bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting PRMT5 enhances the radiosensitivity of tumor cells grown in vitro and in vivo
Authors: Degorre Charlotte , Lohard Steven , Bobrek Christina N. , Rawal Komal N. , Kuhn Skyler , Tofilon Philip J. 
Published: July 2024

AbstractPRMT5 is a widely expressed arginine methyltransferase that regulates processes involved in tumor cell proliferation and survival. In the study described here, we investigated whether PRMT5 provides a target for tumor radiosensitization. Knockdown of PRMT5 using siRNA enhanced the radiosensitivity of a panel of cell lines corresponding to tumor types typically treated with radiotherapy. To extend these studies to an experimental therapeutic setting, the PRMT5 inhibitor LLY-283 was used. Exposure of the tumor cell lines to LLY-283 decreased PRMT5 activity and enhanced their radiosensitivity. This increase in radiosensitivity was accompanied by an inhibition of DNA double-strand break repair as determined by γH2AX foci and neutral comet analyses. For a normal fibroblast cell line, although LLY-283 reduced PRMT5 activity, it had no effect on their radiosensitivity. Transcriptome analysis of U251 cells showed that LLY-283 treatment reduced the expression of genes and altered the mRNA splicing pattern of genes involved in the DNA damage response. Subcutaneous xenografts were then used to evaluate the in vivo response to LLY-283 and radiation. Treatment of mice with LLY-283 decreased tumor PRMT5 activity and significantly enhanced the radiation-induced growth delay. These results suggest that PRMT5 is a tumor selective target for radiosensitization.
Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis
Authors: Pollard Samantha , Chan Brandon , Gerrie Alina S. , Raymakers Adam J. N. , Regier Dean A. 
Published: July 2024

AbstractCostly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491–$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.
Positron unveiling high mobility graphene stack interfaces in Li-ion cathodes
Authors: Zheng Meiying , Kuriplach Jan , Makkonen Ilja , Ferragut Rafael , Di Noto Vito , Pagot Gioele , Laakso Ekaterina , Barbiellini Bernardo 
Published: July 2024

AbstractCarbon-based coatings in Li-ion battery cathodes improve electron conductivity and enable rapid charging. However, the mechanism is not well understood. Here, we address this question by using positrons as non-destructive probes to investigate nano-interfaces within cathodes. We calculate the positron annihilation lifetime in a graphene stack LiCoO2 heterojunction using an ab initio method with a non-local density approximation to accurately describe the electron-positron correlation. This ideal heterostructure represents the standard carbon-based coating performed on cathode nanoparticles to improve the conduction properties of the cathode. We characterize the interface between LiCoO2 and graphene as a p-type Schottky junction and find positron surface states. The intensity of the lifetime component for these positron surface states serves as a descriptor for positive ion ultra-fast mobility. Consequently, optimizing the carbon layer by enhancing this intensity and by analogizing Li-ion adatoms on graphene layers with positrons at surfaces can improve the design of fast-charging channels.
Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial
Authors: Verbout Norah G. , Lorentz Christina U. , Markway Brandon D. , Wallisch Michael , Marbury Thomas C. , Di Cera Enrico , Shatzel Joseph J. , Gruber András , Tucker Erik I. 
Published: July 2024

Abstract
Background
The protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit.

Methods
This phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four.

Results
Here we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002.

Conclusions
As far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations.
Multi‐modal video search by examples—A video quality impact analysis
Authors: Wu Guanfeng , Haider Abbas , Tian Xing , Loweimi Erfan , Chan Chi Ho , Qian Mengjie , Muhammad Awan , Spence Ivor , Cooper Rob , Ng Wing W. Y. , Kittler Josef , Gales Mark , Wang Hui 
Published: July 2024

AbstractAs the proliferation of video content continues, and many video archives lack suitable metadata, therefore, video retrieval, particularly through example‐based search, has become increasingly crucial. Existing metadata often fails to meet the needs of specific types of searches, especially when videos contain elements from different modalities, such as visual and audio. Consequently, developing video retrieval methods that can handle multi‐modal content is essential. An innovative Multi‐modal Video Search by Examples (MVSE) framework is introduced, employing state‐of‐the‐art techniques in its various components. In designing MVSE, the authors focused on accuracy, efficiency, interactivity, and extensibility, with key components including advanced data processing and a user‐friendly interface aimed at enhancing search effectiveness and user experience. Furthermore, the framework was comprehensively evaluated, assessing individual components, data quality issues, and overall retrieval performance using high‐quality and low‐quality BBC archive videos. The evaluation reveals that: (1) multi‐modal search yields better results than single‐modal search; (2) the quality of video, both visual and audio, has an impact on the query precision. Compared with image query results, audio quality has a greater impact on the query precision (3) a two‐stage search process (i.e. searching by Hamming distance based on hashing, followed by searching by Cosine similarity based on embedding); is effective but increases time overhead; (4) large‐scale video retrieval is not only feasible but also expected to emerge shortly.
Supermassive Primordial Black Holes for Nano-Hertz Gravitational Waves and High-redshift JWST Galaxies
Authors: Huang Hai-Long , Cai Yong , Jiang Jun-Qian , Zhang Jun , Piao Yun-Song 
Published: July 2024

Abstract
Recently, observational hints for supermassive black holes have been accumulating, prompting the question: Can primordial black holes (PBHs) be supermassive, particularly with masses M ≳ 109
M
⊙? A supercritical bubble, containing an inflating baby universe, that nucleated during inflation can evolve into a PBH in our observable universe. We find that when the inflaton slowly transitions past a neighboring vacuum, the nucleation rate of supercritical bubbles inevitably peaks, leading to a mass distribution of multiverse PBHs with a peak mass up to M ≳ 1011
M
⊙. Thus, our mechanism naturally provides a primordial origin for supermassive black holes.
Tbx-Zn1-x-BDC MOF films synthesized in-situ by the aero-sol-assisted chemical vapor deposition
Authors: Espinoza–Tapia Julio César , Becerril–Landero Luis Alberto , Barrera–Calva Enrique , Vigueras Ramírez Juan Gabriel , González–Reyes Leonardo , Falcony–Guajardo Ciro 
Published: July 2024

Abstract
Tbx-Zn1-x-BDC MOF films were deposited in situ on glass substrates using the aerosol-assisted chemical vapor deposition (AACVD) technique with an ultrasonic spray pyrolysis system, with x ranging from 0 to 1. Various precursors and solvents were used in the precursor solutions, which were precisely nebulized onto the substrate. The resulting films were characterized using techniques such as x-ray diffraction, Raman spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), and Photoluminescence Spectroscopy. The findings revealed the evolution of Zn-BDC and/or Tb-BDC crystalline structures within the films and changes in the physical properties of the Metal Organic Frameworks (MOFs), such as film thickness and roughness. Moreover, these insights offer vital information for the design and control of MOF films with specific properties, highlighting their potential applications in various fields.
Interaction between visual impairment and genetic risk of dementia and psychosis in older adults
Authors: Hamedani Ali G , Ellis Colin A , Ehrlich Joshua R , Willis Allison W 
Published: July 2024

Abstract

Background
Visual impairment (VI) is associated with dementia and other neuropsychiatric outcomes, but previous studies have not considered genetic sources of confounding or effect modification.

Methods
We analysed data from the Health and Retirement Study, an ongoing nationally representative survey of older US adults, a subset of whom underwent genetic testing from 2006 to 2012 (n = 13 465). Using discrete time proportional hazards models and generalised estimating equations, we measured the association between VI and dementia, depression and hallucinations adjusting for demographics and comorbidities, ancestry-specific principal components and polygenic risk scores (PRS) for Alzheimer’s disease, major depressive disorder or schizophrenia. Effect modification was assessed using VI–PRS interaction terms and stratified analyses.

Results
VI was associated with dementia, depression and hallucinations after adjusting polygenic risk and other confounders. There was no VI–PRS interaction for dementia or depression. However, the association between VI and hallucinations varied by genetic risk of schizophrenia. Within the bottom four quintiles of schizophrenia PRS, VI was not associated with hallucinations among White (OR 1.16, 95% CI: 0.87–1.55) or Black participants (OR 0.96, 95% CI: 0.49–1.89). In contrast, VI was strongly associated with hallucinations among White (OR 2.08, 95% CI: 1.17–3.71) and Black (OR 10.63, 95% CI: 1.74–65.03) participants in the top quintile of schizophrenia PRS.

Conclusions
The association between VI and neuropsychiatric outcomes is not explained by shared genetic risk factors, and there is a significant interaction between VI and polygenic risk of hallucinations in older adults.
Cross-sectional description of hospital pharmacy services in Puerto Rico in 2022 using the Practice Advancement Initiative 2030 Self-Assessment Tool
Authors: Rodríguez-Escudero Idaliz , Bonilla-Medina Glorimar , Cabrera-Martínez Janice , Cintrón-Zayas Víctor 
Published: July 2024

Abstract

Purpose
The American Society of Health-System Pharmacists (ASHP) developed the Practice Advancement Initiative 2030 (PAI 2030) to support the continuous improvement of hospital pharmacy services in the United States. Puerto Rico (PR) hospitals’ level of compliance with PAI 2030 recommendations is not currently known. The primary objective of this study was to describe the hospital pharmacy scenario in PR in the 5 areas addressed in PAI 2030 recommendations.

Summary
Through a collaboration between the state affiliate, a school of pharmacy, and ASHP, completion of the PAI 2030 Self-Assessment Tool was promoted among hospital pharmacy directors between August 2022 and March 2023. A total of 18 out of 66 hospitals completed the survey. The results were compared with national data provided by ASHP from 163 US hospitals. Areas where PR hospitals rated high were in PAI 2030 domain A (Pharmacy Technician Role, Education, and Training) and domain E (Pharmacist Leadership in Medication Use and Safety). PR hospitals rate their performance lower in domain A (Patient-Centered Care) and domain B (Pharmacist Role, Education, and Training). Specific focus areas for improvement by PR hospitals include pharmacist participation in medication reconciliation, 24/7 access to advanced clinical pharmacy services, expansion of the pharmacist’s scope of practice, and training through the Board of Pharmacy Specialties and residency programs.

Conclusion
This study illustrates how the PAI 2030 Self-Assessment Tool can be used to benchmark pharmacy services at the state level. We suggest that changes are needed to close the gap between hospital pharmacies working towards optimizing the role of pharmacists in healthcare systems and those still struggling with dedicating staff to well-recognized pharmacist roles and responsibilities.
Exploring geography and evolutionary history as drivers of variation in floral scent chemistry in western sessile-flowered Trillium using parsimony-constrained phylogenetics
Authors: Blanco-Moreno Candela , Wayman Kjirsten A , Tomescu Alexandru M F 
Published: July 2024

Abstract

Background and Aims
The sessile-flowered Trillium species from western North America have been challenging to distinguish morphologically owing to overlapping characters and intraspecific variation. Molecular phylogenetic analyses, currently inconclusive for this group, have not sampled multiple populations of the different species to account for this. Here, we query the diversity of floral volatile composition to understand its bearings on the taxonomy, distribution and evolution of this group.

Methods
We explored taxonomic and geographical patterns in average floral volatile composition (105 different compounds) among 42 wild populations of four sessile-flowered Trillium species and the outgroup, Pseudotrillium, in California, Oregon and Washington, by means of parsimony-constrained phylogenetic analyses. To assess the influence of character construction, we coded compound abundance in three different ways for the phylogenetic analyses and compared the results with those of statistical analyses using the same dataset and previously published statistical analyses.

Key Results
Different codings of floral volatile composition generated different phylogenetic topologies with different levels of resolution. The different phylogenies provide similar answers to taxonomic questions but support different evolutionary histories. Monophyly of most populations of each taxon suggests that floral scent composition bears phylogenetic signal in the western sessile-flowered Trillium. Lack of correlation between the distribution of populations and their position in scent-based phylogenies does not support a geographical signal in floral scent composition.

Conclusions
Floral scent composition is a valuable data source for generating phylogenetic hypotheses. The way in which scent composition is coded into characters is important. The phylogenetic patterns supported by floral volatile compounds are incongruent with previously reported phylogenies of the western sessile-flowered Trillium obtained using molecular or morphological data. Combination of floral scent data with gene sequence data and detailed morphological data from multiple populations of each species in future studies is needed for understanding the evolutionary history of western sessile-flowered Trillium.
Marker discovery in the large
Authors: Vieira Mourato Beatriz , Tsers Ivan , Denker Svenja , Klötzl Fabian , Haubold Bernhard 
Published: July 2024

Abstract

Motivation
Markers for diagnostic polymerase chain reactions are routinely constructed by taking regions common to the genomes of a target organism and subtracting the regions found in the targets’ closest relatives, their neighbors. This approach is implemented in the published package Fur, which originally required memory proportional to the number of nucleotides in the neighborhood. This does not scale well.

Results
Here, we describe a new version of Fur that only requires memory proportional to the longest neighbor. In spite of its greater memory efficiency, the new Fur remains fast and is accurate. We demonstrate this by applying it to simulated sequences and comparing it to an efficient alternative. Then we use the new Fur to extract markers from 120 reference bacteria. To make this feasible, we also introduce software for automatically finding target and neighbor genomes and for assessing markers. We pick the best primers from the 10 most sequenced reference bacteria and show their excellent in silico sensitivity and specificity.

Availability and implementation
Fur is available from github.com/evolbioinf/fur, in the Docker image hub.docker.com/r/beatrizvm/mapro, and in the Code Ocean capsule 10.24433/CO.7955947.v1.
Best practices to evaluate the impact of biomedical research software—metric collection beyond citations
Authors: Afiaz Awan , Ivanov Andrey A , Chamberlin John , Hanauer David , Savonen Candace L , Goldman Mary J , Morgan Martin , Reich Michael , Getka Alexander , Holmes Aaron , Pati Sarthak , Knight Dan , Boutros Paul C , Bakas Spyridon , Caporaso J Gregory , Del Fiol Guilherme , Hochheiser Harry , Haas Brian , Schloss Patrick D , Eddy James A , Albrecht Jake , Fedorov Andrey , Waldron Levi , Hoffman Ava M , Bradshaw Richard L , Leek Jeffrey T , Wright Carrie 
Published: July 2024

Abstract

Motivation
Software is vital for the advancement of biology and medicine. Impact evaluations of scientific software have primarily emphasized traditional citation metrics of associated papers, despite these metrics inadequately capturing the dynamic picture of impact and despite challenges with improper citation.

Results
To understand how software developers evaluate their tools, we conducted a survey of participants in the Informatics Technology for Cancer Research (ITCR) program funded by the National Cancer Institute (NCI). We found that although developers realize the value of more extensive metric collection, they find a lack of funding and time hindering. We also investigated software among this community for how often infrastructure that supports more nontraditional metrics were implemented and how this impacted rates of papers describing usage of the software. We found that infrastructure such as social media presence, more in-depth documentation, the presence of software health metrics, and clear information on how to contact developers seemed to be associated with increased mention rates. Analysing more diverse metrics can enable developers to better understand user engagement, justify continued funding, identify novel use cases, pinpoint improvement areas, and ultimately amplify their software’s impact. Challenges are associated, including distorted or misleading metrics, as well as ethical and security concerns. More attention to nuances involved in capturing impact across the spectrum of biomedical software is needed. For funders and developers, we outline guidance based on experience from our community. By considering how we evaluate software, we can empower developers to create tools that more effectively accelerate biological and medical research progress.

Availability and implementation
More information about the analysis, as well as access to data and code is available at https://github.com/fhdsl/ITCR_Metrics_manuscript_website.
Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells
Authors: Povoleri Giovanni A M , Ridley Michael L , Marrow Rebecca J , Lalnunhlimi Sylvine , Ryan Sarah E , Kelly Audrey , Lavender Paul , Taams Leonie S 
Published: July 2024

Abstract
CD4+ T cells are key players in immune-mediated inflammatory diseases (IMIDs) through the production of inflammatory mediators including tumour necrosis factor (TNF). Anti-TNF therapy has revolutionized the treatment of several IMIDs and we previously demonstrated that in vitro treatment of human CD4+ T cells with anti-TNF promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in CD4+ T cells, isolated from PBMCs of healthy volunteers, stimulated in vitro for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted before performing gene expression profiling and chromatin accessibility analysis. Gene expression analysis of CD45RA-CD4+ T cells showed a distinct anti-TNF specific gene signature of 183 genes (q-value &lt; 0.05). Pathway enrichment analysis of differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22, and CXCL10 were significantly downregulated (q-value &lt; 0.05). Transcription factor motif analysis at the differentially open chromatin regions, after anti-TNF treatment, revealed 58 transcription factor motifs enriched at the IL10 locus. We identified seven transcription factor candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF treatment. Correlation analysis between the expression of these transcription factors and IL10 suggests a role for MAF, PRDM1, and/or EOMES in regulating IL10 expression in CD4+ T cells upon anti-TNF treatment.