bluuebunny/crossref_metadata_2025 huggingface dataset:
The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis
Authors: Sahasrabuddhe Anagh A. , Chen Xiaofei , Ma Kaiyu , Wu Rui , Liang Huan-Chang , Kapoor Richa , Chhipa Rishi R. , Onder Ozlem , McFetridge Courtney , Van Arnam John S. , Zhang Xiao , Morrissette Jennifer J.D. , Pillai Vinodh , Li Marilyn M. , Szankasi Philippe , Basrur Venkatesha , Conlon Kevin P. , Raabe Tobias D. , Bailey Nathanael G. , Hogaboam Cory M. , Rottapel Robert , Kim Junhyong , López Cristina , Schlesner Matthias , Siebert Reiner , Dreval Kostiantyn , Morin Ryan D. , Moro Loredana , Pagano Michele , Staudt Louis M. , Lim Megan S. , Elenitoba-Johnson Kojo S.J.
Published: January 2025

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation. Double genetic ablation of Fbxo45 and Arhgef2 ameliorated lymphoma formation. Transgenic knock-in mice harboring a GEF-H1 mutant unable to bind FBXO45 develop B-cell lymphomas with ~50% penetrance. Genome sequencing in human lymphomas identified mutually-exclusive FBXO45 copy number losses and ARHGEF2 gains, with combined frequencies ranging from 26.32% in FL to 45.12% in DLBCL. Notably, FBXO45 silencing enhances sensitivity to MEK1/2 inhibition. These results identify FBXO45 and ARHGEF2 as a novel tumor-suppressor and oncogene pair involved in the pathogenesis of B-cell lymphomas with significant implications for targeted therapies.
Figure S5 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Gating strategy for antigen-specific CD8+ T cells and Tregs in the blood.
A primeira edição da Arte Explicada (1729-1734) de João de Morais Madureira Feijó (1688-1741)
Authors: Kemmler Rolf , Coelho Sónia , Fontes Susana , Moura Teresa , Assunção Carlos
Published: January 2025

The Arte Explicada (1729-1734) constitutes the most complete of all the neo-Alvaresian cartapácios (i.e., Latin commentaries of Álvares’ Latin grammar in the Portuguese vernacular) to be published in Portugal and even among the overall number of grammars belonging the complex universe of Alvaresian and neo-Alvaresian manuals of the Latin language all over the world. In this paper, thanks to the identification of some new elements to which we previously did not have access, it is our aim to offer an introductory analysis of the hitherto unknown complete set of volumes belonging to the first edition of the Arte Explicada, disclosing the constituent parts of each one of the volumes, based on the most representative paratexts of the respective books.
As orações sem sujeito e a Estrutura da Proposição
Authors: Vitral Lorenzo
Published: January 2025

Analisa-se o problema das chamadas orações sem sujeito que afrontam a definição clássica da proposição a qual prevê a estrutura sujeito-predicado. Comentamos os pressupostos e as implicações da análise tradicional de Said Ali (1950) bem como a análise gerativista sobre esse tema. De acordo com este quadro teórico, uma condição formal, a saber, a categoria T (tense), núcleo da sentença, que dispõe de um traço-D (D-feature), por meio do qual é tratado o princípio de projeção estendido (EPP), exige que a posição do sujeito seja, invariavelmente, ocupada por um constituinte, o qual poderá ser ou não realizado fonologicamente e interpretado ou não tematicamente (Chomsky, 1995; Shim, 2001). Entretanto, a solução gerativista é exclusivamente formal e não resolve o problema da ocorrência de um constituinte funcionando como predicado, mas que não é, nos termos de Frege, saturado, ou seja, não predica, de fato, nenhum constituinte. Considerando que, nas orações sem sujeito que se referem ao tempo e que são existenciais, está subjacente, de forma inerente, que tais enunciados dizem respeito ao que existe ou ao tempo que faz num lugar tomado de forma genérica ou num lugar específico indeterminado, aventamos a hipótese de que, nesses enunciados, é por meio de um tipo de juízo analítico, que extrai do predicado, utilizando-se uma operação semântica, um locativo nulo, ou não pronunciado, que se obtém um constituinte que termina por funcionar como o sujeito dessas orações no sentido de sujeito lógico ou psicológico como proposto por Paul (1970[1880]).
O estatuto funcional de sintagmas preposicionais dos verbos ‘ir’ e ‘morar’: adjunto ou complemento?
Authors: Vitral Lorenzo
Published: January 2025

The article takes up the traditional discussion on the distinction between the functions of adjunct and complement, verifying which is the appropriate analysis for the prepositional phrases that appear with the verbs ‘ir’ (to go) and ‘morar’ (to live). We initially present some elements of Apollonio Discolo’s analysis of transitivity through the notion of verbal diathesis and show that indecision about the function of these phrases is present in French, Portuguese and Brazilian grammatical traditions. We identified the difficulty of analysis in the fact that these phrases express locative content, which is not compatible with the proposed analysis of transitive diathesis according to Apollonio Discolo. This view was favored by the Latin adaptation of the Apollonian term ‘hypokeímenón’ as object. Finally, we defend the proposal, based on the notions of function (or predicate) and argument of Frege (2013 [1879]), that these prepositional phrases are arguments capable of saturating a predicate and that they should be analyzed as indirect complements of the verbs ‘ir’ (to go) and ‘morar’ (to live).
As formas de referência ao interlocutor ao longo de dois séculos em cartas portuguesas
Authors: Souza Janaina Pedreira Fernandes de , Lopes Célia Regina dos Santos
Published: January 2025

There are several studies about the forms of reference to the interlocutor in Brazilian Portuguese, which made it possible to establish an overview on the subject in this variety. However, there are still few studies, especially of a quantitative nature, on the subject in the context of European Portuguese. Therefore, the present study aims to make a brief analysis of the forms of treatment used as a subject pronoun, in European Portuguese, based on the analysis of personal letters, written between the 19th and 20th centuries. For this, we started from the main hypothesis that tu would be the most used form and the pronoun você would be less frequent because it is negatively marked, having very specific contexts for its use. In general, the main hypothesis was confirmed, however, other treatment strategies were used, such as Vossa Mercê and other nominal forms, being even more used than tu (null or full), depending on the theme of the letters and the relationship sphere and the level of intimacy of the writers.
Produção e percepção caminham juntas? Um estudo comparado entre produção e percepção das interrogativas totais neutras no Português do Brasil
Authors: Silva Joelma Castelo Bernardo da , Fernandes-Svartman Flaviane Romani , Kluge Denise Cristina , Lima Júnior Ronaldo Mangueira
Published: January 2025

O presente estudo objetiva estudar a percepção da entoação nos tipos frásicos interrogativos totais nas seguintes variedades do Português do Brasil: João Pessoa (PB), Aracaju (SE), Rio de Janeiro (RJ), São Paulo (SP), Florianópolis (SC) e Porto Alegre (RS). Estudos prévios de produção desenvolvidos sob o aparato teórico da fonologia métrica autossegmental para entoação (Ladd, 2008[1996]) indicam duas regiões dialetais no PB: Nordeste (PB, SE), caracterizada por um contorno nuclear interrogativo predominantemente ascendente; e Sudeste-Sul (BA, RJ, SP, MG, SC e RS), caracterizada por um contorno nuclear interrogativo ascendente-descendente. A distribuição desses padrões sugere fortemente a formação de um continuum dialetal de Norte a Sul da Costa Atlântica brasileira, confirmada por meio de estudo de percepção para as duas macrorregiões (Castelo et al., 2018). Com base nesses estudos, era esperado que, ao ampliar a amostra de variedades, se confirmassem tanto as regiões dialetais como o continuum encontrado no nível da produção. Embora a distribuição bidialetal tenha sido confirmada, a gradação na percepção entre as variedades não foi encontrada para o atual conjunto de variedades investigadas, o que sugere relações indiretas entre produção e percepção bem como a complexidade envolvida na concepção e aplicação de experimentos de percepção em variação prosódica.
Vogais tônicas orais do kabuverdianu do Príncipe: uma análise fonética
Authors: Freitas Shirley , Balduino Amanda Macedo
Published: January 2025

Com a migração caboverdiana para São Tomé e Príncipe, iniciada em 1903, o kabuverdianu foi levado para o Golfo da Guiné e passou a fazer parte da ecologia linguística da região. Considerando esse cenário, este estudo se debruça sobre o kabuverdianu da ilha do Príncipe (KVP), apresentando uma descrição fonética acústica do primeiro (F1) e segundo formantes (F2) e da duração que caracterizam as vogais orais tônicas nessa língua. Como corpora, utilizamos dados coletados no Príncipe em 2018 com quatro falantes de kabuverdianu como língua materna (Bandeira; Freitas, 2018). Os dados foram analisados com auxílio do programa Praat (Boersma; Weenick, 2022). Em posição tônica, foram encontrados nove fones vocálicos orais ([i, e, ɛ, ə, ɐ, a, ɔ, o, u]), ampliando as descrições do kabuverdianu de Santiago que mencionavam somente 2 vogais centrais. O comportamento das vogais médias e centrais sugere que a dispersão acústica é relevante na definição das vogais da língua. As vogais médias parecem estar mais próximas entre si (com a diferença entre F1 sendo de 75 Hz para as coronais e 98 Hz para as dorsais). Esse fato aproxima acusticamente as vogais médias-altas e médias-baixas, uma vez que os dois pares ([e] e [ɛ], [o] e [ɔ]) passam a ficar menos dispersos no espaço acústico.
Correlações entre percepção e produção de palavras heterotônicas do espanhol por aprendizes brasileiros
Authors: Milan Pollianna
Published: January 2025

Esta pesquisa investigou se a percepção de palavras heterotônicas do espanhol, por aprendizes brasileiros, transforma a produção das mesmas. Para isso, o estudo, que conta com uma etapa de treinamento perceptual, tem 26 aprendizes brasileiros, 17 pertencem ao grupo denominado com menos exposição acadêmica (dez que receberam treinamento e sete que não receberam treinamento) e nove do grupo com mais exposição acadêmica (quatro que receberam treinamento e cinco que não receberam treinamento). Os aprendizes ouviram heterotônicos falados por locutores hispano-falantes e, depois, produziram os mesmos heterotônicos em frases com contexto e frases-veículo. Os Testes de Correlação de Spearman demonstraram que há uma tendência maior de correlação entre percepção e produção no grupo com menos exposição acadêmica e que participou do treinamento perceptual.
Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage
Authors: Dupont Sébastien , Lebas Héloïse , Mavouna Sabrina , Pascal Eloïse , Perrot Astride , Cogo Adrien , Bourrienne Marie‐Charlotte , Farkh Carine , Solo Nomenjanahary Mialitiana , Ollivier Véronique , Zemali Fatima , Nieswandt Bernhard , Loyau Stéphane , Jandrot‐Perrus Martine , Camerer Eric , Desilles Jean‐Philippe , Mazighi Mikael , Boulaftali Yacine , Ho‐Tin‐Noé Benoît
Published: January 2025

Background

Antiplatelet drugs represent potential candidates for protecting the penumbral microcirculation during cerebral ischemia and improving the benefits of arterial recanalization in ischemic stroke. Yet while the efficacy of such adjuvant strategies has been shown to be highly time dependent, antiplatelet therapy at the acute phase of ischemic stroke cannot be envisioned until the diagnosis of stroke and its ischemic nature have been confirmed because of the presumed risk of worsening bleeding in case of intracranial hemorrhage (ICH). Here, we investigated this risk for 2 antiplatelet drugs currently being tested in clinical trials for ischemic stroke, glenzocimab and eptifibatide, in 2 mouse models of ICH.

Methods and Results

The severity of ICH was assessed in mice humanized for glycoprotein VI treated or not with glenzocimab or eptifibatide at effective dose, in a model of primary ICH caused by unilateral striatal injection of collagenase type VII, and in a model of hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Glenzocimab had no impact on bleeding severity in either model of ICH. Conversely, eptifibatide caused a significant increase in intracranial bleeding in both models, and a drastic increase in death after hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury.

Conclusions

Unlike eptifibatide, glenzocimab is safe in the setting of ICH. These results suggest that glenzocimab could be administered upon suspicion of ischemic stroke, before assessment of its ischemic nature, thus opening the way to hastening of treatment initiation.
Teachers as Beacons of Hope: The Mediating Role of Future Expectations on the Association Between Student-Teacher Relationships and Justice-Involved Adolescents’ Grades and Offending
Authors: Smith Curtis D. , Beardslee Jordan , Frick Paul J. , Steinberg Laurence D. , Cauffman Elizabeth
Published: January 2025

Justice-involved adolescents are at increased risk for poor academic outcomes and reoffending. However, strong bonds with teachers have been shown to promote academic success and encourage desistance. The current study examined whether more hopeful future expectations mediated the association between student-teacher relationships and justice-involved adolescents’ offending and grades, respectively, using data from a longitudinal study of male youth recruited after their first arrest. Findings revealed that stronger student-teacher relationships predicted more positive future expectations which, indirectly, predicted better grades and less offending. These findings underscore the mechanism by which justice-involved adolescents’ school connectedness cultivates hopeful expectancies for the future, which can deter delinquency and promote academic success. Implications for fostering these relationships during re-entry for justice-involved adolescents are discussed.
The use of external breast prostheses in post-operative care for women after breast cancer mastectomy: A scoping review
Authors: Zheng Lin , Zhou Beibei , Liang Ruixin , Yip Joanne
Published: January 2025

This paper provides a comprehensive scoping review of external breast prostheses, an essential component of post-operative care for breast cancer patients, the most common cancer globally. Mastectomy, a frequent treatment, often leads to physical and psychological issues. External breast prostheses help improve body image and psychosocial well-being after surgery. We included studies on the views, evaluations, opinions, and experiences of women who had had a mastectomy and medical personnel regarding external breast prostheses, as well as the assessment, design, and simulation of these prostheses. A scoping review was conducted using Web of Science Core Collection, PubMed, Medline, Scopus, and Google Scholar. We reviewed relevant English research articles published in peer-reviewed journals up to December 2023, focusing on “breast cancer,” “mastectomy,” “post-mastectomy recovery,” “breast prosthesis satisfaction/dissatisfaction,” and “external breast prosthesis/prostheses.” Thirty-four studies were analyzed, covering various prosthesis types, user feedback, effects on daily activities, and new technologies and designs. This review reveals the prosthesis’ significantly positive effect on women’s lives after mastectomy, but also such persistent issues as weight, price, and body movement compatibility. Moreover, the paper suggests the potential for advances to improve comfort, aesthetics, and affordability.
Effect of hierarchical structure on the shape recovery properties and load-carrying capacity of 4D-printed kirigami-inspired honeycomb
Authors: Yang Yong , Han Yang , Wang Yukai , Lu Xiaohui , Peng Xiang , Li Jiquan , Jiang Shaofei
Published: January 2025

Kirigami-inspired honeycomb structures demonstrate outstanding self-expanding capabilities and exceptional mechanical properties. To further enhance the shape recovery properties and load-carrying capacity of kirigami-inspired honeycomb, the hierarchical structure is introduced by importing porous structures into cell walls of 4D-printed kirigami-inspired honeycomb (Structure II), and then an innovative honeycomb structure (Structure I) is designed for achieving the hierarchical effect. Additionally, three hierarchical structures with different shape configurations (Structure III–V) are also designed for comparing with traditional Structure II. The finite element analysis and experiments are conducted to compare the compression deformation behavior and energy absorption capacity of Structure I–V. It is found that Structure I exhibits significantly improved properties compared with the traditional Structure II. The stiffness of Structure I is increased by 50.43%, and the energy absorption performance is also increased by 65.00%. The recovery time has been shortened by 27.27% and it has a better shape recovery rate. Structure III–V can also enhance the performances compared with traditional Structure II. Structure IV exhibits the best energy absorption capacity, with an increase of 76.25%. Thus, the developed hierarchical kirigami-inspired honeycombs have broad application prospects for the multifunctional applications of honeycomb structures in the future.
Chronic inflammatory demyelinating polyneuropathy associated with active systemic lupus erythematous: Anifrolumab as a potentially successful add-on therapy to intravenous immunoglobulins
Authors: Marques-Gomes Carlos , Diz-Lopes Mariana , Braz Luís , Martins Ana , Oliveira Daniela , Nicolau Rafaela , Santos Inês , Costa Lúcia , Bernardes Miguel
Published: January 2025

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy, rarely reported as being associated with systemic lupus erythematous (SLE). We report the case of 53-year-old women with a long history of SLE, diagnosed with CIDP during a lupus flare beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. She received treatment with steroids, intravenous immunoglobulins and anifrolumab and showed clinical and immunological improvement. It is important to take into account the presence of peripheral neurological disorders in patients with SLE, considering CIDP as an uncommon manifestation. Controlling severe active disease is an imperative issue to manage this neurological manifestation which has a serious impact on health-related quality of life and physical function.
Talimogene laherparepvec (T-VEC) as a treatment for melanoma: A systematic review
Authors: Alla Sai Santhosha Mrudula , Tekuru Yogesh , Lokesh Moraboina Sai , Alla Deekshitha , Tvisha Patel , Tirupati Soujanya , Singh Aradhya , Tejaswini Yeshala , Mahmood Mariya , Siingh Nanki Pratap , Vineetha Bodipudi
Published: January 2025

Background and aims

Melanoma now presents an average risk of 1 in 50 in the Western world. Talimogene laherparepvec (T-VEC), an FDAapproved oncolytic virus derived from Herpes Simplex Virus type 1 (HSV-1), has proven effective in reducing morbidity and mortality from melanoma but causes adverse effects like chills, fever, exhaustion, and injection site discomfort. Research focuses on combining T-VEC with immune checkpoint inhibitors, such as pembrolizumab, to enhance its efficacy and broaden its application.

Methods

A systematic search was conducted using PubMed, Scopus, Web of Science, Google Scholar, and ProMED, adhering to PRISMA guidelines. Results were tabulated and analyzed.

Results

This review included 15 studies comprising nine cohorts, four case reports, a case series, and a randomized control trial, involving 779 melanoma patients in stages IIIB to IV, 58% of whom were male with a mean age of 65 years. Treatment duration with T-VEC averaged 35.07 weeks, with dosages ranging from 10^6 to 10^8 PFU/ml. The intervention yielded a mean DRR of 41.87% and an ORR of 62.2%. The most common side effect was chills, affecting 21.69% of participants. Pyrexia was reported by 20.41% of participants, followed by influenzalike illness (14.89%).

Conclusion

T-VEC effectively improves ORR and DRR in melanoma patients. However, further research is needed on combination therapy prospects and its adverse effects.
Groundwater Potential Assessment Using Integrated Geospatial and Analytic Hierarchy Process Techniques (AHP) in Chemoga Watershed, Upper Blue Nile Basin, Ethiopia
Authors: Kassa Samuel Berihun , Zimale Fasikaw Atanaw , Mulu Arega , Worku Tadege Aragaw , Wossene Mindesilew Lakew , Meshesha Taye Minichil , Hailu Yoseph Buta , Aman Tadele F. , Kifelew Mekash S. , Mekonnen Habtamu Asrat
Published: January 2025

Groundwater is an invaluable natural resource that sustains human life and supports the economic development of nations. However, its unsustainable utilization has emerged as a critical issue, particularly in developing countries. This study investigates the groundwater potential of the Chemoga watershed to address these challenges. Conventional groundwater assessments have typically relied on labor-intensive and time-consuming field surveys, which are resource-demanding and often fail to provide accurate estimates due to the inherent complexity of groundwater systems. In response, this research utilizes geospatial and analytic hierarchy process (AHP) techniques to assess groundwater potential in the Chemoga Watershed, aiming to overcome these challenges. Eight critical biophysical and environmental factors: geology, slope, rainfall, land use/land cover (LULC), soil type, elevation, lineament density, and drainage density were selected for analysis using Saaty’s AHP methodology. Data was gathered from satellite imagery, existing thematic maps, local water offices, and national meteorological agencies. The integration of these thematic maps was performed through a weighted overlay analysis using ArcGIS 10.8, which resulted in the delineation of groundwater potential zones (GWPZ). The model was validated by cross-referencing the generated GWPZ with existing data from dug wells and boreholes. The results reveal five groundwater potential zones: very high (0.73%), high (24.39%), moderate (43.38%), poor (31.25%), and very poor (0.25%). The most suitable zones are in the south, southeast, and southwest of the watershed, particularly near Debre Markos Town. These high-potential zones were validated with a significant 81.5% match to ground truth data from shallow wells. The findings of this study provide crucial insights for decision-makers, enabling the formulation of more effective groundwater management strategies. By identifying cost-effective and suitable well sites, this research contributes to ensuring a sustainable water supply for Debre Markos Town.
Metaverse economics for tourism and hospitality: economic fundamentals in a semi-imaginary world
Authors: Ivanov Stanislav , Seyitoğlu Faruk , Webster Craig
Published: January 2025

This study elaborates on the economics of the Metaverse in tourism and hospitality. It identifies the Metaverse stakeholders from a tourism perspective, namely: IT companies (infrastructure), IT companies (Metaverse presence), tourism and hospitality companies, other (non-tourism) companies, destination management organisations, tourists, and public authorities. The paper elaborates on the activities each stakeholder would be able to perform in the Metaverse and the associated revenue and costs. Based on this, the paper discusses the economic relationships between the stakeholders, their impacts on the financial performance of tourism and hospitality companies, and the potential economic externalities of the Metaverse. Theoretical, managerial and policy implications, limitations and future research directions are outlined as well.
Exploring Profiles of College Access Program Participants Associated with Postsecondary Enrollment
Authors: Wright Annie , Kara Yusuf , Cunningham LaChelle , Johns Rachel , Ticzon Catherine , Petrosino Anthony J.
Published: January 2025

Disparities remain in who enters and completes college, with lower income, ethnic minority and first-generation students being less likely to achieve four-year degrees. To address this disparity, numerous federally-funded college access (CA) programs are provided to underrepresented high school students nationwide. However, mixed evidence exists to demonstrate that CA programs are effective strategies to increase enrollment in postsecondary education. This study utilized secondary data collected by providers of one CA program, Upward Bound. Mixed-effects multinomial logistic regression analysis is used to investigate the predictors of postsecondary enrollment that are associated with student profiles including demographic and academic backgrounds. Results showed that male students were less likely to enroll in any postsecondary setting compared to female students. Academic predictors such as dual enrollment and enrollment in advanced placement courses had strong predictive power for whether participating students enrolled in postsecondary education.
MGATAF: multi-channel graph attention network with adaptive fusion for cancer-drug response prediction
Authors: Saeed Dhekra , Xing Huanlai , AlBadani Barakat , Feng Li , Al-Sabri Raeed , Abdullah Monir , Rehman Amir
Published: January 2025

Background

Drug response prediction is critical in precision medicine to determine the most effective and safe treatments for individual patients. Traditional prediction methods relying on demographic and genetic data often fall short in accuracy and robustness. Recent graph-based models, while promising, frequently neglect the critical role of atomic interactions and fail to integrate drug fingerprints with SMILES for comprehensive molecular graph construction.

Results

We introduce multimodal multi-channel graph attention network with adaptive fusion (MGATAF), a framework designed to enhance drug response predictions by capturing both local and global interactions among graph nodes. MGATAF improves drug representation by integrating SMILES and fingerprints, resulting in more precise predictions of drug effects. The methodology involves constructing multimodal molecular graphs, employing multi-channel graph attention networks to capture diverse interactions, and using adaptive fusion to integrate these interactions at multiple abstraction levels. Empirical results demonstrate MGATAF’s superior performance compared to traditional and other graph-based techniques. For example, on the GDSC dataset, MGATAF achieved a 5.12% improvement in the Pearson correlation coefficient (PCC), reaching 0.9312 with an RMSE of 0.0225. Similarly, in new cell-line tests, MGATAF outperformed baselines with a PCC of 0.8536 and an RMSE of 0.0321 on the GDSC dataset, and a PCC of 0.7364 with an RMSE of 0.0531 on the CCLE dataset.

Conclusions

MGATAF significantly advances drug response prediction by effectively integrating multiple molecular data types and capturing complex interactions. This framework enhances prediction accuracy and offers a robust tool for personalized medicine, potentially leading to more effective and safer treatments for patients. Future research can expand on this work by exploring additional data modalities and refining the adaptive fusion mechanisms.
Natural and sexual selection and functional roles influence colouration but not the amount of variation in butterfly wing colour patterns
Authors: Dharmaraaj Bhavya , Kunte Krushnamegh
Published: January 2025

Background

Trait variation is shaped by functional roles of traits and the strength and direction of selection acting on the traits. We hypothesized that in butterflies, sexually selected colouration is more variable owing to condition-dependent nature and directional selection on sexual ornaments, whereas naturally selected colouration may be less variable because of stabilising selection. We measured reflectance spectra, and extracted colour parameters, to compare the amount of variation in sexually versus naturally selected colour patches across wing surfaces and sexes of 20 butterfly species across 4 families (Nymphalidae, Papilionidae, Pieridae, Lycaenidae).

Results

We found that: (a) males had more conspicuous, i.e., brighter and more saturated colour patches compared with females (as expected of sexually selected traits but not necessarily of naturally selected traits), and (b) dorsal surfaces in both sexes had more conspicuous sexual ornaments as well as protective (aposematic/mimetic) colour patches on darker wing backgrounds, compared with ventral surfaces. However, colour patches did not differ in the amount of variation either in selection (ecological/sexual functions), sex or wing surface-specific manner.

Conclusions

These findings show that functional roles and selection influence colour parameters but not the amount of variation in butterfly wing colour patterns.
Blood pressure control with active ultrafiltration measures and without antihypertensives is essential for survival in hemodiafiltration and hemodialysis programs for patients with CKD: a prospective observational study
Authors: Mora-Bravo Franklin Geovany , Torres Pamela Tatiana Morales , Campoverde Nelson Rojas , Carcelen Guillermina Lucía Blum , Mancheno Juan Cristobal Santacruz , Tipanta Ángel Cristóbal Santacruz , Perez-Grovas Hector , Abarca Willan Patricio Robles
Published: January 2025

Background

High blood pressure is a prevalent condition in patients with chronic kidney disease on hemodialysis. Adequate control of high blood pressure is essential to reducing deaths in this group. The present study aimed to observe mortality prospectively in a group of patients in hemodialysis and hemodiafiltration programs in whom the use of antihypertensives was optimized with the point-of-care dry weight (POC-DW) technique.

Methods

The present observational, prospective study was carried out at the Pafram hemodiafiltration unit in Morona Santiago, Ecuador, and the hemodialysis unit of the Fundación Renal del Ecuador in Guayaquil, Ecuador, from August 2019 to December 2023. Patients who were receiving hemodiafiltration were included. Weight was optimized with POC-DW for eight weeks. In Group 1, patients whose use of antihypertensive drugs was not required to control systolic blood pressure with a value less than 150 mmHg predialysis, less than 130 mmHg postdialysis, and a peridialytic blood pressure (defined as post-HD minus pre-HD SBP) between 0 and − 20 mmHg were analyzed. In Group 2, patients who required antihypertensive drugs for not meeting the aims of systolic blood pressure were included. The variables included clinical, demographic, mortality, description of the treatment, and routine laboratory tests in dialysis programs. The sample was nonprobabilistic. Survival analysis was performed for the study groups. The log-rank test (Mantel-Cox) was used for survival comparisons.

Results

The study included 106 patients. Optimal blood pressure control without antihypertensive treatment was achieved in 52 patients (49.1%) (Group 1). In 54 patients (50.9%), antihypertensive agents were required (Group 2). There was more significant mortality in the group that received antihypertensives: 11 patients in group 1 (21.2%) versus 25 patients in group 2 (46.3%) (P = 0.005). Survival was more significant in group 1, with an HR of 2.2163 (1.125–4.158) (P = 0.0243).

Conclusion

In hemodiafiltration and hemodialysis programs, blood pressure control with active ultrafiltration measures and without using antihypertensives is essential for survival in patients with CKD.
Preparing physiotherapists for the future: the development and evaluation of an innovative curriculum
Authors: Stolwijk Niki , van Bergen Anne , Jetten Evy , Maas Marjo
Published: January 2025

Background

Educational innovation in health professional education is needed to keep up with rapidly changing healthcare systems and societal needs. This study evaluates the implementation of PACE, an innovative curriculum designed by the physiotherapy department of the HAN University of Applied Sciences in The Netherlands. The PACE concept features an integrated approach to learning and assessment based on pre-set learning outcomes, personalized learning goals, flexible learning routes, and programmatic assessment. PACE distinguishes itself from traditional education because of the flexible learning routes, vertical organization in learning communities, absence of pre-defined learning activities and class schedules, and a culture of continuous learning and development. PACE is based on three guiding principles: 1) flexible and varied, 2) self-directed and collaborative, 3) future-oriented. PACE was implemented in 2021 for first-year students. This study evaluates the implementation to inform future curriculum development.

Methods

A sequential explanatory mixed methods design was used to evaluate the implementation of PACE using a questionnaire, focus groups, in-depth interviews, and a national progress test allowing for benchmarking results. Participants were undergraduate physiotherapy students of cohort 2021–2022, the first group who experienced PACE and teachers involved with this cohort. Questionnaire data were analyzed using descriptive statistics. To compare mean total scores of the national progress test between four different universities a one-way ANOVA was conducted including a post-hoc analysis. Reflexive thematic analysis guidelines were applied to analyze the interview data.

Results

In total 82 first year students (44,6%) of cohort 2021–2022 and 36 teachers (60%) completed the questionnaire. Results show that the guiding principles were implemented as intended. Results of the national progress test on knowledge and clinical reasoning showed that students of the HAN University performed well compared to other universities. Thematic analysis of interviews and focus groups resulted in three themes and nine subthemes: 1) navigating a personalized curriculum, 2) caring and sharing, and 3) shaping professional identity. PACE contributed positively to students' intrinsic motivation, learning joy, identity development, and life-long learning skills. Areas for improvement were self-directed learning support, and teaching strategies to prompt deep learning.

Conclusion

The evaluation showed that the guiding principles of PACE were implemented as intended and that the innovation positively contributed to student learning,
Dietary rosemary oil with/without zymogen forte improves water quality, growth hormones, immune-physiological response, stress resilience, and health status of Chelon ramada grown in groundwater
Authors: Elhetawy Ashraf I. G. , El Basuini Mohammed F. , Mansour Ahmed I. A. , Shahin Shimaa A. , Omar Amira A. , Zayed Mohamed M. , Abdel-Rahim Mohamed M.
Published: January 2025

With freshwater resources becoming scarce worldwide, mariculture is a promising avenue to sustain aquaculture development, especially by incorporating brackish and saline groundwater (GW) use into fish farming. A 75-day rearing trial was conducted to evaluate fish growth, immune response, overall health, and water quality of Chelon ramada cultured in brackish GW and fed on a basal diet (BD) augmented with rosemary oil (RO) or RO + zymogen forte™ (ZF) as an anti-flatulent. Five treatments were administrated in triplicate: T1: fish-fed BD without additives (control group); T2: fish-fed BD + 0.5 g RO /kg diet; T3: fish-fed BD + 0.5 g RO and 1 g ZF /kg diet; T4: fish-fed BD + 1 g RO /kg diet; T5: fish-fed BD + 1 g RO and 1 g ZF /kg diet. Three hundred fish (8.51 ± 0.01 g/fish) were housed in 15 fiberglass tanks (1500-L tank). The results revealed significant improvements (P < 0.05) in growth performance, survival, growth hormone, and insulin-like growth factor-1. Additionally, there were decreases in the feed conversion ratio (FCR) and the levels of nitrogen by-products (NH4, NH3, and NO2) and pathogenic bacterial counts in the rearing water when fish were fed diets supplemented with RO and RO + ZF. Furthermore, significant reductions in the levels of plasma stress indicators (cortisol, creatinine, and glucose) were detected. In addition, there were significant enhancements observed in the levels of innate immune markers, such as white blood cells, total protein, albumin, and immunoglobulin. The complement system, specifically complement 3 and complement 4, also showed considerable improvements. Furthermore, there were increases in plasma heat shock proteins HSP70 and HSP90, as well as enhanced antioxidant activity. These gains were associated with healthier liver and intestines. The investigation demonstrated that adding 0.5–1 g RO / kg diet or RO + ZF to a C. ramada diet has many benefits, including reducing the levels of nitrogen by-product chemicals and pathogenic bacterial load in GW used in growth tanks. Furthermore, significant improvements were observed in the rates of growth and associated hormones, efficiency of feed utilization, blood indicators, immune function, condition of internal organs (namely the intestine and liver), and overall health of the fish.
A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom
Authors: McKee Martin , Vaughan Louella K. , Russo Giuliano
Published: January 2025

Background

Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case presentation

In the early 2000s the United Kingdom created a new occupational role, that of physician assistant. They had a science degree and then underwent a 2-year postgraduate training course. The name soon changed, to physician associate, and the range of roles and responsibilities expanded greatly, although in a largely unregulated manner; by 2024, some were undertaking complex procedures or managing undifferentiated patients in primary care. Catalysed by some high-profile failings, this expansion has generated major concerns, over patient safety and consent, the scope of practice and preferential employment conditions of this group, the adverse consequences for medical training, and the additional medical workload involved in supervision. This has led to a widespread grassroots backlash by the medical profession, often challenging their leaders who had supported this idea. As a consequence, professional bodies that were initially in favour are now expressing serious concerns and it seems likely that the roles and responsibilities of physician associates (and related occupations) will be curtailed. We review published literature and official documentation about this policy to understand the drivers of its development, its benefits, and risks.

Conclusions

The experience in the UK offers cautionary lessons for other European countries contemplating similar ideas. It underscores the importance of maintaining trust with those affected by change, undertaking a detailed systems analysis with attention to risks of unintended consequences, agreeing clear role definitions, providing adequate regulatory oversight, and the need to avoid damaging training of future doctors. This case study highlights the need for a carefully thought-out approach that considers both the potential benefits and pitfalls of integrating new roles like physician associates into a healthcare system. The failure to do so has created a new occupational group with unrealistic expectations and has further demoralised an already unhappy medical profession.
Ground state solutions for a class of Schrödinger–Poisson–Slater equation with Coulomb–Sobolev critical exponent
Authors: Du Jingai , He Pengfei , Suo Hongmin
Published: January 2025

This paper is concerned with the Schrödinger–Poisson–Slater equation involving the Coulomb–Sobolev exponent. We apply the concentration compactness principle and the Pohožaev-type identity to overcome loss of compactness caused by the Coulomb exponent and obtain a ground state solution, which generalizes and improves some recent results in the literature.
Rationale and design of a randomized clinical trial of integrated eHealth for PrEP and medications for opioid use disorders for women in the criminal legal system. The Athena study
Authors: Meyer Jaimie P. , Brunson Stacey , Price Carolina R. , Mulrain Morgan , Nguyen Julie , Altice Frederick L. , Kyriakides Tassos C. , Cropsey Karen , Eaton Ellen
Published: January 2025

Background

Women involved in the criminal legal system have elevated rates of opioid use disorder, which is treatable, and HIV, which is preventable with pre-exposure prophylaxis (PrEP). There are significant social and structural barriers to integrated delivery of PrEP and medications for opioid use disorder (MOUD), limiting women’s ability to access these life-saving interventions. In a two parallel-arm randomized controlled trial, we are assessing an innovative eHealth delivery model that integrates PrEP with MOUD and is tailored to meet the specific needs of women involved in the criminal legal system.

Methods

We will recruit and enroll 250 women involved in the criminal legal system with opioid use disorder across two diverse settings (New Haven, CT and Birmingham, AL). Participants will be randomized to (a) the “Athena strategy,” which includes a PrEP decision aid and integrated PrEP/MOUD delivery via eHealth; or (b) enhanced standard of care (SOC) that includes a decision aid-only. During 6-month follow-up, we will assess PrEP initiation as the primary clinical outcome and implementation outcomes that include acceptability, adoption, feasibility, fidelity, implementation cost, and sustainability.

Discussion

Results could help determine if reducing the social and structural barriers to PrEP and MOUD for women involved in the criminal legal system will facilitate engagement in treatment and prevention services, thus alleviating health disparities.

Trial registration

Clinicaltrials.gov (NCT05547048). Registered September 15, 2022. https://clinicaltrials.gov/study/NCT05547048?term=NCT05547048&rank=1.
The challenges of evidence-based prehabilitation in a real-life context for patients preparing for colorectal surgery—a cohort study and multiple case analysis
Authors: Talen A. D. , van Meeteren N. L. U. , Barten J. A. , Pereboom I. , Krijnen W. P. , Jager-Wittenaar H. , Bongers B. C. , van der Sluis G.
Published: January 2025

Background

Multimodal prehabilitation programs are effective at reducing complications after colorectal surgery in patients with a high risk of postoperative complications due to low aerobic capacity and/or malnutrition. However, high implementation fidelity is needed to achieve these effects in real-life practice. This study aimed to investigate the implementation fidelity of an evidence-based prehabilitation program in the real-life context of a Dutch regional hospital.

Methods

In this observational cohort study with multiple case analyses, all patients who underwent colorectal surgery from January 2023 to June 2023 were enrolled. Patients meeting the criteria for low aerobic capacity or malnutrition were advised to participate in a prehabilitation program. According to recent scientific insights and the local care context, this program consisted of four exercise modalities and three nutrition modalities. Implementation fidelity was investigated by evaluating: (1) coverage (participation rate), (2) duration (number of days between the start of prehabilitation and surgery), (3) content (delivery of prescribed intervention modalities), and (4) frequency (attendance of sessions and compliance with prescribed parameters). An aggregated percentage of content and frequency was calculated to determine overall adherence.

Results

Fifty-eight patients intended to follow the prehabilitation care pathway, of which 41 performed a preoperative risk assessment (coverage 80%). Ten patients (24%) were identified as high-risk and participated in the prehabilitation program (duration of 33–84 days). Adherence was high (84–100%) in five and moderate (72–73%) in two patients. Adherence was remarkably low (25%, 53%, 54%) in three patients who struggled to execute the prehabilitation program due to multiple physical and cognitive impairments.

Conclusion

Implementation fidelity of an evidence-based multimodal prehabilitation program for high-risk patients preparing for colorectal surgery in real-life practice was moderate because adherence was high for most patients, but low for some patients. Patients with low adherence had multiple impairments, with consequences for their preparation for surgery. For healthcare professionals, it is recommended to pay attention to high-risk patients with multiple impairments and further personalize the prehabilitation program. More knowledge about identifying and treating high-risk patients is needed to provide evidence-based recommendations and to obtain higher effectiveness.

Trial registration

NCT06438484.