bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trajectories of blood-based protein biomarkers in chronic traumatic brain injury
Authors: Hicks Amelia J. , Plourde Jay , Selmanovic Enna , de Souza Nicola L. , Blennow Kaj , Zetterberg Henrik , Dams-O’Connor Kristen 
Published: February 2025

AbstractBlood-based protein biomarkers may provide important insights into the long-term neuropathology of traumatic brain injury (TBI). This is urgently required to identify mechanistic processes underlying post-traumatic neurodegeneration (PTND); a progressive post-recovery clinical decline experienced by a portion of TBI survivors. The aim of this study was to examine change over time in protein levels in a chronic TBI cohort. We selected six markers (Aβ42/Aβ40, GFAP, NfL, BD-tau, p-tau231, and p-tau181) with known importance in acute TBI and/or other neurodegenerative conditions.We used a longitudinal design with two time points approximately 3.5 years apart on average (SD 1.34). Proteins were measured in plasma using the ultrasensitive Single molecule array technology for 63 participants with mild to severe chronic TBI (sustained ≥ 1 year ago; M 28 years; SD 16.3 since their first blow to the head) from the Late Effects of TBI study (48% female; current age M 52 years; SD 13.4). Multivariate linear mixed effect models with adjustments for multiple comparisons were performed to examine trajectories in proteins over time with age and age squared as covariates. A series of sensitivity analyses were conducted to account for outliers and to explore effects of key covariates: sex,APOEε4 carrier status, medical comorbidities, age at first blow to the head, time since first blow to the head, and injury severity.Over an average of 3.5 years, there were significant reductions in plasma Aβ42/Aβ40(β = −0.004, SE = 0.001, t = −3.75, q = .001) and significant increases in plasma GFAP (β = 12.96, SE = 4.41, t = 2.94, q = .01). There were no significant changes in NFL, BD-tau, p-tau231, or p-tau181.Both plasma Aβ42/Aβ40and GFAP have been associated with brain amyloidosis, suggesting a role for Aβ mis-metabolism and aggregation in the long-term neuropathological consequences of TBI. These findings are hypothesis generating for future studies exploring the diverse biological mechanisms of PTND.
Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation
Authors: Gokhale Avanti , Mendez-Vazquez Hadassah , Sampson Maureen M. , Moctezuma Felix G Rivera , Harbuzariu Adriana , Sing Anson , Zlatic Stephanie A. , Roberts Anne M. , Prajapati Milankumar , Roberts Blaine R. , Bartnikas Thomas B. , Wood Levi B. , Sloan Steven A. , Faundez Victor , Werner Erica 
Published: February 2025

AbstractManganese (Mn) is an essential trace element required for various biological functions, but excessive Mn levels are neurotoxic and lead to significant health concerns. The mechanisms underlying Mn-induced neurotoxicity remain poorly understood. Neuropathological studies of affected brain regions reveal astrogliosis, and neuronal loss, along with evidence of neuroinflammation. Here, we present a novel Mn-dependent mechanism linking mitochondrial dysfunction to neuroinflammation. We found that Mn disrupts mitochondrial transcriptome processing, resulting in the accumulation of complementary RNAs that form double-stranded RNA (dsRNA). This dsRNA is released to the cytoplasm, where it activates cytosolic sensor pathways, triggering type I interferon responses and inflammatory cytokine production. This mechanism is present in 100-day human cerebral organoids, where Mn-induced inflammatory responses are observed predominantly in mature astrocytes. Similar effects were observed in vivo in a mouse model carrying mutations in the SLC30A10 gene, which results in Mn accumulation. These findings highlight a previously unrecognized role for mitochondrial dsRNA in Mn-induced neuroinflammation and provide insights into the molecular basis of manganism. We propose that this mitochondrial dsRNA-induced inflammatory pathway has broad implications in for neurodegenerative diseases caused by environmental or genetic insults.
Characterisation of CD4 Th subsets as well as dietary, exercise and lifestyle factors in an established Rheumatoid Arthritis cohort; pilot study
Authors: Venkataraman Shweta , D’Cunha Nathan , Kozlovskaia Maria , Naumovski Nenad , McKune Andrew , Bruestle Anne , Xu Tony , Marie Julien C , Hernandez-Vargas Hector , Raj Anna Dorai , Tsai Ted , Pyne David B. , Goldsmith Chloe 
Published: February 2025

AbstractBackgroundSex disparities in the incidence and severity of Rheumatoid Arthritis (RA) are well-documented, with females experiencing more aggressive disease and different responses to treatment. While underlying mechanisms remain elusive, immune factors and lifestyle components, such as diet and physical activity, could play a role in shaping disease outcomes. Since Th cells are key drivers of RA, this study characterised CD4 Th subset frequencies, including Th1, Th2, Th17 and Th1/17 cells, in a cohort of males and females with established RA. Considering the role of diet and lifestyle in RA development, we also evaluated participant diet and lifestyle patterns.MethodsAn observational cross-sectional cohort study profiling 39 individuals (19 RA and 20 age and sex matched controls) with no major co-morbidities was conducted. Percentages of Th1, Th2, Th17 and Th1/17 cells from peripheral blood were determined by flow cytometry as well as serum levels of RF and cytokines IL17α, IFN-γ, TNF-α, GM-CSF, TGF-β, IL-6, and CRP by ELISA. Dietary intake was assessed by Food Frequency Questionnaire (FFQ), the Dietary inflammatory Index (DII) calculated from nutrient intake. Physical activity levels were evaluated by Global Physical Activity Questionnaire (GPAQ).ResultsSex-specific differences of Th17, Th1 an Th2 cells were observed in RA groups. Males had lower levels of Th1 cells and higher levels of Th17 cells than control subjects, while females had lower levels of Th2 cells than controls. Female RA subjects had higher ratio of Th1:Th2 cells than controls, while male RA subjects had higher Th17:Th1 ratio than controls. Interestingly, circulating CD4 Th subset levels were predictive of RA in this cohort. No changes in cytokine levels were observed. The male RA group consumed 30% less carbohydrate (RA = 156g +/-57g, Control = 253g +/-59g;p=0.003), 37% less sugar (RA = 74.1g +/-29g, Control = 118g +/-33g;p=0.004) and 30% less dietary fibre (R = 33g +/-8g, Control = 48g +/-13 g;p=0.008) than the male control group. The female RA group had the lowest consumption of alcohol in comparison to female control group (RA = 0.31g, Control = 8.97g;p=0.047). Male subjects had a 4x higher DII than females (p=0.012).ConclusionsOur findings highlight potential sex-specific differences in CD4+ Th cell subsets in individuals with established RA, indicating that sex may influence immune cell composition in this disease. Furthermore, dietary components showed sex-specific consumption patterns, underscoring the potential role of tailored lifestyle interventions in modulating immune responses in RA. Evaluating immunological sex differences and dietary and lifestyle factors may be important for enhancing management strategies in RA.
Inertial interface cavitation creates complex, flow-like structures within a soft solid
Authors: Yang Jin , McGhee Alexander , Tong Zixiang , Radtke Griffin , Rodriguez Mauro , Franck Christian 
Published: February 2025

Inertial interface cavitation is a well-appreciated phenomenon in many natural, biological, and physical processes. The existence of impedance changes across an interface can generate complex fluid motion within a fluid but whether such motion persists, or is similar, within the adjacent solid has yet to be determined. Here, by leveraging recent technological advances in quantitative full-field imaging, deformation/motion characterization, and laser-based cavitation, we document the complex deformation fields that arise in a model soft solid of gelatin during interfacial cavitation. Specifically, we identify stagnation points, vortex pairs, and vortex ring-like structures as a function of the cavitation bubble standoff distance within the solid, for which we identify four distinct regimes. While two of the regimes have been previously studied, we show that the additional two regimes close to the interface generate most of the complex, fluid-like deformations within the gel. Finally, we quantify the associated material stresses and residual, permanent strains that can occur during such events providing both length and time scale estimates of the destructive power of cavitation.Significance StatementThe study of interfacial cavitation dynamics has historically focused on resolving cavitation bubble morphology and surface deformations due to an inability to measure subsurface behavior. However, understanding the intricate dynamics of cavitation at these interfaces and below holds significant implications for engineering, medical, and life science applications. Leveraging recent technological advances, we provide the first, full-field sub-surface measurements during interfacial cavitation revealing complex, flow-like structures such as dynamically-evolving stagnation points and vortex pairs. Our results also provide insight into the unusual stresses and strains generated by the violent collapse of interfacial cavitation bubbles within the soft solid. These measurements provide an important first step in understanding how certain species in nature harness this power whereas others aim to mitigate it.
Targeted knockdown ofin vitrocandidates does not alterWolbachiadensityin vivo
Authors: Dainty Kimberley R. , Duyvestyn Johanna M. , Flores Heather A. 
Published: February 2025

AbstractThe bacterial endosymbiontWolbachiahas emerged as an effective biocontrol method to reduce arbovirus transmission. Transinfection ofwMelWolbachiafromDrosophila melanogastertoAedes aegyptiresults in the transfer of importantWolbachia-induced phenotypes including the reproductive modification, cytoplasmic incompatibility, and inhibition of viruses including dengue and chikungunya. However, the mechanisms underlying these critical traits as well otherWolbachia-host interactions are still not fully understood. Recently anin vitrogenome wide RNAi screen was performed onwMel-infected Drosophila S2 cells and identified large cohorts of host genes that alterwMel density when targeted. If these findings can be replicatedin vivo, this would provide a powerful tool for modulatingwMel density both systemically and in a tissue-specific manner allowing for interrogation ofwMel-host interactions. Here, we used the GAL4/UAS system to express RNAi molecules targeting host gene candidates previously identified to dysregulatewMel densityin vitro. We found systemic knockdown of two candidateD. melanogastergenes does not lead towMel density dysregulation. To explore the lack of consistency between our study and previous work, we also examined native tissue-specific density ofwMel inD. melanogaster. We show density is varied between tissues and find that individual tissue densities are not reliable linear predictors of other tissue densities. Our results demonstrate the complexities of implementingin vitrofindings in systemic applications.
Neural-physics adaptive reconstruction reveals 3D subcellular nanostructures over a large depth of field
Authors: Fu Shuang , Shi Wei , Fei Yue , Wang Ruixiong , Zhang Tianlun , Li Yiming 
Published: February 2025

AbstractAchieving large depth-of-field super-resolution imaging deep inside samples is often hindered by unknown aberrations and overlapping molecular signals in 3D single-molecule localization microscopy. Here, we present LUNAR, a blind localization method that simultaneously resolves overlapping molecular signals and corrects for aberrations using a neural-physics model. Through self-supervised learning on single-molecule data without requiring prior knowledge or accurate calibration, LUNAR synergistically optimizes a physical model with a neural network to estimate key physical parameters (e.g., 3D positions, photons, aberrations) of molecules. Its hybrid Transformer network effectively handles PSFs of varying sizes, achieving theoretically maximum localization precision of consecutive blinking events. Extensive simulations and experiments demonstrate that LUNAR consistently outperforms current state-of-the-art methods, reducing localization error by up to sixfold in the presence of unknown aberrations and molecular overlaps, enabling high-fidelity whole-cell reconstruction of mitochondria, nucleus, and neuronal cytoskeleton at great depths.
Deciphering the Genetic Architecture of Parkinson’s Disease in India
Authors: Kishore Asha , Ashok Kumar Sreelatha Ashwin , Tenghe Amabel M. M. , Borgohain Rupam , Puthanveedu Divya Kalikavil , Rajan Roopa , Urulangodi Madhusoodanan , Gonzalez-Ricardo Luis-Giraldo , Pal Pramod Kumar , Kandadai Rukmini Mridula , Khodaee Saeideh , Yadav Ravi , Mehta Sahil , Kumar Hrishikesh , Kumar Niraj , Kukkle Prashanth Lingappa , Desai Soaham Dilip , Shetty Kuldeep , Wadia Pettarusp , Aggarwal Annu , Agarwal Pankaj , Abbas Mirza Masoom , Wali Gurusideshwar Mahadevappa , Krishnan Syam , Radhakrishnan Divya Madathiparambil , Kamble Nitish , Srivastava Achal Kumar , Lal Vivek , Ferreira Teresa Maria Costa , Chacko Manas , Raghavan Cibin Thoppil , Sarma Gangadhara , Solle Justin , Fiske Brian , Thalakkatttu Amiya , Garg Divyani , Krüger Jens , Lichtner Peter , Vitale Dan , Nalls Mike , Blauwendraat Cornelis , Singleton Andy , Debnath Monojit , Sarkar Swagata , Ansari Sabbir , Adukia Sachin , Vidyadharan Pravi , Kanthimathi R , Santhi CKV , Syed Tazeem Fathima , Mohareer Sindhuja ,   Global Parkinson’s Genetics program (GP2),   Lux-GIANT consortium, Sharma Manu 
Published: February 2025

AbstractThe genomic landscape of the Indian population, particularly for age-related disorders like Parkinson’s disease (PD) remains underrepresented in global research. Genetic variability in PD has been studied predominantly in European populations, offering limited insights into its role within the Indian population. To address this gap, we conducted the first pan-India genomic survey of PD involving 4,806 cases and 6,364 controls, complemented by a meta-analysis integrating summary statistics from a multi-ancestry PD meta-analysis (N=611,485). We further leveraged RNA-sequencing data from lymphoblastoid cell lines of 731 individuals from the 1000 Genomes project to evaluate the expression of key loci across global populations. Our findings reveal a higher genetic burden of PD in the Indian population compared to Europeans, accounting for ∼30% of the previously unexplained heritability. Thirteen genome-wide significant loci were identified, including two novel loci, with an additional three loci uncovered through meta-analysis. Polygenic risk score analysis showed moderate transferability from European populations. Our results highlight the importance of genetic loci in immune function, lipid metabolism andSNCAaggregation in PD pathogenesis, with gene expression variability emphasizing population-specific differences. We also established South Asia’s largest PD biobank, providing a foundation for patient-centric approaches to PD research and treatment in India.
Acute plasma VEGF-A levels are associated with raised intracranial pressure and chronic lesion volume after Traumatic Brain Injury
Authors: Li Lucia M. , Kodosaki Eleftheria , Heslegrave Amanda , Soreq Eyal , Nattino Giovanni , Garbero Elena , Zimmerman Karl A. , Graham Neil S.N. , Moro Federico , Novelli Deborah , Gradisek Primoz , Magnoni Sandra , Zetterberg Henrik , Bertolini Guido , Sharp David J 
Published: February 2025

AbstractBackground and ObjectivesSevere Traumatic Brain Injury (TBI) is associated with secondary injury and poor outcomes, but the underlying mechanisms are poorly understood. Vascular mechanisms may be important. We aimed to characterise how blood vascular endothelial growth factor A (VEGF-A) levels are affected by TBI, and its associations with secondary injury and functional outcome.MethodsWe retrospectively analysed data from two multi-centre, international, prospective observational studies (CREACTIVE and BIO-AX-TBI) with follow-up of up to 1 year. These cohorts comprised adults with moderate-severe TBI (Mayo classification), recruited on admission to hospital (BIO-AX-TBI) and the intensive care unit (ICU) (CREACTIVE). Controls included non-TBI trauma (NTT) and uninjured adults. Plasma VEGF-A levels and TBI biomarkers (Neurofilament light [NFL], glial fibrillary acidic protein [GFAP], total Tau, UCH-L1, S100B) were measured on ICU admission and ∼5 days later (CREACTIVE), or at 5 timepoints from admission to 12 months post-TBI (BIO-AX-TBI), and compared to NTT and control groups. In BIO-AX-TBI, MRI assessment was performed at subacute and chronic timepoints. Functional outcomes (Glasgow Outcome Scale-Extended) were measured at 6 and 12 months. Plasma VEGF-A was measured using the OLINK® Target 96 Inflammatory platform, which reports in arbitrary standardised units (NPX), and TBI biomarkers were measured using Simoa® or Millipore platforms.ResultsData was available from 195 TBI (21% female, mean age 45.30years), 24 NTT (8%, 43.98) and 89 CON (44%, 42.39) in BIO-AX-TBI, and 1146 TBI (25%, 56.29) in CREACTIVE. Plasma VEGF-A was elevated acutely after both TBI (estimated mean difference=0.45NPX, SE=0.09, p<0.001) and NTT (estimated mean difference=0.74NPX, SE=0.16, p<0.001), but remained raised after the initial timepoint only in TBI patients, peaking at day 16. Higher acute VEGF-A was associated with increased odds of refractory raised intracranial pressure (r-rICP) (maximum Odds Ratio for r-rICP=1.69, p=0.031), higher lesion volume (estimated increased lesion volume=20.14ml, SE=8.20ml, p=0.02), and worse functional outcomes (maximum Odds Ratio for worse outcome category=2.51, p<0.001).DiscussionThere is a sustained rise in plasma VEGF-A after TBI, which is associated with r-rICP and chronic injury markers, suggesting vascular pathophysiology is important after TBI. Further research is needed to explore mechanisms.
Longitudinal Validation of a Deep Learning Index for Aortic Stenosis Progression
Authors: Park Jiesuck , Kim Jiyeon , Yoon Yeonyee E. , Jeon Jaeik , Lee Seung-Ah , Choi Hong-Mi , Hwang In-Chang , Cho Goo-Yeong , Chang Hyuk-Jae , Park Jae-Hyeong 
Published: February 2025

ABSTRACTAimsAortic stenosis (AS) is a progressive disease requiring timely monitoring and intervention. Transthoracic echocardiography (TTE) remains the gold standard for AS assessment, while deep learning (DL)-based approaches have emerged as promising tools for enhanced evaluation. This study examined the longitudinal changes in a previously developed DL-derived index for AS continuum (DLi-ASc) and its association with AS progression. Additionally, we evaluated its utility in identifying high-risk patients prone to progression to severe AS.Methods and ResultsA total of 2,563 patients with follow-up TTE (8,053 TTEs) from two tertiary hospitals were included. DLi-ASc, generated from limited TTE views, was tracked over time. The longitudinal trends in AS severity showed a progressive shift toward advanced stages, with a corresponding increase in DLi-ASc (p for trend <0.001). DLi-ASc demonstrated positive correlations with conventional AS parameters, including AV maximal velocity (Vmax) (Pearson correlation coefficients [PCC] = 0.68) and mean pressure gradient (mPG) (PCC = 0.69). Higher baseline DLi-ASc was associated with a faster AS progression rate (p for trend <0.001). Furthermore, baseline DLi-ASc was an independent predictor of progression to severe AS, with area under the curve (AUC) values of 0.92, 0.88, and 0.87 within 1-, 2-, and 3-year follow-up windows, respectively. A DLi-ASc threshold of 50 was identified as a threshold for rapid progression to severe AS.ConclusionDLi-ASc increased in parallel with AS progression and independently predicted severe AS progression. These findings support its role as a non-invasive imaging-based digital marker for longitudinal AS monitoring and risk stratification.
Cefazolin versus Antistaphylococcal Penicillins for the Treatment of Methicillin-SusceptibleStaphylococcus aureusBacteremia: A Systematic Review and Meta-Analysis
Authors: Prosty Connor , Noutsios Dean , Lee Todd C. , Daneman Nick , Davis Joshua S. , Jager Nynke G. L. , Ghanem-Zoubi Nesrin , Goodman Anna L. , Kaasch Achim J. , Kouijzer Ilse , McMullan Brendan J. , McDonald Emily G. , Tong Steven Y. C. , Ong Sean W. X. ,   the Staphylococcus aureus Network Adaptive Platform MSSA/PSSA domain specific working group
Published: February 2025

ABSTRACTBackgroundThere is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptibleStaphylococcus aureus(MSSA) bacteremia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings would apply to other antistaphylococcal penicillins.ObjectiveWe conducted a systematic review and meta-analysis comparing cefazolin to each of the individual antistaphylococcal penicillins for MSSA bacteremia.MethodsData SourcesWe updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins.Study Eligibility CriteriaComparative observational studies.ParticipantsPatients with MSSA bacteremia.InterventionsCefazolin versus the antistaphylococcal penicillins.Assessment of Risk of BiasThe risk of bias in non-randomized studies of interventions tool.Methods of Data SynthesisThe primary outcome was 30-day all-cause mortality, and we assessed for non-inferiority of cefazolin using a prespecified non-inferiority margin of a pooled odds ratio (OR) <1.2. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity.ResultsNo randomized data have been published. 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11644 patients who received antistaphylococcal penicillins (flucloxacillin=6721, unspecified=2440, nafcillin=1305, cloxacillin=1258, and oxacillin=120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR=0.73, 95%CI=0.62-0.85) compared to antistaphylococcal penicillins, meeting pre-specified non-inferiority as well as superiority. This effect was consistent versus flucloxacillin (OR=0.92, 95%CI=0.73-1.16), nafcillin (OR=0.58, 95%CI=0.28-1.17), cloxacillin (OR=0.42, 95%CI=0.11-1.58), and oxacillin (OR=0.31, 95%CI=0.03-2.75). Point estimates favored cefazolin for 90-day mortality, TRAEs, nephrotoxicity, and discontinuation due to toxicity overall and in each comparison with individual antistaphylococcal penicillins, except for TRAEs versus cloxacillin.ConclusionsIn moderate to low quality observational data, cefazolin was associated with superior effectiveness and safety as compared to antistaphylococcal penicillins overall and individually.