bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of ultrasound imaging Omics in predicting molecular typing and assessing the risk of postoperative recurrence in breast cancer
Authors: Song Xinyu , Xu Haoyi , Wang Xiaoli , Liu Wen , Leng Xiaoling , Hu Yue , Luo Zhimin , Chen Yanyan , Dong Chao , Ma Binlin 
Published: July 2024

Abstract
Background
The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer.

Methods
A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves.

Results
In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability.

Conclusion
The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.
Mortality in sea lions is associated with the introduction of the H5N1 clade 2.3.4.4b virus in Brazil October 2023: whole genome sequencing and phylogenetic analysis
Authors: de Carvalho Araujo Andreina , Cho Andrew Yong , Silva Laura Morais Nascimento , Corrêa Thais Camilo , de Souza Gabriela Cristini , Albuquerque Adriana Silva , Macagnan Eduardo , Kolesnikvoas Cristiane K. M. , Meurer Rafael , Vieira Jenyffer Vierheller , Lemos Giulia Gaglianone , Barreto André Silva , Dick Jeferson Luis , Groch Karina Rejane , de Castilho Pedro Volkmer , Amgarten Deyvid , Malta Fernanda , Miller Michael , Dorlass Erick G. , Palameta Soledad , Lee Sun-Hak , Arns Clarice Weis , Durigon Edison L. , Pinho João Renato R. , Lee Dong-Hun , Ferreira Helena Lage 
Published: July 2024

AbstractClade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.
Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia
Authors: Nouri Zahra , Sarmadi Akram , Narrei Sina , Kianersi Hamidreza , Kianersi Farzan , Tabatabaiefar Mohammad Amin 
Published: July 2024

Abstract
Background
Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals.

Methods
Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022.

Results
All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis.

Conclusions
Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.
Amino acids regulating skeletal muscle metabolism: mechanisms of action, physical training dosage recommendations and adverse effects
Authors: Li Guangqi , Li Zhaojun , Liu Junyi 
Published: July 2024

AbstractMaintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research.
Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus
Authors: Mayo Francisco , González-Vinceiro Lourdes , Hiraldo-González Laura , Rodríguez-Gómez Francisco D. , Calle-Castillejo Claudia , Mayo Manuel , Netti Vanina , Ramírez-Lorca Reposo , Echevarría Miriam 
Published: July 2024

AbstractAQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4−/− mice (KO) due to stenosis of Silvio’s aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4−/− mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.
A high-efficiency transient expression system mediated by Agrobacterium tumefaciens in Spinacia oleracea leaves
Authors: Zhang Yumeng , Qiu Liuliu , Zhang Yongxue , Wang Yiran , Fu Chunxiang , Dai Shaojun , Sun Meihong 
Published: July 2024

Abstract
Background
Optimization of a highly efficient transient expression system is critical for the study of gene function, particularly in those plants in which stable transformation methods are not widely available. Agrobacterium tumefaciens‑mediated transient transformation is a simple and low-cost method that has been developed and applied to a wide variety of plant species. However, the transient expression in spinach (Spinacia oleracea L.) is still not reported.

Results
We developed a transient expression system in spinach leaves of the Sp75 and Sp73 varieties. Several factors influencing the transformation efficiency were optimized such as Agrobacterium strain, spinach seedling stage, leaf position, and the expression time after injection. Agrobacterium strain GV3101 (pSoup-p19) was more efficient than AGL1 in expressing recombinant protein in spinach leaves. In general, Sp75 leaves were more suitable than Sp73 leaves, regardless of grow stage. At four-leaf stage, higher intensity and efficiency of transient expression were observed in group 1 (G1) of Sp75 at 53 h after injection (HAI) and in G1 of Sp73 at 64 HAI. At six-leaf stage of Sp75, group 3 (G3) at 72 HAI were the most effective condition for transient expression. Using the optimized expression system, we detected the subcellular localization of a transcriptional co-activator SoMBF1c and a NADPH oxidase SoRbohF. We also detected the interaction of the protein kinase SoCRK10 and the NADPH oxidase SoRbohB.

Conclusion
This study established a method of highly efficient transient expression mediated by Agrobacterium in spinach leaves. The transient expression system will facilitate the analysis of gene function and lay a solid foundation for molecular design breeding of spinach.
MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma
Authors: Palizkaran Yazdi Mahsa , Barjasteh Amirhosein , Moghbeli Meysam 
Published: July 2024

AbstractGlioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.
Addressing bioreactor hiPSC aggregate stability, maintenance and scaleup challenges using a design of experiment approach
Authors: Yehya Haneen , Raudins Sofija , Padmanabhan Roshan , Jensen Jan , Bukys Michael A. 
Published: July 2024

Abstract
Background
Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability.

Methods
Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power.

Results
Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1–1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion.

Conclusion
This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges.
Sex-related differences in left atrial substrate among patients with atrial fibrillation: evidence from high-density voltage mapping
Authors: Huang Wenchao , Sun Huaxin , Xiong Shiqiang , Luo Yan , Tang Yan , Zhang Zhen , Liu Hanxiong 
Published: July 2024

Abstract
Background
There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear.

Methods
We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation.

Results
Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (− 0.29, 95% confidence interval [CI] − 0.64 to − 0.13, P = 0.004) and AF type (− 0.32, 95% CI − 0.69 to − 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101–18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients.

Conclusion
Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.
Centering and flourishing: an online intervention study assessing the effects of a Christian contemplative practice on stress-reduction and human flourishing
Authors: Rohde Julia S. , Goldy Sean , Graziosi Marianna , Ferguson Michael A. , Thrul Johannes , Yaden David B. 
Published: July 2024

AbstractDespite widespread engagement in contemplative religious practices, comparatively little research has been conducted on their potential effects on well-being. Furthermore, few studies have focused on how an explicitly religious framing may impact the outcomes of such practices. In this online randomized controlled trial (N = 702), we tested the well-being effects of a contemplative prayer practice called Centering Prayer on self-identifying Christians. We compared 1) presenting the practice with an explicitly religious framing (experimental condition), 2) presenting the practice without an explicitly religious framing (active control), and 3) presenting simple instructions to reflect on the day, without any instructions regarding a meditation-like practice (passive control). After randomization into one of these three conditions, participants were asked to complete their assigned practice daily for 28 days. We hypothesized that the religious framing version of the practice would increase well-being over the active and passive control conditions. Well-being was assessed at three follow-up time points: one day, one week, and one month after the practice period. We found no group differences between the conditions on our primary outcome measure of well-being at one-week post-intervention. Each group increased in well-being from baseline to follow-up. We found significant group differences on acute measures of spiritual experience, the Mystical Experience Questionnaire (MEQ-30) and Daily Spiritual Experience Questionnaire (DSES). These results suggest that a religious framing may not enhance well-being effects but may alter spiritual outcomes related to contemplative practices.
Habitat and movement selection processes of American lobster/jakej within a restricted bay in the Bras d’Or Lake/Pitu’paq, Nova Scotia, Canada
Authors: Landovskis Shannon , Bailey Megan , Iverson Sara , Jeddore Skyler , Lennox Robert J. , Murray Caelin , Whoriskey Fred 
Published: July 2024

AbstractAmerican lobster inhabit the unique, brackish Bras d’Or Lake system, although densities are low compared to areas with similar habitats in the Atlantic Ocean. Nevertheless, lobsters are an important part of local First Nation (Mi’kmaq) food and culture. We used acoustic telemetry and habitat mapping, combined with local Mi’kmaw knowledge, to document the movements and habitat use of adult lobsters within a section of the Lake. Movement patterns of acoustically tagged individual lobsters were analyzed with both resource selection functions and integrated step selection functions using data obtained from a high-resolution VEMCO Positioning System within a restricted bay in the Bras d’Or Lake. The resource selection function suggested stronger selections of substrates that contained a combination of soft and hard sediments. While the integrated step selection functions found substantial individual variability in habitat selections, there was a trend for lobsters to exhibit more resident behaviour on the combined soft/hard substrates despite the fact these sediments provided little in the way of obvious shelters for the animals. Adult lobsters at this site have very little risk of predation, which presumably allows them to freely exhibit exploratory behaviours and reduce their association with substrates that provide shelters.
Single-nucleus multi-omics of Parkinson’s disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks
Authors: Shwab E. Keats , Gingerich Daniel C. , Man Zhaohui , Gamache Julia , Garrett Melanie E. , Crawford Gregory E. , Ashley-Koch Allison E. , Serrano Geidy E. , Beach Thomas G. , Lutz Michael W. , Chiba-Falek Ornit 
Published: July 2024

AbstractThe genetic architecture of Parkinson’s disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.