bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocarditis—A Helpful Algorithm to Overcome Diagnostic Challenges in the Pediatric Population
Authors: Knoler Nitzan , Krymko Hanna , Slanovic Leonel , Grunseid Michael , Paran Nave , Hassan Lior , Levitas Aviva 
Published: March 2024

Objectives
This study was designed to investigate clinical differences between pediatric patients who presented with chest pain, tachycardia, and/or tachypnea who subsequently were or were not diagnosed with myocarditis. The results were used to develop a decision tree to aid in rapid diagnosis of pediatric myocarditis.

Methods
A retrospective case-control study was performed using the electronic medical records of children aged 0 to 18 years between the years 2003 and 2020 with a complaint of chest pain, tachycardia, and/or tachypnea. Patients included in the study were those diagnosed with myocarditis and those with suspected myocarditis, which was ultimately ruled out. Demographic and clinical differences between the research groups were analyzed. A decision tree was rendered using the rpart (Recursive Partitioning and Regression Trees) package.

Results
Four thousand one hundred twenty-five patients were screened for eligibility. Seventy-three myocarditis patients and 292 nonmyocarditis patients were included. Compared with the control group, the study group was found to have a higher mean respiratory rate (37 ± 23 vs 23 ± 7 breaths per minute) and mean heart rate (121 ± 44 vs 97 ± 25 beats per minute) and lower mean systolic and diastolic blood pressure (102 ± 27/56 ± 17 mm Hg vs 114 ± 14/67 ± 10 mm Hg). The mean white blood cell count was greater in the case group (13 ± 6 vs 10 ± 5 × 103/μL). A decision tree was rendered using simple demographic and clinical variables. The accuracy of the algorithm was 85.2%, with 100% accuracy in patients aged 0 to 2.5 years and 69% in patients aged 2.5 to 18 years.

Conclusion
The clinical and laboratory characteristics described in this study were similar to what is described in the literature. The decision tree may aid in the diagnosis of myocarditis in patients 2.5 years and younger. In the population aged 2.5 to 18 years, the decision tree did not constitute an adequate tool for detecting myocarditis.
Changes of urine proteome after intragastric administration of polysaccharide iron complex in rats
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Gao Youhe 
Published: March 2024

AbstractIron is an essential trace element to maintain the normal physiological function of organisms. In this study, the urine proteome of rats before and after short-term intragastric administration of polysaccharide-iron complex (28mg/kg/d iron, which is equivalent to the dose of anemia prevention in adults) was compared and analyzed by using two analysis methods: individual comparison and group comparison. Many different proteins were reported to be related to iron, including 2’, 3’ -cyclic nucleotide 3’ -phosphodiesterase (CNPase) (7.7 times higher than that after gavage, p=0.0039), p38 (14.5 times higher than that before gavage, p=0.003), etc. In the individual comparison, Hepcidin was up-regulated in 4 rats simultaneously. The biological processes of differential protein enrichment include carbohydrate metabolism, iron ion reaction, apoptosis regulation, hematopoietic progenitor cell differentiation, etc. Molecular functions (e.g., complement binding, hemoglobin binding, etc.), KEGG pathways (e.g., complement and coagulation cascade, cholesterol metabolism, malaria, etc.) have also been shown to be associated with iron. This study contributes to the in-depth understanding of the biological function of iron from the perspective of urine proteomics, and provides a new research perspective for the prevention, diagnosis, treatment and monitoring of iron-related disorders.
Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 model of frontotemporal dementia
Authors: Matos Marina Souza , Sil Annesha , Riedel Gernot , Platt Bettina , Delibegovic Mirela 
Published: March 2024

AbstractMetabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of decreased brain glucose metabolism and insulin resistance in patients with dementia. Given the rising prevalence of age-related diseases, lifestyle adjustments and nutritional interventions are gaining interest. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations. Since the potential impact of MR on neurodegenerative diseases like dementia is not fully understood, we here examined the metabolic and behavioural phenotypes of a murine tauopathy model (rTg4510), which overexpresses human P301L mutated tau, and assessed the impact of an 8-week dietary MR. The rTg4510 mice and wild type (WT) littermates were assessed at 6 and 12 months of age. While rTg4510 mice displayed progressive behavioural and motor impairments at 6 and 12 months of age, MR led to significant benefits in the aged 12-month-old cohort, improving motor coordination and learning, short-term memory, and social recognition. These effects were accompanied by increased glycolysis in the hippocampus and higher FGF21 levels in the cortex. These benefits occurred in the absence of alterations in glucose metabolism/adiposity in this model. Overall, our results support the positive impact of MR on rTg4510 mice, suggesting this as a potential therapeutic intervention to delay and/or improve the progression in tau-related disease.
Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution
Authors: Feulner Lara , Wünnemann Florian , Liang Jenna , Hofmann Philipp , Hitz Marc-Phillip , Schapiro Denis , Leclerc Severine , van Vliet Patrick Piet , Andelfinger Gregor 
Published: March 2024

AbstractHeart maturation and remodelling during the foetal and early postnatal period are critical for proper survival and growth of the foetus, yet our knowledge of the molecular processes involved are lacking for many cardiac cell types. To gain a deeper understanding of the transcriptional dynamics of the heart during the perinatal period, we performed single-cell RNA-seq on E14.5, E16.5, E18.5, P0, P4 and P7 mouse hearts to establish a catalogue of 49,769 cells. Gene regulatory network and pathway activity analyses underscored that heart maturation is strongly associated with regulation of cell growth and proliferation via pathways such as TGFβ. We additionally identified a common, cell type-independent signature for imprinted genes over time. Surprisingly, bioinformatics analyses and confirmation with RNAscope confirmed that while lncRNA H19 expression decreased over time in multiple cardiac cell types, it remained stably expressed in endocardial cells between E14.5 and P7. This suggests a differential requirement for H19 in the endocardium, and points towards an endocardium-specific maturation process when compared to other cardiac cell types. We envision this dataset to serve as a resource for better understanding perinatal heart maturation at the transcriptomic level, and to help bridge the gap between early developmental and adult heart stages for single-cell transcriptomics.
Understanding flux switching in metabolic networks through an analysis of synthetic lethals
Authors: Manojna Sowmya , Malpani Tanisha , Mohite Omkar S. , Nath Saketha , Raman Karthik 
Published: March 2024

AbstractBiological systems are extremely robust and exhibit high levels of redundancy for multiple cellular functions. Some of this redundancy manifests as alternative pathways in metabolism. Synthetic double lethals in metabolic networks comprise pairs of reactions, which, when deleted simultaneously, abrogate cell growth. However, when one reaction from such pairs is removed, the cell reroutes its metabolites through alternative pathways. Very little is known about the set of reactions through which fluxes are rerouted. Analysing this redistribution would help us to uncover the linkage between the reactions in a synthetic double lethal and also understand the complexity underlying the reroutings. Studying synthetic lethality in the context of pathogenic bacteria can offer valuable insights into therapeutic interventions. In this work, we propose a constraint-based approach to unravel these alternate pathways and complex interdependencies within and across metabolic modules. The approach involves a generic optimisation that minimises the extent of rerouting between two reaction deletions, corresponding to synthetic lethal pairs. We also include a systematic analysis of synthetic lethals by identifying the reaction classes that make up these synthetic lethals. We applied our computational workflow to several existing high-quality genome-scale models to show that these rerouted reactions span across metabolic modules, thereby illustrating the complexity and uniqueness of metabolism. Our results provide interesting insights into the organisation of metabolic networks and their redundancy.The algorithm is available athttps://github.com/RamanLab/minRerouting.Contact:kraman@iitm.ac.in
A novel protein Moat prevents ectopic epithelial folding by limiting Bazooka/Par3-dependent adherens junctions
Authors: Gu Lingkun , Sauceda Rolin , Brar Jasneet , Fessahaye Ferdos , Joo Minsang , Lee Joan , Nguyan Jacqueline , Teng Marissa , Weng Mo 
Published: March 2024

ABSTRACTCortical myosin contraction and cell adhesion work together to promote tissue shape changes, but how they are modulated to achieve diverse morphogenetic outcomes remains unclear. Epithelial folding occurs via apical constriction, mediated by apical accumulation of contractile myosin engaged with adherens junctions, as in Drosophila ventral furrow formation. While levels of contractile myosin correlate with apical constriction, whether levels of adherens junctions modulate apical constriction is unknown. We identified a novel Drosophila genemoatthat maintains low levels of Bazooka/Par3-dependent adherens junctions and thereby restricts apical constriction to ventral furrow cells with high-level contractile myosin. Inmoatmutants, abnormally high levels of Bazooka/Par3-dependent adherens junctions promote ectopic apical constriction in cells with low-level contractile myosin, insufficient for apical constriction in wild type. Such ectopic apical constriction expands infolding behavior from ventral furrow to ectodermal anterior midgut, which normally forms a later circular invagination. Inmoat mutant ventral furrow, a perturbed apical constriction gradient delays infolding. Our results indicate that levels of adherens junctions can modulate the outcome of apical constriction, providing an additional mechanism to define morphogenetic boundaries.Summary StatementCharacterization of a novel gene moat demonstrates ectopic expansion of apical constriction due to abnormally high levels of Bazooka/Par3-dependent adherens junctions without defects in early patterning gene expression.
CMTM6 maintains B cell-intrinsic CD40 expression to regulate anti-tumor immunity
Authors: Long Yiru , Chen Runqiu , Chang Wenlong , Li Fanglin , Gu Longhua , Sun Jianhua , Chen Jing , Gong Likun 
Published: March 2024

SUMMARYHighlightsB cells participate in anti-tumor immunity by influencing the intratumoral infiltration and function of T cells;CMTM6 cis-interacts with CD40 and inhibits ubiquitin/proteasome-mediated CD40 degradation to maintain CD40 cell membrane levels;Loss of B cell-intrinsic CMTM6 significantly reduces CD40 signaling-mediated B cell activation, survival, differentiation, T/B cell interaction and anti-tumor immunity;B cell-intrinsic CMTM6 deficiency leads to a significant reduction in the anti-tumor activity CD40 agonists and ICB therapy.In BriefLong et al. demonstrate that B-cell intrinsic CMTM6 regulates CD40 signaling and function via maintaining the cell membrane level of B-cell CD40 through ubiquitin-proteasome pathway inhibition, thereby affecting B cell function, anti-tumor B-cell immunity and the efficacy of CD40 agonist and ICB therapy.Abstract FigureGraphic AbstractsThe essential role of B cells and B cell intrinsic molecules in tumor immunity is beginning to be recognized. Tumor cell CMTM6 is a novel tumor immunoregulator involved in maintaining membrane levels of several important molecules, such as PD-L1 and CD58. Host CMTM6 may also play a function in the tumor microenvironment. Here, we found that CMTM6 was highly expressed in splenic B cells and tumor-infiltrating B cells. CMTM6 deficiency resulted in impaired splenic development, germinal center B cell differentiation, memory B cell differentiation, T/B cell interaction and B cell anti-tumor immune responses. Through multi-omics data mining and B-cell agonist screening, we identified that CMTM6 interacted with CD40 and maintained CD40 membrane levels in B cells. CMTM6 cis-interacts with CD40 and inhibits ubiquitin/proteasome-mediated CD40 degradation. CMTM6 deficiency led to impaired CD40 signaling-mediated B cell activation, survival, proliferation, differentiation and T/B cell interaction. In vivo, CMTM6 deficiency leads to a significant decrease in the anti-tumor activity of ICB therapy and B cell-dependent CD40 agonists. Collectively, B-cell intrinsic CMTM6 maintains B cell CD40 levels and signaling to promote B cell function and anti-tumor immunity.
Epithelial heme oxygenase-1 enhances colonic tumorigenesis by inhibiting ferroptosis
Authors: Callahan Rosemary C. , Bhagavatula Geetha , Curry Jillian , Staley Alyse W. , Schaefer Rachel E. M. , Minhajuddin Faiz , Zhou Liheng , Neuhart Rane , Atif Shaikh M. , Orlicky David J. , Cartwright Ian M. , Gerich Mark , Theiss Arianne L. , Hall Caroline H. T. , Colgan Sean P. , Onyiah Joseph C. 
Published: March 2024

AbstractColorectal cancer has been linked to chronic colitis and red meat consumption, which can increase colonic iron and heme. Heme oxygenase-1 (Hmox1) metabolizes heme and releases ferrous iron, but its role in colonic tumorigenesis is not well-described. Recent studies suggest that ferroptosis, the iron-dependent form of cell death, protects against colonic tumorigenesis. Ferroptosis culminates in excessive lipid peroxidation that is constrained by the antioxidative glutathione pathway. We observed increased mucosal markers of ferroptosis and glutathione metabolism in the setting of murine and human colitis, as well as murine colonic neoplasia. We obtained similar results in murine and human colonic epithelial organoids exposed to heme and the ferroptosis activator erastin, especially induction ofHmox1. RNA sequencing of colonic organoids from mice with deletion of intestinal epithelialHmox1 (Hmox1ΔIEC) revealed increased ferroptosis and activated glutathione metabolism after heme exposure. In a colitis-associated cancer model we observed significantly fewer and smaller tumors inHmox1ΔIECmice compared to littermate controls. Transcriptional profiling ofHmox1ΔIECtumors and tumor organoids revealed increased ferroptosis and oxidative stress markers in tumor epithelial cells. In total, our findings reveal ferroptosis as an important colitis-associated cancer signature pathway, andHmox1as a key regulator in the tumor microenvironment.
Rarγ -Foxa1 signaling promotes luminal identity in prostate progenitors and is disrupted in prostate cancer
Authors: Felice Dario De , Alaimo Alessandro , Bressan Davide , Genovesi Sacha , Marmocchi Elisa , Annesi Nicole , Beccaceci Giulia , Dalfovo Davide , Cutrupi Federico , Foletto Veronica , Lorenzoni Marco , Gandolfi Francesco , Kannan Srinivasaraghavan , Verma Chandra S. , Vasciaveo Alessandro , Shen Michael M. , Romanel Alessandro , Chiacchiera Fulvio , Cambuli Francesco , Lunardi Andrea 
Published: March 2024

AbstractRetinoic acid (RA) signaling is a master regulator of vertebrate development with crucial roles in directing body axis orientation and tissue differentiation, including in the reproductive system. However, a mechanistic understanding of how RA signaling promotes cell lineage identity in different tissues is often missing.Here, leveraging prostate organoid technology, we demonstrated that RA signaling orchestrates the commitment of adult mouse prostate progenitors to glandular identity, epithelial barrier integrity, and ultimately, proper specification of the prostatic lumen. Mechanistically, RA-dependent RARγ activation promotes the expression of the pioneer factor Foxa1, which synergizes with the androgen pathway for proper luminal expansion, cytoarchitecture and function.FOXA1nucleotide variants are common in human prostate and breast cancers and considered driver mutations, though their pathogenic mechanism is incompletely understood. Combining functional genetics experiments with structural modeling of FOXA1 folding and chromatin binding analyses, we discovered that FOXA1F254E255is a loss-of-function mutation leading to compromised transcriptional function and lack of luminal fate commitment of prostate progenitors.Overall, we define RA as a crucial instructive signal for glandular identity in adult prostate progenitors. We propose deregulation of vitamin A metabolism as a risk factor for benign and malignant prostate disease, and identified cancer associated FOXA1 indels affecting residue F254 as loss-of-function mutations promoting dedifferentiation of adult prostate progenitors.Summary: Retinoic acid signaling orchestrates luminal differentiation of adult prostate progenitors
Cooperative involvement of zipper-interacting protein kinase (ZIPK) and the dual-specificity cell-division cycle 14A phosphatase (CDC14A) in vascular smooth muscle cell migration
Authors: Al-Ghabkari Abdulhameed , Carlson David A. , Haystead Timothy A. J. , MacDonald Justin A. 
Published: March 2024

ABSTRACTZipper-interacting protein kinase (ZIPK) is a Ser/Thr protein kinase with regulatory involvement in vascular smooth muscle cell (VSMC) actin polymerization and focal adhesion assembly dynamics. ZIPK silencing can induce cytoskeletal remodeling with disassembly of actin stress fiber networks and coincident loss of focal adhesion kinase (FAK)-pY397 phosphorylation. The link between ZIPK inhibition and FAK phosphorylation is unknown, and critical interactor(s) and regulator(s) are not yet defined. In this study, we further analyzed the ZIPK-FAK relationship in VSMCs. The application of HS38, a selective ZIPK inhibitor, to coronary artery vascular smooth muscle cells (CASMCs) suppressed cell migration, myosin light chain phosphorylation (pT18&pS19) and FAK-pY397 phosphorylation as well. This was associated with the translocation of cytoplasmic FAK to the nucleus. ZIPK inhibition with HS38 was consistently found to suppress the activation of FAK and attenuate the phosphorylation of other focal adhesion protein components (i.e., pCas130, paxillin, ERK). In addition, our study showed a decrease in human cell-division cycle 14A phosphatase (CDC14A) levels with ZIPK-siRNA treatment and increased CDC14A with transient transfection of ZIPK. Proximity ligation assays (PLA) revealed CDC14A localized with ZIPK and FAK. Silencing CDC14A showed an increase of FAK-pY397 phosphorylation. Ultimately, the data presented herein strongly support a regulatory mechanism of FAK in CASMCs by a ZIPK-CDC14A partnership; ZIPK may act as a key signal integrator to control CDC14A and FAK during VSMC migration.
Effects of Hydrolyzed Collagen as a Dietary Supplement on Fibroblast Activation: A Systematic Review
Authors: Querido Inacio Pedro Augusto , Chalupe Felipe Augusto , Vieira Rodolfo P 
Published: March 2024

AbstractPurposeOur objective was to conduct a systematic review of the effects of hydrolyzed collagen supplementation on the proliferation and activation of fibroblasts.MethodsThe search was conducted for journals that published articles in the English language, peer-reviewed, meeting the following criteria: a) randomized clinical trials, b) randomized studies in animals or humans, c) in vitro studies, d) studies using hydrolyzed collagens or collagen peptides, d) studies assessing alterations on fibroblasts as primary or secondary outcome. We utilized the main journal databases PUBMED/WEB OF SCIENCE and ongoing reviews by PROSPERO. For bias risk and methodological quality, we used an adaptation of the Downs and Black checklist. Our review followed the PRISMA checklist, conducted from February 2024 to the first week of March 2024, by two independent researchers (P.A.Q.I. and R.P.V.).ResultsEleven studies were included in this review, where our findings reinforce the notion that hydrolyzed collagens or collagen peptides at concentrations of 50-500 μg/ml are sufficient to stimulate fibroblasts in human and animal tissues without inducing toxicity. Different enzymatic processes may confer distinct biological properties to collagens, allowing for scenarios favoring fibroblast promotion or antioxidant effects. Lastly, collagens with lower molecular weights exhibit greater bioavailability to adjacent tissues.ConclusionHydrolyzed collagens or collagen peptides with molecular sizes ranging from <3 - 3000 KDa promote the stimulation of fibroblasts in human tissues.
A single cell RNA sequence atlas of the earlyDrosophilalarval eye
Authors: Raja Komal Kumar Bollepogu , Yeung Kelvin , Li Yumei , Chen Rui , Mardon Graeme 
Published: March 2024

AbstractTheDrosophilaeye has been an important model to understand principles of differentiation, proliferation, apoptosis and tissue morphogenesis. However, a single cell RNA sequence resource that captures gene expression dynamics from the initiation of differentiation to the specification of different cell types in the larval eye disc is lacking. Here, we report transcriptomic data from 13,000 cells that cover six developmental stages of the larval eye. Our data show cell clusters that correspond to all major cell types present in the eye disc ranging from the initiation of the morphogenetic furrow to the differentiation of each photoreceptor cell type as well as early cone cells. We identify dozens of cell type-specific genes whose function in different aspects of eye development have not been reported. These single cell data will greatly aid research groups studying different aspects of early eye development and will facilitate a deeper understanding of the larval eye as a model system.