bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway
Authors: Zeng Rong , Zhang Dong , Zhang Jintao , Pan Yun , Liu Xiaofei , Qi Qian , Xu Jiawei , Xu Changjuan , Shi Shuochuan , Wang Junfei , Liu Tian , Dong Liang 
Published: June 2024

Abstract
Background
Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma.

Methods
The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor.

Results
Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-β1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression.

Conclusions
Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.
Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT
Authors: Shen Mengling , Guo Li , Zhang Hengyu , Zheng Bingshu , Liu Xinpei , Gu Jingyu , Yang Tao , Sun Chunfeng , Yi Xuan 
Published: June 2024

AbstractRadiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.
Graphical Abstract
Long non-coding RNA MEG3 knockdown represses airway smooth muscle cells proliferation and migration via sponging miR-143-3p/FGF9 in asthma
Authors: Gu Jiaying , Zhou Dengfeng 
Published: June 2024

Abstract
Background
Asthma is a respiratory disease characterized by airway remodeling. We aimed to find out the role and mechanism of lncRNA MEG3 in asthma.

Methods
We established a cellular model of asthma by inducing human airway smooth muscle cells (HASMCs) with PDGF-BB, and detected levels of lncRNA MEG3, miR-143-3p and FGF9 in HASMCs through qRT-PCR. The functions of lncRNA MEG3 or miR-143-3p on HASMCs were explored by cell transfection. The binding sites of miR-143-3p and FGF9 were subsequently analyzed with bioinformatics software, and validated with dual-luciferase reporter assay. MTT, 5-Ethynyl-2’-deoxyuridine (EdU) assay, and Transwell were used to detect the effects of lncRNA MEG3 or miR-143-3p on proliferation and migration of HASMCs. QRT-PCR and western blot assay were used to evaluate the level of proliferation-related marker PCNA in HASMCs.

Results
The study found that lncRNA MEG3 negatively correlated with miR-143-3p, and miR-143-3p could directly target with FGF9. Silence of lncRNA MEG3 can suppress migration and proliferation of PDGF-BB-induced HASMCs via increasing miR-143-3p. Further mechanistic studies revealed that miR-143-3p negatively regulated FGF9 expression in HASMCs. MiR-143-3p could inhibit PDGF-BB-induced HASMCs migration and proliferation through downregulating FGF9.

Conclusion
LncRNA MEG3 silencing could inhibit the migration and proliferation of HASMCs through regulating miR-143-3p/FGF9 signaling axis. These results imply that lncRNA MEG3 plays a protective role against asthma.
Risk factors of pneumothorax in computed tomography guided lung nodule marking using autologous blood: a retrospective study
Authors: Wu Shaohang , Wu Jianyang , Xiong Junkai , Huang Chengbin , Lin Yiwei , Guan Jun , Xu Jianxin 
Published: June 2024

Abstract
Background
To investigate the risk factors of pneumothorax of using computed tomography (CT) guidance to inject autologous blood to locate isolated lung nodules.

Methods
In the First Hospital of Putian City, 92 cases of single small pulmonary nodules were retrospectively analyzed between November 2019 and March 2023. Before each surgery, autologous blood was injected, and the complications of each case, such as pneumothorax and pulmonary hemorrhage, were recorded. Patient sex, age, position at positioning, and nodule type, size, location, and distance from the visceral pleura were considered. Similarly, the thickness of the chest wall, the depth and duration of the needle-lung contact, the length of the positioning procedure, and complications connected to the patient’s positioning were noted. Logistics single-factor and multi-factor variable analyses were used to identify the risk factors for pneumothorax. The multi-factor logistics analysis was incorporated into the final nomogram prediction model for modeling, and a nomogram was established.

Results
Logistics analysis suggested that the nodule size and the contact depth between the needle and lung tissue were independent risk factors for pneumothorax.

Conclusion
The factors associated with pneumothorax after localization are smaller nodules and deeper contact between the needle and lung tissue.
“Decompression illness” on extracorporeal membrane oxygenation
Authors: Hu Jiannan , zhao Huijing , Bian BingBing , San Renfei , Yang Peng , Jiang Yongpo 
Published: June 2024

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) is increasingly being used for critically ill patients with cardiopulmonary failure. Air in the ECMO circuit is an emergency, a rare but fatal complication.

Case presentation
We introduce a case of a 76-year-old female who suffered from cardiac arrest complicated with severe trauma and was administered veno-arterial extracorporeal membrane oxygenation. In managing the patient with ECMO, air entered the ECMO circuit, which had not come out nor was folded or broken. Although the ECMO flow was quickly re-established, the patient died 6 h after initiating ECMO therapy.

Conclusions
In this case report, the reason for the complication is drainage insufficiency. This phenomenon is similar to decompression sickness. Understanding this complication is very helpful for educating the ECMO team for preventing this rare but devastating complication of fatal decompression sickness in patients on ECMO.
Primary graft dysfunction in heart transplantation: the challenge to survival
Authors: Sicim Hüseyin , Tam Wing Sum Vincy , Tang Paul C. 
Published: June 2024

AbstractPrimary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the initial 24 h following heart transplantation, in the absence of a discernible secondary cause. Given its intricate nature, definitive definition and diagnosis of PGD continues to pose a challenge. The pathophysiology of PGD encompasses numerous underlying mechanisms, some of which remain to be elucidated, including factors like myocardial damage, the release of proinflammatory mediators, and the occurrence of ischemia-reperfusion injury. The dynamic characteristics of both donors and recipients, coupled with the inclination towards marginal lists containing more risk factors, together contribute to the increased incidence of PGD. The augmentation of therapeutic strategies involving mechanical circulatory support accelerates myocardial recovery, thereby significantly contributing to survival. Nonetheless, a universally accepted treatment algorithm for the swift management of this clinical condition, which necessitates immediate intervention upon diagnosis, remains absent. This paper aims to review the existing literature and shed light on how diagnosis, pathophysiology, risk factors, treatment, and perioperative management affect the outcome of PGD.
Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma
Authors: Chang Esther Wei Yin , Tan Ya Hwee , Chan Jason Yongsheng 
Published: June 2024

AbstractPeripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage strategy. With further understanding of the molecular pathobiology of PTCL, several innovative approaches incorporating immunomodulatory agents, epigenetic therapies, oncogenic kinase inhibitors and immunotherapeutics have come to the forefront. In this review, we provide a comprehensive overview of the progress in developing clinical prognostic indices for PTCL and describe the broad therapeutic landscape, emphasizing novel targetable pathways that have entered early phase clinical studies.
Integrin-linked kinase-frizzled 7 interaction maintains cancer stem cells to drive platinum resistance in ovarian cancer
Authors: Atwani Rula , Nagare Rohit Pravin , Rogers Amber , Prasad Mayuri , Lazar Virginie , Sandusky George , Tong Yan , Pin Fabrizio , Condello Salvatore 
Published: June 2024

Abstract
Background
Platinum-based chemotherapy regimens are a mainstay in the management of ovarian cancer (OC), but emergence of chemoresistance poses a significant clinical challenge. The persistence of ovarian cancer stem cells (OCSCs) at the end of primary treatment contributes to disease recurrence. Here, we hypothesized that the extracellular matrix protects CSCs during chemotherapy and supports their tumorigenic functions by activating integrin-linked kinase (ILK), a key enzyme in drug resistance.

Methods
TCGA datasets and OC models were investigated using an integrated proteomic and gene expression analysis and examined ILK for correlations with chemoresistance pathways and clinical outcomes. Canonical Wnt pathway components, pro-survival signaling, and stemness were examined using OC models. To investigate the role of ILK in the OCSC-phenotype, a novel pharmacological inhibitor of ILK in combination with carboplatin was utilized in vitro and in vivo OC models.

Results
In response to increased fibronectin secretion and integrin β1 clustering, aberrant ILK activation supported the OCSC phenotype, contributing to OC spheroid proliferation and reduced response to platinum treatment. Complexes formed by ILK with the Wnt receptor frizzled 7 (Fzd7) were detected in tumors and correlated with metastatic progression. Moreover, TCGA datasets confirmed that combined expression of ILK and Fzd7 in high grade serous ovarian tumors is correlated with reduced response to chemotherapy and poor patient outcomes. Mechanistically, interaction of ILK with Fzd7 increased the response to Wnt ligands, thereby amplifying the stemness-associated Wnt/β-catenin signaling. Notably, preclinical studies showed that the novel ILK inhibitor compound 22 (cpd-22) alone disrupted ILK interaction with Fzd7 and CSC proliferation as spheroids. Furthermore, when combined with carboplatin, this disruption led to sustained AKT inhibition, apoptotic damage in OCSCs and reduced tumorigenicity in mice.

Conclusions
This “outside-in” signaling mechanism is potentially actionable, and combined targeting of ILK-Fzd7 may lead to new therapeutic approaches to eradicate OCSCs and improve patient outcomes.
Structure–function characterization of two enzymes from novel subfamilies of manganese peroxidases secreted by the lignocellulose-degrading Agaricales fungi Agrocybe pediades and Cyathus striatus
Authors: Sánchez-Ruiz María Isabel , Santillana Elena , Linde Dolores , Romero Antonio , Martínez Angel T. , Ruiz-Dueñas Francisco Javier 
Published: June 2024

AbstractBackgroundManganese peroxidases (MnPs) are, together with lignin peroxidases and versatile peroxidases, key elements of the enzymatic machineries secreted by white-rot fungi to degrade lignin, thus providing access to cellulose and hemicellulose in plant cell walls. A recent genomic analysis of 52 Agaricomycetes species revealed the existence of novel MnP subfamilies differing in the amino-acid residues that constitute the manganese oxidation site. Following this in silico analysis, a comprehensive structure–function study is needed to understand how these enzymes work and contribute to transform the lignin macromolecule.ResultsTwo MnPs belonging to the subfamilies recently classified as MnP-DGD and MnP-ESD—referred to as Ape-MnP1 and Cst-MnP1, respectively—were identified as the primary peroxidases secreted by the Agaricales speciesAgrocybe pediadesandCyathus striatuswhen growing on lignocellulosic substrates. Following heterologous expression and in vitro activation, their biochemical characterization confirmed that these enzymes are active MnPs. However, crystal structure and mutagenesis studies revealed manganese coordination spheres different from those expected after their initial classification. Specifically, a glutamine residue (Gln333) in the C-terminal tail of Ape-MnP1 was found to be involved in manganese binding, along with Asp35 and Asp177, while Cst-MnP1 counts only two amino acids (Glu36 and Asp176), instead of three, to function as a MnP. These findings led to the renaming of these subfamilies as MnP-DDQ and MnP-ED and to re-evaluate their evolutionary origin. Both enzymes were also able to directly oxidize lignin-derived phenolic compounds, as seen for other short MnPs. Importantly, size-exclusion chromatography analyses showed that both enzymes cause changes in polymeric lignin in the presence of manganese, suggesting their relevance in lignocellulose transformation.ConclusionsUnderstanding the mechanisms used by basidiomycetes to degrade lignin is of particular relevance to comprehend carbon cycle in nature and to design biotechnological tools for the industrial use of plant biomass. Here, we provide the first structure–function characterization of two novel MnP subfamilies present in Agaricales mushrooms, elucidating the main residues involved in catalysis and demonstrating their ability to modify the lignin macromolecule.
Metals profile of milled shrimps and the potential risk associated with their consumption
Authors: Nkansah Marian Asantewah , Adrewie Dominic , Quarm Ida Sandra , Obiri -Yeboah Seth , Dodd Matt 
Published: June 2024

AbstractThe presence of metals in milled shrimps sold on some major markets in Kumasi were investigated to ascertain their levels and the potential health risk they may pose to humans when ingested, due to the level of pollution in the marine environment where these shrimps are obtained from. The samples, which comprised of 30 composites, were analysed using x-ray florescence spectrometry and found to contain Co, Cr, Cu, Fe, K, Mo, Ca, Zn, As, Sr, and Zr with average concentrations of 4.09 mg kg− 1, 5.17 mg kg− 1, 25.14 mg kg− 1, 351.47 mg kg− 1, 9050.74 mg kg− 1, 4.08 mg kg− 1, 21984.48 mg kg− 1, 696.89 mg kg− 1, 8.99 mg kg− 1, 328.54 mg kg− 1, and 9.86 mg kg− 1 respectively. Non-carcinogenic risk indicators analysed suggested a likelihood of health hazard when the milled shrimps are ingested, particularly concerning is the levels of arsenic determined. The arsenic may, however, be in organic form which will make it less of a concern. The levels of the metals could not be linked statistically to the milling process after comparing them to procured controls, which may suggest that these metals may have been picked up in the aquatic environment and/or prior to milling. There is a need, therefore, for action to reduce pollution and remediate the aquatic environment.
The effect of the sense of Community on Depression, Anxiety, and Stress: the mediation role of a balanced time perspective
Authors: Micillo Luigi , Canale Natale , Naddeo Davide , Cellini Nicola , Mioni Giovanna 
Published: June 2024

Abstract
Purpose
Social context and time are two dimensions within which our entire existence is embedded. Therefore, prompting a positive set of attitudes and beliefs towards these elements is fundamental for individuals’ psychological well-being. Currently, there is limited understanding regarding the interplay between the sense of community and time perspective in relation to psychological distress. The present study aims, at investigating the effects that the sense of community and time perspective have on the levels of anxiety, depression, and stress. Particular attention has been dedicated to testing whether the effect of sense of community on anxiety, depression, and stress is mediated by the deviation from a balanced time perspective.

Methods
To accomplish our purposes, we asked 352 participants to complete an online survey and respond to the Depression, Anxiety, Stress Scale (DASS-21), the Zimbardo Time Perspective Inventory (ZTPI), and the Multi-Dimensional Sense of Community Scale (MTSOCS). From these scales, we obtained the scores for anxiety, depression, and stress as well as a general score for the sense of community and the deviation from a balanced time perspective. We computed three General Linear Mediation Models, one for each scale of the DASS-21.

Results
The results showed that the relationship between sense of community and psychological distress was mediated by the deviation from a balanced time perspective extending previous findings and enriching the existing literature on time perspective.

Conclusion
The results described so far could be applied to build a series of interventions aimed at promoting psychological well-being in the general population. Considering our findings, we suggest that individuals’ health could be promoted by both improving their sense of community, which in turn would decrease their levels of stress, and by restructuring their time perspective when it became dysfunctional and unbalanced.
The power of animation: encouraging doctors to access support for psychological wellbeing
Authors: Tooman Tricia R. , Wakeling Judy , Cunningham Kathryn B. , Smith Kathrine Gibson , Walker Kim A. , Cecil Joanne E. , Laidlaw Anita 
Published: June 2024

AbstractThe COVID-19 pandemic has exacerbated already high rates of poor psychological wellbeing in doctors. Many doctors perceive a stigma associated with acknowledging psychological wellbeing concerns, resulting in a reluctance to seek support for those concerns. The aim of this study was to develop a theoretically-informed and evidence-based composite narrative animation (CNA) to encourage doctors to access support for psychological wellbeing, and to evaluate the acceptability of the CNA.A composite narrative was developed from an evidence-base of interviews with 27 GP participants across Scotland (May–July 2020). The Behaviour Change Wheel was used to identify behaviour change techniques (BCTs) to be embedded within the CNA. The narrative was turned into a script in collaboration with an animation company. A brief animation ‘Jane the GP’ was developed reflecting specific BCTs.Scottish doctors (n = 83) were asked for their views on acceptability of the CNA concept, and subsequently asked to provide views on the acceptability of the CNA after viewing it. Participants thought the concept of a CNA was novel but may not appeal to all. After viewing the CNA, the widespread view was that it portrayed an authentic experience, could reduce stigma around seeking support for psychological wellbeing, and highlighted formal routes to access such support.CNAs are a novel and acceptable intervention method for encouraging doctors to access support for psychological wellbeing. The use of a theory driven intervention development framework to create the CNA facilitates the link between theory and practice.
Destinations after higher education non-completion: the role of social background and pre-tertiary vocational qualifications
Authors: Tieben Nicole 
Published: June 2024

AbstractPrior research has shown that students from lower socio-economic backgrounds are less likely to graduate. We examine if this can be explained by background-specific pathways into higher education. Many students in Germany enter higher education with a vocational qualification and prior vocational qualifications occur more often among students from lower socio-economic backgrounds. We argue that vocational qualifications shift opportunity structures and opportunity costs of students who have to decide between continuing higher education and alternative options. We therefore examine if parental background and vocational qualifications are associated with the destinations after non-completion. We distinguish the destinations “re-entering higher education”, “vocational training” and “skilled employment”. Using the German Educational Panel Study (NEPS starting cohort 6), we apply competing risks models. Our results show that non-completers from higher socio-economic backgrounds are more likely to re-enter higher education than non-completers from lower socio-economic backgrounds. The higher rates of transfer to skilled employment among non-completers from lower backgrounds are mainly due to the fact that they more often hold a vocational qualification and have good chances to enter the skilled labour market without additional educational investments. Our results hence shed some new light on the question how vocational training “diverts” lower background students from higher education.