bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization, genomic analysis and preclinical evaluation of the lytic Staphylococcus bacteriophage PSK against methicillin-resistant Staphylococcus aureus wound isolate
Authors: Zanaty Abanoub A. , Dishisha Tarek , El-Sayed-Ahmed Mohamed Abd El-Gawad , Abdel-Fattah Maha M. , Ahmed Kawkab A. , Abdelkader Karim 
Published: February 2025

Abstract

Background
The dissemination of multi-drug-resistant bacteria, particularly Methicillin-resistant Staphylococcus aureus (MRSA), necessitates exploring new alternatives for their control. Bacteriophages are promising antibiotic alternatives with unique features. Here, we have performed a comprehensive characterization of a newly isolated bacteriophage (PSK) and compared its therapeutic potential with vancomycin in vivo.

Methods
Sewage samples were processed and enriched with the MRSA S. aureus SK1 strain in a search for isolation of a lytic bacteriophage. The isolated bacteriophage was assessed in vitro in terms of thermal and pH stability and kinetic parameters using absorption and one step growth curve assays. Moreover, its potential antibacterial activity was evaluated against S. aureus SK1 lone and in combination of standard of care antibiotics used for treatment of wound infections. We further analyzed its genome to exclude the presence of any potential toxin or antibiotic resistance genes. Finally, its antibacterial potential and capability to alleviate wound infection were assessed using a murine wound-infection model.

Results
The lytic bacteriophage (PSK) was isolated as a new species of the genus Rosenblumvirus with a genome size of 17,571 bp that is free from potential resistance or virulence genes. PSK displays infectivity against 4/10 S. aureus strains including two vancomycin-resistant strains. Moreover, it demonstrates favorable infection kinetics of fast adsorption with latent period and burst size of 20 min and 123 PFU/infected cell, respectively. Stability analysis revealed thermal stability up to 60 °C with wide pH range stability (4–11). In vitro, PSK kills S. aureus SK1 with multiplicity of infection (MOI) as low as 10− 4 with an overall mutation frequency of 2.47 × 10− 6 CFU/mL that is further improved when combined with 0.25× MIC of oxacillin, fusidic acid or vancomycin. In vivo, a single dose of PSK in murine wound infection model exhibited a comparable performance to four doses of vancomycin, when treatment started 2 h post-infection. However, when applied 2 days post-infection, PSK demonstrates superior antibacterial activity (up to 4.58 log unit count reduction) and enhances wound closure and tissue healing.

Conclusion
These findings represent PSK as a potential vancomycin alternative effective in treating S. aureus- induced wound infections.
In vitro activity of rifampicin, rifapentine and rifabutin in combination with their 25-deacetyl-metabolites against various Mycobacterium tuberculosis lineages
Authors: Genestet Charlotte , Bourg Chloé , Hodille Elisabeth , Bahuaud Olivier , Ader Florence , Goutelle Sylvain , Dumitrescu Oana ,   On behalf of the Lyon TB study group
Published: February 2025

Abstract

Objectives
Rifamycin agents (rifampicin (RIF), rifapentine (RFP), rifabutin (RFB)) are the cornerstone of tuberculosis (TB) therapy. Rifamycins are metabolized into 25-deacetyl-metabolites, which have been described has active and may contribute to in vivo drug effect. However, little is known about the combined effect of rifamycins and their metabolites across different Mycobacterium tuberculosis complex (MTBC) lineages.

Methods
This study included 14 MTBC strains representing the main lineages. Minimum inhibitory concentrations (MICs) were determined using microdilution assays for the three rifamycins and their metabolites. A checkerboard assay was used to assess drug interactions, with the fractional inhibitory concentration (FIC) index calculated for synergy or antagonism.

Results
MICs varied across rifamycins, RIF and its metabolite showed the highest MICs, followed by RFP and RFB and their respective metabolites. FIC indices for rifamycin-metabolite combinations indicated additive effects (FIC between 0.5 and 1.25), with no antagonism observed, even at clinically relevant metabolite-to-parent drug ratios, and without impact of MTBC lineage.

Conclusions
Rifamycin metabolites exhibit additive effects with parent drugs, potentially enhancing bactericidal activity. This highlights that rifamycin susceptibility testing should account for both parent drugs and their metabolites, as these metabolites also exhibit antimicrobial activity. Additionally, these findings support further pharmacokinetic/pharmacodynamic studies to optimize TB treatment regimens, particularly in relation to metabolite-to-parent drug ratios in patients.
Myelin-reactive CD8+ T cells influence conventional dendritic cell subsets towards a mature and regulatory phenotype in experimental autoimmune encephalomyelitis
Authors: Upadhye Mohit , Wilhelm Connor R. , Rogers Kai J. , Vemulawada Chakrapani , Borcherding Nicholas , Boyden Alexander W. , Legge Kevin L. , Karandikar Nitin J. 
Published: February 2025

Abstract
Multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is modeled in mice as experimental autoimmune encephalomyelitis (EAE). While CD4+ T cells, primarily Th1 and Th17 subsets, drive disease pathogenesis, the exact function of CD8+ T cells remains unclear. We previously demonstrated that adoptively transferred myelin-reactive CD8+ T cells (PLP-CD8) prevent EAE induction and suppress ongoing disease through the engagement of MHC Class-I in recipient mice. Here, we show that PLP-CD8 induce regulatory changes in both subsets of conventional dendritic cells (cDC1 and CD11b+ cDC) in vivo and in vitro. Adoptively transferred PLP-CD8 promoted both cDC subsets to adopt a mature and regulatory phenotype with an anti-inflammatory cytokine profile and a reduced capacity to support CD4+ T cell proliferation. In vitro, PLP-CD8 induced similar phenotypic changes in both cDC subsets in an antigen-specific, dose-dependent manner. PLP-CD8 directly interacted with cDC1 and indirectly influenced CD11b+ cDC through paracrine signaling. Notably, direct interaction with PLP-CD8 had detrimental effects on CD11b+ cDC. Single-cell RNA sequencing revealed upregulation of key immunoregulatory genes, such as Foxo3, in both cDC subsets with enrichment of pathways involved in immune regulation and T cell differentiation. Our study highlights a novel mechanism in which myelin-reactive CD8+ T cells directly interact with cDC1 and modulate CD11b+ cDC through paracrine mechanisms to induce mature, regulatory dendritic cells, which leads to inhibited CD4+ T cell responses and reduced EAE pathogenesis.
Acute hepatic porphyria in Denmark; a retrospective study
Authors: Wagner Magnus Emil Ulrich , Frost Morten , Frystyk Jan 
Published: February 2025

Abstract

Background
Acute hepatic porphyria (AHP) constitutes a class of rare diseases caused by reduced function in enzymes of the heme-biosynthetic pathway. AHP includes acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP) and the extremely rare δ-aminolevulinic-dehydrase deficiency porphyria (ADP). This retrospective study describes characteristics of the Danish AHP patient population.

Methods
Department of Endocrinology at Odense University Hospital serves as national AHP center. We performed a 5-year retrospective description of our AHP cohort using electronic patient journals. We included general symptoms, number of acute attacks, hospitalization rates, long-term sequelae and symptoms, and grouped patients according to creatinine-adjusted urinary baseline excretion (i.e., outside attacks) of the porphyrin precursor porphobilinogen (PBG) in normal-, moderate- and high-excretion and unknown.

Results
The cohort contained 129 AHP patients, hereof 100 AIP, 12 HCP and 17 VP. Median age was 46.3 (32.1–62.0) years, and 85 (65.9%) were female. During the 5-years, 38 (29.5%) patients experienced symptoms. Hereof, 20 patients were hospitalized with acute attacks or chronic symptoms and treated with human hemin (n = 14). Most frequently reported symptoms were abdominal pain, nausea, vomiting, and neurological disturbances. Symptoms were more common in patients with high PBG baseline excretion (n = 39) as compared to those with moderate (n = 31) or normal (n = 40) PBG excretion (p = 0.002). Furthermore, females dominated the symptomatic group (68.4%).

Conclusion
As reported internationally, AHP is more commonly diagnosed and symptomatic in women, and AIP was the most frequent AHP subtype. Those with an elevated urinary baseline PBG secretion were more likely to report AHP-related symptoms.
Analysis of SMN protein in umbilical cord blood and postnatal peripheral blood of neonates with SMA: a rationale for prompt treatment initiation to prevent SMA development
Authors: Otsuki Noriko , Kato Tamaki , Yokomura Mamoru , Urano Mari , Matsuo Mari , Kobayashi Emiko , Haginoya Kazuhiro , Awano Hiroyuki , Takeshima Yasuhiro , Saito Toshio , Saito Kayoko 
Published: February 2025

Abstract

Background
Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease caused by insufficient functional survival motor neuron protein (SMN). The SMN expression level in the spinal cord is highest during the 2nd trimester of the foetal period. We previously reported the SMN spot analysis in peripheral blood using imaging flow cytometry (IFC) as a biomarker of functional SMN protein expression. In this study, we analysed neonatal cord blood, postnatal peripheral blood, and maternal peripheral blood in presymptomatic five infants whose sibling has type 1 SMA to estimate prenatal and postnatal SMN dynamics before the onset of severe SMA.

Results
Data from 37 untreated patients with SMA showed that SMN-spot+ cells were significantly correlated with SMA clinical classification and the copy numbers of the SMN2 gene. The range of values for cord blood, converted from each SMN2 copy number statistics, was − 0.7 to + 2.0 standard deviation (SD) (0.1–24.0%) for SMN-spot+ cells in patients with SMA. Subsequent analyses of the peripheral blood of neonates ranged from − 0.8 to + 0.8 SD (0.4–15.2%). The analysis of each maternal blood, converted from carrier statistics, ranged from − 0.2 to + 2.4 SD (1.4–25.2%). A correlation was observed between the cord blood and maternal peripheral blood.

Conclusions
This study suggests that the status of the motor neuron pool in the spinal cord can be presumed by cord blood SMN-spot+ cells and that SMN protein depletion determines the timing of disease onset. As the SMN spot analysis values tended to decrease with time after birth, they may eventually lead to the development of SMA. Furthermore, a correlation was found between the SMN spot analysis values of neonatal cord blood and maternal blood, which predicts disease severity after birth. In other words, the SMN protein supplied from the mother to the foetus may suppress the development of SMA in the infant at birth, and depletion of the SMN protein may occur after birth, causing the infant to develop SMA. Our findings demonstrated the effectiveness of newborn screening and the potential of maternally mediated treatment strategies by providing a rationale for prompt treatment initiation in SMA.
Tumour mutational burden using a targeted panel approach for comprehensive tumour profiling focusing on colorectal cancer
Authors: Scott Rodney J. , Ziolkowski Andrew , Mossman David , Hipwell Michael 
Published: February 2025

Abstract
There is an increasing recognition that comprehensive tumour profiling (CTP) represents an important adjunct to the diagnosis of malignancy providing not only an assessment of how many mutations there are in any given tumour which reflects the probability of immune checkpoint inhibitor success, but also which mutations are associated with targeted therapies, a signature that reflects environmental insult and potentially the identification of cancers of unknown origin.
This short review describes an approach to assaying tumour mutational burden (TMB), what the difficulties are in the assessment of the TMB and what it can be applied to in regards to improving patient outcomes. A final section of the review delves into some examples of colorectal cancer studies that identify findings that suggest there remains much to learn about tumour development.
Admixture as a source for HLA variation in Neolithic European farming communities
Authors: da Silva Nicolas Antonio , Özer Onur , Haller-Caskie Magdalena , Chen Yan-Rong , Kolbe Daniel , Schade-Lindig Sabine , Wahl Joachim , Berszin Carola , Francken Michael , Görner Irina , Schierhold Kerstin , Pechtl Joachim , Grupe Gisela , Rinne Christoph , Müller Johannes , Lenz Tobias L. , Nebel Almut , Krause-Kyora Ben 
Published: February 2025

Abstract

Background
The northern European Neolithic is characterized by two major demographic events: immigration of early farmers from Anatolia at 7500 years before present, and their admixture with local western hunter-gatherers forming late farmers, from around 6200 years before present. The influence of this admixture event on variation in the immune-relevant human leukocyte antigen (HLA) region is understudied.

Results
We analyzed genome-wide data of 125 individuals from seven archeological early farmer and late farmer sites located in present-day Germany. The late farmer group studied here is associated with the Wartberg culture, from around 5500–4800 years before present. We note that late farmers resulted from sex-biased admixture from male western hunter-gatherers. In addition, we observe Y-chromosome haplogroup I as the dominant lineage in late farmers, with site-specific sub-lineages. We analyze true HLA genotypes from 135 Neolithic individuals, the majority of which were produced in this study. We observe significant shifts in HLA allele frequencies from early farmers to late farmers, likely due to admixture with western hunter-gatherers. Especially for the haplotype DQB1*04:01-DRB1*08:01, there is evidence for a western hunter-gatherer origin. The HLA diversity increased from early farmers to late farmers. However, it is considerably lower than in modern populations.

Conclusions
Both early farmers and late farmers exhibit a relatively narrow HLA allele spectrum compared to today. This coincides with sparse traces of pathogen DNA, potentially indicating a lower pathogen pressure at the time.
Exploring the mediating roles of motivation and boredom in basic psychological needs and behavioural engagement in English learning: a self-determination theory perspective
Authors: Liu Honggang , Wang Ying , Wang Haoyue 
Published: February 2025

Abstract
In second language acquisition research, the psychological factors associated with language learning have been a prominent focus. The affective turn in and introduction of positive psychology in this field have further boosted research on the roles of positive learner psychological factors (e.g. motivation) in performance (e.g. engagement). However, the theoretical lens for investigating these variables requires further clarification, and the roles of some variables (e.g. boredom) in language learning have been under-researched. Guided by this background, this study aims to explore the complex relationships between learners’ basic psychological needs, self-determined motivation, boredom and behavioural engagement among 687 Chinese senior high school EFL learners from the perspective of self-determination theory (SDT). Quantitative data collection and analysis revealed that students’ basic psychological needs directly predicted behavioural engagement. Basic psychological needs also indirectly predicted behavioural engagement through the simple mediation of boredom and the chain mediation of self-determined motivation and boredom. However, the simple mediation of self-determined motivation in the relationship between basic psychological needs and behavioural engagement was non-significant. The findings enrich the application of SDT in the language learning engagement research, providing valuable implications for teachers and educators.
Policies on artificial intelligence chatbots among academic publishers: a cross-sectional audit
Authors: Bhavsar Daivat , Duffy Laura , Jo Hamin , Lokker Cynthia , Haynes R. Brian , Iorio Alfonso , Marusic Ana , Ng Jeremy Y. 
Published: February 2025

Abstract

Background
Artificial intelligence (AI) chatbots are novel computer programs that can generate text or content in a natural language format. Academic publishers are adapting to the transformative role of AI chatbots in producing or facilitating scientific research. This study aimed to examine the policies established by scientific, technical, and medical academic publishers for defining and regulating the authors’ responsible use of AI chatbots.

Methods
This study performed a cross-sectional audit on the publicly available policies of 162 academic publishers, indexed as members of the International Association of the Scientific, Technical, and Medical Publishers (STM). Data extraction of publicly available policies on the webpages of all STM academic publishers was performed independently, in duplicate, with content analysis reviewed by a third contributor (September 2023—December 2023). Data was categorized into policy elements, such as ‘proofreading’ and ‘image generation’. Counts and percentages of ‘yes’ (i.e., permitted), ‘no’, and ‘no available information’ (NAI) were established for each policy element.

Results
A total of 56/162 (34.6%) STM academic publishers had a publicly available policy guiding the authors’ use of AI chatbots. No policy allowed authorship for AI chatbots (or other AI tool). Most (49/56 or 87.5%) required specific disclosure of AI chatbot use. Four policies/publishers placed a complete ban on the use of AI chatbots by authors.

Conclusions
Only a third of STM academic publishers had publicly available policies as of December 2023. A re-examination of all STM members in 12–18 months may uncover evolving approaches toward AI chatbot use with more academic publishers having a policy.
Lateral-directional wind tunnel tests of the PROSIB 19-pax aircraft model
Authors: Ciliberti Danilo , Nicolosi Fabrizio 
Published: February 2025

Abstract
This paper presents the power-off, lateral-directional wind tunnel tests on the fixed-wing, 19-passenger aircraft model developed within the Italian PROSIB project. The concept is an innovative small air transport airplane with distributed propellers and hybrid-electric powerplant. By measuring the aerodynamic forces and moments, the experimental investigation focused on the estimation of the power-off stability and control derivatives, highlighting the effects of the aerodynamic interference. Tests included a belly-mounted pod, simulating a battery storage unit, and two distinct empennage configurations: a body-mounted (low) horizontal tail and a T-tail (high). Numerical analyses were also used to further highlight the role of aerodynamic interference in the generation of forces and moments. For instance, wind tunnel data have shown a beneficial effect of the belly pod on the aircraft directional stability (+13%), but were in contrast with the results of numerical analyses (−30%). The measured sidewash depends also from the empennage layout, not only from the vertical tail planform area. Simulations confirmed an excessive directional stability with respect to the directional control in the ratio of 1.65, suggesting that such class of airplane should have a larger rudder chord ratio or a horn balance. Combined tests at different angles of attack and flap deflections revealed some issues on the lateral stability of the model, which are related to the velocity circulation on the wing in high-lift conditions counteracting the effective dihedral of the model’s layout. The collected dataset of aerodynamic derivatives will serve as reference for a next experimental investigation on the aero-propulsive effects and provide useful information to researchers and professionals involved in similar design studies.
Computational Modeling for Circulating Cell-Free DNA in Clinical Oncology
Authors: Nguyen Phuong Linh , Salas Sébastien , Benzekry Sébastien 
Published: February 2025

PURPOSE
Liquid biopsy, specifically circulating cell-free DNA (cfDNA), has emerged as a powerful tool for cancer early diagnosis, prognosis, and treatment monitoring over a wide range of cancer types. Computational modeling (CM) of cfDNA data is essential to harness its full potential for real-time, noninvasive insights into tumor biology, enhancing clinical decision making.

DESIGN
This work reviews CM-cfDNA methods applied to clinical oncology, emphasizing both machine learning (ML) techniques and mechanistic approaches. The latter integrate biological principles, enabling a deeper understanding of cfDNA dynamics and its relationship with tumor evolution.

RESULTS
Key findings highlight the effectiveness of CM-cfDNA approaches in improving diagnostic accuracy, identifying prognostic markers, and predicting therapeutic outcomes. ML models integrating cfDNA concentration, fragmentation patterns, and mutation detection achieve high sensitivity and specificity for early cancer detection. Mechanistic models describe cfDNA kinetics, linking them to tumor growth and response to treatment, for example, immune checkpoint inhibitors. Longitudinal data and advanced statistical constructs further refine these models for quantification of interindividual and intraindividual variability.

CONCLUSION
CM-cfDNA represents a pivotal advancement in precision oncology. It bridges the gap between extensive cfDNA data and actionable clinical insights, supporting its integration into routine cancer care. Future efforts should focus on standardizing protocols, validating models across populations, and exploring hybrid approaches combining ML with mechanistic modeling to improve biological understanding.