bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bni5 tethers myosin-II to septins to enhance retrograde actin flow and the robustness of cytokinesis
Authors: Okada Hiroki , Chen Xi , Wang Kangji , Marquardt Joseph , Bi Erfei 
Published: November 2023

AbstractThe collaboration between septins and myosin-II in driving processes outside of cytokinesis remains largely uncharted. Here, we demonstrate that Bni5 in the budding yeastS. cerevisiaeinteracts with myosin-II, septin filaments, and the septin-associated kinase Elm1 via distinct domains at its N- and C-termini, thereby tethering the mobile myosin-II to the stable septin hourglass at the division site from bud emergence to the onset of cytokinesis. The septin and Elm1-binding domains, together with a central disordered region, of Bni5 control timely remodeling of the septin hourglass into a double ring, enabling the actomyosin ring constriction. The Bni5-tethered myosin-II enhances retrograde actin cable flow, which contributes to the asymmetric inheritance of mitochondria-associated protein aggregates during cell division, and also strengthens cytokinesis against various perturbations. Thus, we have established a biochemical pathway involving septin-Bni5-myosin-II interactions at the division site, which can inform mechanistic understanding of the role of myosin-II in other retrograde flow systems.SummaryOkada et al. have determined the molecular mechanism underlying the Bni5 interactions with septins and myosin-II at the cell division site and uncovered its roles in promoting retrograde actin flow and the robustness of cytokinesis in budding yeast.
Mimicking Clinical Trials with Synthetic Acute Myeloid Leukemia Patients Using Generative Artificial Intelligence
Authors: Eckardt Jan-Niklas , Hahn Waldemar , Röllig Christoph , Stasik Sebastian , Platzbecker Uwe , Müller-Tidow Carsten , Serve Hubert , Baldus Claudia D. , Schliemann Christoph , Schäfer-Eckart Kerstin , Hanoun Maher , Kaufmann Martin , Burchert Andreas , Thiede Christian , Schetelig Johannes , Sedlmayr Martin , Bornhäuser Martin , Wolfien Markus , Middeke Jan Moritz 
Published: November 2023

AbstractClinical research relies on high-quality patient data, however, obtaining big data sets is costly and access to existing data is often hindered by privacy and regulatory concerns. Synthetic data generation holds the promise of effectively bypassing these boundaries allowing for simplified data accessibility and the prospect of synthetic control cohorts. We employed two different methodologies of generative artificial intelligence – CTAB-GAN+ and normalizing flows (NFlow) – to synthesize patient data derived from 1606 patients with acute myeloid leukemia, a heterogeneous hematological malignancy, that were treated within four multicenter clinical trials. Both generative models accurately captured distributions of demographic, laboratory, molecular and cytogenetic variables, as well as patient outcomes yielding high performance scores regarding fidelity and usability of both synthetic cohorts (n=1606 each). Survival analysis demonstrated close resemblance of survival curves between original and synthetic cohorts. Inter-variable relationships were preserved in univariable outcome analysis enabling explorative analysis in our synthetic data. Additionally, training sample privacy is safeguarded mitigating possible patient re-identification, which we quantified using Hamming distances. We provide not only a proof-of-concept for synthetic data generation in multimodal clinical data for rare diseases, but also full public access to synthetic data sets to foster further research.Graphical Abstract
Development of a privacy preserving large language model for automated data extraction from thyroid cancer pathology reports
Authors: Lee Denise T , Vaid Akhil , Menon Kartikeya M , Freeman Robert , Matteson David S , Marin Michael P , Nadkarni Girish N 
Published: November 2023

AbstractBackgroundPopularized by ChatGPT, large language models (LLM) are poised to transform the scalability of clinical natural language processing (NLP) downstream tasks such as medical question answering (MQA) and may enhance the ability to rapidly and accurately extract key information from clinical narrative reports. However, the use of LLMs in the healthcare setting is limited by cost, computing power and concern for patient privacy. In this study we evaluate the extraction performance of a privacy preserving LLM for automated MQA from surgical pathology reports.Methods84 thyroid cancer surgical pathology reports were assessed by two independent reviewers and the open-source FastChat-T5 3B-parameter LLM using institutional computing resources. Longer text reports were converted to embeddings. 12 medical questions for staging and recurrence risk data extraction were formulated and answered for each report. Time to respond and concordance of answers were evaluated.ResultsOut of a total of 1008 questions answered, reviewers 1 and 2 had an average concordance rate of responses of 99.1% (SD: 1.0%). The LLM was concordant with reviewers 1 and 2 at an overall average rate of 88.86% (SD: 7.02%) and 89.56% (SD: 7.20%). The overall time to review and answer questions for all reports was 206.9, 124.04 and 19.56 minutes for Reviewers 1, 2 and LLM, respectively.ConclusionA privacy preserving LLM may be used for MQA with considerable time-saving and an acceptable accuracy in responses. Prompt engineering and fine tuning may further augment automated data extraction from clinical narratives for the provision of real-time, essential clinical insights.
Identifying markers of health-seeking behaviour and healthcare access in UK electronic health records
Authors: Graham S. , Walker J.L. , Andrews N. , Nitsch D. , Parker P.K.E. , McDonald H. I 
Published: November 2023

AbstractObjectiveTo assess the feasibility of identifying markers of health-seeking behaviour and healthcare access in UK electronic health records (EHR), for identifying populations at risk of poor health outcomes, and adjusting for confounding in epidemiological studies.DesignCross sectional observational study using the Clinical Practice Research Datalink (CPRD) Aurum pre-linked to Hospital Episode Statistics.SettingIndividual-level routine clinical data from 13 million patients across general practices (GPs) and secondary data in England.ParticipantsIndividuals aged ≥66 years on 01/09/2019.Main outcome measuresWe used the Theory of Planned Behaviour (TPB) model and the literature to iteratively develop criteria for markers selection. Based on this we selected 15 markers: those that represented uptake of public health interventions, markers of active healthcare access/use and markers of lack of access/underuse. We calculated the prevalence of each marker using relevant lookback periods prior to index date (01/09/2019) and compared to national estimates. We assessed the correlation coefficients (phi) between markers with inferred hierarchical clustering.ResultsWe included 1,991,284 individuals (mean age: 75.9 and 54.0% females). The prevalence of markers ranged from <0.1% (low-value prescriptions) to 92.6% (GP visits), and most were in line with national estimates; e.g., 73.3% for influenza vaccination in the 2018/2019 season, compared to 72.4% in national estimates. Screening markers e.g., abdominal aortic aneurysm screening were under-recorded even in age-eligible groups (54.3% in 65–69 year-olds vs 76.1% in national estimates in men). Overall, marker correlations were low (<0.5) and clustered into groups according to underlying determinants from the TPB model.ConclusionOverall, markers of health-seeking behaviour and healthcare access can be identified in UK EHRs. The generally low correlations between different markers of health-seeking behaviour and healthcare access suggest a range of variables are needed to capture different determinants of healthcare use.Strengths and limitations of this studyThis is the first known study in the UK that has identified proxies or markers of health-seeking behaviour or healthcare access.We utilised linked electronic health records from primary and secondary care so that a range of different health utilisation markers could be identified.We identified a large population of over 2 million individuals.For some of the markers (e.g., bone density scans), health need could not be entirely separated from health behaviour and access.Marker prevalences showed different patterns by age, and these findings might not be generalisable to younger age groups (<65 years).
Heart generation via blastocyst complementation in Mesp1/2-deficient mice
Authors: Abe Yuto , Sadahiro Taketaro , Fujita Ryo , Yamada Yu , Akiyama Tatsuya , Nakano Koji , Honda Seiichiro , Tanimoto Yoko , Suzuki Hayate , Mizuno Seiya , Takahashi Satoru , Yamaguchi Tomoyuki , Masaki Hideki , Hattori Kosuke , Mashimo Tomoji , Ieda Masaki 
Published: November 2023

SummaryHeart transplantation is the only curative option available for patients with advanced heart failure. However, donor organ shortage and graft rejection remain critical challenges in heart transplantation. Blastocyst complementation using pluripotent stem cells (PSCs) can be used to generate organs such as the pancreas and kidneys in animal models with abnormalities in essential developmental genes. Nonetheless, whether functional adult hearts can be generated with blastocyst complementation remains unclear, and it is unknown if parenchyma, blood vessels, and stroma can be generated concomitantly from PSCs using blastocyst complementation to avoid graft rejection. Here, we show the generation of functional adult hearts in acardiac Mesp1 and Mesp2 double-knockout (Mesp1/2-DKO) mice via blastocyst complementation using mouse PSCs. Our result shows that the generated hearts were structurally and functionally normal and restored embryonic lethality in Mesp1/2-DKO mice. All four cardiovascular lineages, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, and cardiac fibroblasts, were virtually entirely derived from exogenous PSCs in the myocardium. Exogenous rat PSCs also generated rat-derived xenogeneic hearts in Mesp1/2-DKO mice via interspecies blastocyst complementation. Thus, blastocyst complementation is a viable technique for generating hearts derived from PSCs and may represent significant progress toward generating rejection-free hearts.
Digitalized organoids: integrated pipeline for 3D high-speed analysis of organoid structures using multilevel segmentation and cellular topology
Authors: Ong Hui Ting , Karatas Esra , Grenci Gianluca , Dilasser Florian , Mohamad Raffi Saburnisha Binte , Blanc Damien , Poquillon Titouan , Drimaracci Elise , Mikec Dimitri , Thiel Cora , Ullrich Oliver , Racine Victor , Beghin Anne 
Published: November 2023

ABSTRACTAnalysing the tissue morphogenesis and function is crucial for unravelling the underlying mechanisms of tissue development and disease. Organoids, 3Din vitromodels that mimic the architecture and function of human tissues, offer a unique opportunity to study effects of external perturbators that are difficult to replicatein vivo. However, large-scale screening procedures for studying the effects of different ‘stress’ on cellular morphology and topology of these 3D tissue-like system face significant challenges, including limitations in high-resolution 3D imaging, and accessible 3D analysis platforms. These limitations impede the scale and throughput necessary to accurately quantify the effects of mechanical and chemical cues. Here, we present a novel, fine-tuned pipeline for screening morphology and topology modifications in 3D cell culture using multilevel segmentations and cellular topology, based on confocal microscopy and validated across different image qualities. Our pipeline incorporates advanced image analysis algorithms and artificial intelligence (AI) for multiscale 3D segmentation, enabling quantification of morphology changes at both the nuclear and cytoplasmic levels, as well as at the organoid scale. Additionally, we investigate cell relative position and employ neighbouring topology analysis to identify tissue patterning and their correlations with organoid microniches. Eventually, we have organized all the extracted features, 3D segmented masks and raw images into a single database to allow statistical and data mining approaches to facilitate data analysis, in a biologist-friendly way. We validate our approach through proof-of-concept experiments, including well-characterized conditions and poorly explored mechanical stressors such as microgravity, showcasing the versatility of our pipeline. By providing a powerful tool for discovery-like assays in screening 3D organoid models, our pipeline has wide-ranging interests from biomedical applications in development and aging-related pathologies to tissue engineering and regenerative medicine.
Liliana Lemaître’s technological race: innovate or fall behind
Authors: Alba Cabañas Marisleidy , Gómez García Luis Demetrio 
Published: November 2023

Learning outcomes
Upon completion of this case study, students will be able to analyze the interplay between small business growth and innovation in sustainable entrepreneurial success; evaluate factors influencing the adoption of technological innovations within startups; and decide on the optimal technological innovation for achieving sustainable growth in a startup.

Case overview/synopsis
This case study is about Liliana, a young Colombian entrepreneur. She had to decide how to innovate in her process of providing regulatory compliance and due diligence consulting services. According to Law 1778 of 2016, compliance and due diligence services became mandatory for companies with international operations in Colombia. Lemaître, Liliana’s venture, provided this service in an artisanal way. However, her market required the incorporation of technologies. Liliana must choose what to automate in her process and what to keep traditional. Not innovating meant Lemaître would be unable to grow, causing the sustainability of the business would to be at risk.

Complexity academic level
This case study is suitable for use for master of business administration students and in executive education short courses.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.
“One size doesn't fit all”. Bank switching decisions and customer vulnerability in Europe
Authors: Fernández-Gutiérrez Marcos , Ashton John 
Published: November 2023

PurposeThis paper examines the relationships between bank switching and both customer vulnerability and consumer-oriented policies (financial education and disclosure practices).Design/methodology/approachThe analysis employs microdata from the Special Eurobarometer on Financial Products and Services, for 24 European nations. It carries out a probit estimation on the factors explaining propensity of bank switching, focusing on three characteristics associated with customer vulnerability: an advanced age, low educational attainment and residence in a rural or a relatively poor region.FindingsThe authors report that the probability of bank switching is significantly lower for three groups of vulnerable customers: the elderly, the less educated and those living in deprived regions. Further the authors identify that national financial education policies and disclosure practices have no significant effects on bank switching.Research limitations/implicationsBased on these results, the authors propose more targeted policies recognising customers' heterogeneity are required to increase bank switching behaviour.Originality/valueThis paper exploits a unique source of information on bank switching behaviour and customer characteristics across European nations. These data are complemented with information about consumer financial education policies and disclosure practices from the World Bank and geographical, market and regulatory factors at the regional and national levels. The paper contributes to two academic areas. First, it presents further evidence on heterogeneity of bank customer switching behaviour, addressed at improving the understanding of customer vulnerability in banking services. Second, it examines the efficacy of consumer-oriented policies (financial literacy and disclosure practices) in encouraging bank switching.
Analysis of output and output volatility connectedness of Nigeria, USA, China and India: new empirical insights from the global financial crisis versus 2016 Nigerian recession
Authors: Anthony-Orji Onyinye Imelda , Nwodo Ikenna Paulinus , Orji Anthony , Ogbuabor Jonathan E. 
Published: November 2023

Purpose
This paper aims to examine Nigeria’s dynamic output and output volatility connectedness with USA, China and India using quarterly data from 1981Q1 to 2019Q4.

Design/methodology/approach
The study adopted the network approach of Diebold and Yilmaz (2014) and used the normalized generalized forecast error variance decomposition from an underlying vector error correction model to build connectedness measures.

Findings
The findings show that the global financial crisis (GFC) increased the connectedness index far more than the 2016 Nigeria economic recession. The moderate effect of the 2016 Nigeria economic recession on the connectedness index underscores the fact that Nigeria is a small, open economy with minimal capacity to spread output shock. For both real output and its volatility, the total connectedness index rose smoothly and systematically through time, thereby leaving the economies more connected in the long run.

Originality/value
To the best of the authors’ knowledge, this paper is among the first to examine Nigeria’s dynamic output and output volatility connectedness with the USA, China and India using new empirical insights from the GFC versus 2016 Nigerian recession. The study, therefore, concludes that the Nigerian economy should be diversified immediately as a hedge against future real output shocks, while the USA, China and India should maintain and sustain their current policy frameworks to remain less vulnerable to real output shocks.
Voting stake of the largest shareholder, ownership concentration and leverage
Authors: Gödecke Timm , Schiereck Dirk 
Published: November 2023

PurposeThis paper aims to investigate the impact of the largest shareholder's voting stake on the firm's capital structure decision.Design/methodology/approachTo empirically analyze the influence of the voting stake on leverage, a large sample of 814 exchange-listed firms is applied. The baseline regression analysis is complemented by several robustness tests and a difference-in-difference regression analysis to mitigate endogeneity concerns.FindingsThe authors find a negative relationship between the voting stake of the largest shareholder and leverage, consistent with the notion that large, undiversified shareholders have the incentive to reduce risk. Additionally, results reveal that family control has a positive moderating effect, indicating that the negative relationship is less pronounced for family controlled firms.Research limitations/implicationsThe authors contribute to the research by suggesting ownership concentration as another determinant of capital structure. Further, the authors add to the literature by showing how the association between ownership concentration and leverage is moderated by family control and that the identity of the largest shareholder is of great importance.Practical implicationsThe paper provides important insights to the current debate on the proposal of the European Commission to reintroduce shares with multiple votes as part of the Listing Act. The authors expect the regulation to exacerbate the concentration of voting rights, which results in lower leverage and thus limits corporate growth.Originality/valueThe authors differentiate from previous studies by focusing the largest shareholders' voting stake, instead of using the ownership stake, to assess the impact of ownership concentration on leverage.
Global impacts of COVID‐19 pandemic on sexual and reproductive health services: An international comparative study on primary care from the INTRePID Consortium
Authors: Peng Kangning , Tu Karen , Li Zhuo , Hallinan Christine Mary , Laughlin Adrian , Manski‐Nankervis Jo‐Anne , Apajee Jemisha , Lapadula María Carla , Ortigoza Angela , Da Roza Cecilia Clara , Baste Valborg , Flottorp Signe , Wensaas Knut‐Arne , Goh Lay Hoon , Ling Zheng Jye , Kristiansson Robert , Gaona Gabriela , Pace Wilson D. , Westfall John M. , Ng Amy Pui Pui , Wong William Chi‐Wai 
Published: November 2023

AbstractObjectiveTo understand how the COVID‐19 pandemic has impacted sexual and reproductive health (SRH) visits.DesignAn ecological study comparing SRH services volume in different countries before and after the onset of the COVID‐19 pandemic.SettingSeven countries from theINTernational ConsoRtium ofPrimary Care BIgData Researchers (INTRePID) across four continents.PopulationOver 3.8 million SRH visits to primary care physicians in Australia, China, Canada, Norway, Singapore, Sweden and the USA.MethodsDifference in average SRH monthly visits before and during the pandemic, with negative binomial regression modelling to compare predicted and observed number of visits during the pandemic for SRH visits.Main outcome measuresMonthly number of visits to primary care physicians from 2018 to 2021.ResultsDuring the pandemic, the average volume of monthly SRH visits increased in Canada (15.6%, 99% CI 8.1–23.0%) where virtual care was pronounced. China, Singapore, Sweden and the USA experienced a decline (−56.5%, 99% CI −74.5 to −38.5%; −22.7%, 99% CI −38.8 to −6.5%; −19.4%, 99% CI −28.3 to −10.6%; and −22.7%, 99% CI −38.8 to −6.5%, respectively); while Australia and Norway showed insignificant changes (6.5%, 99% CI −0.7 to –13.8% and 1.7%, 99% CI −6.4 to –9.8%). The countries that maintained (Australia, Norway) or surpassed (Canada) pre‐pandemic visit rates had the greatest use of virtual care.ConclusionsIn‐person SRH visits to primary care decreased during the pandemic. Virtual care seemed to counterbalance that decline. Although cervical cancer screening appeared insensitive to virtual care, strategies such as incorporating self‐collected samples for HPV testing may provide a solution in a future pandemic.
Three‐dimensional modelling and morphological investigation of the bones of the Articulatio genus using computed tomography images in Van cats
Authors: Dursun Süleyman , Yilmaz Osman , Demircioğlu İsmail 
Published: November 2023

AbstractIn this study, it was aimed to make three‐dimensional reconstruction of the stifle joint computed tomography (CT) images of the Van cats, to obtain their osteometric measurements, and to determine the statistical biometric differences of these measurement values in terms of both sexual dimorphism and homotypic variations. A total of 16 healthy adult Van cats of both sexes were used. The stifle joints of the cats were scanned with a CT device and images were obtained. Three‐dimensional reconstructions of the bony structures of the stifle joint were performed using CT images using the MIMICS 20.1 modelling program. Then, osteometric measurements were calculated, and statistical analysis was performed. When the morphometric measurement values were examined in terms of gender, it was observed that almost all of the osteometric measurement values of the stifle joint in Van cats (except SPW measurement) were higher in male cats. According to homotypic variations, right side TPW (p = 0.009), TPCMA (p = 0.003) and TPMCA (p = 0.032) measurement values in female cats and right side TPLCA (p = 0.002) measurement values in male cats were found to be statistically significantly higher than the left side from the measurements of only the proximal tibia (p < 0.05). In general, although there were negative correlations between morphometric measurement values with age and body weight, mostly strong positive correlations were seen. As a result, statistical differences of the biometric values and anatomical features of the stifle joint between the sexes in Van cats between the sexes were examined using CT and a three‐dimensional modelling program.