bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of direct therapeutic ultrasound exposure of ovaries on histopathology, inflammatory response, and oxidative stress in dogs
Authors: Rajabi Arian , Mogheiseh Asghar , Nazifi Saeed , Ahrari-Khafi MohammadSaeed , Dehghanian AmirReza , Vesal Nasser , Bigham-Sadegh Amin 
Published: July 2023

Abstract
Background
This research was designed to evaluate the effects of therapeutic ultrasound waves on ovarian germinal tissue and inflammatory cytokines (interleukin-6 (IL-6), IL1β, tumor necrosis factor-α (TNF-α)), acute phase proteins (serum amyloid A (SAA), C reactive protein (CRP)) and oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) in dogs. Twenty-six clinically healthy adult mix-breed female dogs were aligned into three groups. Laparotomy was performed in control (n = 6) and treatment (T5, n = 10; T10, n = 10) groups. The ultrasonic exposure of ovaries in treatment groups was performed during laparotomy by round motions of the therapeutic ultrasonic transducer on both ovaries (1 MHz frequency, 1.5 W⁄cm2) for 5 min in the T5 group and for 10 min in the T10 group. Blood samples were collected from the jugular vein into a plain glass tube on days 0 (before laparotomy), 3, 6, and 9 after surgery. All control and treatment groups’ dogs were ovariectomized for histological evaluation on day 60 after laparotomy or laparotomy + ultrasound exposure.

Results
Direct exposure of ovaries with therapeutic ultrasound waves induced inflammation and oxidative stress comparison with the control group. Histopathological evaluation of treated ovaries with ultrasound waves indicated a decreased number of primordial follicles (ovarian reserve) and oocyte preservation scores compared with ovaries in the control group.

Conclusions
These changes may cause subfertility in the long term. It seems that inflammatory response and oxidative stress are factors in the permanent damage of ovarian tissue.
The role of community health workers in primary healthcare in the WHO-EU region: a scoping review
Authors: Van Iseghem Tijs , Jacobs Ilka , Vanden Bossche Dorien , Delobelle Peter , Willems Sara , Masquillier Caroline , Decat Peter 
Published: July 2023

AbstractBackgroundExisting evidence on the role of community health workers (CHWs) in primary healthcare originates primarily from the United States, Canada and Australia, and from low- and middle-income countries. Little is known about the role of CHWs in primary healthcare in European countries. This scoping review aimed to contribute to filling this gap by providing an overview of literature reporting on the involvement of CHWs in primary healthcare in WHO-EU countries since 2001 with a focus on the role, training, recruitment and remuneration.MethodsThis systematic scoping review followed the guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analyses, extension for Scoping Reviews. All published peer-reviewed literature indexed in PubMed, Web of Science, and Embase databases from Jan 2001 to Feb 2023 were reviewed for inclusion. Included studies were screened on title, abstract and full text according to predetermined eligibility criteria. Studies were included if they were conducted in the WHO-EU region and provided information regarding the role, training, recruitment or remuneration of CHWs.ResultsForty studies were included in this review, originating from eight countries. The involvement of CHWs in the WHO-EU regions was usually project-based, except in the United Kingdom. A substantial amount of literature with variability in the terminology used to describe CHWs, the areas of involvement, recruitment, training, and remuneration strategies was found. The included studies reported a trend towards recruitment from within the communities with some form of training and payment of CHWs. A salient finding was the social embeddedness of CHWs in the communities they served. Their roles can be classified into one or a combination of the following: educational; navigational and supportive.ConclusionFuture research projects involving CHWs should detail their involvement and elaborate on CHWs’ role, training and recruitment procedures. In addition, further research on CHW programmes in the WHO-EU region is necessary to prepare for their integration into the broader national health systems.
Extracellular vesicles: a rising star for therapeutics and drug delivery
Authors: Du Shuang , Guan Yucheng , Xie Aihua , Yan Zhao , Gao Sijia , Li Weirong , Rao Lang , Chen Xiaojia , Chen Tongkai 
Published: July 2023

AbstractExtracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood–brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.
Graphical Abstract
Core patient-reported outcome measures for chronic pain patients treated with spinal cord stimulation or dorsal root ganglia stimulation
Authors: Huygen Frank , Hagedorn Jonathan M. , Falowski Steven , Schultz David , Vesper Jan , Heros Robert D. , Patterson Denis G. , Dehghan Soroush , Ross Erika , Kyani Anahita , Mansouri Misagh B. , Kallewaard Jan Willem 
Published: July 2023

Abstract
Background
Neurostimulation is a highly effective therapy for the treatment of chronic Intractable pain, however, due to the complexity of pain, measuring a subject’s long-term response to the therapy remains difficult. Frequent measurement of patient-reported outcomes (PROs) to reflect multiple aspects of subjects’ pain is a crucial step in determining therapy outcomes. However, collecting full-length PROs is burdensome for both patients and clinicians. The objective of this work is to identify the reduced set of questions from multiple validated PROs that can accurately characterize chronic pain patients’ responses to neurostimulation therapies.

Methods
Validated PROs were used to capture pain, physical function and disability, as well as psychometric, satisfaction, and global health metrics. PROs were collected from 509 patients implanted with Spinal Cord Stimulation (SCS) or Dorsal Root Ganglia (DRG) neurostimulators enrolled in the prospective, international, post-market REALITY study (NCT03876054, Registration Date: March 15, 2019). A combination of linear regression, Pearson’s correlation, and factor analysis were used to eliminate highly correlated questions and find the minimal meaningful set of questions within the predefined domains of each scale.

Results
The shortened versions of the questionnaires presented almost identical accuracy for classifying the therapy outcomes as compared to the validated full-length versions. In addition, principal component analysis was performed on all the PROs and showed a robust clustering of pain intensity, psychological factors, physical function, and sleep across multiple PROs. A selected set of questions captured from multiple PROs can provide adequate information for measuring neurostimulation therapy outcomes.

Conclusions
PROs are important subjective measures to evaluate the physiological and psychological aspects of pain. However, these measures are cumbersome to collect. These shorter and more targeted PROs could result in better patient engagement, and enhanced and more frequent data collection processes for digital health platforms that minimize patient burden while increasing therapeutic benefits for chronic pain patients.
Perspectives in Immunotherapy: meeting report from Immunotherapy Bridge (Naples, November 30th–December 1st, 2022)
Authors: Ascierto Paolo A. , Avallone Antonio , Bifulco Carlo , Bracarda Sergio , Brody Joshua D. , Emens Leisha A. , Ferris Robert L. , Formenti Silvia C. , Hamid Omid , Johnson Douglas B. , Kirchhoff Tomas , Klebanoff Christopher A. , Lesinski Gregory B. , Monette Anne , Neyns Bart , Odunsi Kunle , Paulos Chrystal M. , Powell Daniel J. , Rezvani Katayoun , Segal Brahm H. , Singh Nathan , Sullivan Ryan J. , Fox Bernard A. , Puzanov Igor 
Published: July 2023

AbstractThe discovery and development of novel treatments that harness the patient’s immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. These new approaches are focused on patients with an inadequate response to current treatments, with emerging evidence of improved responses in various cancers with new immunotherapy agents, often in combinations with existing agents. The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th–December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer.
Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma
Authors: Zhang Dawei , Ni Yuanli , Wang Yongquan , Feng Juan , Zhuang Na , Li Jiatao , Liu Limei , Shen Wenhao , Zheng Ji , Zheng Wei , Qian Cheng , Shan Juanjuan , Zhou Zhansong 
Published: July 2023

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response.

Methods
Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response.

Results
We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype.

Conclusion
Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.
Ensemble learning model for identifying the hallmark genes of NFκB/TNF signaling pathway in cancers
Authors: Su Yin-Yuan , Liu Yu-Ling , Huang Hsuan-Cheng , Lin Chen-Ching 
Published: July 2023

Abstract
Background
The nuclear factor kappa B (NFκB) regulatory pathways downstream of tumor necrosis factor (TNF) play a critical role in carcinogenesis. However, the widespread influence of NFκB in cells can result in off-target effects, making it a challenging therapeutic target. Ensemble learning is a machine learning technique where multiple models are combined to improve the performance and robustness of the prediction. Accordingly, an ensemble learning model could uncover more precise targets within the NFκB/TNF signaling pathway for cancer therapy.

Methods
In this study, we trained an ensemble learning model on the transcriptome profiles from 16 cancer types in the TCGA database to identify a robust set of genes that are consistently associated with the NFκB/TNF pathway in cancer. Our model uses cancer patients as features to predict the genes involved in the NFκB/TNF signaling pathway and can be adapted to predict the genes for different cancer types by switching the cancer type of patients. We also performed functional analysis, survival analysis, and a case study of triple-negative breast cancer to demonstrate our model's potential in translational cancer medicine.

Results
Our model accurately identified genes regulated by NFκB in response to TNF in cancer patients. The downstream analysis showed that the identified genes are typically involved in the canonical NFκB-regulated pathways, particularly in adaptive immunity, anti-apoptosis, and cellular response to cytokine stimuli. These genes were found to have oncogenic properties and detrimental effects on patient survival. Our model also could distinguish patients with a specific cancer subtype, triple-negative breast cancer (TNBC), which is known to be influenced by NFκB-regulated pathways downstream of TNF. Furthermore, a functional module known as mononuclear cell differentiation was identified that accurately predicts TNBC patients and poor short-term survival in non-TNBC patients, providing a potential avenue for developing precision medicine for cancer subtypes.

Conclusions
In conclusion, our approach enables the discovery of genes in NFκB-regulated pathways in response to TNF and their relevance to carcinogenesis. We successfully categorized these genes into functional groups, providing valuable insights for discovering more precise and targeted cancer therapeutics.
Occurrence of Eucoleus aerophilus in wild and domestic animals: a systematic review and meta-analysis
Authors: Samorek-Pieróg Małgorzata , Cencek Tomasz , Łabuć Emilia , Pac-Sosińska Małgorzata , Pieróg Mateusz , Korpysa-Dzirba Weronika , Bełcik Aneta , Bilska-Zając Ewa , Karamon Jacek 
Published: July 2023

Abstract
Background
Eucoleus aerophilus (syn. Capillaria aerophila) is a nematode with a worldwide geographical distribution. It causes a disease called lung capillariosis by affecting the respiratory tract of wild and domestic animals, and has also occasionally been described in humans. Despite steady increases in knowledge of the morphology of this neglected parasite, many aspects are still poorly understood. Epidemiological data regarding, for example, geographic distribution, range of hosts, clinical relevance and the actual zoonotic potential of this nematode are scarce and incomplete.

Methods
This article is a systematic review based on the screening of three databases (PubMed, Web of Science and Science Direct) to identify eligible studies published from 1973 to the end of 2022.

Results
From a total of 606 studies describing the occurrence of E. aerophilus, 141 articles from 38 countries worldwide were included in this meta-analysis, all of which presented results obtained mainly with flotation and necropsy. Due to the occurrence of E. aerophilus in many different species and different matrices (lungs and faeces), we decided to conduct the meta-analysis separately for each species with a given matrix. This systematic review confirmed the status of the Red fox as the main reservoir and main transmitter of E. aerophilus (average prevalence of 43% in faeces and 49% in lungs) and provided evidence of a higher prevalence of E. aerophilus in wild animals in comparison to domestic animals, such as dogs (3% in faeces) and cats (2% in faeces and 8% in lungs). Previous studies have investigated many host-related factors (age, sex, environmental/living conditions) in relation to the prevalence of E. aerophilus, but they show wide variations and no simple relationship has been demonstrates. Furthermore, mixed infections with other pulmonary nematodes, such as Crenosoma vulpis and/or Angiostrongylus vasorum, are reported very frequently, which greatly complicates the diagnosis.

Conclusions
This systematic review focused on identifying data gaps and promoting future research directions in this area. To the best of our knowledge, this is the first systematic review that evaluates and summarizes existing knowledge on the occurrence and prevalence of E. aerophilus in wild and domestic animals originating from different geographical locations worldwide.

Graphical Abstract
The impact of medical insurance on family financial support: evidence from CHARLS in China
Authors: Cao Yuan , Chen Hua , Yang Xiaoxu 
Published: July 2023

Abstract
Background
In China, public medical insurance has expanded rapidly in the past 20 years. Many studies have discussed the benefits of medical insurance in improving residents’ health and financial stability, and increasing the utilization of medical services. Less attention is paid to the effect of medical insurance on family support between parents and children. This study focuses on the effect of medical insurance on promoting family financial support in China.

Method
Fifty-five thousand sixty-two individual samples were obtained from four waves of the China Health and Retirement Longitudinal Study (CHARLS): 2011, 2013, 2015 and 2018. Linear-regression model and propensity score matching are used to determine the relationship between medical insurance and family financial support. Then, mediation model is introduced to identify the mediation mechanisms. Also, moderation model is used to estimate the moderation effect of parental education and health.

Results
Medical insurance has significantly increased family financial support between the insured parents and their children. Moreover, this positive effect is heterogeneous since only families living in rural areas were affected, and the direction of family financial support changed with the aging of the parents. The welfare of medical insurance on financial status have also been proven in this paper. The results indicate that medical insurance reduces the out-of-pocket ratio of medical expenses and increases health investment, which can perform as as two mediation mechanisms to affect family financial support. Besides, the education and health status of the insured parents play a role in moderating the effect of medical insurance.
TurboID screening of ApxI toxin interactants identifies host proteins involved in Actinobacillus pleuropneumoniae-induced apoptosis of immortalized porcine alveolar macrophages
Authors: Hu Yaofang , Jiang Changsheng , Zhao Yueqiao , Cao Hua , Ren Jingping , Zeng Wei , Zhang Mengjia , Li Yongtao , He Qigai , Li Wentao 
Published: July 2023

AbstractActinobacillus pleuropneumoniae (APP) is a gram-negative pathogenic bacterium responsible for porcine contagious pleuropneumonia (PCP), which can cause porcine necrotizing and hemorrhagic pleuropneumonia. Actinobacillus pleuropneumoniae-RTX-toxin (Apx) is an APP virulence factor. APP secretes a total of four Apx toxins, among which, ApxI demonstrates strong hemolytic activity and cytotoxicity, causing lysis of porcine erythrocytes and apoptosis of porcine alveolar macrophages. However, the protein interaction network between this toxin and host cells is still poorly understood. TurboID mediates the biotinylation of endogenous proteins, thereby targeting specific proteins and local proteomes through gene fusion. We applied the TurboID enzyme-catalyzed proximity tagging method to identify and study host proteins in immortalized porcine alveolar macrophage (iPAM) cells that interact with the exotoxin ApxI of APP. His-tagged TurboID-ApxIA and TurboID recombinant proteins were expressed and purified. By mass spectrometry, 318 unique interacting proteins were identified in the TurboID ApxIA-treated group. Among them, only one membrane protein, caveolin-1 (CAV1), was identified. A co-immunoprecipitation assay confirmed that CAV1 can interact with ApxIA. In addition, overexpression and RNA interference experiments revealed that CAV1 was involved in ApxI toxin-induced apoptosis of iPAM cells. This study provided first-hand information about the proteome of iPAM cells interacting with the ApxI toxin of APP through the TurboID proximity labeling system, and identified a new host membrane protein involved in this interaction. These results lay a theoretical foundation for the clinical treatment of PCP.
A qualitative interview study of patient experiences of receiving motivational enhancement therapy in a Swedish addiction specialist treatment setting
Authors: Ingesson Hammarberg Stina , Sundbye Jennie , Tingvall Rebecca , Hammarberg Anders , Nehlin Christina 
Published: July 2023

Abstract
Background
Motivational enhancement therapy (MET) has shown to be efficacious as treatment of alcohol use disorder (AUD), in reducing alcohol consumption and related consequences. However, qualitative research on how patients perceive this treatment is lacking. The aim of this study was to explore how patients experience MET as a treatment for AUD.

Methods
Fifteen patients (8/7 female/male) participated in semi-structured interviews after receiving MET at a specialized addiction outpatient clinic in Sweden. Data were analyzed by thematic analysis.

Results
Five themes were identified: the therapist conveyed the MI-spirit, the therapist did not guide on how to reach the goal, participants were committed to change before starting treatment, participants were uncertain if treatment was enough to maintain change, and significant others were not wanted in sessions. Participants appreciated the supportive relationship with their therapist, but some experienced therapy as overly positive, with no room to talk about failure. Further, they experienced a low level of guidance in goal-setting. For some, this was empowering, while others requested more direction and advice. Participants perceived their motivational process to have started before treatment. MET was considered to be too brief. None of the participants brought a significant other to a session.

Conclusions
Therapist behaviors in line with MI spirit were emphasized as key to the development of a positive therapeutic relationship. More specific advice on goal-setting may be effective for supporting change in some patients. Longer treatment is requested among patients to support the patient’s self-efficacy for change. Significant others can support change without necessarily being present in sessions.
Trial registration: The current trial was retrospectively registered at isrtcn.com (14539251).