bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel framework for the automated characterization of Gram-stained blood culture slides using a large-scale vision transformer
Authors: McMahon Jack , Tomita Naofumi , Tatishev Elizabeth S. , Workman Adrienne A. , Costales Cristina R. , Banaei Niaz , Martin Isabella W. , Hassanpour Saeed 
Published: February 2025

ABSTRACT

This study introduces a new framework for the artificial intelligence-based characterization of Gram-stained whole-slide images (WSIs). As a test for the diagnosis of bloodstream infections, Gram stains provide critical early data to inform patient treatment in conjunction with data from rapid molecular tests. In this work, we developed a novel transformer-based model for Gram-stained WSI classification, which is more scalable to large data sets than previous convolutional neural network-based methods as it does not require patch-level manual annotations. We also introduce a large Gram stain data set from Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire, USA) to evaluate our model, exploring the classification of five major categories of Gram-stained WSIs: gram-positive cocci in clusters, gram-positive cocci in pairs/chains, gram-positive rods, gram-negative rods, and slides with no bacteria. Our model achieves a classification accuracy of 0.858 (95% CI: 0.805, 0.905) and an area under the receiver operating characteristic curve (AUC) of 0.952 (95% CI: 0.922, 0.976) using fivefold nested cross-validation on our 475-slide data set, demonstrating the potential of large-scale transformer models for Gram stain classification. Results were measured against the final clinical laboratory Gram stain report after growth of organism in culture. We further demonstrate the generalizability of our trained model by applying it without additional fine-tuning on a second 27-slide external data set from Stanford Health (Palo Alto, California, USA) where it achieves a binary classification accuracy of 0.926 (95% CI: 0.885, 0.960) and an AUC of 0.8651 (95% CI: 0.6337, 0.9917) while distinguishing gram-positive from gram-negative bacteria.

IMPORTANCE
This study introduces a scalable transformer-based deep learning model for automating Gram-stained whole-slide image classification. It surpasses previous methods by eliminating the need for manual annotations and demonstrates high accuracy and generalizability across multiple data sets, enhancing the speed and reliability of Gram stain analysis.
UV-irradiated rotifers for the maintenance of gnotobiotic zebrafish larvae
Authors: Márquez Rosales Susana , Bouchard Peter I. , Olmstead Emily M. , Parthasarathy Raghuveer 
Published: February 2025

ABSTRACT

Host-associated microbial communities profoundly impact the health of humans and other animals. Zebrafish have proven to be a useful model for uncovering mechanisms of host-microbe interactions, but the difficulty of maintaining germ-free or gnotobiotic zebrafish beyond 1 week post-fertilization has limited their utility. To address this, we have developed a simple protocol using UV irradiation of rotifers, a common and nutrient-rich prey species for larval zebrafish, to reduce the bacterial load associated with the rotifers by several orders of magnitude while maintaining their motility and viability. We find that though feeding with UV-treated rotifers does not preserve the sterility of germ-free fish, it enables the maintenance of pre-existing bacterial communities. Normal feeding, in striking contrast, leads to the near-total depletion of these prior populations. We measure the abundance of single- and three-species consortia of zebrafish-commensal bacteria inoculated into initially germ-free larvae in a series of experiments extending to 8 days of feeding, or 13 days post-fertilization. We find, in fish-fed UV-treated rotifers, the persistence of bacterial populations on timescales of days, together with strong species-specific variation. In addition, re-inoculation of differently labeled strains of the same zebrafish-commensal species alongside feeding leads to colonization by the new bacteria without displacement of earlier microbes. Our method will facilitate the use of gnotobiotic zebrafish for investigations of phenomena that emerge later in animal development and for studies that probe microbiome composition fluctuations and stability over extended timescales.

IMPORTANCE
All animals, including humans, are host to vast microbial communities that contribute to health and disease through mechanisms that remain largely mysterious. These microbiomes are challenging to study, spurring the use of various model organisms, including zebrafish. Zebrafish, however, are difficult to raise beyond 1 week post-fertilization under gnotobiotic conditions, in other words, germ free or with known microbial constituents, a consequence of normally feeding on live prey that brings their own, generally unknown, microbes. Therefore, we developed a simple protocol in which UV irradiation of rotifers, a widely used small-animal food for larval zebrafish, facilitates the maintenance of gnotobiotic larvae. We show that pre-existing bacterial communities in larvae are minimally affected by feeding on UV-treated rotifers, in strong contrast to feeding on untreated rotifers. We demonstrate that this feeding method allows investigations of zebrafish-associated bacterial community stability over several days, allowing investigation of previously intractable questions about microbiome stability.
Plain versus drug balloon and stenting in severe ischaemia of the leg (BASIL-3): open label, three arm, randomised, multicentre, phase 3 trial
Authors: Bradbury Andrew W , Hall Jack A , Popplewell Matthew A , Meecham Lewis , Bate Gareth R , Kelly Lisa , Deeks Jon J , Moakes Catherine A 
Published: February 2025

Abstract

Objective
To determine which primary endovascular revascularisation strategy represents the most clinically effective treatment for patients with chronic limb threatening ischaemia who require endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.

Design
Three arm, open label, pragmatic, multicentre, randomised, phase 3 superiority trial (BASIL-3).

Setting
35 UK NHS vascular units.

Participants
Patients with chronic limb threatening ischaemia who required endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.

Interventions
Participants were randomly assigned (1:1:1) to femoro-popliteal plain balloon angioplasty with or without bare metal stenting (PBA±BMS), drug coated balloon angioplasty with or without bare metal stenting (DCBA±BMS), or drug eluting stenting (DES) as their first revascularisation strategy.

Main outcome measures
The primary outcome was amputation free survival defined as time to first major amputation or death from any cause. Secondary outcomes included the composite components of the primary outcome, major adverse limb events, major adverse cardiac events, and other prespecified clinical and patient reported outcome measures. Serious adverse events were collected up to 30 days after the first revascularisation procedure.

Results

Between 29 January 2016 and 31 August 2021, 481 participants were randomised (167 (35%) women, mean age 71.8 years (standard deviation 10.8)). Major amputation or death occurred in 106 of 160 (66%) participants in the PBA±BMS group, 97 of 161 (60%) in the DCBA±BMS group, and 93 of 159 (58%) in the DES group (adjusted hazard ratios: PBA±BMS
v
DCBA±BMS: 0.84, 97.5% confidence interval 0.61 to 1.16, P=0.22; PBA±BMS
v
DES: 0.83, 0.60 to 1.15, P=0.20). No differences in serious adverse events were reported between the groups.

Conclusions
Neither DCBA±BMS nor DES conferred significant clinical benefit over PBA±BMS in the femoro-popliteal segment in patients with chronic limb threatening ischaemia undergoing endovascular femoro-popliteal, with or without infra-popliteal, revascularisation.

Trial registration
ISRCTN registry ISRCTN14469736
Co-creating tools for embedding meaningful patient and public involvement and engagement in real-world data and evidence research in the pharmaceutical industry setting: a multistakeholder participatory co-design study
Authors: Dews Sally A , Corner Lynne , Butfield Rebecca , Araghi Mary , Monelle Hannah , Westergaard Polly , Moloney Susan , Wontor Viola , Campbell Burton Alexia 
Published: February 2025

Objectives
This study aimed to (1) gauge patients understanding and expectations of real-world data and evidence (RWDE) research and (2) use this understanding and patients lived experience to co-create resources and a framework for embedding meaningful patient and public involvement and engagement (PPIE) in RWDE research within the pharmaceutical industry setting.

Setting and participants
An academic organisation, a pharmaceutical company and a PPIE panel of 12 patients or carers partnered to form the project team. The PPIE panel was purposively selected to maximise diversity.

Design
Participatory and co-design methods were used to engender an understanding of the PPIE perspective on RWDE research and the PPIE role within that. Interactive workshops explored understanding and expectations of RWDE research as well as perceived barriers and facilitators of PPIE within each stage of the RWDE research cycle. Workshops were audio and video recorded, with notes captured. Summaries were analysed thematically and shared back with the PPIE panel for validation and further reflection.

Results
We identified a lack of trust and understanding of real-world data, its collection and use and the need to educate the public and researchers. Four themes were identified for meaningful PPIE in RWDE research; equality, diversity and inclusion; feeling valued; ownership and understanding and evaluating impact. We co-created learning resources (video, infographic) and a novel PPIE framework, incorporating potential PPIE activities, resources and support needs for use by researchers conducting RWDE research.

Conclusions
To our knowledge, this is the first project to explore the practicalities of PPIE in RWDE research from the perspective of patients and carers. Some findings confirm PPIE experience and guidance derived from other areas, with some specific insights into the pharmaceutical industry. These underpin the PPIE framework to enable robust and meaningful PPIE in RWDE research. This article includes a plain language summary in the supplement.
Exercise rehabilitation for people with postural tachycardia syndrome at two secondary care centres in the UK: the PULSE feasibility randomised controlled trial
Authors: McGregor Gordon , Evans Becky , Sandhu Harbinder Kaur , Bruce Julie , Devi Gita , Hayat Sajad , Hee Siew Wan , Heine Peter , Holliday Nikki , Joshi Shivam , Kavi Lesley , Boon Lim , Noufaily Angela , Parsons Nicholas , Patel Shilpa , Pearce Gemma , Powell Richard , Schultz Eva , Simmonds Jane , Zhupaj Albiona , Eftekhari Helen , Panikker Sandeep 
Published: February 2025

Objectives
The aim of the study was to assess the feasibility of conducting a definitive multicentre randomised controlled trial (RCT) testing an online exercise rehabilitation and behavioural/motivational support intervention for people with postural tachycardia syndrome (PoTS).

Design
Feasibility RCT.

Setting
Two secondary care centres.

Participants
Adults aged 18 to 60 years with PoTS. Exclusions were serious mental health/cognitive problem preventing safe participation; currently undertaking physical activity equivalent to the Chief Medical Officer guidelines; pregnancy.

Interventions
Participants were randomly assigned (1:1) to best-practice usual care (a single 1:1 session of advice) or the ‘postural tachycardia syndrome exercise’ (PULSE) intervention: (1) individual online consultation, (2) 12 weeks of supervised online group exercise and behavioural/motivational support, and (3) home exercise programme with recumbent exercise bike.

Outcomes
The primary outcome was feasibility: (1) patients screened, eligible, recruited, randomised, withdrawn; (2) adherence; (3) physiological, clinical and patient-reported outcomes (4 and 7 months); and (4) embedded qualitative study to evaluate acceptability.

Results
209 patients screened between 5 May 2021 and 1 December 2022, 44 (female 98%; age 29.9 SD, 7.5) were randomised to usual care (n=21) or PULSE (n=23) (71% of target). Follow-up at 4 months was n=12 and n=17 respectively (66% of target). Median live exercise/support session attendance was 15 (IQR 12 to 17) of 18 sessions. Home exercise bike usage was highly variable. There were two serious adverse events in each treatment arm, both unrelated to the trial. Exercise rehabilitation was considered important by participants, and trial procedures, outcomes and interventions were acceptable.

Conclusions
The PULSE trial procedures and interventions were acceptable, and important design considerations were identified. A definitive RCT testing a remotely supervised exercise rehabilitation and behavioural/motivational support intervention for people with PoTS is feasible in the UK National Health Service.

Trial registration number

ISRCTN45323485
.
Numerical approach of unsteady free convective Casson–Williamson nanofluid flow over the radiative vertical cone surface with cross-diffusion
Authors: Supriya P , Pullepu Bapuji , Chamkha Ali J. , Senthil Ramalingam 
Published: February 2025

The unsteady Casson and Williamson nanofluid flow via a radiative cone in a magnetic surface with cross-diffusion and chemical processes is investigated numerically. The Casson and Williamson nanofluid models characterize the behavior of non-Newtonian fluids. We transform the nonlinear dimensional PDEs into dimensionally free PDEs by implementing dimensionless parameters. The governed partial differential equations are addressed by adopting the Crank–Nicolson implicit approach. A parametric analysis is used to determine the outcomes of skin friction, Nusselt and Sherwood numbers. Increased Brownian motion and the Soret effect promote the transfer of heat and mass. The thermal and mass transfer characteristic of the Casson nanofluid is higher than the Williamson nanofluid. Regarding momentum dispersion, the Williamson nanofluid clearly dominates the Casson nanofluid. Conical mixers are used in polymer blending and plastics manufacturing. The relevance of this mixing step in achieving specified product attributes shows how mass and heat transfer concepts can boost productivity and output in engineering industries.
Sustainable Potentiometric Sensors for Determination of Irinotecan in Different Matrices and in The Presence of Co Administrated Drugs
Authors: Nabil Nada , El-Mosallamy Sally , Zaazaa Hala , Sedik Ghada 
Published: February 2025

Abstract
Irinotecan (IRNO) is used as a first line anticancer drug for the treatment of mainly metastatic colorectal cancer. Globally, cancer is sorted as the second cause of death. It is important to analyze anticancer drugs carefully and rapidly in different pharmaceutical formulations. The purpose of our work was to develop and validate green, simple, cost-effective, and portable ion-selective electrodes for the quantitation of IRNO in pharmaceutical formulation, spiked human plasma with other co-administrated antiemetic drugs such as Granisetron and Ondansetron. Liquid and solid contact ion-selective electrodes were developed for the determination of IRNO in different matrices. The cornerstone of the suggested solid contact electrode is a network of multi-walled carbon nanotubes serving as a solid transducer material, positioned between an ionophore-doped polyvinylchloride membrane and a screen-printed electrode. The proposed sensors were optimized to determine IRNO, and their effectiveness was evaluated according to the guidelines set by IUPAC. The measurements were implemented using phosphate buffer (pH: 2.80) within linearity range 1 × 10− 7 – 1 × 10− 2.5 M, with LOD 4 × 10− 8 M . The greenness of the electrochemical approach was evaluated using different tools, such as the analytical ECO-scale, AGREE, and GAPI.
Central Composite Design and Artificial Neural Network for the Evaluation and Optimization of an Electrochemical HHO Gas Generator
Authors: Hernández Ramírez Daniel , Reyes-Cruz V.E. , Rebolledo-Perales L. E. , Cobos Murcia José Angel , Alvarez Romero Giaan Arturo , Urbano-Reyes G. , Terrezas-Rodríguez2 J.E. 
Published: February 2025

Abstract
Central composite experimental design (CCD) and artificial neural networks (ANN) is not so popular in electrochemical systems, even though they present several advantages (lower number of experiments, evaluation of variable interactions, and correct analysis of overlapping data). In the present work, CCD and ANN were used for the analysis of an electrochemical cell with dimensionally stable electrodes modified with IrO₂ and an alkaline electrolyte solution, for the evaluation and optimization of an electrochemical HHO gas generator. With the CCD it was possible to maximize HHO gas generation (64.85 g/LNaOH and 10.2 amp) with a low standard deviation (0.004), a R-sq of 98.02%, and a R-sq (pred) of 92.04%, demonstrated that the experimental data fitted properly with the theoretical model. An ANN was trained from a large data set, obtaining recovery values close to 100%, R values close to 1 for the training (0.9894) and test stages (0.9677), and a good fit according to the Chi-squared test for the predictive values in both stages; with this ANN it was possible to solve overlapping issues in the HHO gas production system. The results indicate that CCD and ANN are viable alternatives to increase the performance of an electrochemical HHO gas generator.
Tailoring Structural, Optical, and Dielectric Properties of PVC/PMMA/PS/ZnO Nanocomposites for Capacitive Energy Storage Applications
Authors: Al-Muntaser A.A. , Alzahrani Eman , Asnag G.M. Muwadh , Yassin Ahmed Y. 
Published: February 2025

Abstract
Using a conventional casting method, flexible polymeric film nanocomposites composed of PMMA (polymethyl methacrylate), PS (polystyrene), PVC (polyvinyl chloride) and ZnO nanoparticles were synthesized. FTIR spectroscopy confirmed characteristic vibrational peaks, with transmission intensities decreasing as ZnO content increased up to 5 wt.%, indicating strong interactions between the PVC/PMMA/PS blend and ZnO nanoparticles. The XRD patterns that ZnO NP-based composites retained the pure blend's peaks but exhibited increased broadness and reduced intensity as ZnO content increased (2.5–10 wt.%), indicating a decrease in crystallinity. The redshift in the absorption edge of ZnO-filled samples strongly indicates the formation of charge transfer complexes within the polymeric matrix. The indirect and direct energy gaps decreased with increasing ZnO NP concentrations, from 3.88 eV and 4.87 eV to 3.31 eV and 4.67 eV, respectively. The σAC value at 100 Hz was 8.41 × 10⁻¹³ S·cm⁻¹ and increased with frequency, reaching 5.12 × 10⁻⁹ S·cm⁻¹ at 10⁶ Hz. Also, A modest increase in σAC values was observed with higher ZnO NP loading, attributed to the enhanced amorphous nature of the nanocomposite. Dielectric studies revealed the best performance at 5 wt.% ZnO, with the imaginary part (ε″) decreasing as ZnO loading increased. These findings recommend these nanocomposites for potential applications in optoelectronics and energy storage devices.
Synthesis of Hybrid ZnO Nanohexagons and Nanorods with CNT Embedded in PVC Film for Advanced Insulation and Optoelectronic Applications
Authors: Ghobashy M. M. , Zaher Ahmed A. , Khalil Sameh , Aldosari Eman , Sharshir A. I. 
Published: February 2025

Abstract
This study focuses on the synthesis, characterization, and application of a novel polyvinyl chloride (PVC)/carbon nanotube (CNT)/zinc oxide (ZnO) hybrid nanocomposite. ZnO nanostructures with two distinct morphologies (nanohexagons and nanorods) were synthesized and embedded within a PVC matrix alongside CNTs to achieve a functional hybrid composite. TEM analysis revealed the presence of both nanohexagon and nanorod ZnO structures alongside CNTs. SEM and EDX analyses confirmed the uniform distribution of ZnO nanostructures and CNTs within the PVC matrix. FTIR and UV-vis analyses revealed successful integration of CNTs and ZnO, exhibiting well-defined morphologies with a high aspect ratio. The optical properties are characterized by a reduction in the optical bandgap from 5.40 eV for PVC/ZnO to 4.60 eV for PVC/ZnO/5%CNT, indicating an increase in absorption in the visible spectrum. Furthermore, the AC conductivity demonstrates significant frequency dependence, with conductivity increasing with CNT concentration due to the formation of conductive pathways. The dielectric constant also shows enhanced values with increased CNT content, attributed to improved interfacial polarization. The simulation of electric field distribution reveals that the PVC/CNT/ZnO nanocomposite exhibits a more uniform electric field distribution than conventional PVC. This study concludes that the PVC/CNT/ZnO nanocomposite has potential applications in optoelectronics devices.
SMARCA4 Inhibits Breast Cancer Progression and Metastasis through RHOA Suppression
Authors: Sun Zheng , Li Zhuo , Wei Yong , Xu Lillian , Hang Xiang , Kang Yibin 
Published: February 2025

Abstract
Triple-negative breast cancer (TNBC) presents the most challenging subtype of the disease due to its aggressive nature and lack of targeted therapy options. To identify regulators of TNBC, we conducted a genome-wide CRISPR-knockout screen in both 3D tumor spheroid and 2D cell culture models. The 3D spheroid model displayed unique potential in identifying putative tumor suppressors due to its closer mimicry of in vivo tumor growth conditions. Notably, the chromatin-remodeling SWI/SNF complex emerged as a potent suppressor of tumor spheroid growth. Specifically, loss of the SWI/SNF ATPase subunit SMARCA4 promoted tumor spheroid growth with reduced compactness and enhanced primary tumor growth and metastasis across multiple TNBC models. SMARCA4 was required for the transcription of Rho GTPase activating factor ARHGAP29 by enhancing DNA accessibility through direct binding to its promoter. SMARCA4 loss resulted in reduced ARHGAP29 levels and hyperactive RHOA signaling, subsequently disrupting cell adhesion, facilitating the formation of a loose spheroid structure in vitro, and enhancing breast cancer growth and metastasis in vivo. These results establish SMARCA4 and SWI/SNF as tumor suppressors of TNBC through suppression of RHOA activity.