bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: A novel R246L mutation in the LMX1B homeodomain causes isolated nephropathy in a large Chinese family
Authors: Li Xian , Fan Jiaojiao , Fu Rong , Peng Ming , He Jujie , Chen Qiufang , Wang Shujing , Chen Chong 
Published: March 2024

Background:
Genetic factors contribute to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Advances in genetic testing have enabled the identification of hereditary kidney diseases, including those caused by LMX1B mutations. LMX1B mutations can lead to nail-patella syndrome (NPS) or nail-patella-like renal disease (NPLRD) with only renal manifestations.

Case presentation:
The proband was a 13-year-old female who was diagnosed with nephrotic syndrome at the age of 6. Then she began intermittent hormone and drug therapy. When she was 13 years old, she was admitted to our hospital due to sudden chest tightness, which progressed to end-stage kidney disease (ESRD), requiring kidney replacement therapy. Whole-Exome Sequencing (WES) results suggest the presence of LMX1B gene mutation, c.737G > T, p.Arg246Leu. Tracing her family history, we found that her father, grandmother, uncle and 2 cousins all had hematuria, or proteinuria. In addition to the grandmother, a total of 9 members of the family performed WES. The members with kidney involved all carry the mutated gene. Healthy members did not have the mutated gene. It is characterized by co-segregation of genotype and phenotype. We followed the family for 9 year, the father developed ESRD at the age of 50 and started hemodialysis treatment. The rest patients had normal renal function. No extra-renal manifestations associated with NPS were found in any member of the family.

Conclusions:
This study has successfully identified missense mutation, c.737G > T (p.Arg246Leu) in the homeodomain, which appears to be responsible for isolated nephropathy in the studied family. The arginine to leucine change at codon 246 likely disrupts the DNA-binding homeodomain of LMX1B. Previous research has documented 2 types of mutations at codon R246, namely R246Q and R246P, which are known to cause NPLRD. The newly discovered mutation, R246L, is likely to be another novel mutation associated with NPLRD, thus expanding the range of mutations at the crucial renal-critical codon 246 that contribute to the development of NPLRD. Furthermore, our findings suggest that any missense mutation occurring at the 246th amino acid position within the homeodomain of the LMX1B gene has the potential to lead to NPLRD.
Mast Cell Sarcoma Mimicking Lymphoma or Metastatic Disease on 18F-FDG PET/CT
Authors: Rosar Florian , Ezziddin Samer , Bittenbring Jörg Thomas , Christofyllakis Konstantinos , Burgard Caroline 
Published: March 2024

AbstractWe report an18F-FDG PET/CT scan of a 47-year-old man diagnosed with diffuse mast cell sarcoma with lymph node, bone, liver, spleen, and lung involvement. This interesting image should remind colleagues to consider mast cell sarcoma as a rare differential diagnosis in patients with multiple, intensely hypermetabolic lesions in various organs and lymph nodes.
Postoperative Radiologic Imaging in Secondary Alveolar Bone Grafting for Cleft Lip and Palate: A Systematic Review and Meta-Analysis
Authors: Groff Connor K. , Obinero Chioma G. , Cepeda Alfredo , Barrera Jose E. , Sobol Danielle L. , Nguyen Phuong D. , Greives Matthew R. 
Published: March 2024

Introduction:
Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG.

Methods:
Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities.

Results:
Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT.

Conclusion:
Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.
The interactive effect of sustained sleep restriction and resistance exercise on skeletal muscle transcriptomics in young females
Authors: Knowles Olivia E. , Soria Megan , Saner Nicholas J. , Trewin Adam J. , Alexander Sarah E. , Roberts Spencer S.H. , Hiam Danielle , Garnham Andrew , Drinkwater Eric J. , Aisbett Brad , Lamon Séverine 
Published: March 2024

AbstractIntroductionBoth sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction, with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females.MethodsTen healthy females aged 18-35 years undertook a randomised cross-over study of nine nights’ sleep restriction (SR; 5-h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-week washout. Participants completed four REx sessions per condition (day 3, 5, 7 and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western Blot, respectively.ResultsThree or nine nights of sleep restriction had no effect on the muscle transcriptome independently of exercise. However, close to 3000 transcripts were differentially regulated (FDR < 0.05) 48 h post the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated and 18% of upregulated genes were common between both conditions, indicating a moderating effect of sleep restriction on the response to exercise.ConclusionSleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.
Probabilistic Inference on Virtual Brain Models of Disorders
Authors: Hashemi Meysam , Ziaeemehr Abolfazl , Woodman Marmaduke M. , Petkoski Spase , Jirsa Viktor K. 
Published: March 2024

AbstractConnectome-based models, also known as Virtual Brain Models (VBMs), have been well established in network neuroscience to investigate pathophysiological causes underlying a large range of brain diseases. The integration of an individual’s brain imaging data in VBMs has improved patient-specific predictivity, although Bayesian estimation of spatially distributed parameters remains challenging even with state-of-the-art Monte Carlo sampling. VBMs imply latent nonlinear state space models driven by noise and network input, necessitating advanced probabilistic machine learning techniques for widely applicable Bayesian estimation. Here we present Simulation-Based Inference on Virtual Brain Models (SBI-VBMs), and demonstrate that training deep neural networks on both spatio-temporal and functional features allows for accurate estimation of generative parameters in brain disorders. The systematic use of brain stimulation provides an effective remedy for the non-identifiability issue in estimating the degradation of intra-hemispheric connections. By prioritizing model structure over data, we show that the hierarchical structure in SBI-VBMs renders the inference more effective, precise and biologically plausible. This approach could broadly advance precision medicine by enabling fast and reliable prediction of patient-specific brain disorders.
A chromosome-level genome assembly ofDrosophila madeirensis, a fruit fly species endemic to the island of Madeira
Authors: Tomihara Kenta , Llopart Ana , Yamamoto Daisuke 
Published: March 2024

AbstractDrosophila subobscurais distributed across Europe, the Near East, and the Americas, while its sister species,D. madeirensis, is endemic to the island of Madeira in the Atlantic Ocean.D. subobscurais known for its strict light-dependence in mating and its unique courtship displays, including nuptial gift giving.D. subobscurahas also attracted the interest of researchers because of its abundant variations in chromosomal polymorphisms correlated to the latitude and season, which have been used as a tool to track global climate warming. AlthoughD. madeirensiscan be an important resource for understanding the evolutionary underpinning of these genetic characteristics ofD. subobscura, little work has been done on the biology of this species. Here, we used a HiFi long-read sequencing dataset to produce ade novogenome assembly forD. madeirensis. This assembly comprises a total of 111 contigs spanning 135.5 Mb, and has an N50 of 24.2 Mb and a BUSCO completeness score of 98.6%. Each of the six chromosomes ofD. madeirensisconsisted of a single contig. Breakpoints of the chromosomal inversions betweenD. subobscuraandD. madeirensiswere characterized using this genome assembly, updating some of the previously identified locations.
Emergence of a synergistic scaffold in the brains of human infants
Authors: Varley Thomas F. , Sporns Olaf , Stevenson Nathan J. , Welch Martha G. , Myers Michael M. , Vanhatalo Sampsa , Tokariev Anton 
Published: March 2024

AbstractThe human brain is a complex organ comprising billions of interconnected neurons which enables interaction with both physical and social environments. Neural dynamics of the whole brain go far beyond just the sum of its individual elements; a property known as “synergy”. Previously it has been shown that synergy is crucial for many complex brain functions and cognition, however, it remains unknown how and when the large number of discrete neurons evolve into the unified system able to support synergistic interactions. Here we analysed high-density electroencephalography data from late fetal to early postnatal period. We found that the human brain transitions from redundancy-dominated to synergy-dominated system around birth. Frontal regions lead the emergence of a synergistic scaffold comprised of overlapping subsystems, while the integration of sensory areas developed gradually, from occipital to central regions. Strikingly, early developmental trajectories of brain synergy were modulated by environmental enrichment associated with enhanced mother-infant interactions, and the level of synergy near term equivalent age was associated with later neurocognitive development.
In silicomodelling of CD8 T cell immune response links genetic regulation to population dynamics
Authors: Nguyen Thi Nhu Thao , Martin Madge , Arpin Christophe , Bernard Samuel , Gandrillon Olivier , Crauste Fabien 
Published: March 2024

AbstractThe CD8 T cell immune response operates at multiple temporal and spatial scales, including all the early complex biochemical and biomechanical processes, up to long term cell population behavior.In order to model this response, we devised a multiscale agent-based approach using Simuscale software. Within each agent (cell) of our model, we introduced a gene regulatory network (GRN) based upon a piecewise deterministic Markov process (PDMP) formalism. Cell fate – differentiation, proliferation, death – was coupled to the state of the GRN through rule-based mechanisms. Cells interact in a 3D computational domain and signal to each other via cell-cell contacts, influencing the GRN behavior.Results show the ability of the model to correctly capture both population behaviour and molecular time-dependent evolution. We examined the impact of several parameters on molecular and population dynamics, and demonstrated the add-on value of using a multiscale approach by showing that a higher degradation rate for the protein controlling cell death induces a later peak in the response.
Adaptation during the transition fromOphiocordycepsentomopathogen to insect associate is accompanied by gene loss and intensified selection
Authors: Ward Chris M. , Onetto Cristobal A. , Borneman Anthony R. 
Published: March 2024

AbstractFungal and bacterial symbiosis is an important adaptation that has occurred within many insect species, which usually results in the relaxation of selection across the symbiont genome. However, the evolutionary pressures and genomic consequences associated with this transition are not well understood. Pathogenic fungi of the genusOphiocordycepshave undergone multiple, independent transitions from pathogen to associate, infecting soft-scale insects trans-generationally without killing them. To gain an understanding of the genomic adaptations underlying this transition, long-read sequencing was utilized to assemble the genomes of bothParthenolecanium corniand itsOphiocordycepsassociate from a single insect. A highly contiguous haploid assembly was obtained forPart. corni, representing the first assembly from a single Coccoidea insect, in which 97% of its 227.8 Mb genome was contained within 24 contigs. Metagenomic-based binning produced a chromosome-level genome forPart. corni’sOphiocordycepsassociate. The associate genome contained 524 gene loss events compared to free-living pathogenicOphiocordycepsrelatives, with predicted roles in hyphal growth, cell wall integrity, metabolism, gene regulation and toxin production. Contrasting patterns of selection were observed between the nuclear and mitochondrial genomes specific to the associate lineage. Intensified selection was most frequently observed across nuclear orthologs, while selection on mitochondrial genes was found to be relaxed. Furthermore, scans for diversifying selection identified associate specific selection within three adjacent enzymes catalyzing acetoacetate’s metabolism to acetyl-COA. This work provides insight into the adaptive landscape during the transition to an associate life history, along with a base for future research into the genomic mechanisms underpinning the evolution ofOphiocordyceps.
Development of DuoMYC: a synthetic cell penetrant miniprotein that efficiently inhibits the oncogenic transcription factor MYC
Authors: Ellenbroek Brecht , Kahler Jan Pascal , Arella Damiano , Lin Cherina , Jespers Willem , Pomplun Sebastian 
Published: March 2024

AbstractThe master regulator transcription factor MYC is implicated in numerous human cancers, and its targeting is a long-standing challenge in drug development. MYC is a typical ‘undruggable’ target, with no binding pockets on its DNA binding domain and extensive intrinsically disordered regions. Rather than trying to target MYC directly with classical modalities, here we engineer synthetic cell penetrating miniproteins that can bind to MYC’s target DNA, the enhancer box (E-Box), with a high affinity and block MYC-driven transcription. We obtained the miniproteins via structure-based design and a combination of solid phase peptide synthesis and site-specific crosslinking. Our lead variant, DuoMYC, binds to E-Box DNA with high affinity (KD= 118 nM) and molecular dynamic simulations provide insights into the structural features leading to the high stability of that DNA binding complex. DuoMYC displays an excellent stability in human serum and is able to enter cells and inhibit MYC-driven transcription with submicromolar potency (IC50= 464 nM) as shown by reporter gene assay. Notably, DuoMYC surpasses the efficacy of several other recently developed MYC inhibitors. Our results highlight the potential of engineered synthetic protein therapeutics for addressing challenging intracellular targets.Abstract Figure
Light and dopamine impact two circadian neurons to promote morning wakefulness
Authors: Le Jasmine Quynh , Ma Dingbang , Dai Xihuimin , Rosbash Michael 
Published: March 2024

SummaryIn both mammals and flies, circadian brain neurons orchestrate physiological oscillations and behaviors like wake and sleep; these neurons can be subdivided by morphology and by gene expression patterns. Recent single-cell sequencing studies identified 17Drosophilacircadian neuron groups. One of these include only two lateral neurons (LNs), which are marked by the expression of the neuropeptide ion transport peptide (ITP). Although these two ITP+LNs have long been grouped with five other circadian evening activity cells, inhibiting the two neurons alone strongly reduces morning activity; this indicates that they are prominent morning neurons. As dopamine signaling promotes activity inDrosophilalike in mammals, we considered that dopamine might influence this morning activity function. Moreover, the ITP+LNs express higher mRNA levels than other LNs of the type 1-like dopamine receptor Dop1R1. Consistent with the importance of Dop1R1, CRISPR/Cas9 mutagenesis of this receptor only in the two ITP+LNs renders flies significantly less active in the morning, andex vivolive imaging shows that dopamine increases cAMP levels in these two neurons; cell-specific mutagenesis ofDop1R1eliminates this cAMP response to dopamine. Notably, the response is more robust in the morning, reflecting higher morning Dop1R1 mRNA levels in the two neurons. As morning levels are not elevated in constant darkness, this suggests light-dependent upregulation of morning Dop1R1 transcript levels. Taken together with enhanced morning cAMP response to dopamine, the data indicate how light stimulates morning wakefulness in flies, which mimics the important effect of light on morning wakefulness in humans.
Identification of Potential Therapeutic Targets and Biomarkers for Glioblastomas Through Integrative Analysis of Gene Expression Data
Authors: Bautista Angélica , Romero Ricardo 
Published: March 2024

AbstractBackgroundIn this study, we conducted a comprehensive analysis of differential gene expression data from studies GSE15824, GSE4290 and GEPIA2 data to identify up-regulated hub genes with potential as therapeutic targets for glioblastomas. Through virtual screening, we also aimed to identify novel VEGFA inhibitors.ResultsSeven up-regulated hub genes (TYROBP, ITGB2, C1QA, C1QB, CTSS, TLR2, and CD163) were identified. Virtual screening of VEGFA inhibitors led to the discovery of six significant hits, including three from the ChemDiv library (D519-0372, G868-0191, and Y031-5201) and three from the ZINC20 database (ZINC57658, ZINC57652, ZINC57679). Molecular dynamics simulations highlighted G868-0191 as the most stable VEGFA inhibitor. Two repurposed drugs, Sunitinib and Ticlopidine hydrochloride, were also identified as potential candidates. In addition, the down-regulated hub genes GABARAPL1, OPTN, and CDH8 were proposed as potential biomarkers for glioblastomas.ConclusionThis study underscores the significance of immune-related hub genes in glioblastoma pathology and suggests new VEGFA inhibitors as promising therapeutic agents. The identification of down-regulated genes as potential biomarkers offers further avenues for clinical application. However, experimental validation is needed to confirm the clinical utility of these findings.
EyeHex toolbox for complete segmentation of ommatidia in fruit fly eyes
Authors: Tran Huy , Dostatni Nathalie , Ramaekers Ariane 
Published: March 2024

AbstractVariation inDrosophilacompound eye size is studied in various research contexts ranging from evolutionary to biomedical studies. Studying this variation requires the collection of large datasets required for the statistical power of the subsequent analyses. EyeHex is a new tool that automatically and fully segments fruit fly compound eyes from both brightfield and scanning electron microscopy images. The system comprises two modules. The first module uses machine-learning to extract the compound eye and ommatidia regions from different types of images. The second module is hard-coded and accurately determines the number and location of individual ommatidia using the hexagonal arrangement of the compound eye. EyeHex is equipped with a manual correction tool that enables control over segmentation accuracy, particularly at the edges of the eyes where ommatidia detection is more challenging due to highly slanted imaging angles and interfering ocular hairs. EyeHex is accompanied by an analysis tool to quantify ommatidia count, position, altitude, density across the eye, and arrangement along the anterior/posterior. Training and applying EyeHex model for ommatidia segmentation requires limited user inputs. It achieves a high level of accuracy (>99% when compared to manual counting) from both Scanning Electron Microscope and multi-focus brightfield images of twoDrosophila melanogasterstrains. This demonstrates that EyeHex can be integrated flexibly in a cheap and fast pipeline to extract statistics on variations ofDrosophilacompound eyes.
Inducible deletion ofEzh2in CD4+ T cells inhibits kidney T cell infiltration and prevents interstitial nephritis in MRL/lprlupus-prone mice
Authors: Zheng Xiaoqing , Dozmorov Mikhail G , Espinoza Luis , Bowes Mckenna M , Bastacky Sheldon , Sawalha Amr H 
Published: March 2024

AbstractSystemic lupus erythematosus is a remitting relapsing autoimmune disease characterized by autoantibody production and multi-organ involvement. T cell epigenetic dysregulation plays an important role in the pathogenesis of lupus. We have previously demonstrated upregulation of the key epigenetic regulator EZH2 in CD4+ T cells isolated from lupus patients. To further investigate the role of EZH2 in the pathogenesis of lupus, we generated a tamoxifen-inducible CD4+ T cellEzh2conditional knockout mouse on the MRL/lprlupus-prone background. We demonstrate thatEzh2deletion abrogates lupus-like disease and prevents T cell differentiation. Single-cell analysis suggests impaired T cell function and activation of programed cell death pathways in EZH2-deficient mice.Ezh2deletion in CD4+ T cells restricts TCR clonal repertoire and prevents kidney-infiltrating effector CD4+ T cell expansion and tubulointerstitial nephritis, which has been linked to end-stage renal disease in patients with lupus nephritis.