bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of network pharmacology, molecular docking-based strategy, and vitro assays to determine potential pharmacological mechanism of Dioscoreae bulbiferae and Bruceae fructus against laryngocarcinoma
Authors: Wu Zhongbiao , Zhu Zhongyan , Cao Jian , Wu Weikun , Deng Chengcheng , Xie Qiang , Hu Shiping 
Published: December 2023

Background:
Based on network pharmacology, molecular docking, and vitro assays, investigate the probable pharmacological mechanism of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma.

Methods:
The active components and targets of Dioscoreae bulbiferae and Bruceae fructus were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Targets linked with laryngocarcinoma were gathered from the GeneCards, DisGeNET, and DrugBank databases. The String database was utilized to build a protein–protein interaction network of common medication and illness targets, after which the core targets were filtered out. The Metascape database served for gene ontology enrichment and Kyoto encyclopedia of genes and genomes pathway analysis of common targets. AutoDock then performed molecular docking between the essential component and the vital target. To investigate the biological effects of diosbulbin B, we assessed the viability of laryngocarcinoma cells after diosbulbin B therapy using the Mahalanobis Taguchi system technique. Following that, we looked at how diosbulbin B affected colony formation after 14 days of culture of treated cells. Flow cytometry was utilized to detect apoptosis in order to examine the influence of diosbulbin B on laryngocarcinoma cell apoptosis.

Results:
According to a study of the literature, the fundamental components of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma include brusatol and diosbulbin B, which may operate on core targets such as cyclin D1, Cyclin Dependent Kinase Inhibitor 1A, and E2F Transcription Factor 1. The significant pathways discovered using Kyoto encyclopedia of genes and genomes enrichment analysis were the phosphoinositide 3-kinase-protein kinase B signaling route, the tumor necrosis factor signaling pathway, and so on. These pathways primarily influence the development and prognosis of laryngeal cancer by controlling cell growth, cell proliferation, angiogenesis, tumorigenesis, and metastasis. The molecular docking studies revealed that the affinity between the heart and crucial targets was robust. The results of vitro assays indicate that diosbulbin B suppressed Hep-2 cell activity in a concentration-dependent manner. Besides, diosbulbin B has powerful antiproliferative properties in Hep-2 cells. Flow cytometry results showed that diosbulbin B promoted laryngocarcinoma cell apoptosis in a concentration-dependent manner.

Conclusion:
The article delivered a preliminary discussion of the probable mechanism of Dioscoreae bulbiferae and Bruceae fructus in the treatment of laryngocarcinoma, which can serve as a theoretical basis and evidence for subsequent experimental investigation.
Effectiveness of PrEPTECH: Findings From a 180-Day Randomized Controlled Trial of a Pre-Exposure Prophylaxis Telehealth Intervention
Authors: Erenrich Rebecca K. , Braun Rebecca A. , Torres-Mendoza David M. , Stevenson Olivia L. , Doan Thuan-Huong P. , Klausner Jeffrey D. 
Published: December 2023

Background:
Telehealth approaches are increasingly being used to provide access to pre-exposure prophylaxis (PrEP), an effective but underused HIV prevention modality. This randomized controlled trial of PrEPTECH, a telehealth intervention for the provision of HIV PrEP, seeks to assess its effects on PrEP access.

Methods:
Young men who have sex with men and transgender women in Florida and California with an indication for PrEP were randomly assigned in a 1:1 allocation to receive access to PrEPTECH or a control condition, access to an online listing of PrEP resources in their communities. This intent-to-treat analysis used logistic and linear regression to compare self-reported PrEP initiation, use, and coverage between control and intervention arm participants at 90 days and 180 days of follow-up.

Results:
A total of 229 participants with a mean age of 23.7 years, 77.3% people of color enrolled in PrEPTECH. At 90 days, postbaseline initiation of PrEP was significantly higher among those in the PrEPTECH arm than among controls (odds ratio [OR]: 6.63, 95% confidence interval [CI]: 2.54 to 17.35), and this held true by 180 days post baseline. The count of sex acts for which participants were not protected by PrEP, PrEP adherence, and recent PrEP use at 180 days post baseline were not significantly different between the study arms.

Conclusions:
Receiving access to a telehealth platform for PrEP access increased PrEP initiation in this cohort of young, predominantly non-White sexual and gender minorities. PrEP telehealth may be a worthy avenue for providing access to PrEP for these populations, but additional strategies may be needed to promote adherence and persistence of PrEP use.
Diagnosis and Severity Assessment of COPD using a Novel Fast-Response Capnometer And Interpretable Machine Learning
Authors: Talker Leeran , Dogan Cihan , Neville Daniel , Lim Rui Hen , Broomfield Henry , Lambert Gabriel , Selim Ahmed B , Brown Thomas , Wiffen Laura , Carter Julian C , Ashdown Helen F , Hayward Gail , Vijaykumar Elango , Weiss Scott T , Chauhan Anoop , Patel Ameera X 
Published: December 2023

AbstractIntroductionSpirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, non-specific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study’s aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense’s N-Tidal™capnometer.MethodsFor COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1-4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity.ResultsThe best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value of 0.834. A potential clinical use for this model is to rule in or rule out a diagnosis in patients where the model is most confident. Performance on test capnograms with probability>80% and<20% was also evaluated, yielding a PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, Sensitivity of 0.958, Specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1.ConclusionThe N-Tidal™device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care, as a rapid rule-in or rule-out test. N-Tidal™also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.Trial registrationPlease seeNCT03615365,NCT02814253,NCT04504838,NCT03356288andNCT04939558.
Macrophages as Key Mediators of Trp-1-Specific CD4+T Cell Therapy for Murine Melanoma
Authors: He Adam Q. , Zou Dawei , Chen Wenhao 
Published: December 2023

ABSTRACTThere is a growing body of evidence indicating that CD4+T cells, alongside CD8+T cells, can effectively combat cancer. However, the mechanisms underlying the anti-tumor properties of CD4+T cells are complex and not yet fully understood. To investigate these mechanisms, we utilized a murine model of tyrosinase-related protein 1 (Trp1)-specific CD4+T cell adoptive transfer therapy for treating melanoma. By employing single-cell RNA sequencing (scRNA-seq), we analyzed the immune cells present in the tumors of mice that received adoptive transfer of Trp1-specific CD4+T cells. Unexpectedly, within the tumor-infiltrating immune cells, the Trp1 CD4+T cell population was relatively small, displaying characteristics indicative of exhaustion. In contrast, the most prominent cell cluster comprised macrophages, expressing high levels of the T cell inhibitory receptor ligand PD-L1 and the pro-inflammatory cytokine IL-1β, suggesting a distinct M1 phenotype. Systemic depletion of macrophages following Trp1 CD4+T cell transfer therapy compromised the antitumor effectiveness and resulted in tumor recurrence. These findings highlight the crucial role of innate macrophages as an effector cell population in Trp1-specific CD4+T cell adoptive cell transfer therapy.
Translational mapping of spatially resolved transcriptomes in human and mouse pulmonary fibrosis
Authors: Franzén Lovisa , Lindvall Martina Olsson , Hühn Michael , Ptasinski Victoria , Setyo Laura , Keith Benjamin , Collin Astrid , Oag Steven , Volckaert Thomas , Borde Annika , Lundeberg Joakim , Lindgren Julia , Belfield Graham , Jackson Sonya , Ollerstam Anna , Stamou Marianna , Ståhl Patrik L , Hornberg Jorrit J 
Published: December 2023

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. To address these limitations, we generated spatially resolved transcriptome maps of human IPF and bleomycin-induced mouse lung fibrosis. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by TGFβ signaling alongside factors such as p53 and ApoE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches, and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.
“Non-viral CRISPR/Cas9 Mutagenesis for Streamlined Generation of Mouse Lung Cancer Models.”
Authors: Lara-Saez Irene , Mencia Angeles , Recuero Enrique , Li Yinghao , García Marta , Oteo Marta , Gallego Marta I , Enguita Ana Belen , de Prado-Verdún Diana , Sigen A , Wang Wenxin , García-Escudero Ramón , Murillas Rodolfo , Santos Mirentxu 
Published: December 2023

AbstractFunctional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. Many lung cancer models have been developed using genetic techniques to create gain- or loss-of-function alleles in genes involved in tumorigenesis; however, because of their labor- and time-intensive nature, these models are not suitable for quick and flexible hypothesis testing. Here we introduce a lung mutagenesis platform that utilizes CRISPR/Cas9 RNPs delivered via cationic polymers. This approach allows for the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specificallyRb1,Rbl1,Pten, andTrp53, which were chosen for their potential to cause lung tumors, namely Small Cell Lung Carcinoma (SCLC). This polymer-based delivery platform enables the modeling of lung tumorigenesis independently of the genetic background, thus simplifying and expediting the process without the need for modifying the mouse germline or creating custom viral vectors.SignificanceThe development of models to rapidly introduce gene mutations into lung tissue to study their impact on tumor growth is critical for advancing the functional genomics of lung cancer. While previous methods using viral vectors and genetic manipulation in mice have been time-consuming and expensive, here we describe a new technique using cationic polymers as non-viral carriers for CRISPR/Cas9 delivery to induce cancer driving mutations that streamlines this process. This approach mimics natural mutations in lung cancer and accelerates the generation of accurate tumor models. Our study demonstrates the effectiveness of this method in generating small cell lung cancer (SCLC) by modifying four tumor suppressor genes in different mouse genetic backgrounds. This innovative strategy holds promise for faster and more cost-effective cancer modeling.Graphical AbstracSmall Cell Lung Cancer(SCLC) tumors are rapidly generated in any mouse genetic background by using cationic polymers to simultaneously deliver Cas9 and gRNAs targeting theRb1,Rbl1,PtenandTrp53tumor-suppressor genes to the adult airway respiratory systemin vivo. Addition of the frt guide in the RC::FLTG mice provides a tdTomato gene editing reporter. This study shows the feasibility of rapidly generating lung cancer mouse models via somatic genome engineering through delivery of all CRISPR components in the form of nanoparticles.
SMC motor proteins extrude DNA asymmetrically and contain a direction switch
Authors: Barth Roman , Davidson Iain F. , van der Torre Jaco , Taschner Michael , Gruber Stephan , Peters Jan-Michael , Dekker Cees 
Published: December 2023

SummaryStructural Maintenance of Chromosomes (SMC) complexes organize the genomeviaDNA loop extrusion. While some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear. Here, we examine the directionality of DNA loop extrusion by SMCs usingin vitrosingle-molecule experiments. We find that cohesin and SMC5/6 do not reel in DNA from both sides, as reported before, but instead extrude DNA asymmetrically, while the direction can switch over time. Asymmetric DNA loop extrusion thus is the shared mechanism across all eukaryotic SMC complexes. For cohesin, direction switches strongly correlate with the turnover of the subunit NIPBL, during which DNA strand switching may occur. STAG1 stabilizes NIPBL on cohesin, preventing NIPBL turnover and direction switches. The findings reveal that SMCs, surprisingly, contain a direction switch subunit.HighlightsAll eukaryotic SMC complexes extrude DNA asymmetrically.Apparent ‘symmetric’ loop extrusion is the result of frequent direction switches.n human cohesin, loop-extrusion direction changes require exchange of NIPBL.STAG1 stabilizes NIPBL on human cohesin.
The perceived authenticity in food among sociological generations: the case of cheeses in Mexico
Authors: Fernández-Sánchez Héctor Yair , Espinoza-Ortega Angélica , Sánchez-Vega Laura Patricia , Moctezuma Pérez Sergio , Cervantes-Escoto Fernando 
Published: December 2023

PurposeThe study aims to identify the perceived authenticity of cheeses by consumers of different sociological generations in Mexico.Design/methodology/approachAn online questionnaire was applied to 1,204 consumers. A Free Word Association (FWA) tool was used to determine the perceived authenticity of cheeses creating categories and dimensions. The sample was segmented into sociological generations. A chi-square test and a correspondence analysis were used to identify differences in the perception between generations. The information was complemented with word clouds of the cheeses mentioned and consumer testimonials about cheese consumption.FindingsA total of 29 categories and ten dimensions revealed consumers' perception of cheese authenticity, most important of which were hedonic, rurality and new consumption. Authenticity is a mix of the pleasure of consuming the product, the link to rural life and new consumer values. Perceived authenticity is different in each sociological generation according to the dimensions of raw material, identity, market, new consumption and distrust, since it is related to the experiences of each generation. The results made it possible to contextualise another vision of the reality of the cheeses in the search for a quality seal.Practical implicationsThe information contributes to the typification and promotion of cheeses in the process of patrimonialisation, by creating differentiated marketing tools that allow their valorisation.Originality/valueThis work contributes to the knowledge of the perceived authenticity of cheeses in the sociological generations, due to their differentiation by age, sociocultural, ethical, political and consumer aspects. It enables the knowledge of the consumer's perspective on these products.
Integrated optimization of facility location, casualty allocation and medical staff planning for post-disaster emergency response
Authors: Oksuz Mehmet Kursat , Satoglu Sule Itir 
Published: December 2023

Purpose
Disaster management and humanitarian logistics (HT) play crucial roles in large-scale events such as earthquakes, floods, hurricanes and tsunamis. Well-organized disaster response is crucial for effectively managing medical centres, staff allocation and casualty distribution during emergencies. To address this issue, this study aims to introduce a multi-objective stochastic programming model to enhance disaster preparedness and response, focusing on the critical first 72 h after earthquakes. The purpose is to optimize the allocation of resources, temporary medical centres and medical staff to save lives effectively.

Design/methodology/approach
This study uses stochastic programming-based dynamic modelling and a discrete-time Markov Chain to address uncertainty. The model considers potential road and hospital damage and distance limits and introduces an a-reliability level for untreated casualties. It divides the initial 72 h into four periods to capture earthquake dynamics.

Findings
Using a real case study in Istanbul’s Kartal district, the model’s effectiveness is demonstrated for earthquake scenarios. Key insights include optimal medical centre locations, required capacities, necessary medical staff and casualty allocation strategies, all vital for efficient disaster response within the critical first 72 h.

Originality/value
This study innovates by integrating stochastic programming and dynamic modelling to tackle post-disaster medical response. The use of a Markov Chain for uncertain health conditions and focus on the immediate aftermath of earthquakes offer practical value. By optimizing resource allocation amid uncertainties, the study contributes significantly to disaster management and HT research.
Is mandatory disclosure an effective panacea for buyer beware?
Authors: Waye Vicki Catherine , Snowden Collette , Knowler Jane , Zito Paula , Burton Jack , McIntyre Joe 
Published: December 2023

Purpose
The purpose of this paper is to examine whether mandatory disclosure of information accompanying the sale of real estate achieves its aim of informed purchasers.

Design/methodology/approach
Using a case study approach focused on mandatory disclosure in South Australia data was collected from interviews and focus groups with key personnel in the property industry involved in the production of information required to fulfil vendors’ disclosure obligations.

Findings
The authors found that purchasers are ill-served by a long and complex form of mandatory disclosure with a short time frame that prevents the use of the information provided. Without good form design and increased digital affordances provided by the cadastral and conveyancing systems, mandatory disclosure is insufficient to ensure minimisation of information asymmetry between vendor and purchaser.

Originality/value
To the best of the authors’ knowledge, this is the first Australian qualitative study that examines the utility of mandatory vendor disclosure in real estate sales and the first to consider the impact of the digitalisation of cadastral and conveyancing systems upon the efficacy of mandatory disclosure regimes.
Utilization of recycled coarse aggregate and high volume of GGBS in self-compacting concrete – an experimental study
Authors: M. Manjunatha , T.S. Kavitha 
Published: December 2023

Purpose
The purpose of this study is to investigate the behaviour of M40 grade of self-compacting concrete (SCC) with high volume of ground granulated blast furnace slag (GGBS) (50%) and recycled concrete aggregate (RCA) content up to 100% to assess the mechanical properties of SCC. As per guidelines of IS: 383 – 2016, the RCA can be replaced up to 20% of natural coarse aggregate up to M25 grade of concrete. This study assesses the mechanical properties of SCC beyond 20% of RCA content. Based on the experimental investigations, the compressive strength of mixes decreases as the content of RCA increases. It is found that concrete mixes with 20% RCA and shows the maximum compressive strength at 56 days.

Design/methodology/approach
The fresh properties as per EFNARC and IS: 10262–2019 guidelines, ultrasonic pulse velocity testing, mechanical properties and microstructure analysis have been conducted to evaluate the performance of SCC with RCA for practical applications.

Findings
From the experimental investigations, it is found that up to 50% of recycled coarse aggregate can be used for structural applications.

Originality/value
The environmental pollution and dumping of waste on green land can be reduced by effective utilization of recycled coarse aggregate and GGBS in the production of SCC.
Exploring participatory health research and its application to speech and language therapy research practices
Authors: Connery Amy , Salsberg Jon 
Published: December 2023

AbstractBackgroundThe role of participatory health research (PHR) is increasingly acknowledged by funding bodies, researchers and civil society globally; however, it continues to be under‐represented in the speech and language therapy (SLT) research literature. This collaborative research approach is associated with the increased application of research evidence, and the generation of positive impacts in practice, policy, health systems and society.AimsTo increase researchers’ and other participatory partners’ understanding of PHR, and to demonstrate its applicability to research in the SLT field.Methods & ProceduresThis aim is achieved through a discussion on PHR, its principles, benefits and challenges, and the evaluation of its impact. A recently developed evaluation framework to support the implementation of best engagement practices is examined, and recommendations for how this framework can be used to plan and evaluate engagement in participatory stuttering research is presented.Main contributionThis paper serves as an important conversation on the value of PHR to SLT research, and presents guidance to support its increased implementation in this research field.Conclusions & ImplicationsConclusions & Implications: PHR remains an under‐represented research approach in the SLT literature, despite increasing evidence demonstrating its effectiveness and value. It offers a potential solution to the research–practice gap, and challenges the ongoing research hierarchies by democrating the process of knowledge production.WHAT THIS PAPER ADDSWhat is already known on this subject
PHR is increasingly attracting the attention of funders, researchers and decision‐makers due to a growing body of evidence in support of this collaborative research approach. Despite its potential to bridge the research–practice gap, PHR remains significantly under‐represented in the SLT research literature.What this paper adds to the existing knowledge
This paper discusses the principles, benefits, challenges and impact evaluation of PHR. A recently developed evaluation framework for supporting the implementation of best engagement practices is examined. A demonstration of how this framework can be used to plan and evaluate engagement in participatory stuttering research is presented.What are the potential or actual clinical implications of this work?
Speech and language therapists play a key role in PHR, as co‐researchers contributing essential context‐based knowledge. It is therefore imperative that they understand the principles and practices of this approach in order to maximize their input in future participatory partnerships.