bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development
Authors: Krenger Pascal S. , Roques Magali , Vogt Anne-Cathrine S. , Pardini Alessandro , Rothen Dominik A. , Balke Ina , Schnider Sophie T. , Mohsen Mona O. , Heussler Volker T. , Zeltins Andris , Bachmann Martin F. 
Published: November 2024

AbstractRTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain. However, neither RTS,S nor R21 targets this junction domain. To test the potential of the NPDP junction domain and other sites of PfCSP as innovative vaccine targets, we developed multiple vaccine candidates based on cucumber mosaic virus-like particles (CuMVTT-VLPs). These candidates vary in several aspects: the number of targeted NANP repeats, the presence or absence of the junction domain, the cleavage site, and up to three NVDP repeats within the target sequence. Immunogenicity and efficacy studies were conducted in BALB/c mice, utilizing chimeric Plasmodium berghei (Pb) sporozoites, in which the endogenous CSP has been replaced by PfCSP (Pb/PfCSP). We observed a positive association between the number of targeted NANP repeats and the induction of specific IgM/IgG antibodies. Elevated humoral responses led to enhanced protection against parasitemia after Pb/PfCSP sporozoite challenge. Especially high-avidity/affinity antibody formation and vaccine protection were NANP repeat-dependent. Intriguingly, vaccine efficacy was not enhanced by targeting sites on PfCSP other than the NANP repeats. Our data emphasize the dominant role of the NANP repeat region for induction of protective antibodies. Furthermore, we present here novel malaria vaccine candidates with an excellent immunogenic profile that confer sterile protection in mice, even in absence of adjuvants.
Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts
Authors: Manghi Paolo , Bhosle Amrisha , Wang Kai , Marconi Roberta , Selma-Royo Marta , Ricci Liviana , Asnicar Francesco , Golzato Davide , Ma Wenjie , Hang Dong , Thompson Kelsey N. , Franzosa Eric A. , Nabinejad Amir , Tamburini Sabrina , Rimm Eric B. , Garrett Wendy S. , Sun Qi , Chan Andrew T. , Valles-Colomer Mireia , Arumugam Manimozhiyan , Bermingham Kate M. , Giordano Francesca , Davies Richard , Hadjigeorgiou George , Wolf Jonathan , Strowig Till , Berry Sarah E. , Huttenhower Curtis , Spector Tim D. , Segata Nicola , Song Mingyang 
Published: November 2024

AbstractAlthough diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components. Here we conducted a multi-cohort, multi-omic analysis of US and UK populations with detailed dietary information from a total of 22,867 participants, which we then integrated with public data from 211 cohorts (N = 54,198). The link between coffee consumption and microbiome was highly reproducible across different populations (area under the curve of 0.89), largely driven by the presence and abundance of the species Lawsonibacter asaccharolyticus. Using in vitro experiments, we show that coffee can stimulate growth of L. asaccharolyticus. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and L. asaccharolyticus. This study reveals a metabolic link between a specific gut microorganism and a specific food item, providing a framework for the understanding of microbial dietary responses at the biochemical level.
Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment
Authors: Li Ruoyan , Strobl Johanna , Poyner Elizabeth F. M. , Balbaa Aya , Torabi Fereshteh , Mazin Pavel V. , Chipampe Nana-Jane , Stephenson Emily , Ramírez-Suástegi Ciro , Shanmugiah Vijaya Baskar Mahalingam , Gardner Louis , Olabi Bayanne , Coulthard Rowen , Botting Rachel A. , Zila Nina , Prigmore Elena , Gopee Nusayhah H. , Chroscik Marta A. , Kritikaki Efpraxia , Engelbert Justin , Goh Issac , Chan Hon Man , Johnson Harriet F. , Ellis Jasmine , Rowe Victoria , Tun Win , Reynolds Gary , Yang Dexin , Foster April Rose , Gambardella Laure , Winheim Elena , Admane Chloe , Rumney Benjamin , Steele Lloyd , Jardine Laura , Nenonen Julia , Pickard Keir , Lumley Jennifer , Hampton Philip , Hu Simeng , Liu Fengjie , Liu Xiangjun , Horsfall David , Basurto-Lozada Daniela , Grimble Louise , Bacon Chris M. , Weatherhead Sophie C. , Brauner Hanna , Wang Yang , Bai Fan , Reynolds Nick J. , Allen Judith E. , Jonak Constanze , Brunner Patrick M. , Teichmann Sarah A. , Haniffa Muzlifah 
Published: November 2024

AbstractCutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.
A multilevel analysis of factors associated with wasting in children one to two years old in Hamadan city
Authors: Manoochehri Sara , Manoochehri Zohreh , Asadi Fatemeh Torkaman , Soltanian Ali Reza 
Published: November 2024

AbstractThe study aimed to identify risk factors for childhood wasting in 1–2 year-olds in Hamadan city, focusing on this age group due to infection and malnutrition risks. Unlike previous cross-sectional studies on children under 5 years old, this longitudinal study tracked weight-to-height changes over time. Data were analyzed from 455 mother-child pairs, aged 1–2 years, collected from health centers and recorded in the Integrated Electronic Health System (SIB). The weight-for-height index, an ordinal response with three categories (wasting, normal, and overweight), was measured several times. A two-level longitudinal ordinal model was used to identify factors associated with wasting. The analysis of data from 230 girls and 225 boys identified several factors associated with wasting: lower birth weight (Adjusted Odds Ratio (AOR) = 0.77), age 12–15 months (AOR = 1.15), lack of health insurance (AOR = 3.09), mother-child residence (AOR = 3.80), maternal height (AOR = 0.92), and age at pregnancy < 24 years (AOR = 4.71). The results of this study showed that most of the factors contributing to childhood wasting can be controlled and prevented. Therefore, implementation of targeted policies and appropriate interventions for mothers before, during, and after pregnancy could reduce the burden of childhood wasting.
Modeling linear and nonlinear viscoelastic oscillatory rheometric stress-strain hysteresis of asphalt binders
Authors: Diab Aboelkasim , You Lingyun , Topa Ameen , Saboo Nikhil , Sukhija Mayank , Awed Ahmed 
Published: November 2024

AbstractUnderstanding the complex stress-strain hysteresis behavior of asphalt binders under varied conditions is critical for optimizing pavement performance. This study addresses the challenge by analyzing and modeling asphalt binder responses in oscillating shear mode across different aging states (unaged, short-term aged, and long-term aged), stretch amplitudes, frequencies, and temperatures. Fifty-three stress-strain hysteresis loops were meticulously analyzed, revealing distinct stress paths relative to applied stretch levels. A nine-parameter parallel rheological framework model was developed, integrating a four-parameter eight-chain (FEC) hyperelastic model in one network and a FEC hyperelastic model with a linear viscoelastic flow element in series in another. This constitutive model was implemented in LS-DYNA finite element simulations to predict experimentally-measured stress-strain hysteresis loops accurately. The research demonstrates the model’s capability to simulate both linear and nonlinear viscoelastic responses of asphalt binders across a wide range of environmental and loading conditions. This approach significantly enhances our ability to capture and understand the stress-strain behavior critical for asphalt pavement durability and performance optimization.
A low-cost perfusion heating system for slice electrophysiology
Authors: Dorst Matthijs , Vervaeke Koen 
Published: November 2024

AbstractTemperature-critical applications, such as patch-clamp electrophysiology, require constant perfusion at a fixed temperature. However, maintaining perfusate at a specific temperature throughout various applications requires heaters or coolers with integrated feedback systems, which has historically increased complexity and cost. This makes such systems prohibitively expensive in research environments with lower funding rates, particularly in developing countries. We developed a custom temperature control system that relies on off-the-shelf components and few custom parts, which can be easily produced with common tools. Our system can be built for less than $30 and maintains a set perfusate temperature within 0.4 °C while introducing negligible electrical interference. Using this system, we demonstrate that Striatal Medium Spiny Neurons exhibit increased membrane resistance, longer membrane time constants, lower firing rates, and increased rheobase current at room temperature compared to physiological temperature.
Locomotor performance parameters as predictors of high-performing male soccer teams. A multiple-season study on professional soccer
Authors: Makar Piotr , Musa Rabiu Muazu , Silva Rui Miguel , Muracki Jarosław , Trybulski Robert , Altundağ Emre , Altaca Murat , Kuczmik Wacław , Studnicki Rafał , Akyildiz Zeki 
Published: November 2024

Abstract
This study aims to explore the interplay between locomotor demands and goal differentials to better understand their combined influence on overall success. Spanning three competitive seasons within the male Turkish Super League, this study analyzed all participating teams across 124 matches. Locomotor demands, including total distance (m) covered (TD), distances covered (m) at different speed thresholds (0.21–2.0 m/s; 2.01–4.0 m/s; 4.01–5.5 m/s; and 5.5–7.7 m/s), and the number of accelerations in range of 5.5–7.0 m/s (n), were quantified using an optical tracking system. Subsequently, regression models were employed to predict the total points earned by all teams over the three seasons. The logistic regression model, tailored to predict team categorization as high-points earners (HPE) or low-points earners (LPE) based on locomotor variables, exhibited a mean accuracy of 74%. Notably, total distance covered, running speed intervals between 4.4 and 5.5 m/s, and the number of accelerations in range of 5.5–7.0 m/s emerged as significant predictors of team success. Our findings highlight the pivotal role of running speed (4.01–5.5 m/s), number of accelerations, and total distance in predicting success for high-performing teams. Coaches can leverage these insights to refine training programs, thereby optimizing team performance, and fostering success in competitive environments.
Bilayered skin equivalent mimicking psoriasis as predictive tool for preclinical treatment studies
Authors: Morgner Bianka , Werz Oliver , Wiegand Cornelia , Tittelbach Jörg 
Published: November 2024

AbstractPsoriasis is a prevalent, inflammatory skin disease without cure. Further research is required to unravel dysregulated processes and develop new therapeutic interventions. The lack of suitable in vivo and in vitro preclinical models is an impediment in the psoriasis research. Recently, the development of 3D skin models has progressed including replicas with disease-like features. To investigate the use of in vitro models as preclinical test tools, the study focused on treatment responses of 3D skin replicas. Cytokine-priming of skin organoids induced psoriatic features like inflammation, antimicrobial peptides (AMP), hyperproliferation and impaired differentiation. Topical application of dexamethasone (DEX) or celastrol (CEL), a natural anti-inflammatory compound reduced the secretion of pro-inflammatory cytokines. DEX and CEL decreased the gene expression of inflammatory mediators. DEX barely affected the psoriatic AMP transcription but CEL downregulated psoriasis-driven AMP genes. Subcutaneous application of adalimumab (ADM) or bimekizumab (BMM) showed anti-psoriatic effects via protein induction of the differentiation marker keratin-10. Dual blockage of TNF-α and IL-17A repressed the inflammatory psoriasis phenotype. BMM inhibited the psoriatic expression of AMP genes and induced KRT10 and cell-cell contact genes. The present in vitro model provides a 3D environment with in vivo-like cutaneous responses and represents a promising tool for preclinical investigations.
Shortcut to chemically accurate quantum computing via density-based basis-set correction
Authors: Traore Diata , Adjoua Olivier , Feniou César , Lygatsika Ioanna-Maria , Maday Yvon , Posenitskiy Evgeny , Hammernik Kerstin , Peruzzo Alberto , Toulouse Julien , Giner Emmanuel , Piquemal Jean-Philip 
Published: November 2024

AbstractUsing GPU-accelerated state-vector emulation, we propose to embed a quantum computing ansatz into density-functional theory via density-based basis-set corrections to obtain quantitative quantum-chemistry results on molecules that would otherwise require brute-force quantum calculations using hundreds of logical qubits. Indeed, accessing a quantitative description of chemical systems while minimizing quantum resources is an essential challenge given the limited qubit capabilities of current quantum processors. We provide a shortcut towards chemically accurate quantum computations by approaching the complete-basis-set limit through coupling the density-based basis-set corrections approach, applied to any given variational ansatz, to an on-the-fly crafting of basis sets specifically adapted to a given system and user-defined qubit budget. The resulting approach self-consistently accelerates the basis-set convergence, improving electronic densities, ground-state energies, and first-order properties (e.g. dipole moments), but can also serve as a classical, a posteriori, energy correction to quantum hardware calculations with expected applications in drug design and materials science.
Restoring brain connectivity by phrenic nerve stimulation in sedated and mechanically ventilated patients
Authors: Bassi Thiago , Rohrs E Elizabeth , Parfait Melodie , Hannigan Brett C. , Reynolds Steven , Mayaux Julien , Decavèle Maxens , Herrero Jose , Demoule Alexandre , Similowski Thomas , Dres Martin 
Published: November 2024

Abstract
Background
In critically ill patients, deep sedation and mechanical ventilation suppress the brain-diaphragm-lung axis and are associated with cognitive issues in survivors.

Methods
This exploratory crossover design study investigates whether phrenic nerve stimulation can enhance brain activity and connectivity in six deeply sedated, mechanically ventilated patients with acute respiratory distress syndrome.

Results
Our findings indicate that adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization in the frontal-temporal-parietal cortices.

Conclusions
Adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization. The observed changes resemble those during diaphragmatic breathing in awake humans. These results suggest that phrenic nerve stimulation has the potential to restore the brain-diaphragm-lung crosstalk when it has been shut down or impaired by mechanical ventilation and sedation. Further research should evaluate the clinical significance of these results.
Predicting individual patient and hospital-level discharge using machine learning
Authors: Wei Jia , Zhou Jiandong , Zhang Zizheng , Yuan Kevin , Gu Qingze , Luk Augustine , Brent Andrew J. , Clifton David A. , Walker A. Sarah , Eyre David W. 
Published: November 2024

Abstract
Background
Accurately predicting hospital discharge events could help improve patient flow and the efficiency of healthcare delivery. However, using machine learning and diverse electronic health record (EHR) data for this task remains incompletely explored.

Methods
We used EHR data from February-2017 to January-2020 from Oxfordshire, UK to predict hospital discharges in the next 24 h. We fitted separate extreme gradient boosting models for elective and emergency admissions, trained on the first two years of data and tested on the final year of data. We examined individual-level and hospital-level model performance and evaluated the impact of training data size and recency, prediction time, and performance in subgroups.

Results
Our models achieve AUROCs of 0.87 and 0.86, AUPRCs of 0.66 and 0.64, and F1 scores of 0.61 and 0.59 for elective and emergency admissions, respectively. These models outperform a logistic regression model using the same features and are substantially better than a baseline logistic regression model with more limited features. Notably, the relative performance increase from adding additional features is greater than the increase from using a sophisticated model. Aggregating individual probabilities, daily total discharge estimates are accurate with mean absolute errors of 8.9% (elective) and 4.9% (emergency). The most informative predictors include antibiotic prescriptions, medications, and hospital capacity factors. Performance remains robust across patient subgroups and different training strategies, but is lower in patients with longer admissions and those who died in hospital.

Conclusions
Our findings highlight the potential of machine learning in optimising hospital patient flow and facilitating patient care and recovery.
Cpx-signalling in Yersinia pseudotuberculosis modulates Lipid-A remodelling and resistance to last-resort antimicrobials
Authors: Gahlot Dharmender K. , Patkowski Jonasz B. , Fernández de Santaella Jaime , Allsopp Luke P. , Pan Zhiqiao , Filloux Alain , Larrouy-Maumus Gerald , Francis Matthew S. , Costa Tiago R. D. 
Published: November 2024

AbstractAntibiotic resistance is a global healthcare crisis. Bacteria are highly adaptable and can rapidly acquire mechanisms of resistance towards conventional antibiotics. The permeability barrier conferred by the Gram-negative bacteria cell envelope constitutes a first line of defence against the action of antibiotics. Exposure to extracytoplasmic stresses can negatively affect cell envelope homoeostasis and this causes localised protein misfolding, compromised envelope integrity and impairs barrier function. The CpxA-CpxR two-component regulatory system has evolved to sense extracytoplasmic stresses and to regulate processes that restore homoeostasis of the cell envelope. Hence, controlled Cpx-signalling assists bacteria in adapting, surviving and proliferating in harsh environments, including exposure to antibiotics. Herein, we determined that an intact Cpx-signalling is key to maintaining the Yersinia pseudotuberculosis resistance to colistin and polymyxin B. The susceptibility displayed by Cpx-signalling defective mutants, correlated with cell-envelope deformity and specific modifications of Lipid-A. In vivo transcriptional analysis and in vitro protein-DNA binding studies demonstrated that these modifications were dependent on the direct regulation of Lipid-A biogenesis and modifications of operons by the active phosphorylated CpxR~P isoform. Altogether, our work defines the regulatory mechanism that enables Cpx-signalling to actively control cell envelope remodelling and the permeability of antibiotics in the clinically relevant enteropathogen Y. pseudotuberculosis.
Interplay between the brain and adipose tissue: a metabolic conversation
Authors: Díaz-Castro Francisco , Morselli Eugenia , Claret Marc 
Published: November 2024

AbstractThe central nervous system and adipose tissue interact through complex communication. This bidirectional signaling regulates metabolic functions. The hypothalamus, a key homeostatic brain region, integrates exteroceptive and interoceptive signals to control appetite, energy expenditure, glucose, and lipid metabolism. This regulation is partly achieved via the nervous modulation of white (WAT) and brown (BAT) adipose tissue. In this review, we highlight the roles of sympathetic and parasympathetic innervation in regulating WAT and BAT activities, such as lipolysis and thermogenesis. Adipose tissue, in turn, plays a dual role as an energy reservoir and an endocrine organ, secreting hormones that influence brain function and metabolic health. In addition, this review focuses on recently uncovered communication pathways, including extracellular vesicles and neuro-mesenchymal units, which add new layers of regulation and complexity to the brain–adipose tissue interaction. Finally, we also examine the consequences of disrupted communication between the brain and adipose tissue in metabolic disorders like obesity and type-2 diabetes, emphasizing the potential for new therapeutic strategies targeting these pathways to improve metabolic health.
A special issue of Essays in Biochemistry on AMPK and AMPK-related kinases
Authors: Salt Ian P. , Carling David 
Published: November 2024

Abstract
In eukaryotic cells, AMP-activated protein kinase (AMPK) plays a central role in responding to nutrient limitation by switching-off ATP-consuming (anabolic) pathways and switching-on ATP generating (catabolic) pathways. Over the last 30 years or so, a considerable body of research has been carried out that has provided us with a wealth of knowledge regarding the regulation and role of AMPK. Despite this, there is still much to learn about AMPK and the field remains highly active, with many groups around the world continuing to explore new roles for AMPK, providing insight into its biological function. This review series was inspired by recent AMPK-focused meetings in Scotland (2022) and Australia (2023) and draws on some of the research presented at those meetings.