bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the diversity and phylogenetic relationships of trypanosomes (Trypanosoma) infecting pelomedusid (Pelomedusidae) freshwater turtles in Southern Africa
Authors: Jordaan Bernard J , du Preez Louis H , Netherlands Edward C 
Published: September 2024

Abstract
Species of Trypanosoma infecting reptiles are poorly understood and understudied. The study of trypanosomes infecting turtles could lead to a greater understanding of the genus and its evolutionary history. The present study re-evaluates and classifies two previously described species of Trypanosoma in freshwater pelomedusid turtles, Trypanosoma (Haematomonas) neitzi and Trypanosoma (Haematomonas) sheppardi, and characterizes a new species, Trypanosoma (Haematomonas) pienaari, using morphological and molecular data. This study provides the first morphological descriptions and molecular data of South African turtle trypanosomes, setting a base for future research of the reptile trypanosomes of Africa.
Corneal Epithelial Hyperplasia Related to Chronic Eye Rubbing Mimicking Keratoconus
Authors: Pollmann André S. , Cohen Mark , Jabbour Samir 
Published: October 2024

Abstract:
We report a case of corneal epithelial hyperplasia associated with chronic eye rubbing mimicking keratoconus. A 32-year-old man was presented with a 3-year history of suboptimal vision and astigmatism in his left eye. His history was significant for chronic left eye rubbing. The anterior corneal curvature map showed inferior steepening in the left eye; however, other features of ectasia were absent. Corneal epithelium thickness mapping with optical coherence tomography was significant for corresponding epithelial thickening. His corneal imaging remained stable at a 6-month follow-up examination. At month 15—and after cessation of eye rubbing behavior—the vision symptoms, refraction, and corneal imaging had normalized. In conclusion, chronic eye rubbing may cause reversible corneal epithelial hypertrophy. Eye rubbing should be considered in the evaluation of patients presenting with unexplained vision symptoms and changes in astigmatism that are not consistent with ectasia on corneal imaging.
Comparison of Elisar-Fast and Sita-Fast Strategies for Visual Field Assessment in Glaucoma
Authors: Narang Priya , Rasheed Fareya Fatheema , Agarwal Amar , Narang Rhea , Agarwal Ashvin 
Published: October 2024

Précis:
The study documents the ability of Elisar-Fast to successfully assess visual field in patients with glaucoma.

Purpose:
To compare 2 fast threshold strategies of visual field assessment: SITA-Fast (SF; Humphrey field analyser) and Elisar-Fast (EF; advanced vision analyser) in patients with glaucoma.

Methods:
In this cross-sectional observational study, of total 192 subjects, 138 subjects (150 eyes, 80 glaucoma subjects [91 eyes] and 58 healthy controls [59 eyes]) were analysed and included. Each subject underwent 24-2 EF and SF in randomized order with a minimum time interval of 1 hour between tests.

Main Outcome Measures:
Mean test-time, pointwise and sectoral sensitivity, significance of values of mean sensitivity (MS) and global indices (mean deviation [MD] and pattern SD [PSD]) and their correlation.

Results:
The mean test-time was 2.59±0.25 and 3.38±0.28 minutes (P = 0.001) with SF and EF, respectively. Correlation coefficient for pointwise threshold values correlated strongly for both devices (range, 0.70–0.92). The intraclass correlation value of ≥0.8 was observed across all sectors, indicating good reliability. Bland-Altman plot denoted 95% of the data for MS values within limit of agreement. The intraclass correlation values for overall MS, MD, and PSD were 0.916, 0.913, and 0.872, respectively, indicating good reliability. High degree of correlation was observed for MD (r=0.912, P=0.00) and PSD values (r=0.732, P=0.00). Comparison of values indicated a difference of 1.09 dB for MD and 0.06 dB for PSD between both strategies.

Conclusions:
A high degree of correlation existed between the global indices and pointwise threshold values. The study documents the ability of EF to successfully assess visual field in patients with glaucoma.
Deep learning-based binary classification of beta-amyloid plaques using 18F florapronol PET
Authors: An Eui Jung , Kim Jin Beom , Son Junik , Jeong Shin Young , Lee Sang-Woo , Ahn Byeong-Cheol , Ko Pan-Woo , Hong Chae Moon 
Published: October 2024

Purpose
This study aimed to investigate a deep learning model to classify amyloid plaque deposition in the brain PET images of patients suspected of Alzheimer’s disease.

Methods
A retrospective study was conducted on patients who were suspected of having a mild cognitive impairment or dementia, and brain amyloid 18F florapronol PET/computed tomography images were obtained from 2019 to 2022. Brain PET images were visually assessed by two nuclear medicine specialists, who classified them as either positive or negative. Image rotation was applied for data augmentation. The dataset was split into training and testing sets at a ratio of 8 : 2. For the convolutional neural network (CNN) analysis, stratified k-fold (k = 5) cross-validation was applied using training set. Trained model was evaluated using testing set.

Results
A total of 175 patients were included in this study. The average age at the time of PET imaging was 70.4 ± 9.3 years and included 77 men and 98 women (44.0% and 56.0%, respectively). The visual assessment revealed positivity in 62 patients (35.4%) and negativity in 113 patients (64.6%). After stratified k-fold cross-validation, the CNN model showed an average accuracy of 0.917 ± 0.027. The model exhibited an accuracy of 0.914 and an area under the curve of 0.958 in the testing set. These findings affirm the model’s high reliability in distinguishing between positive and negative cases.

Conclusion
The study verifies the potential of the CNN model to classify amyloid positive and negative cases using brain PET images. This model may serve as a supplementary tool to enhance the accuracy of clinical diagnoses.
Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism
Authors: Barkman Todd J. 
Published: September 2024

Studies of enzymes in modern-day plants have documented the diversity of metabolic activities retained by species today but only provide limited insight into how those properties evolved. Ancestral sequence reconstruction (ASR) is an approach that provides statistical estimates of ancient plant enzyme sequences which can then be resurrected to test hypotheses about the evolution of catalytic activities and pathway assembly. Here, I review the insights that have been obtained using ASR to study plant metabolism and highlight important methodological aspects. Overall, studies of resurrected plant enzymes show that (i) exaptation is widespread such that even low or undetectable levels of ancestral activity with a substrate can later become the apparent primary activity of descendant enzymes, (ii) intramolecular epistasis may or may not limit evolutionary paths towards catalytic or substrate preference switches, and (iii) ancient pathway flux often differs from modern-day metabolic networks. These and other insights gained from ASR would not have been possible using only modern-day sequences. Future ASR studies characterizing entire ancestral metabolic networks as well as those that link ancient structures with enzymatic properties should continue to provide novel insights into how the chemical diversity of plants evolved.
This article is part of the theme issue ‘The evolution of plant metabolism’.
Evolutionary trajectory of transcription factors and selection of targets for metabolic engineering
Authors: Lee Yun Sun , Braun Edward L. , Grotewold Erich 
Published: September 2024

Transcription factors (TFs) provide potentially powerful tools for plant metabolic engineering as they often control multiple genes in a metabolic pathway. However, selecting the best TF for a particular pathway has been challenging, and the selection often relies significantly on phylogenetic relationships. Here, we offer examples where evolutionary relationships have facilitated the selection of the suitable TFs, alongside situations where such relationships are misleading from the perspective of metabolic engineering. We argue that the evolutionary trajectory of a particular TF might be a better indicator than protein sequence homology alone in helping decide the best targets for plant metabolic engineering efforts.
This article is part of the theme issue ‘The evolution of plant metabolism’.
The evolution of plant responses underlying specialized metabolism in host–pathogen interactions
Authors: Agorio Astrid , Mena Eilyn , Rockenbach Mathias F. , Ponce De León Inés 
Published: September 2024

In the course of plant evolution from aquatic to terrestrial environments, land plants (embryophytes) acquired a diverse array of specialized metabolites, including phenylpropanoids, flavonoids and cuticle components, enabling adaptation to various environmental stresses. While embryophytes and their closest algal relatives share candidate enzymes responsible for producing some of these compounds, the complete genetic network for their biosynthesis emerged in embryophytes. In this review, we analysed genomic data from chlorophytes, charophytes and embryophytes to identify genes related to phenylpropanoid, flavonoid and cuticle biosynthesis. By integrating published research, transcriptomic data and metabolite studies, we provide a comprehensive overview on how these specialized metabolic pathways have contributed to plant defence responses to pathogens in non-vascular bryophytes and vascular plants throughout evolution. The evidence suggests that these biosynthetic pathways have provided land plants with a repertoire of conserved and lineage-specific compounds, which have shaped immunity against invading pathogens. The discovery of additional enzymes and metabolites involved in bryophyte responses to pathogen infection will provide evolutionary insights into these versatile pathways and their impact on environmental terrestrial challenges.
This article is part of the theme issue ‘The evolution of plant metabolism’.
Identification and characterization ofugpErequired for the full virulence of Streptococcus suis
Authors: Yang Qiulei , Li Na , Tian Yanyan , Liang Qiao , Zhao Miaomiao , Chu Hong , Gong Yan , Wu Tong , Wei Shaopeng , Wang He , Yan Guangmou , Li Fengyang , Lei Liancheng 
Published: September 2024

ABSTRACTStreptococcus suis(S. suis) is an emerging zoonotic pathogen that threatens both animal and human health worldwide. UgpE is a protein subunit of the Ugp (uptake ofglycerolphosphate) transporter system that is involved in glycerophospholipid synthesis in bacterial membranes. In this study, anugpEdeletion mutant was constructed and the effects ofugpEdeletion on cell morphology, biofilm formation, and virulence were investigated. Deletion ofugpEdid not affect bacterial growth but impaired cell chain formation and capsular synthesis by downregulating the mRNA levels of the capsular regulon genescps-2B,cps-2C, andcps-2S. Deletion ofugpEalso led to decreased tolerance to heat, oxidative, and acid-base stress. Crystal violet staining and scanning electron microscopy demonstratedugpEnegatively regulated biofilm formation in liquid culture and the rdar biofilm morphotype on agar plates. Moreover,ugpEdeletion not only reduced hemolysin activity, survival in whole human blood, and anti-phagocytosis ability against porcine alveolar macrophages (PAM) but also enhanced bacterial adhesion and invasion of human cerebral microvascular endothelial cells (hCMEC/D3) by upregulating the expression of multiple genes associated with cell adhesion. In a mouse infection model,ugpEdeletion significantly attenuated virulence and lowered the number of viable bacteria in the blood and major organs, as well as distribution of macrophages. In conclusion, this study identified UgpE as a novel virulence factor that plays a pivotal role in the regulation of virulence and biofilm formation ofS. suis.
Advancing precision care in pregnancy through an actionable fetal findings list
Authors: Cohen Jennifer L. , Duyzend Michael , Adelson Sophia M. , Yeo Julie , Fleming Mark , Ganetzky Rebecca , Hale Rebecca , Mitchell Deborah M. , Morton Sarah U. , Reimers Rebecca , Roberts Amy , Strong Alanna , Tan Weizhen , Thiagarajah Jay R. , Walker Melissa A. , Green Robert C. , Gold Nina B. 
Published: October 2024

SummaryThe use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype, but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS.In the United States, GS for adults and children is recommended to include a list of “secondary findings” genes (ACMG SF v3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v3.2 predominantly cause adult-onset disorders. Importantly, many genetic disorders with fetal and infantile onset are actionable as well.A proposed solution is to create a “fetal actionable findings list,” which can be offered to pregnant patients undergoing fetal GS or eventually, as a standalone cell-free fetal DNA screening test. In this integrative review, we propose criteria for an actionable fetal findings list, then identify genetic disorders with clinically available or emerging fetal therapies, and those for which clinical detection in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of an actionable fetal findings list.
Individual-specific strategies inform category learning
Authors: Collina Jared S. , Erdil Gozde , Xia Mingyi , Angeloni Christopher F. , Wood Katherine C. , Sheth Janaki , Kording Konrad P. , Cohen Yale E. , Geffen Maria N. 
Published: October 2024

ABSTRACTCategorization is an essential task for sensory perception. Individuals learn category labels using a variety of strategies to ensure that sensory signals, such as sounds or images, can be assigned to proper categories. Categories are often learned on the basis of extreme examples, and the boundary between categories can differ among individuals. The trajectories for learning also differ among individuals, as different individuals rely on different strategies, such as repeating or alternating choices. However, little is understood about the relationship between individual learning trajectories and learned categorization. To study this relationship, we trained mice to categorize auditory stimuli into two categories using a two-alternative forced choice task. Because the mice took several weeks to learn the task, we were able to quantify the time course of individual strategies and how they relate to how mice categorize stimuli around the categorization boundary. Different mice exhibited different trajectories while learning the task. Mice displayed preferences for a specific category, manifested by a choice bias in their responses, but this bias drifted with learning. We found that this drift in choice bias correlated with variability in the category boundary for sounds with ambiguous category membership. Next, we asked how stimulus-independent, individual-specific strategies informed learning. We found that the tendency to repeat choices, which is a form of perseveration, contributed to long-term learning. These results indicate that long-term trends in individual strategies during category learning affect learned category boundaries.
Increased bone inflammation in type 2 diabetes and obesity correlates with Wnt signaling downregulation and reduced bone strength
Authors: Leanza Giulia , Faraj Malak , Cannata Francesca , Viola Viola , Pellegrini Niccolò , Tramontana Flavia , Pedone Claudio , Vadalà Gianluca , Piccoli Alessandra , Strollo Rocky , Zalfa Francesca , Civitelli Roberto , Maccarrone Mauro , Papalia Rocco , Napoli Nicola 
Published: September 2024

AbstractType 2 diabetes (T2D) and obesity (OB) are associated with chronic low-grade inflammation and increased fracture risk.In vitrostudies showed that inflammation induces bone erosion and inhibits bone formation by increasing Wnt canonical pathway inhibitors. However, the impact of inflammation on Wnt pathway regulation and bone quality in T2D and OB remains unclear. To this end, we studied 63 postmenopausal women (age >65 years) undergoing hip replacement for osteoarthritis. Among these women, 19 had T2D and OB (HbA1c 6.8±0.79%; BMI 29.9±5.2 kg/m2), 17 had OB but they were normoglycemic (BMI 32.5±5.4 kg/m2), and 27 served as controls (BMI 23.1±5.5 kg/m2). Serum inflammatory cytokines by automated immunoassay (ELLA), revealed higher TNF-α (p=0.0084) and lower adiponectin (p=0.0402) in T2D, and higher IL-6 (p=0.0003) levels in OB vs controls. Gene expression analysis of trabecular bone showed increased TNF-α (p=0.0019) and SFRP5 (p=0.0084) in T2D vs controls. IL-10 was lower in both T2D (p=0.0285), and OB (p=0.0324), while adiponectin (ADIPOQ) was only lower in T2D (p=0.0041) vs controls. Interestingly, the Wnt inhibitor SOST was higher in T2D (p<0.0001) and OB (p<0.0001) vs controls. Conversely, WNT10B mRNA levels were lower in T2D (p=0.0071) and in OB (p=0.0196) vs controls, while LEF-1 were only lower in T2D (p=0.0009). WNT5A (p=0.0025) and GSK3β (p=0.0003) mRNA levels were higher only T2D vs controls. Importantly, TNF-α mRNA levels positively correlated with SOST (r=0.5121, p=0.0002), WNT5A (r=0.3227, p=0.0396) and GSK3β (r=0.3789, p=0.0146) mRNA levels, but negatively correlated with WNT10B (r=0.3844, p=0.0188) and LEF-1(r=-0.3310, p=0.0322) mRNA levels. Conversely, IL-10 was negatively correlated with SOST mRNA levels (r=0.3100, p=0.0457). ADIPOQ was negatively correlated with SOST (r=-0.3864, p=0.0105) and WNT5A (r=-0.3025, p=0.0515) mRNA levels. Moreover, SFRP5 was negatively correlated with LEF-1 mRNA levels (r=0.3991, p=0.0131). Finally, serum levels of TNF-α (r=-0.3473, p=0.0352) and IL-6 (r=-0.3777, p=0.0302) negatively correlated with Young’s Modulus, an index of bone strength. These findings suggest that increased inflammation in bone of subjects with T2D and obesity is negatively associated with Wnt pathway and bone strength, shedding light on pathophysiology of bone impairment in T2D and obesity.
Somatic mutant selection is altered by priorNOTCH1mutation in aging esophageal epithelium
Authors: King Charlotte , Abby Emilie , Fowler Joanna C. , Abnizova Irina , Sood Roshan K. , Ong Swee Hoe , Hall Michael W. J. , Lynch-Williams Faye , Hall Benjamin A. , Jones Philip H. 
Published: September 2024

AbstractIn cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. MutantNOTCH1clones colonized most of the epithelium by age 60 and the tissue became saturated with mutants under strong competitive selection by age 70. Compared to samples that were mostlyNOTCH1wildtype, samples predominantly mutant forNOTCH1showed weaker selection of mutantTP53and increased selection ofNOTCH2mutants. In mouse esophagus lackingNotch1we observed strong selection of mutantNotch2, not seen in wild type epithelium. In aging esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutational selection and by restricting space available for the expansion of other mutant clones.
Effects of alcohol on the transcriptome, methylome, and metabolome ofin vitrogastrulating human embryonic cells
Authors: Wallén E , Rämö K , Vehviläinen J , Sokka J , Lehtonen M , Otonkoski T , Trokovic R , Auvinen P , Kärkkäinen O , Kaminen-Ahola N 
Published: September 2024

ABSTRACTPrenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neurodevelopmental disorders and birth defects. To explore the effects of PAE on gastrulation, we used anin vitromodel with subchronic moderate (20 mM) and severe (70 mM) ethanol exposures during the differentiation of human embryonic stem cells into germ layer cells. We analysed genome-wide gene expression (mRNA sequencing), DNA methylation (EPIC Illumina microarrays), and metabolome (non-targeted LC-MS method) of the endodermal, mesodermal, and ectodermal cells. The largest number of ethanol-induced alterations were observed in the endodermal cells, whereas the most prominent changes were seen in the ectodermal cells. Genes of the major morphogen signaling pathways involved in gastrulation and body patterning were affected by ethanol. Many of the altered genes, such asBMP4,FGF8,SIX3,andLHX2, have been previously associated with PAE and phenotypes of FASD, like defects in heart and corpus callosum development as well as holoprosencephaly. Furthermore, methionine metabolism was altered in all germ layer cells. Our findings support the early origin of alcohol-induced developmental disorders and strengthen the role of methionine cycle in the etiology of FASD.
Alternative splicing of transposable elements in human breast cancer
Authors: Nesta Alex , Veiga Diogo F. T. , Banchereau Jacques , Anczukow Olga , Beck Christine R. 
Published: September 2024

AbstractTransposable elements (TEs) drive genome evolution and can affect gene expression through diverse mechanisms. In breast cancer, disrupted regulation of TE sequences may facilitate tumor-specific transcriptomic alterations. We examine 142,514 full-length isoforms derived from long-read RNA sequencing (LR-seq) of 30 breast samples to investigate the effects of TEs on the breast cancer transcriptome. Approximately half of these isoforms contain TE sequences, and these contribute to half of the novel annotated splice junctions. We quantify splicing of these LR-seq derived isoforms in 1,135 breast tumors from The Cancer Genome Atlas (TCGA) and 1,329 healthy tissue samples from the Genotype-Tissue Expression (GTEx), and find 300 TE-overlapping tumor-specific splicing events. Some splicing events are enriched in specific breast cancer subtypes – for example, a TE-driven transcription start site upstream ofERBB2in HER2+ tumors, and several TE-mediated splicing events are associated with patient survival and poor prognosis. The full-length sequences we capture with LR-seq reveal thousands of isoforms with signatures of RNA editing, including a novel isoform belonging toRHOA; a gene previously implicated in tumor progression. We utilize our full-length isoforms to discover polymorphic TE insertions that alter splicing and validate one of these events in breast cancer cell lines. Together, our results demonstrate the widespread effects of dysregulated TEs on breast cancer transcriptomes and highlight the advantages of long-read isoform sequencing for understanding TE biology. TE-derived isoforms may alter the expression of genes important in cancer and can potentially be used as novel, disease-specific therapeutic targets or biomarkers.One Sentence SummaryTransposable elements generate alternative isoforms and alter post-transcriptional regulation in human breast cancer.