bluuebunny/crossref_metadata_2025_split huggingface dataset:
32-year-old diabetic patient with progressive vision loss and crystalline retinopathy
Authors: Bousquet Elodie , Khanna Sheena , Song Delu , Borooah Shyamanga , Ginsberg Charles , King Andrew , Goldbaum Michael , Nudleman Eric , Sarraf David 
Published: December 2023

Purpose: To report the case of severe bilateral retinal vascular occlusion in a patient with hyperoxalosis and chronic renal failure.
Methods: Observational case report. Medical and imaging records were retrospectively reviewed. The patient was imaged with ultra-widefield (UWF) fundus photography and fluorescein angiography (UWF-FA), cross sectional and en face spectral-domain optical coherence tomography (SD-OCT), and OCT angiography.
Results: A 32-year-old diabetic patient receiving peritoneal dialysis was referred because of severe vision loss. UWF color fundus photography showed diffuse sclerotic retinal vessels and diffuse intraretinal crystals in both eyes. UWF-FA illustrated near-complete retinal vascular occlusion and capillary wipe out in both eyes. SD-OCT demonstrated diffuse inner and middle retina thinning in both eyes and multiple intraretinal hyperreflective foci consistent with crystalline deposits in all retina layers of both eyes. OCT angiography revealed severe capillary and large vessel non-perfusion in the superficial and deep retinal capillary plexus of each eye. The serum oxalate levels were increased at 28 µmol/L (reference range < 2 µmol/L) and genetic testing was positive for a heterozygous mutation of the AGXT (Alanine-Glyoxylate Amino Transferase) gene that causes type 1 autosomal recessive primary hyperoxaluria.
Conclusion: A diagnosis of hyperoxalosis causing severe retinal vascular occlusion was rendered. Hyperoxalosis was the result of multiple factors including heterozygous AGXT mutation, chronic renal failure insufficiently treated with peritoneal dialysis, and a diet high in oxalate. This case highlights the importance of ruling out retinal oxalosis in patients on peritoneal dialysis in order to initiate prompt hemodialysis and prevent severe retinal vascular occlusion.
RADIATION RETINOPATHY AND BENIGN LYMPHOPROLIFERATIVE ORBITAL TUMOR PRESENTING 47 YEARS AFTER TREATMENT OF HEREDITARY RETINOBLASTOMA
Authors: Sabbagh Mohammad Amr , Munro Monique P. , Mieler William F. 
Published: December 2023

Purpose:
The objective of this study was to better understand the onset of radiation retinopathy and secondary orbital tumors in the setting of retinoblastoma treated with radiation and chemotherapy.

Methods:
This was a case report.

Results:
Here, the authors present a 48-year-old woman with a history of bilateral hereditary retinoblastoma after enucleation of the left eye and radiation therapy to the right eye along with systemic chemotherapy. She underwent bladder leiomyosarcoma resection at the age of 24 years. In 2020, she presented with significantly delayed radiation retinopathy complicated by cystoid macular edema, and bevacizumab injections were initiated. An incidental benign lymphoproliferative tumor in the right lacrimal gland was found on B-scan ultrasound and was successfully excised.

Conclusion:
It is rare for radiation retinopathy to present with significant delay after local radiation treatment, with only two other cases found in the literature describing a similar late onset. In addition, there have been no other published cases of a secondary benign lymphoproliferative tumor in the setting of retinoblastoma treated with radiation and chemotherapy.
Prediction of general high-order lump solutions in the Davey–Stewartson II equation
Authors: Yan Xue-Wei , Long Haie , Chen Yong 
Published: December 2023

Under investigation in this work is the Davey–Stewartson (DS) II equation. Based on the Kadomtsev–Petviashvili (KP) reduction method and Schur polynomial theory, we construct the general high-order lump solutions. The prediction solutions consisting of fundamental lumps and their positions are derived by extracting leading-order asymptotics of the Schur polynomials of true solutions. When indexes of the solutions are chosen as different positive integer combinations, the prediction solutions at large time reflect two classes of lump patterns of the true solutions. The first class of lump pattern with triangle shape is analytically described by root structure of the Yablonskii–Vorob’ev polynomial. When time

t

evolves from large negative to large positive, the triangle lump reverses itself along the

y

-direction. The second class of lump pattern consists of non-triangle in outer region, which is analytically described by non-zero root structure of the Wronskian–Hermit polynomial, together with possible triangle in the inner region, which is analytically described by root structure of the Yablonskii–Vorob’ev polynomial. In addition, the non-triangle lump pattern in outer regions rotates at an angle while the possible triangle lump pattern in the inner region reverses itself along the

y

-direction when time

t

evolves from large negative to large positive. The obtained results improve our understanding of time evolution mechanisms of high-order lumps.
CC-Tempo: A cell-cell communication aware temporal model of cellular dynamics
Authors: Jony Sheikh Saifur Rahman , Rahman M. Sohel , Samee Md. Abul Hassan 
Published: December 2023

AbstractDelineating the mechanisms underlying cell state changes is key to gaining insights into organismal development and disease prognosis. Various methods have been proposed to study cellular differentiation and cell fate specification. However, they either do not incorporate temporal information or do not consider the vital role of intercellular communication in cellular differentiation and cell fate determination. Furthermore, many of these methods lack interpretability, making it difficult to identify the critical genes and pathways that influence the differentiation process. Here we propose CC-Tempo, a cell-cell communication-aware model of cellular dynamics that leverages intercellular communication scores and can help identify important genes and pathways crucial for different stages of differentiation in various lineages. While previous studies have indicated that scRNA-seq data alone may not suffice for accurately predicting cell fates, CC-Tempo demonstrates that incorporating intercellular communication significantly enhances the performance of such models. CC-Tempo can predict the significance of genes and pathways at different stages of the differentiation process. By perturbing these genes in silico, CC-Tempo reveals their efficacy for manipulating cell fate, which can be crucial for defining efficient reprogramming factors.
Healthy microbiome - moving towards functional interpretation
Authors: Zielińska Kinga , Udekwu Klas I. , Rudnicki Witold , Frolova Alina , Łabaj Paweł P 
Published: December 2023

AbstractMicrobiome-based disease prediction has significant potential as an early, non-invasive marker of multiple health conditions linked to dysbiosis of the human gut microbiota, thanks in part to decreasing sequencing and analysis costs. Microbiome health indices and other computational tools currently proposed in the field often are based on a microbiome’s species richness and are completely reliant on taxonomic classification. A resurgent interest in a metabolism-centric, ecological approach has led to an increased understanding of microbiome metabolic and phenotypic complexity revealing substantial restrictions of taxonomy-reliant approaches. In this study, we introduce a new metagenomic health index developed as an answer to recent developments in microbiome definitions, in an effort to distinguish between healthy and unhealthy microbiomes, here in focus, inflammatory bowel disease (IBD). The novelty of our approach is a shift from a traditional Linnean phylogenetic classification towards a more holistic consideration of the metabolic functional potential underlining ecological interactions between species. Based on well-explored data cohorts, we compare our method and its performance with the most comprehensive indices to date, the taxonomy-based Gut Microbiome Health Index (GMHI), and the high dimensional principal component analysis (hiPCA)methods, as well as to the standard taxon-, and function-based Shannon entropy scoring. After demonstrating better performance on the initially targeted IBD cohorts, in comparison with other methods, we retrain our index on an additional 27 datasets obtained from different clinical conditions and validate our index’s ability to distinguish between healthy and disease states using a variety of complementary benchmarking approaches. Finally, we demonstrate its superiority over theGMHIand thehiPCAon a longitudinal COVID-19 cohort and highlight the distinct robustness of our method to sequencing depth. Overall, we emphasize the potential of this metagenomic approach and advocate a shift towards functional approaches in order to better understand and assess microbiome health as well as provide directions for future index enhancements. Our method,q2-predict-dysbiosis (Q2PD),is freely available (https://github.com/Kizielins/q2-predict-dysbiosis).
Integrated Molecular-Phenotypic Profiling Reveals Metabolic Control of Morphological Variation in Stembryos
Authors: Villaronga Luque Alba , Savill Ryan , López-Anguita Natalia , Bolondi Adriano , Garai Sumit , Gassaloglu Seher Ipek , Poddar Aayush , Bulut-Karslioglu Aydan , Veenvliet Jesse V 
Published: December 2023

SUMMARYMammalian stem-cell-based models of embryo development (stembryos) hold great promise in basic and applied research. However, considerable phenotypic variation despite identical culture conditions limits their potential. The biological processes underlying this seemingly stochastic variation are poorly understood. Here, we investigate the roots of this phenotypic variation by intersecting transcriptomic states and morphological history of individual stembryos across stages modeling post-implantation and early organogenesis. Through machine learning and integration of time-resolved single-cell RNA-sequencing with imaging-based quantitative phenotypic profiling, we identify early features predictive of the phenotypic end-state. Leveraging this predictive power revealed that early imbalance of oxidative phosphorylation and glycolysis results in aberrant morphology and a neural lineage bias that can be corrected by metabolic interventions. Collectively, our work establishes divergent metabolic states as drivers of phenotypic variation, and offers a broadly applicable framework to chart and predict phenotypic variation in organoid systems. The strategy can be leveraged to identify and control underlying biological processes, ultimately increasing the reproducibility of in vitro systems.HighlightsTime-resolved single-cell RNA-sequencing and imaging-based quantitative charting of hundreds of individual stembryos generates molecular and phenotypic fingerprintsMachine learning and integration of molecular and phenotypic fingerprints identifies features and biological processes predictive of phenotypic end-stateEarly imbalance of oxidative phosphorylation and glycolysis results in aberrant morphology and cellular compositionMetabolic interventions tune stembryo end-state and can correct derailment of differentiation outcomes
Four-Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage
Authors: Panten Jasper , Prete Stefania Del , Cleland James P. , Saunders Lauren M. , van Riet Job , Schneider Anja , Ginno Paul , Schneider Nina , Koch Marie-Luise , Gerstung Moritz , Stegle Oliver , Turner James M. A. , Heard Edith , Odom Duncan T. 
Published: December 2023

AbstractThe Four Core Genotypes (FCG) is a mouse model system heavily used to disentangle the function of sex chromosomes and hormones. We report that a copy of a 3.2 MB region of the X chromosome has translocated to the YSry-chromosome and thus increased the expression of multiple genes including the auto-immune master regulatorTlr7. This previously-unreported X-Y translocation complicates the interpretation of studies reliant on FCG mice.
Functional displacement of cortical neuromagnetic somatosensory responses: enhancing embodiment in the rubber hand illusion
Authors: Isabella Silvia L. , D’Alonzo Marco , Mioli Alessandro , Arcara Giorgio , Pellegrino Giovanni , Pino Giovanni Di 
Published: December 2023

AbstractThe integration of an artificial limb as part of one’s body involves complex neuroplastic changes resulting from various sensory inputs to the brain. While sensory feedback is known to be crucial for embodiment, current evidence points merely to the attenuation of somatosensory processing, while the positive contributions of somatosensory areas to embodiment remain unknown. This study investigated the relationship between embodiment and adaptive neuroplasticity of early-latency somatosensory evoked fields (SEFs) in the primary somatosensory cortex (S1) following the Rubber Hand Illusion (RHI), known to induce short-term artificial limb embodiment. Nineteen healthy adults underwent neuromagnetic recordings during electrical stimulation of the little finger and thumb, before and after the RHI. We found a displacement of early SEF sources. In particular, we observed a correlation between the extent of rubber hand embodiment and specific changes to the m20 component (magnetic equivalent to the N20) in Brodmann Area 3b: a larger displacement and a greater reduction in m20 magnitude predicted the amount of embodiment, highlighting an important functional contribution of this first cortical input. Furthermore, we observed a posteriorly directed m35 displacement towards Area 1, known to be important for visual integration during touch perception (Rosenthal et al., 2023). Our finding that the larger displacement for the m35 did not correlate with the extent of embodiment implies a functional distinction between neuroplastic changes across these two components and areas in their contributions to successful artificial limb embodiment: (i) the earlier neuroplastic changes to m20 may shape the extent of artificial limb ownership, and (ii) the posteriorward shift of the m35 into Area 1 is suggestive of a mechanistic contribution to early visual-tactile integration that initially establishes the embodiment. Taken together, these findings suggest that multiple distinct changes occur during early-latency SEFs and their displacement in S1 last beyond the duration of the illusion and are important for the successful integration of an artificial limb within the body representation.
Spatial heterogeneity in myelin sheathing impacts signaling reliability and susceptibility to injury
Authors: Talidou Afroditi , Lefebvre Jérémie 
Published: December 2023

AbstractAxons in the mammalian brain show significant diversity in myelination motifs, displaying spatial heterogeneity in sheathing along individual axons and across brain regions. However, its impact on neural signaling and susceptibility to injury remains poorly understood. To address this, we leveraged cable theory and developed model axons replicating the myelin sheath distributions observed experimentally in different regions of the mouse central nervous system. We examined how the spatial arrangement of myelin affects propagation and predisposition to conduction failure in axons with cortical versus callosal myelination motifs. Our results indicate that regional differences in myelination significantly influence conduction timing and signaling reliability. Sensitivity of action potential propagation to the specific positioning, lengths, and ordering of myelinated and exposed segments reveals non-linear and path-dependent conduction. Furthermore, myelination motifs impact signaling vulnerability to demyelination, with callosal motifs being particularly sensitive to myelin changes. These findings highlight the crucial role of myelinating glia in brain function and disease.
Genotype, antimicrobial resistance and virulence profiles of livestock-derived enterotoxigenicEscherichia coli(ETEC) in the United States, 1970-2023
Authors: Fu Yezhi , Nawrocki Erin M. , M’ikanatha Nkuchia M. , Dudley Edward G. 
Published: December 2023

AbstractEnterotoxigenicEscherichia coli(ETEC) is a significant pathogen in both cattle and pigs, causing diarrhea in these animals and leading to economic losses in the livestock industry. Understanding the dissimilarity in genotype, antimicrobial resistance (AMR), and virulence between bovine and swine ETEC is crucial for development of targeted preventive and therapeutic approaches for livestock. However, a comprehensive study on this area remains lacking. Here, we performed whole-genome sequencing-based analyses of bovine (n= 554) and swine (n= 623) ETEC collected in the US over a 53-year period. We identified distinct ETEC genotypes (fimHtype, O antigen, H antigen, sequence type) in cattle and pigs. Further, specific AMR and virulence profiles were associated with bovine and swine ETEC. Compared to swine ETEC, bovine ETEC were less diverse in genotypes, had a significantly (p< 0.001) lower number of AMR genes per isolate but higher co-occurrence of Shiga toxin and enterotoxin genes. Our results provide an overview of the key genomic differences between bovine and swine ETEC in the US, which might be attributed to host adaptation and antibiotic usage practice. Ongoing surveillance and research are essential to monitor the genetic diversity and AMR patterns of ETEC in different host species.
Characterization of the mutational landscape of high-grade gliomas in a Latin American cohort
Authors: Fernández-Gajardo Rodrigo , Urra Hery , Saéz Mauricio , Pihán Philippe , Fonseca Beatriz , Sanchez-Doñas Carolina , Ali Maruf M. U. , Rouse Sarah L. , Cavada Gabriel , Tissera Claudia , Melo Rómulo , Rojas David , Matamala José M. , Hetz Claudio 
Published: December 2023

AbstractBackgroundGlioblastoma, an aggressive form of high-grade glioma, exhibits variations in the incidence and mortality patterns between populations of different ancestry. However, Hispanic and Latino populations remain largely underrepresented in studies of molecular characterization. Here we characterized the mutagenic landscape of high-grade gliomas within a Chilean population focusing on well characterized genetic variants associated with glioblastoma classification, progression, and prognosis.MethodsWe conducted a targeted genomic analysis using next-generation sequencing techniques in 70 Chilean patients with high-grade gliomas from a national single-center referral institution. We focused on the most relevant molecular markers such as isocitrate dehydrogenase 1/2 (IDH) mutations, telomerase reverse transcriptase promoter (TERTp) mutations, histone 3 (H3) gene family mutations, TP53 and PTEN mutations, epidermal growth factor receptor (EGFR) gene amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletions. Survival analyses were performed to assess the clinical relevance of these markers and their impact on patient prognosis. Additionally, due to our interest in the role of proteostasis and glioblastoma, we investigated possible ERN1 variants in our Chilean cohort.ResultsOur findings mostly align with other international cohorts of non-Latin-American origin, confirming the importance of established molecular markers in glioblastoma. Notably, we identified novel TP53 and PTEN mutations with a predicted damaging effect, expanding the genetic spectrum of alterations in these brain tumors. Furthermore, a lower-than-expected mutation rate in the NF1 gene was observed, emphasizing a distinctive genetic profile of glioblastoma in this Latin American population. Prognostic assessments based on TERT promoter and IDH mutations mirrored previous studies on non-Latino American and European populations. Of note, we identified the germline ERN1 variant rs139229826 in 11% of our patient cohort, a variant previously unreported in glioblastoma patients.ConclusionThis study underscores the importance of conducting glioblastoma research in underrepresented populations, providing insights into the molecular characteristics of high-grade gliomas within a Latin American context. Our findings contribute to the growing body of evidence suggesting molecular diversity across diverse glioblastoma populations, offering a foundation for future international comparative studies.
Intronic polyadenylation isoforms in the 5’ part of genes constitute a source of microproteins and are involved in cell response to cisplatin
Authors: Devaux Alexandre , Tanaka Iris , Cadix Mandy , Heneman-Masurel Amélie , Michallet Sophie , Fouilleul Quentin , Chakraborty Alina , Labbe Céline M. , Fontrodona Nicolas , Claude Jean-Baptiste , Deloger Marc , Gestraud Pierre , Tessier Ludovic , Mortada Hussein , Lameiras Sonia , Raynal Virginie , Baulande Sylvain , Servant Nicolas , Auboeuf Didier , Eymin Béatrice , Vagner Stéphan , Dutertre Martin 
Published: December 2023

ABSTRACTTranscript isoforms generated by intronic polyadenylation (IPA) are widely regulated in various biological processes and often encode protein isoforms. Microproteins are small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown. Using 3’-seq and long-read RNA-seq analyses in lung cancer cells, we show that cisplatin, a DNA-crosslinking anticancer agent, upregulates IPA isoforms relative to full-length mRNAs in long genes. A subset of cisplatin-regulated IPA isoforms are poorly associated with heavy polysomes and terminate upstream of the annotated translation initiation codon of genes. Such IPA isoforms in thePHF20andPRKAR1Bgenes are associated with light polysomes, contain Ribo-Seq-supported sORFs in an alternative last exon within the annotated 5’UTR part of genes, and are translated into microproteins. ForPRKAR1B, the microprotein was detected by Western blot and immunofluorescence after transfection of a tagged isoform; and siRNA depletion of the endogenous IPA isoform, CRISPR deletion of the IPA site, or CRISPR mutation of the sORF initiation codon led to increased cell survival to cisplatin. Based on Ribo-Seq and mass-spectrometry data sets, we identified 156 genes producing both a canonical protein-coding mRNA and a microprotein-coding 5’UTR-located IPA isoform (coined miP-5’UTR-IPA isoform) regulated by cisplatin. Finally, the regulation of (miP-5’UTR-)IPAversusfull-length isoforms by cisplatin involved an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. Altogether, these findings reveal the novel paradigm of miP-5’UTR-IPA genes and their role in cancer cell response to a genotoxic agent.HIGHLIGHTS- Cisplatin increases intronic-polyadenylationversusfull-length transcript isoforms in long genes through a FANCD2 and senataxin-dependent decrease of transcription processivity- A subset of cisplatin-regulated intronic-polyadenylation isoforms terminate in the annotated 5’UTR part of genes and encode microproteins, thus we coined them miP-5’UTR-IPA isoforms- The miP-5’UTR-IPA isoform ofPRKAR1Bimpacts cisplatin sensitivity and its effect is mediated by its small ORF- We identify 156 genes producing both a canonical protein-coding mRNA and a microprotein-coding miP-5’UTR-IPA transcript