bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of Simulated Patients Involved in Difficult Conversations With Undergraduate and Postgraduate Health Professionals
Authors: Wiechula Laura A. , Chur-Hansen Anna , Davies Ellen L. 
Published: February 2024

Introduction
Simulated patients (SPs) are trained to simulate real patient scenarios for health professionals' education and training. The value of including SPs in simulated scenarios, particularly in relation to difficult and complex conversations, has been studied in various contexts, with a focus on learner experiences and outcomes. What has not been as extensively explored is the impact of difficult and complex conversations on the SPs. The aim of this study was to explore the perspectives, motivations, and experiences of SPs, particularly regarding difficult or complex conversations.

Methods
A qualitative approach was taken to gather and interpret SP experiences. Open-ended interviews were the primary means of obtaining data. Thematic analysis guided the interpretation of interview data to generate key themes that encapsulated the SP experience.

Results
Twelve participants shared their experiences of working as SPs in scenarios that involved difficult or complex conversations. From these data, 4 major themes were determined: Care for Students, Pedagogical Focus, Emotional Regulation, and Organizational Environment. The importance of empathy and safe design and support for simulations was apparent.

Conclusions
This study presents insights into the experiences and perspectives of SPs regarding difficult and complex conversations. Participants highlighted the necessity of uniformity in standards of practice in simulation and the need for advocacy for awareness of simulation-based practices.
Radiation therapy options in kidney cancer
Authors: Zaorsky Nicholas G. , Louie Alexander V. , Siva Shankar 
Published: February 2024

Purpose of review
In this review, the authors discuss the use of stereotactic body radiation therapy (SBRT) for the treatment of primary and metastatic renal cell carcinoma (RCC).

Recent findings
For primary RCC treated with SBRT, local control is estimated at >95%, and grade 3–4 toxicity is limited at ≤5%. The difference in glomerular filtration rate pretreatment versus posttreatment was about 7.7 ml/min. For metastatic RCC treated with SBRT, the 1-year local control is ~90%. The incidence of any grade 3–4 toxicity is ~1%. Several ongoing trials are evaluating SBRT in combination or in lieu of systemic therapy. There are many unknowns remaining in the treatment of RCC, including tumor prognostication, treatment selection, and treatment delivery.

Summary
Stereotactic body radiation therapy is a safe and effective treatment option for patients with primary and metastatic RCC.
Comprehensive quality evaluation of Magnolia officinalis leaves based on wavelength fusion fingerprint, content determination, and antioxidant activity analysis
Authors: Lan Xuemei , Lin Lujie , Yang Lixin , Wang Yunhong , Ke Xiumei , Yang Rongping , Li Hua , Yang Bin 
Published: February 2024

Abstract
A valid, novel, and comprehensive evaluation method for assessing the quality of Magnolia officinalis leaves (MOLs) from different origins has been established based on multiwavelength fusion fingerprint, quantitative analysis, and antioxidant activity screening. The four wavelength fingerprints for MOL samples at 258, 266, 290, and 327 nm were collected by high performance liquid chromatography, and then data fusion was conducted. In addition, the content of multiple components was determined by high performance liquid chromatography at four wavelengths. 1,1-Diphenyl-2-pyridyl hydrazine scavenging assay was applied to study in vitro antioxidant activity. The effective distinction of 18 batches of MOLs was realized based on hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis combined with multiwavelength fusion fingerprint. The orthogonal partial least squares discriminant analysis model exhibited huge advantages in distinguishing among different samples and screening three quality markers of the tested samples, including rutin, isoquercitrin, and chlorogenic acid. This established method of multitechnology fusion is simple, reliable, and efficient for the qualitative and quantitative bioactivity evaluation of MOLs. This study aims to investigate the development of new medicinal parts of traditional Chinese medicines (TCMs), so as to enhance the efficiency of utilizing TCM resources and promote the high-quality development of the TCM industry.
The dilemma of valuing geodiversity: geoconservation versus geotourism
Authors: Anougmar S. , Meesters A. , van Ree D. , Compernolle T. 
Published: February 2024

Geodiversity and geosystem services are confronting global threats. However, the majority of conservation strategies tend to overlook the geological component within ecosystems. The existing literature centres on biodiversity, ecosystem services and their economic valuation. In this paper, we conduct a systematic literature review to identify the gap in the assessment of geological diversity, pinpointing areas where scientific contributions are needed to safeguard geological resources. Our findings reveal a concentration of studies assessing geodiversity in European and Asian countries. While the majority of the reviewed papers emphasizes the recreational features and associated values of geological resources, promoting geotourism and recognizing its potential for economic growth, there is a significant oversight concerning the impact of tourism on geological resources. Existing assessments predominantly focus on visitors' perceptions and preferences, sidelining the inhabitants’ perspective and their crucial roles in the conservation of geodiversity.
This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Geoconservation at the International Union for Conservation of Nature (IUCN)
Authors: Monge-Ganuzas Manu , Guillén-Mondéjar Francisco , Díaz-Martínez Enrique , Herrero Nadia , Brilha José 
Published: February 2024

This work describes the achievements made towards geoconservation within the International Union for Conservation of Nature (IUCN) from the 1990s onwards. The key milestones in the recognition of geoconservation within the IUCN are presented. Initially, the IUCN's geoconservation efforts were focused on refining the criteria for World Heritage (WH) designation. Subsequently, the actions focused on spreading the geoconservation framework within the IUCN World Conservation Congresses (WCCs), the establishment of an expert group on geoconservation within the IUCN World Commission on Protected Areas (IUCN-WCPA) and the publication of guidelines for geoconservation. We describe how the inclusion within the IUCN membership of three organizations—two of them Spanish: The Geological Society of Spain (SGE) and the Society for the Defence of Geological and Mining Heritage (SEDPGYM); and one international, ProGEO—has been a key factor. These organizations have achieved the adoption of resolutions in which geoconservation, its vision, its principles and its definitions have been taken into account in the IUCN WCC (2008–2020 period), and have promoted the geoconservation conceptual framework among nature conservationists. We also analyse the progress made and offer a series of recommendations to improve geoconservation in the future adopting a more integrated approach to nature conservation within the IUCN.
This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Geodiversity in the Amazon drainage basin
Authors: Alsbach Cécile M. E. , Seijmonsbergen Arie C. , Hoorn Carina 
Published: February 2024

The Amazon is the largest drainage basin on Earth and contains a wide variety of abiotic landscape features. In spite of this, the geodiversity in this basin has not yet been objectively evaluated. We address this knowledge gap by combining a meta-analysis of an existing global geodiversity map and its components with a systematic literature review, to identify the key characteristics of geodiversity in the Amazon drainage basin (ADB). We also evaluate how these global geodiversity component maps, that are based on the geology, geomorphology, soils and hydrology, could be refined to better reflect geodiversity in the basin. Our review shows that geology—through lithological diversity and geological structures—and hydrology—through hydrological processes that influence geomorphology and soil diversity—are the main determinants of geodiversity. Based on these features, the ADB can be subdivided into three principal regions: (i) the Andean orogenic belt and western Amazon, (ii) the cratons and eastern Amazon, and (iii) the Solimões-Amazon river system. Additional methods to map geomorphological and hydrological diversity have been identified. Future research should focus on investigating the relationship between the geodiversity components and assess their relationship with biodiversity. Such knowledge can enhance conservation plans for the ADB.
This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Chronic alcohol exposure induces cerebral microbleeds by TGF-β1/Smad signaling pathway mediated remodeling of cerebral small vessels
Authors: Lu Hengjian , Wang Hongxuan , Li Xiangpen , Lin Xinrou , Li Chenguang , Chen Wanru , Zou Lubin , Pan Jingrui , Zhang Xiaoni , He Lei , Rong Xiaoming , Peng Ying 
Published: February 2024

AbstractBackgroundLong-term heavy drinking is a major risk factor for cerebral microbleeds(CMBs), which are increasingly gaining attention as a pathological phenotype of cerebral small vessel diseases(CSVD). Under pathological conditions, remodeling of the extracellular matrix(ECM) on the walls of small vessels causes disarray in the structure and function of these vessels, leading to cerebral small vessel sclerosis and consequent rupture and bleeding. This can result in cognitive and emotional disorders, abnormal gait and increased risk of falling. However, the mechanisms underlying how long-term alcohol consumption leads to CMBs and decline in motor function remain unknown.MethodsWe constructed a chronic alcohol exposure mouse model and measured the deposition of ECMs on the small vessels in motor-related brain regions. The presence of microbleeds was confirmed through Prussian blue staining and Magnetic Resonance Imaging. We also extracted primary cerebral microvascular smooth muscle cells (CMVSMCs) from the newborn mice and explored the effects of alcohol on the phenotypic transformation and substance synthesis function. Additionally, we conducted interventional experiments on the cell and animal models with an anti-fibrotic drugs Pirfenidone(PFD).ResultsWe found that mice with long-term alcohol exposure showed decreased motor function. In their motor-related brain regions, such as the motor cortex(MC), thalamus/basal ganglia(Tha/BG), and cerebellum(CB), we observed microbleeds. On the small vessels in these areas, we detected excessive deposited ECM proteins. In vitro experiments with primary CMVSMCs revealed that after alcohol treatment, the cells underwent a transformation into fibroblast-like phenotypes, and excessive production of the aforementioned ECM proteins, which is regulated by upstream TGFβ1/Smad signaling pathway. Additionally, PFD applied on cell and animal models could reverse the above processes to some extent.ConclusionsOur study found that the remodeling of ECM accompanied by activation of TGF-β1/Smad signaling pathway may be involved in alcohol-induced CMBs. It could be a potential therapeutic target for CMBs or CSVD.
Causal relationship between mental disorders and abdominal aortic aneurysm: insights from the genetic perspective
Authors: Deng Ming-Gang , Chai Chen , Wang Kai , Zhao Zhi-Hui , Nie Jia-Qi , Liu Fang , Liang Yuehui , Liu Jiewei 
Published: February 2024

AbstractObjectiveThis study investigated the genetic link between mental disorders—depression, schizophrenia (SCZ), and bipolar disorder (BIP)—and abdominal aortic aneurysm (AAA).MethodsWe used global/local genetic correlation analyses and identified shared genomic loci. Bidirectional univariable Mendelian Randomization (UMR) assessed causal directions, with multivariable MR (MVMR) refining the analysis. Mediation analyses examined if known AAA risk factors influenced this relationship.ResultsGlobal correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95% CI 1.071-1.504;p= 0.006) and SCZ (OR 1.047; 95% CI 1.010-1.084;p= 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ’s impact.ConclusionThis study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.
Improving Adherence to Pulmonary Embolism Evaluation Consensus Guidelines: A Multimodal Approach
Authors: D’Silva E Ethan , Zaidi Syed , Ramis Phil , Rohren Eric M. 
Published: February 2024

AbstractObjectiveDespite the publication of multiple widely accepted guidelines, Computed Tomography pulmonary angiography (CTPA) remains overutilized in the emergency (ED) setting for evaluating suspected pulmonary embolism (PE). We developed and evaluated a multimodal program that aimed to improve ordering provider adherence to CTPA use guidelines, and consequently positivity rate.MethodsWe retrospectively identified all CTPA studies ordered for suspected PE over three years for each provider at a single-center ED, and reviewed radiology reports to determine PE positivity. We then implemented a program that included an education session, individualized performance feedback, and discussion of possible incentives to improve guideline adherence. We prospectively collected CTPA results for the following year. Our primary outcome was the difference in positivity rate between the final preintervention year and the post-intervention year. Our secondary outcome was individual provider positivity rate between the pre-intervention and post-intervention period. We compared the primary outcome using chi-squared testing, defining statistical significance as P<0.05.ResultsWe identified 4265 CTPA studies performed during the pre-intervention period, ordered by 25 providers. 1582 studies were ordered during the final year, with an 11.00% positivity rate (174/1582). In the post-intervention year, 1339 studies were ordered, with a significantly greater positivity rate of 13.67% (183/1339, P = 0.028). For our secondary outcome, mean provider positivity rate was 11.49% during the preintervention period, and increased to 14.24% in the post-intervention period.DiscussionWe successfully implemented a multimodal program for ED providers that significantly increased the positivity rate of CTPAs ordered for suspected PE evaluation.
A Prodrug Strategy to Reposition Atovaquone as a Long-Acting Injectable for Malaria Chemoprotection
Authors: Gupta Anil K. , Eliasen Anders M. , Andahazy Wil , Zhou Fei , Henson Kerstin , Chi Victor , Woods Ashley K. , Joseph Sean B. , Kuhen Kelli L. , Wisler John , Ramachandruni Hanu , Duffy James , Burrows Jeremy N. , Vadas Elizabeth , Slade Andrew , Schultz Peter G. , McNamara Case W. , Chatterjee Arnab K. 
Published: February 2024

ABSTRACTRecent malaria drug discovery approaches have been extensively focused on the development of oral, smallmolecule inhibitors for disease treatment whereas parenteral routes of administration have been avoided due to limitations in deploying a shelf-stable injectable even though it could be dosed less frequently. However, an updated target candidate profile from Medicines for Malaria Venture (MMV) and stakeholders have advocated for long-acting injectable chemopreventive agents as an important interventive tool to improve malaria prevention. Here, we present strategies for the development of a long-acting, intramuscular, injectable atovaquone prophylactic therapy. We have generated three prodrug approaches that are contrasted by their differential physiochemical properties and pharmacokinetic profiles: mCBK068, a docosahexaenoic acid ester of atovaquone formulated in sesame oil, mCKX352, a heptanoic acid ester of atovaquone formulated as a solution in sesame oil, and mCBE161, an acetic acid ester of atovaquone formulated as an aqueous suspension. As a result, from a single 20 mg/kg intramuscular injection, mCKX352 and mCBE161 maintain blood plasma exposure of atovaquone above the minimal efficacious concentration for >70 days and >30 days, respectively, in cynomolgus monkeys. The differences in plasma exposure are reflective of the prodrug strategy, which imparts altered chemical properties that ultimately influence aqueous solubility and depot release kinetics. On the strength of the pharmacokinetic and safety profiles, mCBE161 is being advanced as a first-in-class clinical candidate for first-in-human trials.
In Silico designed cell-penetrating anti-cancer peptide specifically inhibits VEGF-A expression
Authors: Banerjee Nilanjan , Roy Laboni , Panda Suman , Roychowdhury Tanaya , Chatterjee Subhrangsu 
Published: February 2024

AbstractVascular Endothelial Growth Factor-A (VEGF-A), a pluripotent cytokine and angiogenic growth factor mediates the switch to an angiogenic phenotype in cancer cells. The interaction of VEGF-A protein with the VEGF receptors (VEGFR-1and VEGFR-2) starts downstream effect that promotes angiogenesis by mediating migration and increasing the permeability of endothelial cells. A cis-regulatory elements consisting of a polypurine/polypyrimidine (pPu/pPy) tract in the proximal 36-bp region (–85 to −50), can participate in the formation of a stable higher order G-quadruplex structure (G4) which is essential for VEGF promoter activity. During cancer progression the VEGF-A G4 succumbs to cellular pressure and fails to maintain the stable structure. This shifts the balance to form duplex structure thereby increasing the rate of transcription. Earlier research has tried to develop small-molecule ligands to target and stabilize G4, however they either lack specificity or non-toxicity. Peptide on the other hand are very less studied. Here we used bioinformatics in-silico tool to develop peptides which can successfully bind and stabilize the VEGF-A G4 while reducing its gene expression. This further alters the expression fate of the VEGF-A signalling cascade and prevents angiogenesis in cancer cells. We used high resolution Nuclear magnetic resonance and molecular dynamics simulation to map the chemistry of the interaction while the qPCR and western blot allowed us to check the expression pattern of the molecules of VEGF-A signalling cascade. In this investigation, we navigate the complex interplay between peptides and quadruplex structures, unravelling valuable insights that can enhance the crafting of pharmacophores directed at the dynamic quadruplex structure. The outcomes of our study are promising, paving the way for progress in the realms of research, characterization, and optimization of peptides binding to G-quadruplexes, with potential implications for therapeutic applications.
mbctools: A User-Friendly Metabarcoding and Cross-Platform Pipeline for Analyzing Multiple Amplicon Sequencing Data across a Large Diversity of Organisms
Authors: Barnabé Christian , Sempéré Guilhem , Manzanilla Vincent , Millan Joel Moo , Amblard-Rambert Antoine , Waleckx Etienne 
Published: February 2024

AbstractWe developed a python package calledmbctools, designed to offer a cross-platform tool for processing amplicon data from various organisms in the context of metabarcoding studies. It can handle the most common tasks in metabarcoding pipelines such as paired-end merging, primer trimming, quality filtering, sequence denoising, zero-radius operational taxonomic unit (ZOTU) filtering, and has the capability to process multiple genetic markers simultaneously.mbctoolsis a menu-driven program that eliminates the need for expertise in command-line skills and ensures documentation of each analysis for reproducibility purposes. The software, designed to run in a console, offers an interactive experience, guided by keyboard inputs, assisting users along the way through data processing and hiding the complexity of command lines by letting them concentrate on selecting parameters to apply in each step of the process. In our workflow, VSEARCH is utilized for processingfastqfiles derived from amplicon-based Next-Generation Sequencing data. This software is a versatile open-source tool for processing amplicon sequences, offering advantages such as high speed, efficient memory usage, and the ability to handle large datasets. It provides functions for various tasks such as dereplication, clustering, chimera detection, and taxonomic assignment. VSEARCH is thus very efficient in retrieving the overall diversity of a sample. To adapt to the diversity of projects in metabarcoding, we facilitate the reprocessing of datasets with the possibility to adjust parameters.mbctoolscan also be launched in a headless mode, making it suited for integration into pipelines running on High-Performance Computing environments.mbctoolsis available athttps://github.com/GuilhemSempere/mbctools,https://pypi.org/project/mbctools/.