bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and evaluation of a non-invasive brain-spine interface using transcutaneous spinal cord stimulation
Authors: Atkinson Carolyn , Lombardi Lorenzo , Lang Meredith , Keesey Rodolfo , Hawthorn Rachel , Seitz Zachary , Leuthardt Eric C. , Brunner Peter , Seáñez Ismael 
Published: September 2024

AbstractMotor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of lower limb movement in the sensorimotor cortex of unimpaired individuals and to quantify the performance of a linear discriminant analysis (LDA) decoder in detecting movement onset from these neural correlates. Our results show that initiation of knee extension was associated with event-related desynchronization in the central-medial cortical regions at frequency bands between 4-44 Hz. Our neural decoder using µ (8-12 Hz), low β (16-20 Hz), and high β (24-28 Hz) frequency bands achieved an average area under the curve (AUC) of 0.83 ± 0.06 s.d. (n = 7) during a cued movement task offline. Generalization to imagery and uncued movement tasks served as positive controls to verify robustness against movement artifacts and cue-related confounds, respectively. With the addition of real-time decoder-modulated tSCS, the neural decoder performed with an average AUC of 0.81 ± 0.05 s.d. (n = 9) on cued movement and 0.68 ± 0.12 s.d. (n = 9) on uncued movement. Our results suggest that the decrease in decoder performance in uncued movement may be due to differences in underlying cortical strategies between conditions. Furthermore, we explore alternative applications of the BSI system by testing neural decoders trained on uncued movement and imagery tasks. By developing a non-invasive BSI, tSCS can be timed to be delivered only during voluntary effort, which may have implications for improving rehabilitation.
Testicular sex cord–stromal tumors in mice with constitutive activation of PI3K and loss of Pten
Authors: Dinevska Marija , Mcaloney Lachlan , Widodo Samuel S. , Filiz Gulay , Anderson Jeremy , Dworkin Sebastian , Windley Simon P. , Wilhelm Dagmar , Mantamadiotis Theo 
Published: September 2024

AbstractTesticular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressorPten, targeted to nestin expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord–stromal Leydig cell tumors. Single cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+T-cells predominating. Further analysis showed that immune cells preferentially localize to or accumulate within stromal regions.Graphical Abstract
Density-Dependent Colour Scanning Electron Microscopy (DDC-SEM). Applications in the study of calcified tissues and visual impact
Authors: Tsolaki Elena , Hunter Luke , Chester Adrian H , Bertazzo Sergio 
Published: September 2024

AbstractScanning Electron Microscopy (SEM) is widely used as a technique for materials characterization. It has also been successfully applied to the imaging of biological samples, providing invaluable insights into the topography, morphology and composition of biological structures. A particular method combining different SEM detectors, named Density-Dependent Coloured SEM (DDC-SEM), has proven to be most useful for the identification and visualization of minerals in soft tissues. The method consists of a manipulation of original greyscale SEM images to produce coloured images that provide both topography and density information for samples with components of different densities. Here we provide a discussion on how to use DDC-SEM to aid the visualization and intuitive understanding of pathological calcification. This method has become popular not only for its scientific improvement of conventional SEM greyscale images, but also for its aesthetical merits.Lay summaryScanning Electron Microscopes (SEM) are widely used tools for examining biological materials such as human tissue. Like other electron microscopes, it only produces images in greyscale. SEM has been useful, for instance, in improving our understanding of calcific diseases. These diseases involve the build-up of mineral in the body’s soft tissues, and frequently affect the heart, kidneys, or eyes. This work provides a discussion on using a SEM technique known as Density-Dependent Colour Scanning Electron Microscopy (DDC-SEM), which enhances SEM images through scanning the same area with different detectors, assigning a unique colour to each detector’s output, and then overlaying these images.
Localization of Albumin with Correlative Super Resolution Light- and Electron Microscopy in the Kidney
Authors: Birtasu Alexandra N. , Ermel Utz H. , Rahm Johanna V. , Seybert Anja , Flottmann Benjamin , Heilemann Mike , Grahammer Florian , Frangakis Achilleas S. 
Published: September 2024

AbstractThe functioning of vertebrate life relies on renal filtration of surplus fluid and elimination of low-molecular-weight waste products, while keeping serum proteins in the blood. In disease, however, there is leak of serum proteins and tracing them to identify the leaking position within tissue with a nanometer resolution poses a significant challenge. Correlative microscopy integrates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Using chemical tagging of albumin with synthetic fluorophores we achieve protein-specific labeling that preserve their post-embedding fluorescence after high-pressure freezing and freeze-substitution of murine kidney tissue. Using advanced registration techniques for super-resolution correlative light and electron microscopy, we can localize the labeled albumin with a high precision in the x-y plane of electron micrographs and cartograph its distribution. Thereby we can quantify the albumin concentration and measure a linear reduction gradient across the kidney filtration barrier. Our study shows the feasibility of combining different microscopy contrasts for tracing fluorescently labeled protein markers with super resolution in various tissue samples and opens new perspectives for correlative imaging in volume electron microscopy.
Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma
Authors: Herrero Alba Díaz , Pelaez-Prestel Hector Fernando , Massenet-Regad Lucile , Veyssiere Maëva , Calvani Julien , Cristinelli Caterina , Lehmann-Che Jacqueline , Meignin Véronique , Thieblemont Catherine , Blanc Véronique , Soumelis Vassili , Tonnerre Pierre 
Published: September 2024

SummaryDiffuse Large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin’s lymphoma for which current therapeutic strategies remain insufficient. The diffuse nature of DLBCL, lacking distinct tissue structures, represents a challenge to elucidate the cellular organization and interactions within the tumor microenvironment (TME). In this study, we applied spatial transcriptomics to identify spatially-resolved gene expression profiles in 10 DLBCL tissue samples, identifying distinct immune cell infiltration and colocalization patterns. These profiles were classified into six cellular ecosystems (Cell-Eco) that differ in cellular composition, functional patterns, and neighborhood characteristics. The spatially-resolved Cell-Eco signatures provided prognostic scores that stratified patients with different overall survival rates. We also found that C1q+ tumor-associated macrophages are the primary cells interacting with malignant B cells and influencing the spatial architecture of the TME. This study provides novel biological insights into the complexity of the TME in DLBCL and highlights the potential prognostic value of its spatial organization.Graphical abstractKey findingsSpatial transcriptomics classifies DLBCL tissues based on immune cell infiltration and colocalization patterns.DLBCL tumor microenvironment consists of cellular ecosystems (Cell-Eco) that differ in cellular composition, transcriptomic profiles and neighborhood characteristics.Spatially-resolved Cell-Eco signatures stratify patients with different overall survival.C1q+ tumor-associated macrophages primarily interact with malignant B cells and contribute to the spatial organization of the tumor microenvironment.
Peristaltic pump-triggered amyloid formation suggests shear stresses arein vivorisk factors of amyloid nucleation
Authors: Goto Yuji , Ota Tomoki , Yuan Wenlou , Yumen Ikuko , Yamaguchi Keiichi , Matsuda Hirokazu , Yamamoto Suguru , Ogi Hirotsugu 
Published: September 2024

AbstractAmyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed linked with the breakdown of supersaturation, causing a series of amyloidosis including Alzheimer’s and Parkinson’s diseases. Although varyingin vitrofactors are known,in vivofactors breaking supersaturation are unclear. We found that flowing by a peristaltic pump effectively triggers amyloid formation of hen egg white lysozyme, a model amyloidogenic protein, and, moreover, amyloidosis-associated proteins (i.e. α-synuclein, amyloid β 1-40, and β2-microglobulin). The peristaltic pump-dependent amyloid formation was visualized by a fluorescence microscope with looped flow system, revealing dynamic motions under flow. Among them, amyloid fibrils of amyloid β 1-40 were stickier than others, self-associating, absorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, β2-microglobulin at a neutral pH showed unique two-step amyloid formation with an oligomeric trapped intermediate, which might mimic amyloid formation in patients. Peristalsis-caused strong shear stresses were considered to mechanically break supersaturation. Shearing stresses occur in vivoat varying levels, suggesting that they break otherwise persistent supersaturation, thus triggering amyloid formation and ultimately leading to amyloidosis. (182 words <200 words)
What influences non-menstruator attitudes and behaviours towards menstruation among Rohingya refugees in Bangladesh? A quantitative analysis
Authors: Hales Georgia , Hutchings Paul , Roelich Katy , Das Mahua , Akram Nowshad , Begum Shajeda , Sultana Zahida 
Published: September 2024

AbstractNon-menstruators play an important yet overlooked role in shaping menstrual health. They may be the family budget holders who purchase menstrual materials, receive health information outside the household, or preserve social stigmas. In response, World Vision, supported by UNICEF, implemented a programme to influence non-menstruators among the Rohingya population living in Kutupalong refugee camp, Bangladesh. The intention was to ensure non-menstruators recognise their important role in supporting family members to improve their menstrual health. We evaluated this intervention using a baseline and endline survey of 150 participants based on the Risk-Attitudes-Norms-Ability-Self-regulation (RANAS) approach to behaviour change. Based on the responses, we categorised participants into ‘doers’ and ‘non-doers’ of positive behaviours. We then performed multiple linear regression analyses and ANOVA comparison of means tests to understand how psychosocial and contextual factors influence the population’s attitudes and behaviours towards menstruation before and after intervention. The regression analyses showed eight psychosocial and contextual factors that had a significant relationship with the desired behaviours. These were the block they lived in, marital status, already having learnt about menstruation from World Vision, how they were introduced to menstruation, who they discuss menstruation with, family members’ reaction, perceptions of their role, and their commitment. Additionally, the ANOVA comparison of means between doers and non-doers showed doers were more likely to be confident to carry out the behaviour, perceive their role as important, and discuss menstruation with family. They were also more likely to be married, older, and have first learnt about menstruation from their family. This is the first study to identify which psychosocial and contextual factors significantly influence positive non-menstruator attitudes and conducive behaviours towards menstruation and menstruators. Humanitarian organisations can use these factors to improve the design and targeting of behaviour change programmes to improve menstrual health.HighlightsMenstrual health is often limited in refugee settingsNon-menstruators can enable and constrain menstrual healthMenstrual health intervention among Rohingya refugees shows positive change in non-menstruator behaviourBehavioural determinants for non-menstruators related to marriage, commitment, and family reaction‘Doers’ more likely to be confident, perceive role as important, and discuss menstruation with family
Biomarkers of atrial fibrillation-related pathways and left atrial structure and function in an overweight and obese population
Authors: Li Linzi , Romaguera Dora , Alonso-Gómez Angel M. , Toledo Estefanía , Shah Amit J. , Mora Marta Noris , Tojal-Sierra Lucas , Martinez-Gonzalez Miguel Angel , Mas-Llado Caterina , Razquin Cristina , Estruch Ramón , Fitó Montserrat , Alonso Alvaro 
Published: September 2024

AbstractBackgroundExploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis.MethodsWe studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models.ResultsThe participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years.ConclusionIn an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.
Development and validation of a 5-year risk model using mammogram risk scores generated from screening digital breast tomosynthesis
Authors: Jiang Shu , Bennett Debbie L. , Colditz Graham A. 
Published: September 2024

ABSTRACTScreening digital breast tomosynthesis (DBT) aims to identify breast cancer early when treatment is most effective leading to reduced mortality. In addition to early detection, the information contained within DBT images may also inform subsequent risk stratification and guide risk-reducing management. We obtained a 5-year area under the curve (AUC) = 0.78 (95% confidence interval (CI) = 0.75 – 0.80) in the internal validation. The model validated in external data (n=6,553 women; AUC = 0.77 (95% CI, 0.74 – 0.80). There was no change in the AUC when age and BI-RADS density are added to the synthetic DBT image. The model significantly outperforms the Tyrer-Cuzick model (p<0.01). Our model extends risk prediction applications to synthetic DBT, provides 5-year risk estimates, and is readily calibrated to national risk strata for clinical translation and application in the setting of US risk management guidelines. The model could be implemented within any digital mammography program.One Sentence SummaryWe develop and externally validate a 5-year risk prediction model for breast cancer using synthetic digital breast tomosynthesis and demonstrate clinical utility by calibrating to the national risk strata.
Reactogenicity and immunogenicity against MPXV of the intradermal administration of Modified Vaccinia Ankara compared to the standard subcutaneous route
Authors: Mazzotta Valentina , Piselli Pierluca , Lepri Alessandro Cozzi , Matusali Giulia , Cimini Eleonora , Esvan Rozenn , Colavita Francesca , Gagliardini Roberta , Notari Stefania , Oliva Alessandra , Meschi Silvia , Casetti Rita , Micheli Giulia , Bordi Licia , Giacinta Alessandro , Grassi Germana , Tekle Saba Gebremeskel , Cimaglia Claudia , Paulicelli Jessica , Caioli Alessandro , Gallì Paola , Duca Giulia Del , Lichtner Miriam , Sarmati Loredana , Tamburrini Enrica , Mastroianni Claudio , Latini Alessandra , Faccendini Paolo , Fontana Carla , Nicastri Emauele , Siddu Andrea , Barca Alessandra , Vaia Francesco , Girardi Enrico , Maggi Fabrizio , Antinori Andrea ,   MPOX Vaccine Lazio Study Group
Published: September 2024

AbstractThe recent resurgence of Mpox in central Africa has been declared again a Public Health Emergency of International Concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine’s need exceeds the currently available doses. Intradermal administration of one-fifth of the standard Modified-Vaccinia-Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC. Studies conducted before 2022 provided evidence about the humoral response against the Vaccinia virus (VACV) after vaccination but not against the Mpox virus (MPXV). Moreover, no data are available on the T-cell response elicited by MVA-BN administered subcutaneously or intradermally. Here, we compare the two vaccine administration routes according to reactogenicity and immunogenicity based on data from 943 vaccine recipients during the 2022 vaccination campaign in Rome, Italy. We found that the intradermal route elicited slightly higher titers of MPXV-specific IgG and nAbs than the subcutaneous one. At the same time, no differences in cellular response were detected. MVA-BN was globally well tolerated despite higher reactogenicity for the intradermal than the subcutaneous route, especially for the reactions at the local injection site. The intradermal dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people.
De novovariant analysis of childhood-onset obsessive-compulsive disorder in the French-Canadian population
Authors: Bornais Kate , Ross Jay P. , Schmilovich Zoe , Medeiros Miranda , Spiegelman Dan , Boileau Bernard , Marier Jean-Jacques , Laurin Ghislain , Dion Patrick A. , Rouleau Guy A. 
Published: September 2024

AbstractChildhood-onset obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with a strong genetic component.De novovariants (DNVs) have been shown to have a role in childhood-onset OCD, but to date, no DNV analysis has been performed in patients from a genetically isolated population. Here, we aimed to investigate the impact of rarede novosingle nucleotide variants (dnSNVs) on childhood-onset OCD risk in the French-Canadian population. In a cohort of 36 French-Canadian trios comprised of 36 probands with childhood-onset OCD and 72 unaffected parents, we identified 34 dnSNVs harboured in 34 different genes. We found that four of these genes were previously associated with OCD, replicating their contribution to its risk. We also observed complete overlap between our 34 candidate genes and genes associated with 11 related neuropsychiatric disorders, supporting a shared underlying genetic susceptibility across psychopathologies. Among genes harbouring DNVs across three childhood-onset OCD cohorts, we observed an overrepresentation of genes involved in clathrin-dependent endocytosis (GO:0072583;p-adj= 0.0498) and phosphatidylinositol binding (GO:0035091;p-adj= 0.0431), offering potential biological mechanisms underlying childhood-onset OCD. No association was found between the number of dnSNVs in childhood-onset OCD probands and OCD symptom severity. Altogether, this study offers a framework for performing DNV analyses of complex disorders in genetically isolated populations. We have provided the first list of candidate childhood-onset OCD genes in the French-Canadian population.
Pre-chronic kidney disease -- Serial creatinine tracks glomerular filtration rate decline above 60 mL/min
Authors: Burke Cyril O. , Toffaletti John G. , Burke Leanne M. , Tanzer Joshua Ray 
Published: September 2024

ABSTRACTOBJECTIVESTo allow primary clinicians to detect early decline in glomerular filtration rates above 60 milliliters per minute, before stage-three chronic kidney disease.METHODSWe re-examine a standard reference that found low tubular secretion of creatinine at glomerular filtration rates above 80 milliliters per minute and suggested “observation of subtle changes in serum creatinine levels”. We explain why that method extends to the 80 to 60 milliliters per minute range by(1)fitting a hyperbolic curve,(2)expanding the Y-axis (to reflect accuracy of modern creatinine assays), and(3)showing reasonable continuity down to 60 milliliters per minute. We summarize why equations estimating glomerular filtration rate are unsuitable above 60 milliliters per minute.RESULTSFour patient cases show how serum creatinine referenced to an individual’s historical maximum can suggest increased risk, triggering investigation to separate benign processes that alter serum creatinine from true decline in glomerular filtration rate of prechronic kidney disease.CONCLUSIONSAt glomerular filtration rates above 60 milliliters per minute, serial creatinine is more reliable than estimating equations and appears practical for clinical monitoring and early intervention.STRENGTHS OF THIS STUDYIncludes serial creatinine proof-of-concept cases that show preCKDReviews properties that favor serial creatinine for early kidney diseaseAddresses mathematical limitations of GFR estimating equationsRe-analyzes a 40-year-old standard reference that still influences research, showing its overlooked importance for early kidney diagnosis