bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions of Telerehabilitation Among Patients Receiving Physical Therapy for Spine Pain
Authors: McLaughlin Kevin H. , Caan Olivia , Skolasky Richard L. 
Published: February 2025

AbstractImportanceTelerehabilitation was widely used during the COVID-19 pandemic to maintain access to physical therapy. However, its use has declined since the pandemic, potentially due to changes in patient demand.ObjectiveTo explore patients’ beliefs, attitudes, and preferences regarding telerehabilitation for spine pain treatment.DesignEmail or telephone administered survey.SettingOutpatient physical therapy network affiliated with an academic healthcare system.ParticipantsPatients recently evaluated for spine pain by a physical therapist (n=100).Main Outcomes and MeasuresSurvey items addressed patients’ perceptions of telerehabilitation effectiveness, preferences for care delivery, barriers to telerehabilitation, and factors influencing telerehabilitation use.ResultsPatients viewed telerehabilitation as effective for treating spine pain but not as effective as in-clinic physical therapy. Patients reported a preference for receiving care in-clinic care or using a hybrid model, rather than receiving care through telerehabilitation alone. Barriers to telerehabilitation included a lack of awareness of who offers telerehabilitation and uncertainty about its effectiveness. Patients indicated that evidence supporting telerehabilitation effectiveness would increase their likelihood of using telerehabilitation in the future. Patients also reported that transportation challenges or increased COVID-19 rates would encourage them to use telerehabilitation in the future.ConclusionsThe results of this survey suggest that patients with spine pain believe telerehabilitation may be an effective treatment approach, but they are skeptical about using telerehabilitation instead of in-clinic physical therapy. These results also suggest that patients are open to hybrid approaches that incorporate telerehabilitation, as well as using telerehabilitation if circumstances prevented them from receiving their care in-clinic. The largest patient concern surrounding telerehabilitation seems to be the lack of evidence supporting its effectiveness.RelevanceThis study suggests that patients believe telerehabilitation will continue to play an important role post-pandemic. However, comparative effectiveness research is needed to address patient concerns surrounding the effectiveness of telerehabilitation and guide informed decision-making.
DUNE: a versatile neuroimaging encoder captures brain complexity across three major diseases: cancer, dementia and schizophrenia
Authors: Barba Thomas , Bagley Bryce A. , Steyaert Sandra , Carrillo-Perez Francisco , Sadée Christoph , Iv Michael , Gevaert Olivier 
Published: February 2025

ABSTRACTMagnetic resonance images (MRI) of the brain exhibit high dimensionality that pose significant challenges for computational analysis. While models proposed for brain MRIs analyses yield encouraging results, the high complexity of neuroimaging data hinders generalizability and clinical application. We introduce DUNE, a neuroimaging-oriented encoder designed to extract deep-features from multisequence brain MRIs, thereby enabling their processing by basic machine learning algorithms. A UNet-based autoencoder was trained using 3,814 selected scans of morphologically normal (healthy volunteers) or abnormal (glioma patients) brains, to generate comprehensive low-dimensional representations of the full-sized images. To evaluate their quality, these embeddings were utilized to train machine learning models to predict a wide range of clinical variables. Embeddings were extracted for cohorts used for the model development (n=21,102 individuals), along with 3 additional independent cohorts (Alzheimer’s disease, schizophrenia and glioma cohorts, n=1,322 individuals), to evaluate the model’s generalization capabilities. The embeddings extracted from healthy volunteers’ scans could predict a broad spectrum of clinical parameters, including volumetry metrics, cardiovascular disease (AUROC=0.80) and alcohol consumption (AUROC=0.99), and more nuanced parameters such as the Alzheimer’s predisposing APOE4 allele (AUROC=0.67). Embeddings derived from the validation cohorts successfully predicted the diagnoses of Alzheimer’s dementia (AUROC=0.92) and schizophrenia (AUROC=0.64). Embeddings extracted from glioma scans successfully predicted survival (C-index=0.608) and IDH molecular status (AUROC=0.92), matching the performances of previous task-oriented models. DUNE efficiently represents clinically relevant patterns from full-size brain MRI scans across several disease areas, opening ways for innovative clinical applications in neurology.One Sentence SummaryWe propose a brain MRI-specialized encoder, which extracts versatile low-dimension embeddings from full-size scans.
Analysis of the current state of frailty indexes and their implementation for aging intervention studies
Authors: Frost Oliver G , Barkovskaya Anna , Rae Michael , Rebbaa Abdelhadi , Sharma Amit 
Published: February 2025

AbstractAnimal lifespan studies are foundational to developing interventions against the biological aging process. In recent years, there has been rising interest in characterizing the effects of longevity therapeutics on health span. Frailty indexes, originally developed to assess clinical frailty in aging humans, have shown promise as measurements of biological age and have been adopted for use in rodent aging biology. This perspective looks at the current state of rodent frailty indexes and how they are implemented. The differences in frailty parameters used to calculate these indexes have led to inconsistencies between studies defining frailty. In this perspective, we have highlighted those differences and made recommendations for implementing protocols for frailty index measurement.
Profiling brain morphology for autism spectrum disorder with two cross-culture large-scale consortia
Authors: Fan Xue-Ru , He Ye , Wang Yin-Shan , Li Lei ,   Lifespan Brain Chart Consortium (LBCC),   China Autism Brain Imaging Consortium (CABIC), Duan Xujun , Zuo Xi-Nian 
Published: February 2025

ABSTRACTWe explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative modeling of cross-cultural cohorts. Leveraging large-scale datasets from Autism Brain Imaging Data Exchange (ABIDE) and China Autism Brain Imaging Consortium (CABIC), the model identifies two ASD subgroups with distinct brain morphological abnormalities: subgroup "L" is characterized by generally smaller brain region volumes and higher rates of abnormality, while subgroup "H" exhibits larger volumes with less pronounced deviations in specific areas. Key areas, such as the isthmus cingulate and transverse temporal gyrus, were identified as critical for subgroup differentiation and ASD trait correlations. In subgroup H, the regional volume of the isthmus cingulate cortex showed a direct correlation with individuals’ autistic mannerisms, potentially corresponding to its slower post-peak volumetric declines during development. These findings offer insights into the biological mechanisms underlying ASD and support the advancement of subgroup-driven precision clinical practices.
Splanchnic and pelvic spinal afferent pathways relay sensory information from the mouse colorectum into distinct brainstem circuits
Authors: Wang QingQing , McGovern Alice E. , Kyloh Melinda , Rychkov Grigori , Spencer Nick J. , Mazzone Stuart B. , Brierley Stuart M. , Harrington Andrea M. 
Published: February 2025

AbstractThis study aimed to identify where the sensory information relayed by the two spinal afferent pathways innervating the distal colon and rectum (colorectum), the splanchnic and pelvic spinal afferent pathways, integrates within the brainstem. Localised injections of transneuronal viral tracer (herpes simplex virus H129 strain expressing EGFP (H129-EGFP)) into the distal colon was used to assess the brainstem structures receiving ascending input from the colorectum. H129-EGFP+ cells were distributed in structures involved in ascending sensory relay, descending pain modulation and autonomic regulation in the medulla from 96 hours and in pontine and caudal midbrain 120 hours after inoculation. In a separate cohort of mice,in vivonoxious colorectal distension (CRD) followed by brainstem immunolabelling for phosphorylated MAP kinase ERK 1/2 (pERK) showed that many of the structures in which H129-EGFP+ labelling was observed were relevant to colorectal sensory processing. Surgical removal of dorsal root ganglia (DRG) containing cell bodies of splanchnic colorectal afferent neurons, significantly reduced CRD evoked neuronal activation within the caudal ventrolateral medulla, rostral ventromedial medulla and the lateral parabrachial nuclei. Whilst, removal of DRG containing cell bodies of pelvic colorectal afferent neurons significantly reduced CRD evoked neuronal activation within the rostral ventromedial medulla, lateral parabrachial nuclei, the locus coeruleus, Barrington’s nucleus and periaqueductal gray. Collectively, this study showed that the two spinal afferent pathways innervating the colorectum differentially shape colorectal processing within the brainstem and provides new insight into their unique roles to mediating visceromotor responses and defecation associated with colorectal nociception.
Evaluation of the antioxidant activity of biologically-active compositions based on plant metabolites produced byin vitrocell cultures
Authors: Mikhailovna Fedorova Anastasia , Sergeevna Milentyeva Irina , Konstantinovna Asyakina Lyudmila , Yuryevich Prosekov Alexander 
Published: February 2025

AbstractFree radicals can cause oxidative stress in the body, which, in turn, leads to various diseases such as cardiovascular diseases, diabetes, Alzheimer’s disease, Parkinson’s disease, and others. To protect against the destructive effects of radicals, living organisms utilize antioxidants. One of the most important classes of antioxidants is polyphenols. The primary effect of polyphenols on the body is associated with their ability to capture and neutralize free radicals, as well as reactive oxygen and nitrogen species. This study focuses on investigating the antioxidant activity (AA) of polyphenols and their compositions based on rutin, quercetin, and trans-cinnamic acid, produced byin vitrocell cultures, with the aim of developing dietary supplements with geroprotective properties. The AA of the studied substances was assessed using the ABTS and DPPH free radical scavenging methods. The study established that, according to the ABTS method, AA decreases in the order of quercetin > rutin > trans-cinnamic acid, while according to the DPPH method, the order is rutin > quercetin > trans-cinnamic acid. Among the tested mixtures, the highest AA was observed in mixture No. 8 and mixture No. 3, regardless of the assessment method. Consequently, to achieve the highest AA in a mixture, a higher content of quercetin and a minimal amount of trans-cinnamic acid should be included, while the optimal amount of rutin could not be determined. It is assumed that the amount of rutin should be at least equal to the amount of trans-cinnamic acid and ideally equal to the amount of quercetin. Thus, when developing dietary supplements with high AA, it is more advisable to include only quercetin rather than mixtures that also contain rutin and trans-cinnamic acid.
NtLLG4-mediated unconventional polar exocytosis of NtPPME1 coordinates cell wall rigidity and membrane dynamics to control pollen tube integrity
Authors: Weng Xun , Wang Hao , Jiang Yifeng , Wang Ziheng , Liu Chuanhao , Chen Zhiheng , Yang Zhiyuan , Gao Jiayang , Jiang Liwen , Zhao Lifeng , Huang Jilei , Wang Hao 
Published: February 2025

AbstractPlant fertilization relies on controlled pollen tube growth that integrates membrane dynamics and cell wall expansion. We previously identified an unconventional exocytic pathway wherein Golgi-derived secretory vesicles (GDSVs) bypass thetrans-Golgi network to deliverNicotiana tabacumpectin methylesterase 1 (NtPPME1), thereby modulating cell wall rigidity. However, the mechanisms linking this patwhay with membrane dynamics and signaling remain elusive. Here, we used cryo-FIB-SEM and 3D tomography to identified GDSVs as a distinct vesicle population at the pollen tube tip. We further demonstrated that tobacco LORELEI-like-GPI-anchored protein 4 (NtLLG4), a key signaling molecule controlling membrane dynamics and integrity, functions as a receptor for NtPPME1, regulating its polar exocytosisviaGDSVs to control cell wall stiffness. Furthermore, we identified trafficking signals which direct the unconventional exocytosis of NtPPME1 across intracellular organelles. Our findings reveal a crucial mechanism coupling cell wall rigidity with membrane signaling to control pollen tube growth and integrity during fertilization.TeaserWe reveal a mechanism coupling cell wall rigidity with member signaling to control pollen tube growth and integrity during plant fertilization.
A novel expression system for imaging single-molecule fluorescence in Haloferax volcanii WR806 enables visualization of Cas1 involvement in UV-light associated DNA repair
Authors: Schrage Paula R , Afonina Uliana , Wörtz Julia , Marchfelder Anita , Martens Koen JA , Sáenz James P , Endesfelder Ulrike 
Published: February 2025

ABSTRACTFluorescence microscopy has become an indispensable tool in biological research, offering powerful approaches to study protein dynamics and molecular biochemistryin vivo. Among archaea,Haloferax volcaniihas emerged as a particularly well-suited model organism for imaging studies, with a growing toolkit of established fluorescent markers, plasmids, and promoter systems. Recent advances in single-molecule imaging techniques have created new opportunities through WR806, a carotenoid-free strain providing reduced autofluorescence background. However, existing plasmid-based expression systems in WR806 show critical limitations in protein expression control and challenges with protein aggregation.To address these limitations, we developed pUE001, a novel expression system specifically designed for WR806. This system achieves precise expression control by decoupling selection and induction through strategic implementation of thetrpAselection marker. Through comprehensive characterization, we demonstrate that pUE001 provides superior control over protein expression compared to the previously established pTA962 system. It enables linear, titratable expression of diverse proteins — from the highly regulated CRISPR-Cas component Cas1 to the abundant structural protein FtsZ1 — while preventing protein aggregation that could compromise native cellular functions. Additionally, we performed a comprehensive analysis of WR806 to show that carotenoid depletion does not affect native cellular physiology. Finally, to demonstrate the system’s utility, we investigated the role of Cas1 in UV-induced DNA repair using single-particle tracking photoactivated localization microscopy (sptPALM). Our findings reveal significant, dose-dependent changes in Cas1 mobility following UV-light induced damage, providing evidence for its involvement in DNA repair processes and offering new insights into the expanding roles of CRISPR-Cas systems beyond adaptive immunity.
Understanding bottlenecks in the microbial production of partially acetylated chitooligosaccharides
Authors: Snoeck Sofie , Malik Hamza , Demeester Wouter , Duchi Dries , Lips Wies , Guidi Chiara , De Mey Marjan 
Published: February 2025

AbstractChitooligosaccharides (COS) are versatile biomolecules with applications across food, pharmaceutical, and cosmetic industries. Expanding the COS portfolio, particularly with partially acetylated COS (paCOS) of defined degree and pattern of acetylation, is essential to unlocking their full potential. This study investigates the co-expression of chitin deacetylases (CDAs) with a chitooligosaccharide synthase (CHS)RhNodC inE. coliforin vivopaCOS production. While this approach shows promise, it is hampered by reduced overall (pa)COS yields and incomplete conversion of fully acetylated COS to paCOS. Our findings reveal thatRhNodC and CDAs co-localize, suggesting potential interactions that influence production efficiency. Additionally, CDA expression induces significant stress responses, including upregulation ofibpA andcpxP promoters linked to inclusion body formation and membrane stress, respectively. This is accompanied by pronounced cellular elongation, further indicating cellular distress. These bottlenecks highlight the need for deeper exploration ofRhNodC-CDA interactions and stress mitigation strategies to optimize scalablein vivopaCOS production.Highlights‒Co-expression of rhizobial NodC and chitin deacetylases reduces chitooligosaccharide yield.‒Conversion of COS into paCOS remains incomplete upon co-expression.‒Upregulation of stress responses suggests protein misfolding and membrane stress.‒NodC and chitin deacetylases possibly co-localize and affect cellular localization.‒Chitin deacetylase expression causes cell elongation up to 30 micrometers.‒Further study needed on rhizobial NodC-chitin deacetylase and substrate interactions.
Dengue virus susceptibility inAedes aegyptilinked to natural cytochrome P450 variants
Authors: Merkling Sarah H. , Couderc Elodie , Crist Anna B. , Dabo Stéphanie , Daron Josquin , Jupatanakul Natapong , Burckbuchler Myriam , Sismeiro Odile , Legendre Rachel , Pain Adrien , Varet Hugo , Jiolle Davy , Ayala Diego , Paupy Christophe , Marois Eric , Lambrechts Louis 
Published: February 2025

AbstractThe mosquitoAedes aegyptiis the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wildAe. aegyptipopulations is governed by genetic factors, but specific causal variants are unknown. Here, we identify a cytochrome P450-encoding gene (CYP4G15) whose variants drive differences in DENV susceptibility in a naturalAe. aegyptipopulation.CYP4G15is transiently upregulated in DENV-resistant midguts, while knockdown increases susceptibility, and transgenic overexpression enhances resistance. A naturally occurring 18-base-pair promoter deletion reducesCYP4G15expression and confers higher DENV susceptibility. The unexpected role of a cytochrome P450 in DENV susceptibility challenges the long-standing focus on canonical immune pathways and opens new avenues for understanding antiviral defense and DENV transmission in mosquitoes.
Endocytosis sculpts distinct cAMP signal transduction by endogenously coexpressed GPCRs
Authors: Blythe Emily E , Fagan Rita R , von Zastrow Mark 
Published: February 2025

AbstractMany G protein-coupled receptors (GPCRs) trigger a second phase of G protein-dependent signaling from internal membranes after agonist-induced endocytosis. However, individual GPCRs differ significantly in their ability to internalize, and it remains unclear if this confers selectivity on cellular signaling through natively coexpressed GPCRs. We addressed this question by examining the activation of the cyclic AMP (cAMP) / cAMP-dependent protein kinase (PKA) pathway by three ligands that stimulate three distinct, endogenously coexpressed GPCRs in HEK293 cells: isoproterenol (Iso) which primarily activates the β2-adrenergic receptor (β2AR), vasoactive intestinal peptide (VIP) which primarily activates the VIP receptor 1 (VIPR1/VPAC1), and 5’-N-ethylcarboxamidoadenosine (NECA) which primarily activates the adenosine 2B receptor (A2BR). Using location-targeted biosensors and a transcriptional reporter, we demonstrate that each ligand triggers a unique cellular signaling profile and that these responses are differentially sensitive to endocytic inhibition. VIP elicited a response that was endocytosis-dependent at every level in the pathway, from upstream global cAMP elevation to downstream activation of nuclear PKA, while Iso elicited a response that was dependent on endocytosis selectively at downstream steps. In contrast, NECA robustly activated the entire cAMP signaling cascade independently of endocytosis, consistent with our observation that human A2BR does not robustly internalize after activation. We conclude that endocytosis indeed sculpts downstream cAMP signaling by GPCRs in a receptor-specific manner. Our results add to the evolving view of compartmentalized signaling in the cAMP / PKA pathway and suggest that differences in GPCR trafficking can encode receptor-specific signaling profiles through a shared signal transduction pathway.
Additive manufacturing of patient-specific intracranial aneurysm cell culture models
Authors: de Nys Chloe M. , Murphy Ashley R. , Wood Jaimee-Lee , Novak James I. , Carluccio Danilo , Winter Craig D. , Allenby Mark C. 
Published: February 2025

AbstractIntracranial aneurysms (IAs) are present in 2-6% of the global population. While rare, rupture results in mortality rates of 30-50% and lifelong disabilities in survivors. While treatment of unruptured IAs carries its own risk of mortality, there are no rigid guidelines indicating which IA presentation is at greater risk of rupture. We develop and evaluate the suitability of various additive manufacturing processes to fabricate patient-specific IA culture models for understanding IA pathophysiology and thereby support future development of a rupture risk prediction tool.Material compatibility of several 3D printed resins, polydimethylsiloxane (PDMS) and collagen gel with immortalised human brain endothelial cells (HBECs) were investigated. Patient angiograms were segmented to producein vitromodels via two fabrication approaches: stereolithography (SLA) 3D printing versus chocolate injection moulding of a sacrificial core embedded in PDMS. These 3D arterial models were then cellularised with HBECs, and geometric accuracy and distension properties evaluated.PDMS, collagen gel and the elastic50A resin materials supported cellularisation on material surfaces with high cell viability and proliferation. Both the 3D printed resin and injection moulding techniques successfully fabricated patient-specific basilar artery IA models with a Dice-Sørensen coefficient of over 90%. However, only PDMS models offered complete cell coverage in 3D geometries. This exceeds current benchmarks on IA fabrication accuracy. Through controlling IA model wall thickness, we demonstrate the ability to create localised distension under pressure in the context of thin– and thick-walled aneurysms.In vitroIA models present a promising platform for investigating IA pathophysiology and rupture risk. The novel chocolate sacrificial core technique offers a biocompatible, support-free fabrication method suitable for 3D cultures. Given the independent effects of fluid dynamics and mechanical strain on cell behaviour, it is essential to characterise distension under pressure and ensure accurate fabrication for reliable analysis into cell behaviour.