within public sector FP services at scale, as adapted and implemented in Uasin Gishu county, Kenya.
Trial registration Trial registered on 28 September 2023 with clinicaltrials.gov NCT06059196.
Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing
Authors: Lu Yining , Luo Yang , Zhang Qi , Chen Wei , Zhang Ning , Wang Ling , Zhang Yingze 
Published: October 2023

Abstract
Background
Hip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune profiles in elderly hip fracture patients from post-trauma to the recovery period, investigating the dynamic changes of immune inflammation regulation subgroups.

Methods
We collected peripheral blood samples from four elderly hip fracture patients (two males and two females, all > 75 years of age) at three different time points (24 h post-trauma, 24 h post-operation, and day 7 post-operation) and applied scRNA-seq technique to analyze the cellular heterogeneity and identify differentially expressed genes in peripheral blood individual immune cells from elderly hip fracture patients.

Results
In this study, we analyzed the composition and gene expression profiles of peripheral blood mononuclear cells (PBMCs) from elderly hip fracture patients by scRNA-seq and further identified new CD14 monocyte subpopulations based on marker genes and transcriptional profiles. Distinct gene expression changes were observed in various cell subpopulations at different time points. C-Mono2 monocyte mitochondria-related genes were up-regulated and interferon-related and chemokine-related genes were down-regulated within 24 h post-operation. Further analysis of gene expression profiles at day 7 post-operation showed that C-Mono2 monocytes showed downregulation of inflammation-related genes and osteoblast differentiation-related genes. However, the expression of these genes in cytotoxic T cells, Treg cells, and B cell subsets exhibited a contrasting trend. GZMK+CD8+ cytotoxic T cells showed downregulation of chemokine-related genes, and Treg cells showed upregulation of genes related to the JAK/STAT signaling pathway. Furthermore, we examined interactions among diverse immune cell subsets, pinpointing specific ligand-receptor pairs. These findings imply cross-talk and communication between various cell types in the post-traumatic immune response.

Conclusions
Our study elucidates the notable alterations in immune cell subpopulations during different stages of hip fracture in elderly patients, both in terms of proportions and differential gene expressions. These changes provide significant clinical implications for tissue repair, infection prevention, and fracture healing in clinic.
Partial sternectomy with reconstruction of a giant cell tumor of the sternum, a case report, Saudi, Arabia
Authors: Eldaabossi Safwat , Al-Ghoneimy Yasser , Antar Ahmad , Lotfy Elsaid , Aljawad Hameed , Abish Yasser G. , Helyl Mohammed , Oraby Haytham , Soliman Hesham , Abdullatif Bassam , Nour Sameh O. , Lotfi Ahmad 
Published: October 2023

Abstract
Background
Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor that rarely affects the sternum.

Case presentation
We report a case of giant cell tumor of the sternum in a 28-year-old Saudi with painful swelling at the lower part of the sternum. Subtotal sternectomy and reconstruction with a neosternum using two layers of proline mesh, a methyl methacrylate prosthesis, and bilateral pectoralis muscle advancement flaps were performed.

Conclusions
Giant cell tumor of the sternum is a rare diagnosis. Surgical resection with negative margins is the ideal management. To avoid defects or instability of the chest wall, reconstruction of the chest wall with neosternum should be considered.
Exploring hematic crasis variations in cancer patients following SARS-CoV-2 vaccination: a real-practice study
Authors: Montella Liliana , Dell’Aversana Carmela , Pacella Daniela , Troise Simona , Russo Paola , Cacciapuoti Valentina , Ottaiano Alessandro , Di Marino Luigi , Coppola Paola , Liguori Carmela , Berretta Massimiliano , Maddaluno Salvatore , Altucci Lucia , Facchini Gaetano 
Published: October 2023

AbstractSARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech’s COMIRNATY (BNT162b2 mRNA) and Moderna’s mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population.
KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations
Authors: Wang Kaiqing , Gong Zhicheng , Chen Yanyan , Zhang Meimei , Wang Suzeng , Yao Surui , Liu Zhihui , Huang Zhaohui , Fei Bojian 
Published: October 2023

Abstract
Background
Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based “one-two punch” therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations.

Results
We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the “one-two punch’ therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin.

Conclusions
This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel ‘one-two punch’ therapeutic strategy for the more malignant gastric cancer subtypes.
Cellular vimentin regulates the infectivity of Newcastle disease virus through targeting of the HN protein
Authors: Lu Xiaolong , Liu Kaituo , Chen Yu , Gao Ruyi , Hu Zenglei , Hu Jiao , Gu Min , Hu Shunlin , Ding Chan , Jiao Xinan , Wang Xiaoquan , Liu Xiufan , Liu Xiaowen 
Published: October 2023

AbstractThe haemagglutinin-neuraminidase (HN) protein plays a crucial role in the infectivity and virulence of Newcastle disease virus (NDV). In a previous study, the mutant HN protein was identified as a crucial virulence factor for the velogenic variant NDV strain JS/7/05/Ch, which evolved from the prototypic vaccine strain Mukteswar. Furthermore, macrophages are the main susceptible target cells of NDV. However, the possible involvement of cellular molecules in viral infectivity remains unclear. Herein, we elucidate the crucial role of vimentin, an intermediate filament protein, in regulating NDV infectivity through targeting of the HN protein. Using LC‒MS/MS mass spectrometry and coimmunoprecipitation assays, we identified vimentin as a host protein that differentially interacted with prototypic and mutant HN proteins. Further analysis revealed that the variant NDV strain induced more significant rearrangement of vimentin fibres compared to the prototypic NDV strain and showed an interdependence between vimentin rearrangement and virus replication. Notably, these mutual influences were pronounced in HD11 chicken macrophages. Moreover, vimentin was required for multiple infection processes of the variant NDV strain in HD11 cells, including viral internalization, fusion, and release, while it was not necessary for those of the prototypic NDV strain. Collectively, these findings underscore the pivotal role of vimentin in NDV infection through targeting of the HN protein, providing novel targets for antiviral treatment strategies for NDV.
Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study
Authors: Giosa Lorenzo , Collins Patrick Duncan , Sciolla Martina , Cerrone Francesca , Di Blasi Salvatore , Macrì Matteo Maria , Davicco Luca , Laguzzi Andrea , Gorgonzola Fabiana , Penso Roberto , Steinberg Irene , Muraccini Massimo , Perboni Alberto , Russotto Vincenzo , Camporota Luigi , Bellani Giacomo , Caironi Pietro 
Published: October 2023

Abstract
Background
in COVID-19 acute respiratory failure, the effects of CPAP and FiO2 on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO2 delivered via oxygen masks.

Methods
In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO2) and Venturi mask (FiO2 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics.

Results
We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH2O, p < 0.01). However, Helmet’s pressure decreased by a comparable amount during inspiration (− 3.1 ± 1.0 cmH2O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from − 4.5 to + 6.1 cmH2O, and from − 5.8 to + 5.7 cmH2O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO2 decreased from NRB to Helmet-CPAP with FiO2 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet’s FiO2 0.9, PaO2 increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO2 fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81).

Conclusions
In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO2 provide better oxygenation with lower respiratory effort.
Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517.
Reliability-aware failure recovery for cloud computing based automatic train supervision systems in urban rail transit using deep reinforcement learning
Authors: Zhu Li , Zhuang Qingheng , Jiang Hailin , Liang Hao , Gao Xinjun , Wang Wei 
Published: October 2023

AbstractAs urban rail transit construction advances with information technology, modernization, information, and intelligence have become the direction of development. A growing number of cloud platforms are being developed for transit in urban areas. However, the increasing scale of urban rail cloud platforms, coupled with the deployment of urban rail safety applications on the cloud platform, present a huge challenge to cloud reliability.One of the key components of urban rail transit cloud platforms is Automatic Train Supervision (ATS). The failure of the ATS cloud service would result in less punctual trains and decreased traffic efficiency, making it essential to research fault tolerance methods based on cloud computing to improve the reliability of ATS cloud services. This paper proposes a proactive, reliability-aware failure recovery method for ATS cloud services based on reinforcement learning. We formulate the problem of penalty error decision and resource-efficient optimization using the advanced actor-critic (A2C) algorithm. To maintain the freshness of the information, we use Age of Information (AoI) to train the agent, and construct the agent using Long Short-Term Memory (LSTM) to improve its sensitivity to fault events. Simulation results demonstrate that our proposed approach, LSTM-A2C, can effectively identify and correct faults in ATS cloud services, improving service reliability.
Upregulation of BMP1 through ncRNAs correlates with adverse outcomes and immune infiltration in clear cell renal cell carcinoma
Authors: Gong Mancheng , Feng Shengxing , Zhou Dongsheng , Luo Jinquan , Lin Tianxin , Qiu Shaopeng , Yuan Runqiang , Dong Wenjing 
Published: October 2023

Abstract
Background
Renal cell carcinoma (RCC) accounts for approximately 2–3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70–80% of all RCC cases, is the most common histological subtype.

Methods
ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated.

Results
BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression.

Conclusion
Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.