bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic potential of NRG1 in benign nerve sheath tumors and its influence on the PI3K-Akt signaling and tumor immunity
Authors: Yan Suwei , Zhao Jingnan , Gao Pengyang , Li Zhaoxu , Li Zhao , Liu Xiaobing , Wang Pengfei 
Published: February 2024

Abstract
Objective
Benign nerve sheath tumors (BNSTs) present diagnostic challenges due to their heterogeneous nature. This study aimed to determine the significance of NRG1 as a novel diagnostic biomarker in BNST, emphasizing its involvement in the PI3K-Akt pathway and tumor immune regulation.

Methods
Differential genes related to BNST were identified from the GEO database. Gene co-expression networks, protein-protein interaction networks, and LASSO regression were utilized to pinpoint key genes. The CIBERSORT algorithm assessed immune cell infiltration differences, and functional enrichment analyses explored BNST signaling pathways. Clinical samples helped establish PDX models, and in vitro cell lines to validate NRG1’s role via the PI3K-Akt pathway.

Results
Nine hundred eighty-two genes were upregulated, and 375 downregulated in BNST samples. WGCNA revealed the brown module with the most significant difference. Top hub genes included NRG1, which was also determined as a pivotal gene in disease characterization. Immune infiltration showed significant variances in neutrophils and M2 macrophages, with NRG1 playing a central role. Functional analyses confirmed NRG1’s involvement in key pathways. Validation experiments using PDX models and cell lines further solidified NRG1’s role in BNST.

Conclusion
NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.
Direct osteosynthesis in the treatment of atlas burst fractures: a systematic review
Authors: Niu He-Gang , Zhang Jing-Jing , Yan Yi-Zhu , Yang Kun , Zhang Yin-Shun 
Published: February 2024

Abstract
Purpose
The treatment of unstable atlas fractures remains a controversial topic. The study aims at assessing the prognosis and efficacy of osteosynthesis for unstable atlas fractures through a review of the current literature and additionally aims to compare outcomes between the transoral and posterior approaches.

Methods
A systematic review of databases including PubMed, EMBASE, Cochrane, Web of Science, CNKI, and Wanfang was conducted. Titles and abstracts were screened by two reviewers to identify studies meeting pre-defined inclusion criteria for comprehensive analysis.

Results
The systematic review included 28 articles, 19 employing the posterior approach and 9 utilizing the transoral approach. It covered osteosynthesis in 297 patients with unstable atlas fractures, comprising 169 treated via the posterior approach and 128 via the transoral approach. Analysis revealed high healing rates and clinical improvement in both approaches, evidenced by improvements in the visual analog scale, range of motion, atlantodens interval, and lateral displacement distance post-surgery.

Conclusion
Osteosynthesis offers effective treatment for unstable atlas fractures. Both transoral and posterior approaches can achieve good clinical outcomes for fracture, and biomechanical studies have confirmed that osteosynthesis can maintain the stability of the occipitocervical region, preserve the motor function of the atlantoaxial and occipito-atlantoaxial joints, and greatly improve the quality of life of patients. However, variations exist in the indications and surgical risks associated with each method, necessitating their selection based on a thorough clinical evaluation of the patient's condition.
Simple and secure thrombectomy without circulatory arrest for acute pulmonary embolism
Authors: Sasaki Hanae , Kowatari Ryosuke , Kondo Norihiro , Minakawa Masahito 
Published: February 2024

Abstract
Background
Surgical pulmonary artery thrombectomy is a well-established emergency treatment for massive pulmonary embolism (PE) in which fibrinolysis or thrombolysis are not effective. However, surgery for massive PE that requires peripheral pulmonary artery thrombus removal remains challenging. We established a simple and secure pulmonary artery thrombectomy method using cardiopulmonary bypass and cardiac arrest. In this procedure, the surgical assistant arm, typically used for coronary artery bypass grafting, is used to obtain a feasible working space during thrombectomy.

Case presentation
We present seven consecutive massive PE cases that were treated with the present surgical method and successfully weaned from cardiopulmonary bypass or extracorporeal membrane oxygenation postoperatively.

Conclusions
This procedure can be used to prevent right ventricular failure after surgery as surgeons can remove the peripheral thrombus with clear vision up to the second branch of the pulmonary artery.
Modified blade: an interventional option in rigid bronchoscopy for non-resectable benign tracheal stenosis
Authors: Messina Gaetana , Di Filippo Vincenzo , Capasso Francesca , Puca Maria Antonietta , Leonardi Beatrice , Grande Mario , Rainone Anna , Leone Francesco , Vicario Giuseppe , De Gregorio Simona , Cerullo Giuseppe , Ponticiello Antonio , Pirozzi Mario , Farese Stefano , Zotta Alessia , Natale Giovanni , Messina Giovanni , Vicidomini Giovanni , Fiorelli Alfonso , Ciardiello Fortunato , Fasano Morena 
Published: February 2024

Abstract
Introduction
Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis.

Materials and methods
The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o’clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure.

Result
We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of ‘Luigi Vanvitelli’ of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis.

Conclusion
Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.
RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling
Authors: Zhou Yu-Jiao , Yang Min-Li , He Xin , Gu Hui-Ying , Ren Ji-Hua , Cheng Sheng-Tao , Fu Zhou , Zhang Zhen-Zhen , Chen Juan 
Published: February 2024

Abstract
Background
Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood.

Methods
By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis.

Results
Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7.

Conclusions
Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.
Molecular insights versus morphological traits: rethinking identification of the closely related Angiostrongylus cantonensis and Angiostrongylus malaysiensis
Authors: Kaenkaew Chanisara , Chan Abigail Hui En , Saralamba Naowarat , Ruangsittichai Jiraporn , Chaisiri Kittipong , Charoennitiwat Vachirapong , Thaenkham Urusa 
Published: February 2024

Abstract
Background
The closely related Angiostrongylus cantonensis and Angiostrongylus malaysiensis have been reported to coexist in Thailand and share similar hosts and life cycles. Recently, in an angiostrongyliasis outbreak in Thailand, both A. cantonensis and A. malaysiensis were found in the cerebrospinal fluid of affected patients. Morphological similarities, overlapping distribution, shared hosts and habitats, and the close genetics of the two Angiostrongylus species can complicate accurate species identification. Addressing these challenges, this study aims to evaluate whether a correlation between the morphological and genetic identities of A. cantonensis and A. malaysiensis can improve species identification accuracy.

Methods
Angiostrongylus spp. specimens from five zoogeographical regions in Thailand were subjected to morphological and molecular identification using the mitochondrial cytochrome b gene and the nuclear internal transcribed spacer 2 region (ITS2). The morphological characters for males and females were then validated using the species identity obtained from the nuclear ITS2 region.

Results
The results revealed that morphological misidentifications between these two closely related species are common due to overlapping morphological characters. Although certain male traits such as body length and width aided species differentiation, female traits were found to be less reliable. Furthermore, hybrid forms (8.2%) were revealed through the ITS2 results, which can further complicate morphological identification. Mito-nuclear discordance was also present in 1.9% of the Angiostrongylus specimens from Thailand, suggesting a complex historical interbreeding between the species.

Conclusions
Based on our findings, we suggest that nuclear ITS2 is a reliable marker for species identification of A. cantonensis and A. malaysiensis, especially in regions where both species coexist. Additionally, the scope and consequences of hybridization between the two closely related Angiostrongylus species should be further investigated in Thailand.

Graphical Abstract
Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg
Authors: Ukalovic Dubravka , Leeb Burkhard F. , Rintelen Bernhard , Eichbauer-Sturm Gabriela , Spellitz Peter , Puchner Rudolf , Herold Manfred , Stetter Miriam , Ferincz Vera , Resch-Passini Johannes , Zwerina Jochen , Zimmermann-Rittereiser Marcus , Fritsch-Stork Ruth 
Published: February 2024

Abstract
Objectives
Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg).

Methods
Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted.

Results
The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54–0.78); adalimumab, 0.70 (95% CI, 0.68–0.74); certolizumab, 0.84 (95% CI, 0.79–0.89); etanercept, 0.68 (95% CI, 0.55–0.87); tocilizumab, 0.72 (95% CI, 0.69–0.77).
The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD.

Conclusion
Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.
Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney
Authors: Sandersfeld Mira , Büttner-Herold Maike , Ferrazzi Fulvia , Amann Kerstin , Benz Kerstin , Daniel Christoph 
Published: February 2024

Abstract
Background
Macrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters.

Methods
Using immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients.

Results
The frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease.

Conclusion
Although M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.
Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report
Authors: Pethő Ákos , Schnabel Karolina , Dézsi László 
Published: February 2024

Abstract
Background
Hemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment.

Case presentation
This report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful.

Conclusion
Numerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here.
The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy
Authors: Ahmed Toka A. , Ahmed Sara M. , Elkhenany Hoda , El-Desouky Mohamed A. , Magdeldin Sameh , Osama Aya , Anwar Ali Mostafa , Mohamed Ihab K. , Abdelgawad Mohamed Essameldin , Hanna Demiana H. , El-Badri Nagwa 
Published: February 2024

Abstract
Background
Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs.

Methods
PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days.

Results
Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-β, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain.

Conclusion
These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Graphical abstract
Diversity of endophytic bacteria isolated from leguminous agroforestry trees in western Kenya
Authors: Emitaro William Omuketi , Kawaka Fanuel , Musyimi David Mutisia , Adienge Asenath 
Published: February 2024

AbstractPlants have diverse and vast niches colonized by endophytic microorganisms that promote the wellbeing of host plant. These microbes inhabit internal plant tissues with no signs of ill health. Bacterial endophytes from many plants have been isolated and characterized due to their beneficial roles however their diversity in leguminous plants still remain unexploited. Diversity of bacterial endophytes isolated from Sesbania sesban, Leucaena diversifolia and Calliandra calothyrsus was assessed using morphological and molecular characteristics. A total of 27 pure isolates were recovered from C. Calothyrsus, L. diversifolia and S. sesban constituting 44.4%, 33.3% and 22.2% from the leaves, stems and roots respectively. The isolates differentiated into Gram positive and negative with rods and spherical shapes. Analysis of 16S rRNA gene sequences revealed 8 closely related bacterial genera that consisted of Bacillus (33.3%), Staphylococcus (22.2%), Alcaligens (11.1%), Pantoea (11.1%), Xanthomonas,and Sphingomonas (7.4%) each. Others included Acinetobacter, and Pseudomonas at 3.7% each. Bacterial endophytes of genus bacillus were isolated from all the three plants. These results indicate the presence of high diversity of endophytic bacteria associated with the different parts of L. diversifolia, S. sesban and C. salothyrsus growing in western Kenya.