bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of endogenous free radicals is required to induce titan-like cell formation in
Cryptococcus neoformans
Authors: García-Barbazán Irene , Torres-Cano Alba , García-Rodas Rocío , Sachse Martin , Luque Daniel , Megías Diego , Zaragoza Oscar 
Published: December 2023

ABSTRACT

Cryptococcus neoformans
is an encapsulated yeast able to cause disease (mainly meningoencephalitis) among immunosuppressed patients, mostly HIV+. This yeast can form the so-called titan cells
in vivo
, which are cells of an abnormally larger size due to an increase in both the capsule and the cell body size (total size reaching between 50–70 μm). This phenomenon can be partially reproduced
in vitro
to obtain cells of an intermediate size (25–30 μm), which have been denominated titan-like cells. In this work, we have screened 1,520 compounds from the Prestwick Chemical Library and identified off-patent drugs that inhibited titan-like cell formation
in vitro
. We developed an automated fluorescence-based microscopy assay and identified 64 compounds as possible inhibitors of titan-like cells. We chose 10 of these compounds to perform dose-response curves and confirmed them as inhibitors of titan-like cell formation. Several of the compounds identified had antioxidant properties (i.e., retinoic acid), indicating a possible role of free radicals during titan cell formation. Using fluorescent probes, we found that there was an endogenous accumulation of reactive oxygen species (ROS) during cell growth, which was inhibited in the presence of retinoic acid. Furthermore, we found that during titanization, there were significant changes in the mitochondria, which is the main organelle where ROS are produced. We hypothesize that an intracellular increase of free radicals at the mitochondria might be a triggering signal to induce titanization.

IMPORTANCE

Cryptococcus neoformans
is an excellent model to investigate fungal pathogenesis. This yeast can produce “titan cells,” which are cells of an abnormally larger size that contribute to the persistence of the yeast in the host. In this work, we have used a new approach to characterize them by identifying drugs that inhibit this process. We have used a repurposing off-patent drug library, combined with an automatic method to image and analyze fungal cell size. In this way, we have identified many compounds that inhibit this transition. Interestingly, several compounds were antioxidants, allowing us to confirm that endogenous ROS and mitochondrial changes are important for titan cell formation. This work provides new evidence of the mechanisms required for titanization. Furthermore, the future characterization of the inhibitory mechanisms of the identified compounds by the scientific community will contribute to better understand the role of titan cells in virulence.
A bacterial sensor taxonomy across earth ecosystems for machine learning applications
Authors: Park Helen , Joachimiak Marcin P. , Jungbluth Sean P. , Yang Ziming , Riehl William J. , Canon R. Shane , Arkin Adam P. , Dehal Paramvir S. 
Published: December 2023

ABSTRACT

Microbial communities have evolved to colonize all ecosystems of the planet, from the deep sea to the human gut. Microbes survive by sensing, responding, and adapting to immediate environmental cues. This process is driven by signal transduction proteins such as histidine kinases, which use their sensing domains to bind or otherwise detect environmental cues and “transduce” signals to adjust internal processes. We hypothesized that an ecosystem’s unique stimuli leave a sensor “fingerprint,” able to identify and shed insight on ecosystem conditions. To test this, we collected 20,712 publicly available metagenomes from
Host-associated
,
Environmental
, and
Engineered
ecosystems across the globe. We extracted and clustered the collection’s nearly 18M unique sensory domains into 113,712 similar groupings with MMseqs2. We built gradient-boosted decision tree machine learning models and found we could classify the ecosystem type (accuracy: 87%) and predict the levels of different physical parameters (R2 score: 83%) using the sensor cluster abundance as features. Feature importance enables identification of the most predictive sensors to differentiate between ecosystems which can lead to mechanistic interpretations if the sensor domains are well annotated. To demonstrate this, a machine learning model was trained to predict patient’s disease state and used to identify domains related to oxygen sensing present in a healthy gut but missing in patients with abnormal conditions. Moreover, since 98.7% of identified sensor domains are uncharacterized, importance ranking can be used to prioritize sensors to determine what ecosystem function they may be sensing. Furthermore, these new predictive sensors can function as targets for novel sensor engineering with applications in biotechnology, ecosystem maintenance, and medicine.

IMPORTANCE
Microbes infect, colonize, and proliferate due to their ability to sense and respond quickly to their surroundings. In this research, we extract the sensory proteins from a diverse range of environmental, engineered, and host-associated metagenomes. We trained machine learning classifiers using sensors as features such that it is possible to predict the ecosystem for a metagenome from its sensor profile. We use the optimized model’s feature importance to identify the most impactful and predictive sensors in different environments. We next use the sensor profile from human gut metagenomes to classify their disease states and explore which sensors can explain differences between diseases. The sensors most predictive of environmental labels here, most of which correspond to uncharacterized proteins, are a useful starting point for the discovery of important environment signals and the development of possible diagnostic interventions.
A systemic approach to identify non-abundant immunogenic proteins in Lyme disease pathogens
Authors: Yaş Ozlem Buyuktanir , Coleman Adam S. , Lipman Rachel M. , Sharma Kavita , Raghunandanan Sajith , Alanazi Fuad , Rana Vipin S. , Kitsou Chrysoula , Yang Xiuli , Pal Utpal 
Published: December 2023

ABSTRACT

Borrelia burgdorferi
, the pathogen of Lyme disease, differentially produces many outer surface proteins (Osp), some of which represent the most abundant membrane proteins, such as OspA, OspB, and OspC. In cultured bacteria, these proteins can account for a substantial fraction of the total cellular or membrane proteins, posing challenges to the identification and analysis of non-abundant proteins, which could serve as novel pathogen detection markers or as vaccine candidates. Herein, we introduced serial mutations to remove these abundant Osps and generated a
B. burgdorferi
mutant deficient in OspA, OspB, and OspC in an infectious 297-isolate background, designated as

Osp
ABC

−
mutant. Compared to parental isolate, the mutant did not reflect growth defects in the cultured medium but showed differential mRNA expression of representative tested genes, in addition to gross changes in cellular and membrane protein profiles. The analysis of differentially detectable protein contents of the

Osp
ABC

−
mutant, as compared to the wild type, by two-dimensional gel electrophoresis followed by liquid chromatography-mass spectrometry, identified several spirochete proteins that are dominated by proteins of unknown functions, as well as membrane transporters, chaperons, and metabolic enzymes. We produced recombinant forms of two of these represented proteins, BBA34 and BB0238, and showed that these proteins are detectable during spirochete infection in the tick-borne murine model of Lyme borreliosis and thus serve as potential antigenic markers of the infection.

IMPORTANCE

The present manuscript employed a systemic approach to identify non-abundant proteins in cultured
Borrelia burgdorferi
that are otherwise masked or hidden due to the overwhelming presence of abundant Osps like OspA, OspB, and OspC. As these Osps are either absent or transiently expressed in mammals, we performed a proof-of-concept study in which their removal allowed the analysis of otherwise less abundant antigens in OspABC-deficient mutants and identified several immunogenic proteins, including BBA34 and BB0238. These antigens could serve as novel vaccine candidates and/or genetic markers of Lyme borreliosis, promoting new research in the clinical diagnosis and prevention of Lyme disease.
Extremely Wide Pairs in the World of Binary Stars
Authors: Dremova G. N. , Dremov V. V. , Tutukov A. V. 
Published: December 2023

Abstract
This article raises the question of the possibility of identifying stellar pairs in which one of the components belongs to the family of near-nuclear central S-stars and the other belongs to a population of hypervelocity stars (HVSs). In the recent past, they could be genetically linked in a single parent binary star (BS), and today its components are separated by hundreds or more parsecs as a result of dynamic capture of a BS by the field of a supermassive black hole (SMBH). There is interest in the mutual reconstruction of populations of S-stars and HVSs calculated in the context of the classical Hills scenario, based on the principle of supplementing their observational data. The paper is based on a report presented at the astrophysical memorial seminar “Novelties in Understanding the Evolution of Binary Stars,” dedicated to the 90th anniversary of Professor M.A. Svechnikov.
Review of emerging trends and projection of future developments in large language models research in ophthalmology
Authors: Wong Matthew , Lim Zhi Wei , Pushpanathan Krithi , Cheung Carol Y , Wang Ya Xing , Chen David , Tham Yih Chung 
Published: December 2023

BackgroundLarge language models (LLMs) are fast emerging as potent tools in healthcare, including ophthalmology. This systematic review offers a twofold contribution: it summarises current trends in ophthalmology-related LLM research and projects future directions for this burgeoning field.MethodsWe systematically searched across various databases (PubMed, Europe PMC, Scopus and Web of Science) for articles related to LLM use in ophthalmology, published between 1 January 2022 and 31 July 2023. Selected articles were summarised, and categorised by type (editorial, commentary, original research, etc) and their research focus (eg, evaluating ChatGPT’s performance in ophthalmology examinations or clinical tasks).FindingsWe identified 32 articles meeting our criteria, published between January and July 2023, with a peak in June (n=12). Most were original research evaluating LLMs’ proficiency in clinically related tasks (n=9). Studies demonstrated that ChatGPT-4.0 outperformed its predecessor, ChatGPT-3.5, in ophthalmology exams. Furthermore, ChatGPT excelled in constructing discharge notes (n=2), evaluating diagnoses (n=2) and answering general medical queries (n=6). However, it struggled with generating scientific articles or abstracts (n=3) and answering specific subdomain questions, especially those regarding specific treatment options (n=2). ChatGPT’s performance relative to other LLMs (Google’s Bard, Microsoft’s Bing) varied by study design. Ethical concerns such as data hallucination (n=27), authorship (n=5) and data privacy (n=2) were frequently cited.InterpretationWhile LLMs hold transformative potential for healthcare and ophthalmology, concerns over accountability, accuracy and data security remain. Future research should focus on application programming interface integration, comparative assessments of popular LLMs, their ability to interpret image-based data and the establishment of standardised evaluation frameworks.
Socially sustainable housing and built environments to support the health and social inclusion of older adults: protocol for a scoping review and stakeholder consultation
Authors: Sturge Jodi , Miedema Elke , Elf Marie , Nordin Susanna 
Published: December 2023

IntroductionHousing and the ageing population are issues that pose challenges for social, health and economic policies. Therefore, there is a need for more knowledge on how to design housing and public infrastructure to improve the social engagement and well-being of older adults who age in place. This project aims to provide an overview of the existing literature on design features that support socially sustainable living environments for older adults.Methods and analysisA systematic scoping methodology was used to identify and summarise the findings. Four databases were searched (CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, Medline and Embase) to identify the articles. Articles were included if published in English in the last 15 years (eg, from January 2008 to June 2023) without restricting the study location or country. Articles were included if they were based on empirical qualitative, quantitative and mixed-method data. The results of the review will be discussed with a panel of 15 stakeholders (n=15) from Canada, Sweden and the Netherlands (five per country). The interdisciplinary stakeholders will have expertise in housing, architecture, engineering and social and health services. The consultations will provide content expertise to the literature findings and an opportunity to build evidence-based solutions that support the design of socially sustainable living environments for older persons.Ethics and disseminationEthical clearance for this project has been granted by the Swedish Ethical Review Authority for Dalarna University (dnr 2023-01543-01) and the Natural Sciences and Engineering Sciences (NES) Ethics Committee at the University of Twente in the Netherlands (dnr 230407) has approved this project. Stakeholders will be asked to provide signed consent to participate in the study. The results of this project will be disseminated through web seminars, community advisory groups, peer-reviewed journals and policy documents to support the development of housing and public health policy.Trial registration numberOSF,https://doi.org/10.17605/OSF.IO/PR2NC.
The moderating and mediating role of eating behaviour traits in acceptance and commitment therapy-based weight management interventions: protocol for an individual participant data meta-analysis
Authors: Kudlek Laura , Mueller Julia , Eustacio Colombo Patricia , Sharp Stephen J. , Griffin Simon J. , Ahern Amy 
Published: December 2023

IntroductionPrecision medicine approaches to obesity aim to maximise treatment effectiveness by matching weight management interventions (WMIs) to characteristics of individuals, such as eating behaviour traits (EBTs). Acceptance and commitment therapy (ACT)-based WMIs may address EBTs such as emotional and uncontrolled eating more effectively than standard interventions, and might be most effective in people with high levels of these traits. However, few studies have examined this directly. We will examine (a) whether ACT-based interventions are more effective for people with certain levels of EBTs (ie, moderation) and (b) whether ACT-based interventions operate through changes in EBTs (ie, mediation).Methods and analysisThis individual participant data (IPD) meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data guidance. We will include studies on ACT-based WMIs that assessed EBTs in people with a body mass index ≥25 kg/m2. We identified studies by screening studies included in a previous review of third wave cognitive behavioural interventions, and updating the search to 20 June 2022. We will request IPD from eligible published and unpublished studies. We will harmonise and re-analyse data using a two-stage random effects meta-analysis pooling within-trial interactions to investigate moderating effects and using a one-stage simultaneous equation model to examine mediating effects. We will assess the risk of bias in included studies using the Cochrane Risk of Bias tool 2 and the Risk of Bias in Non-randomised Studies of Interventions tool.Ethics and disseminationEthical approval has been obtained from the Cambridge Psychology Research Ethics Committee (Application No: PRE.2023.121). Data sharing will follow data transfer agreements and coauthorship will be offered to investigators contributing data. Findings will be disseminated through peer-reviewed journals and conferences and will contribute to the lead author’s PhD thesis.PROSPERO registration numberCRD42022359691.
Experiences of using artificial intelligence in healthcare: a qualitative study of UK clinician and key stakeholder perspectives
Authors: Fazakarley C A , Breen Maria , Leeson Paul , Thompson Ben , Williamson Victoria 
Published: December 2023

ObjectivesArtificial intelligence (AI) is a rapidly developing field in healthcare, with tools being developed across various specialties to support healthcare professionals and reduce workloads. It is important to understand the experiences of professionals working in healthcare to ensure that future AI tools are acceptable and effectively implemented. The aim of this study was to gain an in-depth understanding of the experiences and perceptions of UK healthcare workers and other key stakeholders about the use of AI in the National Health Service (NHS).DesignA qualitative study using semistructured interviews conducted remotely via MS Teams. Thematic analysis was carried out.SettingNHS and UK higher education institutes.ParticipantsThirteen participants were recruited, including clinical and non-clinical participants working for the NHS and researchers working to develop AI tools for healthcare settings.ResultsFour core themes were identified: positive perceptions of AI; potential barriers to using AI in healthcare; concerns regarding AI use and steps needed to ensure the acceptability of future AI tools. Overall, we found that those working in healthcare were generally open to the use of AI and expected it to have many benefits for patients and facilitate access to care. However, concerns were raised regarding the security of patient data, the potential for misdiagnosis and that AI could increase the burden on already strained healthcare staff.ConclusionThis study found that healthcare staff are willing to engage with AI research and incorporate AI tools into care pathways. Going forward, the NHS and AI developers will need to collaborate closely to ensure that future tools are suitable for their intended use and do not negatively impact workloads or patient trust. Future AI studies should continue to incorporate the views of key stakeholders to improve tool acceptability.Trial registration numberNCT05028179;ISRCTN15113915; IRAS ref: 293515.
Physician Perceptions of Cannabidiol (CBD) and Cannabis in Sports Medicine and Performance
Authors: Ross Brendon , Trojian Thomas , Cushman Daniel M. 
Published: December 2023

Objectives. There is growing evidence regarding cannabinoid use in sports medicine and performance, especially cannabidiol (CBD). This study aims to determine if sports medicine physicians are recommending cannabinoids for therapeutic purposes, as well as analyze perceptions of cannabinoids within sports medicine and performance. Methods. Physician members of the American Medical Society for Sports Medicine (AMSSM) completed an anonymous survey on demographics, CBD and Cannabis recommendations, as well as attitudes toward cannabinoid products within sports medicine. Factors associated with CBD and cannabis recommendations as well as perceptual differences were found using multivariate regression modelling. Results. Responses from 333 physicians were recorded. The following groups were less likely to agree with allowing cannabis for recreational purposes: female gender (coeff. = 0.79 (0.33–1.25),

p
=
0.001

), increasing age (coeff. = 0.04 (0.02, 0.07),

p

<

0.001

), and rural respondents (compared to baseline urban, coeff. = 1.16 (0.36, 1.95),

p
=
0.004

). Similarly, these three factors were associated with a higher likelihood of disagreeing with WADA removing cannabis from the prohibited substance list and with the NCAA allowing CBD use by collegiate athletes (

p
≤
0.045

). CBD was less likely to be recommended by pediatricians, rural physicians, and academic physicians (

p
≤
0.030

). Male physicians and younger physicians were less likely to identify cannabis as performance-enhancing (

p
≤
0.042

). Conclusions. Sports medicine physicians have varying views on cannabinoids. While sports medicine physicians generally have favorable attitudes toward CBD and cannabis, these perceptions appear to be significantly affected by age, practice type, and gender.
Indian Ocean Basin Warming in 2020 Forced by Thermocline Anomalies of the 2019 Indian Ocean Dipole
Authors: Wang Jing , Zhang Shouwen , Jiang Hua , Yuan Dongliang 
Published: December 2023

Abstract
The Indian Ocean basin (IOB) mode is the dominant mode of the interannual sea surface temperature (SST) variability in the Indian Ocean, with the Indian Ocean dipole (IOD) as the second mode. An IOB event normally occurs after an El Niño or a concurrent IOD–El Niño event, the dynamics of which are traditionally believed as forced by ENSO through the Walker circulation anomalies over the tropical Indian Ocean. A strong IOB in 2020 took place after the strongest 2019 IOD on record but independent of El Niño, which challenges the traditional atmospheric bridge dynamics of the IOB event. In this study, the dynamics of the 2020 IOB event are investigated using the numerical seasonal climate prediction system of the National Marine Environmental Forecasting Center of China. It is found that the initialization of the Indian Ocean subsurface temperature during the 2019 IOD event has led to the outburst of the 2020 IOB event successfully, the dynamics of which are the propagation and the western boundary reflection of the equatorial and off-equatorial Rossby waves, inducing heat content recharge over the tropical Indian Ocean upper thermocline. In comparison, experiments of SST initialization over the tropical Indian Ocean, with the subsurface temperature in a climatological state, were unable to reproduce the onset of the 2020 IOB event, suggesting that the local air–sea interaction within the Indian Ocean basin is of secondary importance. The numerical experiments suggest that the thermocline ocean wave dynamics play an important role in forcing the IOB event. The revealed thermocline dynamics are potentially useful in climate prediction associated with IOB events.