bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging Language Gaps in Neurology Patient Education Through Large Language Models: a Comparative Analysis of ChatGPT, Gemini, and Claude
Authors: Haq Mahdi , Ur Rehman Muhammad Mushhood , Derhab Mohamed , Saeed Reeda , Kalia Junaid 
Published: September 2024

AbstractThis study evaluates the capability to translate neurology patient education material using three Large Language Models (LLMs) - ChatGPT-4 Omni, Gemini 1.5 Pro, and Claude 3.5 Sonnet. Five neurological conditions (Bell’s palsy, multiple sclerosis, stroke, migraine, and epilepsy) were translated from English into Spanish, Urdu, and Arabic. The translations were assessed by physicians using four metrics: accuracy, clarity, comprehensiveness, and readability at a 6th grade level. Results showed that Claude outperformed both ChatGPT and Gemini overall, particularly excelling in Spanish and Urdu translations, while Gemini led in Arabic. All LLMs demonstrated superior performance in Spanish compared to Urdu and Arabic. This study highlights the potential of LLMs in enhancing patient education across languages, while also identifying areas for improvement in translation accuracy and readability.
An integrative modelling approach to the mitochondrial cristae
Authors: Brown Chelsea M. , Westendorp Marieke S. S. , Zarmiento-Garcia Rubi , Stevens Jan A. , Rouse Sarah L. , Marrink Siewert J. , Wassenaar Tsjerk A. 
Published: September 2024

AbstractMitochondria are implicated in many cellular functions such as energy production and apoptosis but also disease pathogenesis. To effectively perform these roles, the mitochondrial inner membrane has invaginations known as cristae that dramatically increase the surface area. This works to provide more space for membrane proteins that are essential to the roles of mitochondria. While separate components of this have been studied computationally, it remains a challenge to combine elements into an overall model. Here we present a workflow to create a comprehensive model of a crista junction from a human mitochondrion. Our coarse-grained representation of a crista shows how various experimentally determined features of organelles can be combined with molecular modelling to give insights into the interactions and dynamics of complicated biological systems. This work is presented as an initial ‘living’ model for this system, intended to be built upon and improved as our understanding, methodology and resources develop.
SGLT2 inhibitors protect against diabetic cardiomyopathy and atrial fibrillation through a CaMKII independent mechanism
Authors: Severino Alex , Reyes-Gaido Oscar E , Nguyen Pauline , Elkarim Ahmed , Luczak Elizabeth D , Mesubi Olurotimi O. 
Published: September 2024

AbstractCa2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated as an important mediator of the increasingly evident cardioprotective benefits exerted by sodium– glucose transport protein 2 channel inhibitors (SGLT2i). However, the exact nature of the relationship between CaMKII and SGLT2i remains unclear. Here, we find that empagliflozin but not dapagliflozin attenuated susceptibility to atrial fibrillation (AF) in a type 2 diabetic (T2D) mouse model. However, both empagliflozin and dapagliflozin protected from diabetic cardiomyopathy in T2D mice. We then used real-time microscopy of neonatal rat ventricular cardiomyocytes (NRVMs) with the CaMKII biosensor - CaMKAR to demonstrate that direct inhibition of CaMKII is not essential for the effects of SGLT2i in these cells. Therefore, we conclude that the benefits of SGLT2i in heart disease likely occur through indirect modulation of CaMKII activity, or possibly through an alternative pathway altogether.
Hepatic aldose reductase drives a Warburg effect-like metabolic reprogramming to promote insulin resistance, fatty liver and obesity
Authors: Song Dan , Yang Dianqiang , Wen Longping , Zheng Feng , Yang James Y. 
Published: September 2024

Background & AimsEmerging evidence suggest that abnormal activation of aldose reductase/the polyol pathway (Ar/PP) is associated with the pathogenesis or development of fatty liver, obesity and metabolic syndrome. However, the underlying mechanisms were unclear. In this study, we investigated the metabolic reprogramming following activation or inhibition of Ar, the first and the rate-limiting enzyme of PP. We also investigated the long-term effects of Ar/PP-mediated metabolic shiftin vivo.MethodsMetabolomic analyses were performed with the AB-SCIE QTRAP-5500 LC-MS/MS System for control mouse hepatocytes and hepatocytes stably overexpressing Ar and exposed to 25 mM glucose. Glycolysis stress tests and mitochondrial stress tests were performed using the Seahorse Bioscience Extracellular Flux Analyzer. Thein vivolong-term effects of Ar overexpression and inhibition were evaluated in either transgenic mice overexpressing AR or a line of double transgenic mice carrying an Ar-null mutation and an Agouti-yellowAymutation.ResultsAbnormal activation of Ar in hepatocytes was found to trigger and drive a drastic Warburg effect-like metabolic reprogramming, inducede novolipogenesis, and alter insulin and AMP-activated protein kinase signaling. In glucose-fedAR-overexpressing transgenic mice, AR activation causes systemic alterations in physiological parameters and the development of overt phenotypes of insulin resistance, fatty liver, obesity. In the yellow obese syndrome mice,Ardeficiency greatly improvesAgouti Aymutation-induced abnormalities.ConclusionsCollectively, the results highlight the important contribution of Ar/PP or the putative pseudo-glycolysis in hepatic metabolic homeostasis and the development of metabolic diseases. These findings have profound implications for the development of therapeutic strategies or drugs against metabolic diseases and cancer.GRAPHICAL ABSTRACTHighlightsActivation of aldose reductase triggers and drives a Warburg effect-like metabolic eprogramming in hepatocytes.Liver-specific activation of the polyol pathway leads to insulin resistance, fatty liver and obesity.Inhibition of aldose reductase greatly amelioratesAgouti Ay-induced metabolic abnormalities.Impact and implicationsThis study reveals that abnormal activation of Ar/PP will trigger and drive a Warburg effect-like metabolic reprogramming in hepatocytes. In normal subjects, Ar/PP mediated metabolic reprogramming tends to promote lipogenesis, insulin resistance, fatty liver and obesity. In cancer cells, Ar/PP mediated metabolic reprogramming will be part of the Warburg effect to support the growth and proliferation of cancer cells. These findings imply that Ar and its down-stream metabolic enzymes are important therapeutic targets for cancers and metabolic diseases.
The exopolysaccharide Poly-N-Acetyl-Glucosamine (PNAG) coatsKlebsiella pneumoniae in vivo
Authors: Bradshaw Jonathan , Sanchez-Garrido Julia , Berkachy Rita , Rattle Jaie , Preston Connor , Pizza Mariagrazia , Ros Immaculada Margarit , Romano Maria Rosaria , Wong Joshua L.C. , Frankel Gad 
Published: September 2024

AbstractThe conserved bacterial polysaccharide Poly-N-Acetyl-Glucosamine (PNAG) is a potential broad-spectrum vaccine candidate. While the immunogenicity of PNAG-based vaccine candidates has been established, characterisation of PNAG production across clinically relevant bacteria remains largely unknown. In particular, PNAG production in the Gram-negative pathogenKlebsiella pneumoniae(KP) is not well understood. Here, we demonstrate that PNAG production is prevalent in clinical KP isolates, where it is secreted as extracellular networks during adherent growth conditions. However, during severe KP pulmonary infection, KP PNAG production undergoes a switch to a cell-associated phenotype, coating the bacterial cell surface. By screening a panel of isogenic KP mutants in prominent cell surface components (ΔwcaJ,ΔrmpADC,Δrfb,ΔompAandΔompk36), we identified KP capsular polysaccharide as a key determinant underpinning the phenotype. Deleting genes involved in capsule synthesis (ΔwcaJ) and regulation (ΔrmpADC) resulted in cell-associated PNAG during adherent growth and infection of alveolar epithelial cellsin vitro. Taken together, we describe a novel interaction between KP surface polysaccharides and detect for the first time, cell-associated PNAG in KP during lung infection, highlighting PNAG as an attractive KP vaccine antigen.Author summaryThe Gram-negative pathogenKlebsiella pneumoniae(KP) is a leading cause of hospital-associated lung and bloodstream infections worldwide. As KP exhibits resistance to most frontline antibiotics, there is a growing demand for immune-based strategies to treat KP infections. Poly-N-Acetyl-Glucosamine (PNAG) is a surface sugar produced by most clinically relevant bacteria, including KP. However, relatively little is known about PNAG production in KP. Therefore, we set out to characterise PNAG production in KP during in vitro growth and following lung infection in a pulmonary mouse model. Duringin vitrogrowth, KP produces extracellular PNAG networks. In contrast, during anin vivosevere lung infection, PNAG is found cell-associated, coating the bacterial surface. We propose that the visible change in KP PNAG betweenin vitroandin vivoenvironments is due to crosstalk with capsule, another polysaccharide on the KP surface. Together, this supports PNAG as an attractive KP antigen.
AI-Augmented R-Group Exploration in Medicinal Chemistry
Authors: Zhao Hongtao , Kwapień Karolina , Nittinger Eva , Tyrchan Christian , Nilsson Magnus , Berglund Susanne , Czechtizky Werngard 
Published: September 2024

ABSTRACTEfficient R-group exploration in the vast chemical space, enabled by increasingly available building blocks or generative AI, remains an open challenge. Here, we developed an enhanced Free-Wilson QSAR model embedding R-groups by atom-centric pharmacophoric features. Regioisomers of R-groups can be distinguished by explicitly accounting for the atomic positions. Good predictivity is observed consistently across 12 public datasets. Integrated into an open-source program, we showcase its application in performing classic Free-Wilson analysis as well as R-group exploration in uncharted chemical space.
Dense but not alpha granules of platelets are required for insulin secretion from pancreatic β cells
Authors: Kolczyńska-Matysiak Katarzyna , Karwen Till , Loeffler Mona , Hawro Izabela , Kassouf Toufic , Stegner David , Sumara Grzegorz 
Published: September 2024

ABSTRACTObjectivesPlatelets, originally described for their role in blood coagulation, are now also recognized as key players in modulating inflammation, tissue regeneration, angiogenesis, and carcinogenesis. Recent evidence suggests that platelets also influence insulin secretion from pancreatic β cells. The multifaceted functions of platelets are mediated by the factors stored in their alpha granules (AGs) and dense granules (DGs). AGs primarily contain proteins, while DGs are rich in small molecules, and both types of granules are released during blood coagulation. Specific components stored in AGs and DGs are implicated in various inflammatory, regenerative, and tumorigenic processes. However, the relative contributions of AGs and DGs to the regulation of pancreatic β cell function have not been previously explored.MethodsIn this study, we utilized mouse models deficient in AG content (neurobeachin-like 2 (Nbeal2) -deficient mice) and models with defective DG release (Unc13d-deficiency in bone marrow-derived cells) to investigate the impact of platelet granules on insulin secretion from pancreatic β cells.ResultsOur findings indicate that AG deficiency has little to no effect on pancreatic β cell function and glucose homeostasis. Conversely, mice with defective DG release exhibited glucose intolerance and reduced insulin secretion. Furthermore,Unc13d-deficiency in hematopoietic stem cells led to a reduction in adipose tissue gain in obese mice.ConclusionsObtained data suggest that DGs, but not AGs, mediate the influence of platelets on pancreatic β cells, thereby modulating glucose metabolism.
Production of the sesquiterpene bisabolene from one-carbon compounds in an engineeredMethanosarcina acetivorans
Authors: Mentrup Andrea , Scheitz Luca V. , Wallenfang Theo , Rother Michael 
Published: September 2024

AbstractThe isoprenoid bisabolene, one of the simplest monocyclic sesquiterpenes, is a natural plant product that, in addition to its biological function, serves as a precursor for many industrial products. Due to the low concentration of bisabolene and the long harvest cycle, industrial production of this isoprenoid in plants is economically challenging. Chemical synthesis of bisabolene also suffers from significant disadvantages, such as low yields, toxic side products and high costs. Archaea appear suitable producers of isoprenoids, as their membrane lipids consist of isoprenoid ethers, which are synthesized via a variant of the mevalonate pathway. Archaeal model species have versatile metabolic capacities, which makes them suitable candidates for biotechnological applications. Here, we engineeredMethanosarcina acetivoransfor production of α-bisabolene from one-carbon substrates by introducing a bisabolene synthase fromAbies grandis. Expression of a codon-optimized bisabolene synthase gene in aM. acetivoranswild-type strain resulted in 10.6 mg bisabolene/ liter of culture. Overexpressing genes of the mevalonate pathway only slightly increased bisabolene yields, which, however, were reached much earlier during incubations than in the corresponding wild-type strain. The data presented argue for the suitability ofM. acetivoransfor the biotechnical production of certain isoprenoids.
CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair
Authors: Li Feng , Zhang Tianpeng , Syed Aleem , Elbakry Amira , Holmer Noella , Nguyen Huy , Mukkavalli Sirisha , Greenberg Roger A. , D’Andrea Alan D. 
Published: September 2024

ABSTRACTThe CHAMP1 complex, a little-known but highly conserved protein complex consisting of CHAMP1, POGZ, and HP1α, is enriched in heterochromatin though its cellular function in these regions of the genome remain unknown. Here we show that the CHAMP complex promotes heterochromatin assembly at multiple chromosomal sites, including centromeres and telomeres, and promotes homology-directed repair (HDR) of DNA double strand breaks (DSBs) in these regions. The CHAMP1 complex is also required for heterochromatin assembly and DSB repair in highly-specialized chromosomal regions, such as the highly-compacted telomeres of ALT (Alternative Lengthening of Telomeres) positive tumor cells. Moreover, the CHAMP1 complex binds and recruits the writer methyltransferase SETDB1 to heterochromatin regions of the genome and is required for efficient DSB repair at these sites. Importantly, peripheral blood lymphocytes from individuals with CHAMP1 syndrome, an inherited neurologic disorder resulting from heterozygous mutations inCHAMP1, also exhibit defective heterochromatin clustering and defective repair of local DSBs, suggesting that a defect in DNA repair underlies this syndrome. Taken together, the CHAMP1 complex has a novel role in heterochromatin assembly and the enhancement of HDR in heterochromatin.
Insights into Health Data Science Education: A Qualitative Content Analysis
Authors: Rohani Narjes , Gallagher Michael , Gal Kobi , Manataki Areti 
Published: September 2024

AbstractBackgroundEarly career researchers in Health Data Science (HDS) struggle to effectively manage their learning process due to the novel and interdisciplinary nature of this field. To date, there is limited understanding about learning strategies in health data science. Therefore, we aim to uncover learning strategies that early career researchers employ to address their educational challenges, as well as shed light on their preferences regarding HDS teaching approach and course design.MethodIn this study, we conducted a qualitative content analysis through semistructured interviews with ten early career researchers, including individuals pursuing master’s, PhD, and postdoctoral research programmes in HDS, across two higher education institutions in the United Kingdom. Interviews were carried out in person from June 2023 to August 2023. Data were analysed qualitatively using NVivo software. Descriptive statistics were employed for quantitative analysis.ResultsRegarding learning strategies, we identified ten main categories with 22 codes, including collaboration, information seeking, active learning, focus granularity, elaboration, organisation, order granularity, goal orientation, reviewing, and deep learning strategies. Regarding course design and teaching, we discovered four categories with 14 codes, including course materials, duration and complexity, online discussion, and teaching approaches.ConclusionsEarly career researchers used a range of learning strategies aligned with well-established learning theories, such as peer learning, information seeking, and active learning. It is also evident that learners in HDS favour interactive courses that provide them with hands-on experience and interactive discussion. The insights derived from our findings can enhance the quality of education in HDS.
Auditory decision-making deficits after permanent noise-induced hearing loss
Authors: Berns Madeline P. , Nunez Genesis M. , Zhang Xingeng , Chavan Anindita , Zemlianova Klavdia , Mowery Todd M. , Yao Justin D. 
Published: September 2024

AbstractLoud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we tested whether a specific sensory deficit, NIHL, can directly impair auditory cognitive function. Gerbils were trained to perform an auditory decision-making task that involves discriminating between slow and fast presentation rates of amplitude-modulated (AM) noise. Decision-making task performance was assessed across pre-versus post-NIHL sessions within the same gerbils. A single exposure session (2 hours) to loud broadband noise (120 dB SPL) produced permanent NIHL with elevated threshold shifts in auditory brainstem responses (ABRs). Following NIHL, decision-making task performance was tested at sensation levels comparable to those prior to noise exposure in all animals. Our findings demonstrate NIHL diminished perceptual acuity, reduced attentional focus, altered choice bias, and slowed down evidence accumulation speed. Finally, video-tracking analysis of motor behavior during task performance demonstrates that NIHL can impact sensory-guided decision-based motor execution. Together, these results suggest that NIHL impairs the sensory, cognitive, and motor factors that support auditory decision-making.
Deconvolving organogenesis in space and time via spatial transcriptomics in thick tissues
Authors: Asami Soichiro , Yin Chenshuo , Garza Luis A. , Kalhor Reza 
Published: September 2024

AbstractOrgan development is guided by a space-time landscape that constraints cell behavior. This landscape is challenging to characterize for the hair follicle – the most abundant mini organ – due to its complex microscopic structure and asynchronous development. We developed 3DEEP, a tissue clearing and spatial transcriptomic strategy for characterizing tissue blocks up to 400 µm in thickness. We captured 371 hair follicles at different stages of organogenesis in 1 mm3of skin of a 12-hour-old mouse with 6 million transcripts from 81 genes. From this single time point, we deconvoluted follicles by age based on whole-organ molecular pseudotimes to animate a stop-motion 3D atlas of follicle development along its trajectory. We defined molecular stages for hair follicle organogenesis and characterized the order of emergence for its structures, differential signaling dynamics at its top and bottom, morphogen shifts preceding and accompanying structural changes, and series of structural changes leading to the formation of its canal and opening. We further found that hair follicle stem cells and their niche are established and stratified early in organogenesis, before the formation of the hair bulb. Overall, this work demonstrates the power of increased depth of spatial transcriptomics to provide a four-dimensional analysis of organogenesis.
Embodied processing in whisker somatosensory cortex during exploratory behaviour in freely moving mice
Authors: Gantar Luka , Burgess Matthew A. , Mansour Neveen , Rusco-Portabella Joaquín , Námešná Alžbeta , Gill David , Harris Isabella , Orlowska-Feuer Patrycja , Ebrahimi Aghileh S. , Storchi Riccardo , Petersen Rasmus S. 
Published: September 2024

AbstractSensory systems have evolved to solve computational challenges that animals face during behaviour in their natural environments. To illuminate how sensory cortex operates under such conditions, we investigated the function of neurons in whisker-related Somatosensory Cortex (wS1) of freely moving mice, engaged in tactile exploratory behaviour. By recording neural activity from wS1 whilst tracking the mouse body in 3D, we found that wS1 neurons are substantially modulated by body state (configuration of individual body-parts and their derivatives), even in the absence of whisker afferent input. Most neurons were modulated by multiple dimensions of body state, with the most prominently encoded being the angle of the head to the body and locomotion speed. Overall, our data suggest that sensory cortex functions as an embodied representation, which integrates signals from its associated sense organ within a body schema.