bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data Management Plan for Healthcare: Following FAIR Principles and Addressing Cybersecurity Aspects. A Systematic Review using InstructGPT
Authors: Stanciu Alexandru 
Published: April 2023

AbstractThis study focuses on data-related aspects and emphasizes the importance of producing a data management plan (DMP) to address the challenges specific to the collection, processing, storage, security, documentation, sharing, and distribution of data in research projects in the healthcare sector. It provides an overview of the DMP and offers guidelines for creating an effective plan that incorporates the FAIR principles. Additionally, the study outlines the main aspects of data management in the healthcare domain and analyzes several security issues, such as cryptography, biometrics, and digital watermarking, that should be considered for healthcare data. A systematic review of the literature is performed to explore the critical aspects of data management and identify emerging trends, challenges, and innovative solutions that can be incorporated into DMPs. Part of the analysis of this survey was performed with the InstructGPT language model.
Context-Aware Deep Learning Enables High-Efficacy Localization of High Concentration Microbubbles for Super-Resolution Ultrasound Localization Microscopy
Authors: Shin YiRang , Lowerison Matthew R. , Wang Yike , Chen Xi , You Qi , Dong Zhijie , Anastasio Mark A. , Song Pengfei 
Published: April 2023

AbstractUltrasound localization microscopy (ULM) is an emerging super-resolution imaging technique for deep tissue microvascular imaging. However, conventional localization methods are constrained by low microbubble (MB) concentration, as accurate localization requires a strict separation of MB point spread functions (PSFs). Furthermore, deep learning-based localization techniques are often limited in their ability to generalize toin vivoultrasound data due to challenges in accurately modeling highly variable MB PSF distributions and ultrasound imaging conditions. To address these limitations, we propose a novel deep learning-pipeline, LOcalization with Context Awareness (LOCA)-ULM, which employs simulation that incorporates MB context to generate synthetic data that closely resemble real MB signals, and a loss function that considers both MB count and localization loss. Inin silicoexperiments, LOCA-ULM outperformed conventional localization with superior MB detection accuracy (94.0% vs. 74.9%) and a significantly lower MB missing rate (13.2% vs 74.8%).In vivo, LOCA-ULM achieved up to three-fold increase in MB localization efficiency and a × 9.5 faster vessel saturation rate than conventional ULM.
How hibernation in frogs drives brain and reproductive evolution in opposite directions
Authors: Liao Wen Bo , Jiang Ying , Jin Long , Lüpold Stefan 
Published: April 2023

AbstractEnvironmental seasonality can promote the evolution of larger brains through cognitive and behavioral flexibility but can also hamper it when temporary food shortage is buffered by stored energy. Multiple hypotheses linking brain evolution with resource acquisition and allocation have been proposed for warm-blooded organisms, but it remains unclear how these extend to cold-blooded taxa whose metabolism is tightly linked to ambient temperature. Here, we integrated these hypotheses across frogs and toads in the context of varying brumation (‘hibernation’) durations and their environmental correlates. We showed that protracted brumation covaried negatively with brain size but positively with reproductive investment, likely in response to brumation-dependent changes in the socio-ecological context and associated selection on different tissues. Our results provide novel insights into resource allocation strategies and possible constraints in trait diversification, which may have important implications for the adaptability of species under sustained environmental change.
A Key Piece of the Puzzle: The central tetramer of theSaccharomyces cerevisiaeseptin protofilament and Its Implications for Self-Assembly
Authors: Marques da Silva Rafael , dos Reis Saladino Giovanna Christe , Leonardo Diego Antonio , Pereira Humberto D’Muniz , Sculaccio Susana Andréa , Ulian Araujo Ana Paula , Garratt Richard Charles 
Published: April 2023

ABSTRACTSeptins, often described as the fourth component of the cytoskeleton, are structural proteins found in a vast variety of living beings. They are related to small GTPases and thus, generally, present GTPase activity which may play an important (although incompletely understood) role in their organization and function. Septins polymerase into long non-polar filaments, in which each subunit interacts with two others by alternating interfaces, NC and G. InSaccharomyces cerevisiaefour septins are organized in the following manner, [Cdc11-Cdc12-Cdc3-Cdc10- Cdc10-Cdc3-Cdc12-Cdc11]nin order to form filaments. Although septins were originally discovered in yeast and much is known regarding their biochemistry and function, only limited structural information about them is currently available. Here we present crystal structures of Cdc3/Cdc10 which provide the first view of the physiological interfaces formed by yeast septins. The G-interface has properties which place it in between that formed by SEPT2/SEPT6 and SEPT7/SEPT3 in human filaments. Switch I from Cdc10 contributes significantly to the interface, whereas in Cdc3 it is largely disorded. However, the significant negative charge density of the latter suggests it may have a unique role. At the NC-interface, we describe an elegant means by which the sidechain of a glutamine from helix α0imitates a peptide group in order to retain hydrogen-bond continuity at the kink between helices α5and α6in the neighbouring subunit, thereby justifying the conservation of the helical distortion. Its absence from Cdc11, along with this structure’s other unusual features are critically discussed by comparison with Cdc3 and Cdc10.GRAPHICAL ABSTRACTHIGHLIGHTSThe first crystal structure of a yeast septin heterodimer (Cdc3-Cdc10) provides important insights into their structural biology.Identification of common features and differences between yeast and human septins, sheds light on the unique characteristics of yeast septin filaments.The Cdc3G-Cdc10Δ1-10crystal structure could be a crucial piece of the puzzle towards obtaining a high-resolution cryo-EM structure of the yeast septin octamer.
Machine Learning-based Phenotypic Imaging to Characterise the Targetable Biology ofPlasmodium falciparumMale Gametocytes for the Development of Transmission-Blocking Antimalarials
Authors: Tsebriy Oleksiy , Khomiak Andrii , Miguel-Blanco Celia , Sparkes Penny C. , Gioli Maurizio , Santelli Marco , Whitley Edgar , Gamo Francisco-Javier , Delves Michael J. 
Published: April 2023

AbstractPreventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priority. Large screening campaigns have identified many new transmission-blocking molecules, however little is known about how they target the mosquito-transmissiblePlasmodium falciparumstage V gametocytes, or how they affect their underlying cell biology. To respond to this knowledge gap, we have developed a machine learning image analysis pipeline to characterise and compare the cellular phenotypes generated by transmission-blocking molecules during male gametogenesis. Using this approach, we studied 40 molecules, categorising their activity based upon timing of action and visual effects on the organisation of tubulin and DNA within the cell. Our data both proposes new modes of action and corroborates existing modes of action of identified transmission-blocking molecules. Furthermore, the characterised molecules provide a new armoury of tool compounds to probe gametocyte cell biology and the generated imaging dataset provides a new reference for researchers to correlate molecular target or gene deletion to specific cellular phenotype. Our analysis pipeline is not optimised for a specific organism and could be applied to any fluorescence microscopy dataset containing cells delineated by bounding boxes, and so is extendible to any disease model.
Genomic and radiocarbon insights into the mystery of mouse mummies on the summits of >6000 m Andean volcanoes
Authors: Storz Jay F. , Liphardt Schuyler , Quiroga-Carmona Marcial , Bautista Naim M. , Opazo Juan C. , Wheeler Timothy B. , D’Elía Guillermo , Good Jeffrey M. 
Published: April 2023

SUMMARYOur understanding of the limits of animal life is continually revised by scientific exploration of extreme environments. Here we report the discovery of numerous mummified cadavers of leaf-eared mice,Phyllotis vaccarum, from the summits of three different Andean volcanoes at elevations 6029-6233 m (19,780-20,449 ft) above sea level in the Puna de Atacama (Chile-Argentina). Such extreme elevations were previously assumed to be completely uninhabitable by mammals. In combination with a live-captured specimen of the same species from the nearby summit of Volcán Llullaillaco (6739 m [=22,110 ft]), the 13 summit mummies represent the highest physical records of mammals in the world. We report a chromosome-level genome assembly forP. vaccarumin combination with a whole-genome re-sequencing analysis and radiocarbon dating analysis that provide insights into the provenance and antiquity of the summit mice. We test alternative hypotheses to explain the existence of mouse graveyards on the summits of Atacama volcanoes. Radiocarbon data indicate that the most ancient of the mummies were at most a few centuries old. Genomic polymorphism data revealed a high degree of continuity between the summit mice and conspecifics from lower elevations in the surrounding Altiplano. Genomic data also revealed equal numbers of males and females among the summit mice and evidence of close kinship between some individuals from the same summit groups. These findings bolster evidence for self-sustaining populations ofPhyllotisat elevations >6000 m and challenge assumptions about the environmental limits of vertebrate life and the physiological tolerances of small mammals.
The Cyclimids: Degron-inspired cereblon binders for targeted protein degradation
Authors: Ichikawa Saki , Payne N. Connor , Xu Wenqing , Chang Chia-Fu , Vallavoju Nandini , Frome Spencer , Flaxman Hope A. , Mazitschek Ralph , Woo Christina M. 
Published: April 2023

AbstractCereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of degraders that engage CRBN.
Infant Left Amygdala Volume Is Negatively Associated with Fecal Microbiota Diversity
Authors: Aatsinki Anna-Katariina , Tuulari Jetro J. , Munukka Eveliina , Lahti Leo , Keskitalo Anniina , Kailanto Henna-Maria , Nolvi Saara , Scheinin Noora M. , Saunavaara Jani , Parkkola Riitta , Lewis John D. , Hashempour Niloofar , Shulist Satu J. , Karlsson Linnea , Karlsson Hasse 
Published: April 2023

AbstractIntroductionRodent studies have addressed the importance of early life gut microbiota in the development of emotional and social functioning. Studies in human infants are still scarce, but associations with cognition and temperament have been reported. Neuroimaging studies have linked the amygdala with fecal microbiota diversity in infants, but crucially these studies have not covered the neonatal period, and the current study addressed this gap.MethodsThe study population included 65 infants drawn from the ongoing, general population based FinnBrain Birth Cohort Study. Brain MRI was performed around the age of one month (mean age 25 days). Fecal microbiota profiles (mean 68 days) were assessed by 16s rRNA amplicon sequencing at the age of 2.5 months.ResultsWe found a negative association between infant left amygdala volume and alpha diversity (n=52, beta =-0.0043, p=0.034, adjusted for infant sex, breastfeeding, delivery mode, age during fecal sampling, age from conception during scan, and intracranial volume, Fig.1). Amygdala volumes were not associated with beta diversity (p=0.21), nor with the abundances of individual genera when adjusted for the same covariates and multiple testing.ConclusionOur results provide first evidence for associations between the brain and fecal microbiota in human neonates. Although the reported data do not allow investigation of underlying mechanisms, i.e. about the directionality of the hypothesized gut-brain connection, the reported connection encourages for future investigations of manifestations of gut-brain axis in early life.
Plasmodium falciparuminfection of human erythroblasts induces transcriptional changes associated with dyserythropoiesis
Authors: Feldman Tamar P. , Ryan Yana , Egan Elizabeth S. 
Published: April 2023

AbstractDuring development down the erythroid lineage, hematopoietic stem cells undergo dramatic changes to cellular morphology and function in response to a complex and tightly regulated program of gene expression. In malaria infection,Plasmodium spp. parasites accumulate in the bone marrow parenchyma, and emerging evidence suggests erythroblastic islands are a protective site for parasite development into gametocytes. While it has been observed thatPlasmodium falciparuminfection of late-stage erythroblasts can delay terminal erythroid differentiation and enucleation, the mechanism(s) underlying this phenomenon are unknown. Here, we apply RNA-seq after fluorescence-activated cell sorting (FACS) of infected erythroblasts to identify transcriptional responses to direct and indirect interaction withPlasmodium falciparum. Four developmental stages of erythroid cells were analyzed: proerythroblast, basophilic erythroblast, polychromatic erythroblast, and orthochromatic erythroblast. We found extensive transcriptional changes in infected erythroblasts compared to uninfected cells in the same culture, including dysregulation of genes involved in erythroid proliferation and developmental processes. Whereas some indicators of cellular oxidative and proteotoxic stress were common across all stages of erythropoiesis, many responses were specific to cellular processes associated with developmental stage. Together, our results evidence multiple possible avenues by which parasite infection can induce dyserythropoiesis at specific points along the erythroid continuum, advancing our understanding of the molecular determinants of malaria anemia.Key PointsErythroblasts at different stages of differentiation have distinct responses to infection byPlasmodium falciparum.P. falciparuminfection of erythroblasts alters expression of genes related to oxidative and proteotoxic stress and erythroid development.
Urine metabolomic profiles of autism and autistic traits – a twin study
Authors: Arora Abishek , Mastropasqua Francesca , Bölte Sven , Tammimies Kristiina 
Published: April 2023

AbstractCurrently, there are no reliable biomarkers for autism diagnosis. The heterogeneity of autism and several co-occurring conditions are key challenges to establishing these. Here, we used untargeted mass spectrometry-based urine metabolomics to investigate metabolic differences for autism diagnosis and autistic traits in a well-characterized twin cohort (N=105). We identified 208 metabolites in the urine samples of the twins. No clear, significant metabolic drivers for autism diagnosis were detected when controlling for other neurodevelopmental conditions. However, we identified nominally significant changes for several metabolites. For instance, phenylpyruvate (p=0.019) and taurine (p=0.032) were elevated in the autism group, while carnitine (p=0.047) was reduced. We furthermore accounted for the shared factors, such as genetics within the twin pairs, and report additional metabolite differences. Based on the nominally significant metabolites for autism diagnosis, the arginine and proline metabolism pathway (p=0.024) was enriched. We also investigated the association between quantitative autistic traits, as measured by the Social Responsiveness Scale 2nd Edition, and metabolite differences, identifying a greater number of nominally significant metabolites and pathways. A significant positive association between indole-3-acetate and autistic traits was observed within the twin pairs (adjusted p=0.031). The utility of urine biomarkers in autism, therefore, remains unclear, with mixed findings from different study populations.Lay summaryEarlier literature has suggested that there are chemical molecules (metabolites) in the urine samples of autistic individuals that could be linked with their diagnosis of autism. However, there are still mixed results and uncertainty if any of these metabolites could be used as biomarkers (chemical molecules that indicate a biological condition). In this study, we analysed urine samples of 105 twins from Sweden, of which 48 were identical or fraternal twins, and the analysed metabolite levels were compared between those twins diagnosed with autism and those without a diagnosis. Additionally, we tested if the metabolite levels were different in relation to the level of autistic behaviour. The metabolite levels were measured using mass spectrometry, allowing us to identify hundreds of chemical molecules present in a urine sample followed with testing their significance for autism diagnosis or autistic traits. No single metabolite was found to be highly associated with a diagnosis of autism. However, indole-3-acetate, a metabolite produced by the breakdown of the amino acid tryptophan, was associated with the level of autistic behaviour within the twins. Nevertheless, several metabolites showed some association with autism or the level of autistic behaviour, while revealing interesting pathways for studies in the future.
The extractive industry and expectations of resource benefits: does CSR promote community well-being?
Authors: Attah Amewu , Amoah Prince 
Published: April 2023

Purpose
This paper aims to examine the effects of extractive activities on the well-being of local communities and assesses stakeholder expectations of resource benefits and the corporate social responsibility (CSR) practices of oil companies in Ghana.

Design/methodology/approach
The paper uses a qualitative approach based on an exploratory research design to investigate the opinions and experiences of stakeholders in the growing oil and gas industry in Ghana.

Findings
The empirical findings demonstrate that entry negotiated agreements and local content requirements in the offshore oil industry have minimal benefits because of the lack of linkages with the economies of local communities. Additionally, the nature of CSR practices within the extractive industry is directly traceable to the resource governance arrangements and plural logics in Ghana’s institutional context.

Research limitations/implications
This study only provides insights into natural resource governance and CSR issues in offshore oil and gas projects. Thus, the findings are not generalisable to the entire industry, including onshore drilling, which have other sustainability issues.

Practical implications
This research highlights the gap in natural resource management in Ghana and the effects of community expectations on CSR practices in the oil and gas industry. Therefore, this study posits the significance for including compliance requirements for improving the well-being of host communities in entry negotiated agreements and local contents.

Originality/value
By highlighting the nuanced issues in natural resource management within the oil and gas industry in Ghana, this paper makes significant contributions to the CSR and sustainability literature.
Serum: differential pricing of the Covid-19 vaccine
Authors: Arora Sunny Vijay , Krishna Malay 
Published: April 2023

Learning outcomes
The learning outcomes of this study are as follows:
1. the benefits of differential pricing over uniform pricing;
2. the differences between second- and third-degree price discrimination;
3. the rationale for charging different prices for segments having different willingness to pay; and
4. how different prices for the same product can lead to perceptions of unfairness and how companies might manage such an issue.

Case overview/synopsis
This case outlines the decisions that Adar Poonawalla, the CEO of Serum Institute of India (Serum), had to make in late April 2021 concerning its pricing for the COVID-19 (Covid) vaccine. Serum was the world’s largest manufacturer of vaccines, and its Covishield vaccine had received regulatory approval, but faced an unusual challenge and opportunity. In most countries, governments had procured Covid vaccines from manufacturers and then delivered the vaccines to consumers free of cost. But in India, there was a three-tier pricing system. While the Government of India had committed to free vaccines in government-run public hospitals, it also allowed vaccine makers to directly sell vaccines to state governments, as well as private hospitals, who were at liberty to charge consumers for the vaccines. This created an interesting pricing dilemma for Serum: as different customers had different willingness to pay, should Serum use differential pricing? Would such a tiered pricing system be considered fair? How many different price points should Serum maintain? By exploring these and related decisions that Poonawalla had to make, the case is intended to teach price discrimination.

Complexity academic level
The case is intended for graduate-level courses in marketing, pricing and economics. This case illustrates the principles of differential pricing/price discrimination. More specifically, it highlights pricing strategies motivated by second- and third-degree price discrimination in an emerging market’s health-care context. From the information in the case, the student can learn to apply the concepts of second- and third-degree price discrimination in marketing. After working through the case and assignment questions, instructors will be able to help students understand the following concepts:
Teaching objective 1: the benefits of differential pricing over uniform pricing.
Teaching objective 2: the differences between second- and third-degree price discrimination.
Teaching objective 3: the rationale for charging different prices for segments having different willingness to pay.
Teaching objective 4: how different prices for the same product can lead to perceptions of unfairness and how companies might manage such an issue.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 8: Marketing