bluuebunny/crossref_metadata_2025_split huggingface dataset:
Musashi-2 in cancer-associated fibroblasts promotes non-small cell lung cancer metastasis through paracrine IL-6-driven epithelial-mesenchymal transition
Authors: Samart Parinya , Heenatigala Palliyage Gayathri , Issaragrisil Surapol , Luanpitpong Sudjit , Rojanasakul Yon 
Published: November 2023

Abstract
Background
Lung cancer, the most common cause of cancer-related mortality worldwide, is predominantly associated with advanced/metastatic disease. The interaction between tumor cells and cancer-associated fibroblasts (CAFs) in tumor microenvironment is known to be essential for regulating tumor progression and metastasis, but the underlying mechanisms, particularly the role of RNA-binding protein Musashi-2 (MSI2) in CAFs in promoting non-small cell lung cancer (NSCLC) invasiveness and metastatic spread, remain obscure.

Methods
Genomic and proteomic database analyses were performed to evaluate the potential clinical significance of MSI2 in NSCLC tumor and stromal clinical specimens. Molecular approaches were used to modify MSI2 in CAFs and determine its functional role in NSCLC cell motility in vitro using 2D and 3D models, and in metastasis in a xenograft mouse model using live-cell imaging.

Results
MSI2, both gene and protein, is upregulated in NSCLC tissues and is associated with poor prognosis and high metastatic risk in patients. Interestingly, MSI2 is also upregulated in NSCLC stroma and activated fibroblasts, including CAFs. Depletion of MSI2 in CAFs by CRISPR-Cas9 strongly inhibits NSCLC cell migration and invasion in vitro, and attenuates local and distant metastatic spread of NSCLC cells in vivo. The crosstalk between CAFs and NSCLC cells occurs via paracrine signaling, which is regulated by MSI2 in CAFs via IL-6. The secreted IL-6 promotes epithelial-mesenchymal transition in NSCLC cells, which drives metastasis.

Conclusion
Our findings reveal for the first time that MSI2 in CAFs is important in CAF-mediated NSCLC cell invasiveness and metastasis via IL-6 paracrine signaling. Therefore, targeting the MSI2/IL-6 axis in CAFs could be effective in combating NSCLC metastasis.
Mechanisms and biomarkers of immune-related adverse events in gastric cancer
Authors: Ding Ping’an , Liu Pengpeng , Meng Lingjiao , Zhao Qun 
Published: November 2023

AbstractImmune-checkpoint inhibitors (ICIs), different from traditional cancer treatment models, have shown unprecedented anti-tumor effects in the past decade, greatly improving the prognosis of many malignant tumors in clinical practice. At present, the most widely used ICIs in clinical immunotherapy for a variety of solid tumors are monoclonal antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) and their ligand PD-L1. However, tumor patients may induce immune-related adverse events (irAEs) while performing immunotherapy, and irAE is an obstacle to the prospect of ICI treatment. IrAE is a non-specific disease caused by immune system imbalance, which can occur in many tissues and organs. For example, skin, gastrointestinal tract, endocrine system and lung. Although the exact mechanism is not completely clear, related studies have shown that irAE may develop through many ways. Such as excessive activation of autoreactive T cells, excessive release of inflammatory cytokines, elevated levels of autoantibodies, and common antigens between tumors and normal tissues. Considering that the occurrence of severe IrAE not only causes irreversible damage to the patient’s body, but also terminates immunotherapy due to immune intolerance. Therefore, accurate identification and screening of sensitive markers of irAE are the main beneficiaries of ICI treatment. Additionally, irAEs usually require specific management, the most common of which are steroids and immunomodulatory therapies. This review aims to summarize the current biomarkers for predicting irAE in gastric cancer and their possible mechanisms.
Classification and analysis of common simplifications in part-scale thermal modelling of metal additive manufacturing processes
Authors: Ranjan Rajit , Langelaar Matthijs , Van Keulen Fred , Ayas Can 
Published: November 2023

AbstractComputational process modelling of metal additive manufacturing has gained significant research attention in recent past. The cornerstone of many process models is the transient thermal response during the AM process. Since deposition-scale modelling of the thermal conditions in AM is computationally expensive, spatial and temporal simplifications, such as simulating deposition of an entire layer or multiple layers, and extending the laser exposure times, are commonly employed in the literature. Although beneficial in reducing computational costs, the influence of these simplifications on the accuracy of temperature history is reported on a case-by-case basis. In this paper, the simplifications from the existing literature are first classified in a normalised simplification space based on assumptions made in spatial and temporal domains. Subsequently, all types of simplifications are investigated with numerical examples and compared with a high-fidelity reference model. The required numerical discretisation for each simplification is established, leading to a fair comparison of computational times. The holistic approach to the suitability of different modelling simplifications for capturing thermal history provides guidelines for the suitability of simplifications while setting up a thermal AM model.
Does early adversity predict aggression among Chinese male violent juvenile offenders? The mediating role of life history strategy and the moderating role of meaning in life
Authors: Gong Yuandong , Li Qingtian , Li Jiazheng , Wang Xinning , Jiang Wenning , Zhao Weiguo 
Published: November 2023

Abstract
Background
Adolescent aggression has long been of interest to researchers. However, few studies have examined the influencing factors and mechanisms of aggression among violent juvenile offenders. This study tests a moderated mediation model with Chinese male violent juvenile offenders as subjects. Specifically, it explores the relationship between early adversity and aggression, as well as the mechanisms of life history strategy and meaning in life in this relationship.

Methods
A total of 537 Chinese male violent juvenile offenders completed the Childhood Environment Scale, the Life History Strategy Short Form Scale, the Aggression Questionnaire, and the Meaning in Life Questionnaire. After controlling for socioeconomic status (SES), the current cross-sectional study used structural equation modeling (SEM) to examine a moderated mediation model.

Results
The results showed that life history strategy mediated the relationship between early adversity and aggression, and early adversity affected individuals’ aggression by accelerating their life history strategies. The results also showed that meaning in life moderated the relationship between early adversity and life history strategy. For individuals with high meaning in life scores, the negative predictive effect of early adversity on life history strategy was stronger than that for individuals with low meaning in life scores.

Conclusion
The results of this study can advance the understanding of how early adversity affects aggression among violent juvenile offenders and provide theoretical support for prison staff to develop educational strategies and subsequent interventions.
Intra‐articular injections in sport‐active patients with degenerative cartilage lesions or osteoarthritis of the knee: a systematic review
Authors: De Marziani Luca , Sangiorgio Alessandro , Bensa Alessandro , Boffa Angelo , Andriolo Luca , Filardo Giuseppe 
Published: November 2023

AbstractPurposeThe aim of this systematic review was to analyse the available clinical evidence on intra‐articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis (OA) in sport‐active patients.MethodsA literature search was performed in July 2023 according to the PRISMA guidelines on three electronic databases (PubMed, Cochrane, Web of Science). Studies addressing intra‐articular injections for degenerative knee cartilage lesions or knee OA in sport‐active patients were included. The Downs and Black’s “checklist for measuring quality” was used to evaluate risk of bias and quality of the included studies.ResultsOnly 10 clinical studies for a total of 296 sport‐active patients were included, with a publication trend increasing over time. The studies were 9 case series and 1 RCT; 7 studies focused on hyaluronic acid (HA), 2 studies focused on platelet‐rich plasma (PRP), while 1 study compared HA and PRP. Overall, safety and positive clinical findings were for both HA and PRP, although not always with satisfactory results in terms of return to sport. The Downs and Black evaluation showed an overall poor quality of the included studies, with an average score of 21.1 points (range 19–25).ConclusionsThe available clinical evidence is still limited, with only a few studies published and an overall low‐quality of evidence, suggesting a potential role of HA and PRP injections to treat these patients. However, further high‐level trials are needed to confirm the real benefits of these treatments for the management of sport‐active patients affected by degenerative cartilage lesions or OA of the knee.
Study on active capacity and detergent application potential of low-temperature alkaline serine protease produced by new strain Exiguobacterium indicum 1.2.3
Authors: Kati Ahmet , Balci Gamze 
Published: November 2023

AbstractMicroorganisms have long captivated researchers for their potential to produce enzymes with diverse industrial applications. Efficient production of proteases from new strains is crucial as these enzymes play a vital role in breaking down protein bonds, enabling their use in industrial applications. Therefore, a novel Exiguobacterium indicum 1.2.3 was isolated (Istanbul, Turkiye) and characterized in this study. This strain produced alkaline serine protease, which works in lower temperatures (20–40 °C) with casein as a specific substrate. The protease was utterly stable for 3 h at 30 °C. The enzyme was also highly stable in the pH range of 8–11. The optimum activity was obtained at pH 10. The crude enzyme activity was enhanced by various metal ions and retained 147%, 125%, 124%, and 117% of its activity within 1 mM Ca2+, Mn2+, Cu2+, and Mg2+, respectively. The crude enzyme was inactive with phenylmethylsulfonyl fluoride, indicating a serine residue on the active side. The enzyme exhibited a significant proteolytic effect in the presence of surfactants and oxidizing agents. The addition of Tween 80, Triton X-100, and sodium perborate improved enzymatic activity up to 135%, 109%, and 105%, respectively. According to the washing results, the crude enzyme effectively removed the blood on different types of standard pre-stained textiles at 30 °C. In conclusion, Exiguobacterium indicum 1.2.3 is a promising candidate for protease production, with its diverse applications spanning various industrial sectors, particularly detergents.
Graphical Abstract
Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer
Authors: Tang Lu , Huang Zhong-Pei , Mei Heng , Hu Yu 
Published: November 2023

AbstractAdvances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice. Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design, guide gene-based T cell modification, and optimize the CAR-T manufacturing conditions, and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes. The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy. Specifically, we provide an overview of single-cell studies focusing on target antigens, CAR-transgene integration, and preclinical research and clinical applications, and then discuss how it will affect the future of CAR-T cell therapy.
Akt signaling pathway: a potential therapy for Alzheimer’s disease through glycogen synthase kinase 3 beta inhibition
Authors: Limantoro Joshua , de Liyis Bryan Gervais , Sutedja Jane Carissa 
Published: November 2023

AbstractAlzheimer’s disease (AD) is a form of dementia marked by the accumulation of neuritic plaques and neurofibrillary tangles through the action of GSK-3β with both significant epidemiological and clinical impact. Current pharmacological treatment approaches are focused on symptomatic relief and aims to suppress AD’s progression rather than disease modification. This issue has triggered further investigations about tau pathology as an important component in AD’s pathophysiology, one of them being the Akt signaling pathway. Based on the problem served by AD, combined with the non-existence of conclusive therapy for this disease; hence, this study strives to further investigate the potential therapeutical benefit of Akt signaling towards AD. A total of 82 studies are included, consisting of both national and international articles creating a narrative review based on the PRISMA checklist. Variables searched on this study, include Alzheimer’s disease (AD), Akt signaling, serine-9 phosphorylation, and GSK-3β. Tau protein accumulation has been a mainstay in the physiopathology of AD, which are largely influenced by the GSK-3β expression. Akt signaling has been shown to inactivate GSK-3β through serine-9 phosphorylation. Thus, modulating and optimizing the Akt signaling pathway present encouraging prospects for the development of innovative and efficacious therapeutic strategies in addressing AD. Several studies have tried to estimate the harm and benefit as well as dose–effect relationship between Akt signaling and AD, concluding a promising beneficial effect for AD therapy. Here, we show the beneficial therapeutic effects of Akt signaling towards AD through both theoretical and empirical standpoints.
Tor network anonymity evaluation based on node anonymity
Authors: Cui Jun , Huang Changqi , Meng Huan , Wei Ran 
Published: November 2023

AbstractIn order to address the shortcomings of traditional anonymity network anonymity evaluation methods, which only analyze from the perspective of the overall network and ignore the attributes of individual nodes, we proposes a dynamic anonymity model based on a self-built anonymous system that combines node attributes, network behavior, and program security monitoring. The anonymity of evaluation nodes is assessed based on stable intervals and behavior baselines defined according to their normal operating status. The anonymity of the network is evaluated using an improved normalized information entropy method that refines anonymity evaluation to the anonymity of each node and expands the dimensionality of evaluation features. This paper compares the effectiveness of our proposed method with static framework information entropy and single indicator methods by evaluating the degree of anonymity provided by a self-built Tor anonymous network under multiple operating scenarios including normal and under attack. Our approach utilizes dynamically changing network anonymity based on multiple anonymous attributes and better reflects the degree of anonymity in anonymous systems.
The alleviative efficacy of sildenafil and chrysin against zinc oxide nanoparticles-provoked hepatic and blood toxicity: role of MyD88/NF-κB1/TNF-α pathway
Authors: Nageeb Mahitab M. , Amer Marwa Abdel-Moniem , Hendawy Doaa M. , Hanafy Sabah Mohamed , Elmenshawi Maha Saad , Elmakromy Gena M. , Moawed Dena Mohamed Naguib Abdel 
Published: November 2023

Abstract
Background
Zinc oxide nanoparticles are nanoparticles of metal oxide with semiconductor properties and proved many noxious effects on the mammalian cell. Sildenafil, a phosphodiesterase inhibitor, and chrysin, one of the flavonoids, proved to have anti-inflammatory and anti-oxidative stress effects.

Methods
48 rats were grouped into 8 groups equally. 1. (Control group) received normal diet and NaOH was added to water, 2. (chrysin group): 250 mg/kg, orally for 10 days, 3. (sildenafil group): 40 mg/kg, orally for 14 days, 4. (ZnO-NPs group): 200 mg/kg, intraperitoneal for 10 days, 5. (ZnO-NPs + chrysin as a prophylactic agent): given in the same previous doses and durations consecutively, 6. (ZnO-NPs + chrysin as a curative agent): given in the same previous doses and durations with chrysin given after ZnO-NPs administration for 10 days, 7. (ZnO-NPs + sildenafil as a curative agent): given in the same previous doses and durations with sildenafil given after ZnO-NPs administration for 10 days, and 8. (Combined treatment group chrysin + sildenafil) as combined treatment were given in the same previous doses and durations after ZnO-NPs administration for 10 days. Blood and samples from tissues were withdrawn for histopathological, biochemical studies, and comet assay at the end of the experiment.

Results
Sildenafil and chrysin proved to protect from hepatotoxicity and hematotoxicity induced by zinc oxide nanoparticles as they lessened aspartate transaminase, alanine transferase, and alkaline phosphatase levels. They also reduced the oxidative stress enzyme levels. Gene expression of myeloid differentiation factor 88, nuclear factor kappa B1, tumor necrosis factor, and DNA damage decreased with treatment. Also, there was an improvement in the histopathological picture of the liver seen with treatment. Concurrent administration of sildenafil and chrysin revealed much better improvement than either drug used alone.

Conclusion
Chrysin and sildenafil have ameliorative effects against ZnO-NPs-induced hepatotoxicity and hematotoxicity, their protective effect is either preventive with chrysin or curative with chrysin and sildenafil.
Herpes zoster ophthalmicus and varicella zoster meningoencephalitis in a newly diagnosed case of retroviral disease: a case report
Authors: Jog Aniruddha , Sawardekar Vinayak M. , Agarwal Arjun 
Published: November 2023

Abstract
Background
Meningoencephalitis and herpes zoster ophthalmicus (HZO) are rare neurological and ocular complications of herpes zoster, respectively. Their co-occurrence is rarer, even in patients with retroviral disease (RVD), and may occur in the presence of normal CD4 count.

Case presentation
A 35-year-old woman presented with altered sensorium. Four days back, she developed left-sided severe, deep burning type headache, and on the next day, painful vesicles developed over the left side of the scalp which progressively involved the forehead, upper part of left cheek, and tip of the nose, with swelling around the eyes. Ophthalmic examination revealed conjunctivitis and keratitis suggesting acute HZO. Neck rigidity was present, and MRI brain was suggestive of acute meningoencephalitis. The DNA polymerase chain reaction of cerebrospinal fluid for varicella zoster virus (VZV) confirmed the diagnosis of acute meningoencephalitis. The search for cause of immunosuppression led to the diagnosis of RVD. Treatment with intravenous acyclovir and dexamethasone led to rapid recovery and clearing of lesions.

Conclusion
VZV infection should be included in the differential diagnosis among patients with newly diagnosed RVD presenting with meningoencephalitis and HZO.
Assessment of atypical pneumonia by chest ultrasonography
Authors: Sayed Ahmed Sameh , Ahmed Mona Mansour , Wagih Khaled Mohamed , Diab Haytham Samy , Hussein Ahmed Mohamed 
Published: November 2023

Abstract
Background
Patients with pneumonia exhibit similar clinical presentations despite having different causative organisms; thus, a rapid and easy test is needed to differentiate between the diseases. Here, we use lung ultrasound to discriminate between causative organisms in correlation with other diagnostic modalities.

Methods
This descriptive cross-sectional study was carried out on 67 patients diagnosed with atypical pneumonia admitted at Ain-Shams University hospitals in the period from July 2019 to June 2021. Study population was divided into three groups according to the causative agent based on the results of PCR: Group 1 included 23 patients (influenza A), group 2 included 30 patients (COVID-19), and group 3 included 14 patients (atypical organisms). Included patients underwent lung ultrasound scan via a 12-zone scanning protocol and CT scan with 24 h in between. The present study was approved by the ethical committee at our institution.

Results
The mean age ranged from 39.93 ± 19.26 SD to 60.3 ± 13.02 SD years; 64.17% of them were males. There was also a highly statistically significant difference between the three groups as regard B-lines and thickened pleural line being higher among group 2; 100% of cases had B-lines in their chest ultrasound assessment, while thickened pleural line was found in 53.3% of cases. Dynamic air bronchogram was found with higher percentage in group 3 (71.4%) with a highly significant association. Higher mean Soldati score was associated with more severe disease among cases with viral pneumonia.

Conclusions
Lung ultrasound may be used as an aiding tool to estimate the etiology of atypical pneumonia. It can be useful during pandemics of acute respiratory diseases for rapid triage and stratification of patients as through calculation of modified Soldati score and detection of the most common finding. Also, modified Soldati score correlates with disease severity.
Safety and efficacy of high flow nasal canula in patients with mild hypercapnia
Authors: Ibrahim Mohammed A. , Emara Magdy , Shehta Mohammed 
Published: November 2023

Abstract
Context
High flow nasal canula is usually used for management of acute hypoxemic failure; however, it may have a potential therapeutic benefits in hypercapnia as it can alter tidal volume, end expiratory volume, positive end expiratory pressure, and respiratory rate.

Aim
Evaluate safety and efficacy of application HFNC (high flow nasal canula) for patients with mild hypercapnia.

Settings and design
A prospective interventional study.

Patients and methods
Over six months, thirty eight patients were enrolled, with mild hypercapnia and PH level not less 7.30 and PaCo2 not more 60 mmhg; with applying HFNC, serial checking of arterial blood gases was done. Checkpoints were at 2 h, 12 h, 24 h, and 48 h post application of HFNC. HFNC can be shifted to NIV or invasive MV at any time whenever indicated.

Results
Primary pulmonary disorder was chronic obstructive pulmonary disorder in (22 patients) and (16 patients) had interstitial lung disease. For PH in overall, mean values had changed from 7.33 until reached 7.37 at 48 h post HFNC with calculation of P value at each checkpoint from baseline value; significant changes were recorded at 24 h and 48 h post HFNC application. A similar observation was observed for PaCO2. No significant changes were observed at any checkpoint for HCO3.

Conclusion
High flow nasal canula is safe in cases with mild hypercapnia with a considerable success rate and a proven high efficacy.

Trial registration
Clinicaltrials.gov/NCT05948527, Registered 14 July 2023—Retrospectively registered, https://www.clinicaltrials.gov/NCT05948527.