bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis
Authors: Jiang Tianshi , Zhu Kaili , Kang Guangli , Wu Guojun , Wang Lili , Tan Yurong 
Published: June 2024

AbstractGlobal attention is riveted on neurodegenerative diseases due to their unresolved aetiologies and lack of efficacious therapies. Two key factors implicated include mitochondrial impairment and microglial ageing. Several viral infections, including Herpes simplex virus‐1 (HSV‐1), human immunodeficiency virus (HIV) and Epstein‐Barr virus, are linked to heightened risk of these disorders. Surprisingly, numerous studies indicate viruses induce these aforementioned precipitating events. Epstein‐Barr virus, Hepatitis C Virus, HIV, respiratory syncytial virus, HSV‐1, Japanese Encephalitis Virus, Zika virus and Enterovirus 71 specifically impact mitochondrial function, leading to mitochondrial malfunction. These vital organelles govern various cell activities and, under specific circumstances, trigger microglial ageing. This article explores the role of viral infections in elucidating the pathogenesis of neurodegenerative ailments. Various viruses instigate microglial ageing via mitochondrial destruction, causing senescent microglia to exhibit activated behaviour, thereby inducing neuroinflammation and contributing to neurodegeneration.
Astrovirus induced nonpurulent encephalomyelitis in sheep: First report from Türkiye by high‐throughput sequencing
Authors: Eroksuz Yesari , Timurkan Mehmet Ozkan , Shams Farzane , Seuberlich Torsten , Karabulut Burak , Incili Canan Akdeniz , Kara Emel , Eroksuz Hatice 
Published: June 2024

AbstractBackgroundThis study presents the case of non‐purulent encephalomyelitis associated with astrovirus infection in a sheep from Eastern Anatolia, Türkiye.MethodsA necropsy was performed on a sheep showing nervous signs. Afterwards, brain tissue samples were taken and examined with histopathological, immunohistochemical and molecular techniques.ResultsNeuropathologic changes included neuronal degeneration, diffuse gliosis, multifocal perivascular cuffing, neuronophagy and neuronal necrosis in the cerebrum, the cerebellum and the cervical spinal cord. Aerobic and anaerobic bacterial culture, selective culture for Listeria monocytogenes, and PCR analysis for rabies virus, tick‐borne encephalitis virus, Türkiye encephalitis virus, small ruminant lentiviruses and border disease virus were negative. However, the presence of astrovirus RNA in cerebral, cerebellar and spinal cord samples was demonstrated by a pan‐astrovirus RT‐PCR. Immunohistochemical examinations revealed astrovirus antigens within the neuronal cytoplasm. High‐throughput sequencing techniques identified the causative agent as a member of the genotype species Mamastrovirus 13 but representing a distinct genetic lineage with similarity to ovine astrovirus 1 in the open‐reading frames (ORF)1ab region and muskox astrovirus in the ORF2 region.ConclusionThis report provides evidence that astroviruses are potentially encephalitis‐causing pathogens in ovine populations in Türkiye, featuring an astrovirus strain distinct from those previously identified in sheep.
NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype
Authors: Muela-Zarzuela Inés , Suarez-Rivero Juan Miguel , Gallardo-Orihuela Andrea , Wang Chun , Izawa Kumi , de Gregorio-Procopio Marta , Couillin Isabelle , Ryffel Bernhard , Kitaura Jiro , Sanz Alberto , von Zglinicki Thomas , Mbalaviele Gabriel , Cordero Mario D. 
Published: June 2024

Abstract
Background
Senescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as senescence-associated secretory phenotype (SASP), some of which are produced by the NLRP3 inflammasome. Here, we present evidence that the NLRP1 inflammasome is a DNA damage sensor and a key mediator of senescence.

Methods
Senescence was induced in fibroblasts in vitro and in mice. Cellular senescence was assessed by Western blot analysis of several proteins, including p16, p21, p53, and SASP factors, released in the culture media or serum. Inflammasome components, including NLRP1, NLRP3 and GSDMD were knocked out or silenced using siRNAs.

Results
In vitro and in vivo results suggest that the NLRP1 inflammasome promotes senescence by regulating the expression of p16, p21, p53, and SASP factors in a Gasdermin D (GSDMD)-dependent manner. Mechanistically, the NLRP1 inflammasome is activated in response to genomic damage detected by the cytosolic DNA sensor cGMP-AMP (cGAMP) synthase (cGAS).

Conclusion
Our findings show that NLRP1 is a cGAS-dependent DNA damage sensor during senescence and a mediator of SASP release through GSDMD. This study advances the knowledge on the biology of the NLRP1 inflammasome and highlights this pathway as a potential pharmcological target to modulate senescence.
Eigenvalue Estimates on Weighted Manifolds
Authors: Branding Volker , Habib Georges 
Published: June 2024

AbstractWe derive various eigenvalue estimates for the Hodge Laplacian acting on differential forms on weighted Riemannian manifolds. Our estimates unify and extend various results from the literature and provide a number of geometric applications. In particular, we derive an inequality which relates the eigenvalues of the Jacobi operator for f-minimal hypersurfaces and the spectrum of the Hodge Laplacian.
Effects of different LED light curing units on the degree of conversion and microhardness of different composites: FT-IR and SEM-EDX analysis
Authors: Bilge Kübra , İpek İrem 
Published: June 2024

AbstractThe aim of this study was to evaluate the degree of conversion (DC), Vickers microhardness (VHN), main components and surface properties of a microhybrid and two bulk-fill composite resins polymerized with second and third generation light emitting diodes (LED). Sixty cylindrical specimens of Filtek™ Bulk-Fill, everX Posterior (bulk technique) and Filtek Z250 (incremental technique) were prepared in plexiglass molds (5 mm in diameter and 4 mm in thickness) and cured with second-generation LED (Woodpecker LED.B) and third-generation LED (Valo) resulting in six groups (n = 10). DC was determined using Fourier transform infrared spectroscopy (FT-IR), and VHN with Vickers microhardness tester. The main components were identified by means of energy-dispersive X-ray spectroscopy (EDX) microanalysis; whereas filler particles and surface properties were analyzed by scanning electron microscopy (SEM). VHN and DC data were analyzed using two-way ANOVA, followed by t-test with Bonferroni correction for pairwise comparison (p < 0.05). When DC and VHN values were evaluated, after polymerization with second and third generation LED, there was a statistical difference in bulk-fill composites, while there was no statistical difference in microhybrid composite. While, the highest DC and VHN values were obtained after polymerization of Filtek Z250 with Valo, the lowest DC and VHN values were obtained with Filtek Bulk-Fill with Woodpecker LED.B. The degree of conversion and microhardness are affected by the structure of the composite resin and LEDs.
Not every knee tumour is a ganglion - retrospective analysis of benign and malign tumour entities around the knee
Authors: Behrendt Peter , Grunow T , K-H Frosch , Krause M , Fahlbusch H , Priemel M 
Published: June 2024

Abstract
Background
Due to a lack of routine, there is often uncertainty regarding diagnostics of tumours around the knee joint. This study aimed to provide knowledge about the frequency, distribution and diagnostic algorithm of different bone and soft tissue tumour entities of the knee at a large referral university hospital in Germany.

Methods
Retrospective, longitudinal, single-centre study that reviewed adult patients from 2010 until 2020 with a suspected tumours diagnosis around the knee at a university cancer centre. Inclusion criteria were adults with true bone or soft-tissue tumours in the knee joint and in its adjacent compartments. Suspected diagnosis, histological tumour entity, localization and its surgical treatment by biopsy, resection, osteosynthesis or tumour endoprosthesis were investigated.

Results
A total number of 310 adult patients were included with a mean age of 54.2 ± 18.8 years. In total 160 (51.6%) soft-tissue tumours (69/43.1% benign; 74/46.2% malignant; 17/10.6% intermediate), 92 (29.6%) primary bone tumours (46/50% benign; 39/42.3% malignant; 7/7.6% intermediate), 36 (11.6%) metastases and 22 (7.1%) lymphomas were detected. 171 (55.1%) tumours were classified as malignant. Suspected diagnosis was matched with histology in 74.5% (231/310) of all cases. In 6 cases a primarily suspected benign diagnosis turned out to be malignant. The majority of primary bone tumours was cartilage derived (63.1%;58/92) and located in the distal 2/3 of the femur, whereas intracapsular tumours of the knee joint were rare (13.0%). Soft-tissue tumours were located primarily in the middle third of the thigh (36.8%). The MRI was the diagnostic tool of choice in 98.1% of soft tissue tumours and 82.6% bone tumours.

Conclusion
Awareness is crucial for detecting rare and malignant tumours around the knee, with adipocytic tumours being the most common soft tissue tumour and chondrogenic tumours as the most prevalent malignant bone tumour. Accurate diagnosis of bone tumours necessitates radiographs and frequently an additional MRI scan, while soft tissue tumours require mandatory MRI scans. Incorrectly diagnosing a tumour can have severe consequences, emphasizing the need for histological confirmation in all cases. Additionally, malignant tumours within joint capsules in adults are infrequent.
An MRI evaluation of white matter involvement in paradigmatic forms of spastic ataxia: results from the multi-center PROSPAX study
Authors: Scaravilli Alessandra , Gabusi Ilaria , Mari Gaia , Battocchio Matteo , Bosticardo Sara , Schiavi Simona , Bender Benjamin , Kessler Christoph , Brais Bernard , La Piana Roberta , van de Warrenburg Bart P. , Cosottini Mirco , Timmann Dagmar ,   PROSPAX Consortium, Daducci Alessandro , Schüle Rebecca , Synofzik Matthis , Santorelli Filippo Maria , Cocozza Sirio 
Published: June 2024

Abstract
Background
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia Type 7 (SPG7) are paradigmatic spastic ataxias (SPAX) with suggested white matter (WM) involvement. Aim of this work was to thoroughly disentangle the degree of WM involvement in these conditions, evaluating both macrostructure and microstructure via the analysis of diffusion MRI (dMRI) data.

Material and methods
In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA). Differences in terms of WM volume or global microstructural WM metrics were probed, as well as the possible occurrence of a spatially defined microstructural WM involvement via voxel-wise analyses, and its correlation with patients’ clinical status.

Results
Data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years), 37 SPG7 (M/F = 24/13; 55.7 ± 10.7 years), and 29 HC (M/F = 13/16; 42.1 ± 17.2 years) were analyzed. While in SPG7, only a mild mean microstructural damage was found compared to HC, ARSACS patients present a severe WM involvement, with a reduced global volume (p < 0.001), an alteration of all microstructural metrics (all with p < 0.001), without a spatially defined pattern of damage but with a prominent involvement of commissural fibers. Finally, in ARSACS, a correlation between microstructural damage and SARA scores was found (p = 0.004).

Conclusion
In ARSACS, but not SPG7 patients, we observed a complex and multi-faced involvement of brain WM, with a clinically meaningful widespread loss of axonal and dendritic integrity, secondary demyelination and, overall, a reduction in cellularity and volume.
Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis
Authors: Shenoy U. Sangeetha , Basavarajappa Dhanraj Salur , Kabekkodu Shama Prasada , Radhakrishnan Raghu 
Published: June 2024

AbstractHomeodomain transcription factor A9 (HOXA9) is a member of the HOX cluster family of transcription factors that are crucially involved in embryo implantation, morphogenesis, body axis development, and endothelial cell differentiation. Despite numerous reports on its aberrant expression in a few malignancies, the molecular and functional complexity of HOXA9 across cancers remains obscure. We aimed to analyze the dynamic role of HOXA9 across cancers by identifying, analyzing, and understanding its multiple modes of regulation and functional implications and identifying possible therapeutic avenues. We conducted a comprehensive analysis to determine the role of HOXA9 across cancers. This approach involved the integration of large-scale datasets from public repositories such as the Genomic Data Commons, specifically the Cancer Genome Atlas (GDC-TCGA), across 33 different cancer types. The multiple modes of HOXA9 regulation by genetic and epigenetic factors were determined using online tools, which comprised experimentally validated observations. Furthermore, downstream pathways were identified by predicting the targets of HOXA9 and by performing functional enrichment analysis. We also assessed the clinical significance of HOXA9 in terms of prognosis and stage stratification. This study evaluated the correlation between HOXA9 and tumor-infiltrating molecules and discussed its association with therapeutically approved antineoplastic drugs. HOXA9 was significantly upregulated in 9 tumors and downregulated in 2 cancers. The deregulation of HOXA9 is primarily attributed to epigenetic factors, including promoter DNA methylation and noncoding RNAs (ncRNAs). The HOXA9 transcription factor interacts with PBX/MEIS cofactors and regulates multiple genes involved in cancer-associated EMT, autophagy, the cell cycle, metabolic pathways, Wnt signaling, TGF-β signaling, the AMPK pathway, PI3K/AKT signaling, and NF-κB signaling, thereby establishing control over downstream mechanisms. Differential expression in various clinical stages across cancers was shown to have prognostic significance and to be correlated with tumor-infiltrating immune molecules. The assessment of the correlation of HOXA9 expression with approved antineoplastic drugs revealed that targeting HOXA9 could be the most reliable strategy for preventing cancer progression. HOXA9 is upregulated in the majority of malignancies and drives cancer progression by regulating multiple signaling mechanisms. Hence, HOXA9 could be a reliable diagnostic indicator and a potential therapeutic candidate for solid cancer types.
Distance-dependent mating but considerable pollen immigration in an isolated Quercus rubra planting in Germany
Authors: Dominguez-Flores Tania , Budde Katharina B. , Carlson John E. , Gailing Oliver 
Published: June 2024

AbstractGene flow affects the genetic diversity and structure of tree species and can be influenced by stress related to changing climatic conditions. The study of tree species planted in locations outside their natural range, such as arboreta or botanical gardens, allows us to analyse the effect of severe fragmentation on patterns and distances of gene flow. Paternity analysis based on microsatellite marker genotyping was used to analyse how fragmentation affects gene flow among individuals of Quercus rubra L. distributed in a small isolated group of trees (15 trees) planted in the arboretum on the North Campus of the University of Göttingen. For paternity analysis, 365 seedlings from four seed parents were selected and genotyped using 16 microsatellites. The analysis revealed the majority of pollen (84.89%) originated from trees within the site and identified three large full-sib families consisting of 145, 63 and 51 full-sibs. The average pollen dispersal distance for the four seed parents ranged from 17.3 to 103.6 meters. We observed substantial genetic differentiation among effective pollen clouds of the four seed parents (G’’ST = 0.407) as a result of cross pollination between neighboring trees. No self-fertilization was observed. Gene dispersal via pollen followed the expected distance-dependent pattern, and we observed a significant influx of external pollen (15.11%, ranging from 8.64 to 26.26% for individual seed parents) from a diverse set of donors (30). Long-distance pollen dispersal could explain the presence of significant genetic variation even in isolated natural Q. rubra populations.
Simulation of coronary fractional flow reserve and whole-cycle flow based on optical coherence tomography in individual patients with coronary artery disease
Authors: Olsen Niels Thue , Sheng Kaining 
Published: June 2024

AbstractComputer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was − 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75–0.95) with sensitivity 0.79 (0.58–0.93) and specificity 0.96 (0.79–1.00). The positive predictive value was 0.95 (0.75–1.00) and the negative predictive value was 0.82 (0.63–0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses.
Conservation genetics of the endangered California Freshwater Shrimp (Syncaris pacifica): watershed and stream networks define gene pool boundaries
Authors: Ada Abdul M. , Vandergast Amy G. , Fisher Robert N. , Fong Darren , Bohonak Andrew J. 
Published: June 2024

AbstractUnderstanding genetic structure and diversity among remnant populations of rare species can inform conservation and recovery actions. We used a population genetic framework to spatially delineate gene pools and estimate gene flow and effective population sizes for the endangered California Freshwater Shrimp Syncaris pacifica. Tissues of 101 individuals were collected from 11 sites in 5 watersheds, using non-lethal tissue sampling. Single Nucleotide Polymorphism markers were developed de novo using ddRAD-seq methods, resulting in 433 unlinked loci scored with high confidence and low missing data. We found evidence for strong genetic structure across the species range. Two hierarchical levels of significant differentiation were observed: (i) five clusters (regional gene pools, FST = 0.38–0.75) isolated by low gene flow were associated with watershed limits and (ii) modest local structure among tributaries within a watershed that are not connected through direct downstream flow (local gene pools, FST = 0.06–0.10). Sampling sites connected with direct upstream-to-downstream water flow were not differentiated. Our analyses suggest that regional watersheds are isolated from one another, with very limited (possibly no) gene flow over recent generations. This isolation is paired with small effective population sizes across regional gene pools (Ne = 62.4–147.1). Genetic diversity was variable across sites and watersheds (He = 0.09–0.22). Those with the highest diversity may have been refugia and are now potential sources of genetic diversity for other populations. These findings highlight which portions of the species range may be most vulnerable to future habitat fragmentation and provide management consideration for maintaining local effective population sizes and genetic connectivity.
Familial confounding or measurement error? How to interpret findings from sibling and co-twin control studies
Authors: Gustavson Kristin , Torvik Fartein Ask , Davey Smith George , Røysamb Espen , Eilertsen Espen M. 
Published: June 2024

AbstractEpidemiological researchers often examine associations between risk factors and health outcomes in non-experimental designs. Observed associations may be causal or confounded by unmeasured factors. Sibling and co-twin control studies account for familial confounding by comparing exposure levels among siblings (or twins). If the exposure-outcome association is causal, the siblings should also differ regarding the outcome. However, such studies may sometimes introduce more bias than they alleviate. Measurement error in the exposure may bias results and lead to erroneous conclusions that truly causal exposure-outcome associations are confounded by familial factors. The current study used Monte Carlo simulations to examine bias due to measurement error in sibling control models when the observed exposure-outcome association is truly causal. The results showed that decreasing exposure reliability and increasing sibling-correlations in the exposure led to deflated exposure-outcome associations and inflated associations between the family mean of the exposure and the outcome. The risk of falsely concluding that causal associations were confounded was high in many situations. For example, when exposure reliability was 0.7 and the observed sibling-correlation was r = 0.4, about 30–90% of the samples (n = 2,000) provided results supporting a false conclusion of confounding, depending on how p-values were interpreted as evidence for a family effect on the outcome. The current results have practical importance for epidemiological researchers conducting or reviewing sibling and co-twin control studies and may improve our understanding of observed associations between risk factors and health outcomes. We have developed an app (SibSim) providing simulations of many situations not presented in this paper.
Cognitive Profiles are Better Predictors of Literacy Attainment Than Diagnostic Outcomes in Children with High ADHD Symptoms
Authors: Rhodes Sinead , Booth Josephine N. , McDougal Emily , Oldridge Jessica , Rivera-Lares Karim , Revueltas Roux Alexia , Stewart Tracy M. 
Published: June 2024

AbstractWe examined whether cognitive profiles or diagnostic outcomes are better predictors of literacy performance for children being considered for an ADHD diagnosis. Fifty-five drug naïve children (Mage = 103.13 months, SD = 18.65; 29.09% girls) were recruited from an ADHD clinical referral waiting list. Children underwent assessment of IQ, Executive Functions (EF) and literacy attainment. Hierarchical cluster analysis was used to generate subgroups of children using EF scores. Data were then grouped based on presence of a clinical ADHD diagnosis and the results compared. Grouping participants by profiles of cognitive test scores led to groups which also differed on literacy scores. However, categorising by whether children had received an ADHD diagnosis or not did not differentiate either cognitive tests scores or literacy scores. Cognitive performance, rather than children’s diagnostic outcomes, is more informative for identifying groups who differ in their literacy attainment which has important implications for remedial support.