bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic Burden of Atrial Fibrillation Disease in Iran
Authors: Mohammadi Saeedeh , Rezapur Aziz , Azari Samad , Moein Mehdi 
Published: January 2024

Abstract

Background: Cardiovascular disease is recognized as the leading cause of death worldwide and is one of the most serious health problems worldwide. The sixth leading cause of death from CVD is atrial fibrillation. Atrial fibrillation has a major impact on public health, especially due to the increased risk of stroke and hospitalization as a result of increased costs. Healthcare policymakers and planners need awareness of the cost of the disease to make decisions to allocate resources optimally.
Methods: This cross-sectional study included 352 AF patients who were chosen at random from a specialist cardiovascular hospital in Iran. The cost of disease and human capital resources were used to calculate the direct and indirect costs of AF. To estimate direct and mortality costs, data were collected using a researcher-made checklist obtained from several sources, including structured interviews; the Statistical Center of Iran; Iran's Ministry of Cooperatives, Labor, and Social Welfare; the Central Bank of Iran; and data on global disease burden obtained from the Institute for Health Metrics and Evaluation. Iranian Rials (IRRs) were used to determine all expenditures.
Results: Atrial fibrillation disease imposes a significant economic burden on the economic system of Iran (study case). The total direct medical cost was calculated to be 718,095,752 riyals for each patient. The average cost of lost time created per patient day due to atrial fibrillation was estimated to be 16,357,092,258 rials. Most of the medical costs were related to hoteling costs (34/30), and the lowest amount of medical costs was related to nursing service costs (5/84). The economic burden for each patient was 1,712,049,0993 riyals during the year, for a discount rate of 3%. The economic burden of AF disease in West Azerbaijan Province was 31,552,693,043,034,628rials, and in Iran, it was 1,326,045,072,463 x 107 million.
Conclusion: AF has significant economic costs for society. The best way to address these diseases and therefore reduce costs is to change and correct risk-taking behaviors that make a person harmless to those diseases. Healthcare policymakers and planners need awareness of these expenses to make decisions to allocate resources optimally. Therefore, policymakers should take this into account in national health policies and, depending on the country’s capabilities, provide facilities and services to prevent and address dangerous behaviors and treat these groups of diseases.
The infectivity of AAV9 is influenced by the specific location and extent of chemically modified capsid residues
Authors: Milagros Sergio , de Erenchun Pablo Ramírez-Ruiz , Guembe Maite , Carte Beatriz , Mendez Miriam , Uribarri Ander , Aldabe Rafael 
Published: January 2024

Abstract
Background
Several treatments for genetic diseases utilizing recombinant adeno-associated viruses (AAVs) have recently gained approval. However, the development of a greater number of therapeutic AAVs is constrained by certain limitations. While extensive efforts have concentrated on screening AAV genetic libraries, an alternative strategy involves modifying the AAV capsid by attaching various moieties. The capsid of AAV plays a pivotal role in transducing target cells and evading immune responses, making modifications a key avenue for engineering improved variants.
Results
In our study, we replaced specific AAV9 capsid residues with an unnatural amino acid bearing a bioorthogonal group, identifying four positions with no adverse impact on production. Utilizing click chemistry, we attached varying proportions of Cy5.5 to these positions, allowing us to assess the impact of these modifications on AAV9 infectivity in cultured cells. Our findings reveal that both the position and degree of capsid modification significantly affect AAV transduction. While higher amounts of attached molecules lead to an increased number of AAV genomes within cells, this does not positively impact transgene expression. Conversely, a negative impact on transgene expression is observed when the AAV capsid is highly modified, with the degree of this effect associated with the modified residue.
Conclusion
Careful control of both the degree and specific position of capsid modifications is crucial for optimizing transduction efficiency and minimizing undesired effects on transgene expression. These results underscore the importance of precision in AAV capsid modification to achieve optimal transduction efficiency while mitigating potential drawbacks on transgene expression.
Transcriptome and metabolome analysis reveals mechanism of light intensity modulating iridoids biosynthesis in Gentiana macrophylla Pall.
Authors: Fu Huanhuan , Wang Yaomin , Mi Fakai , Wang Li , Yang Ye , Wang Fang , Yue Zhenggang , He Yihan 
Published: January 2024

Abstract

Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanism of metabolites and genes in G. macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities at 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML) and 200 µmol/m2/s (high light, HL), and the leaves were collected at 5-day for further investigation. A total of 2162 metabolites were detected, in which, the abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differential expression genes (DEGs) were identified after HL and LL groups, respectively, compared to the ML group, enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. In which, the transcription factors GmMYB5 and GmbHLH20 were found to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was changed under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway and thus affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, thus, delaying glycolysis, accumulating certain amino acids and decreasing loganic acid production, while high light got an opposite trend. Our research contributed significantly to understanding the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.
MicroRNA320e augments the synthetic lethality of olaparib by regulating homologous recombination repair via PI3K-AKT-mTOR pathway
Authors: Zheng Wei , Meng Qianlong , Deng Yunhan , Liu Ruizhen , Bai Siyu , Jia Lonyu , Wang Jing , Bai Huimin 
Published: January 2024

Abstract
Background: With the increase of drug resistance in ovarian cancer(OC), poly ADP-ribose polymerase inhibitors (PARPi) for the treatment of homologous recombination repair defects (HRD) have faced new challenges. MicroRNA320e (miR-320e) plays a negative regulatory role in the progression of many cancers. Therefore, we overexpressed miR-320e in both A2780 cells with HRD and SKOV3 cells without HRD.
Methods: 20 patients with high-grade serous ovarian cancer (HGSOC)and 20 patients with benign conditions were included in the experiment, and the expression
of miR-320e and FN1 were measured through fluorescence in situ hybridization (FISH) and immunohistochemistry experiments. CCK8, clone formation experiment, EdU assay and Transwell experiment were used to determine the proliferation, invasion, and migration ability of OC cells. The determination of the degree of cell apoptosis were achieved through flow cytometry and immunofluorescence experiments. The effects of miR-320e on the PI3K-AKT-mTOR signaling pathway and autophagy and cell apoptosis were validated through Western Blot experiments. In addition, the xenograft tumor growth study in nude mice investigated how miR-320e affects ovarian cancer progression in vivo. In addition, this study also investigated whether miR-320e affects the sensitivity of OC cells to Olaparib treatment in vitro and in vivo.
Results: The expression level of miR-320e is low, while the expression level of FN1 is actually high in the HGSOC patients. The results showed that after transfection with miR-320e, the proliferation, invasion, and migration abilities of both cells were significantly reduced, while the degree of autophagy and apoptosis increased(all p<0.05). The PI3K-AKT-mTOR signaling pathway was also significantly inhibited in the two-cell treatment groups (all p<0.05). Meanwhile, overexpression of miR-320e significantly inhibited tumor growth in nude mice(P<0.05). At the same time, the experimental results showed that overexpression of miR-320e could enhance the sensitivity of OC cells to olaparib therapy (all p<0.05).
Conclusions: Our study showed that miR-320e, as a key signaling molecule upstream affecting the malignant progression of ovarian cancer, inhibits the activation of PI3K-AKT-mTOR signaling pathway by negatively regulating the expression of downstream FN1 gene, thereby inhibiting the malignant development of ovarian cancer and promoting the sensitivity of cancer cells to olaparib therapy in vivo and in vitro.
Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin
Authors: Kobayashi Yukiko , Taniguchi Rikako , Shirasaki Emiko , Yoshimoto-Segawa Yuko , Aoi Wataru , Kuwahata Masashi 
Published: January 2024

Abstract
Purpose Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear.Methods We examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club over a 2-month period of continuous training and rest periods.Results Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period.Conclusion Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Therefore, the relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.
Combined SERS-Raman screening of HER2-overexpressing or silenced breast cancer cell lines
Authors: Spaziani Sara , Esposito Alessandro , Barisciano Giovannina , Quero Giuseppe , Elumalai Satheeshkumar , Leo Manuela , Colantuoni Vittorio , Mangini Maria , Pisco Marco , Sabatino Lina , de luca anna chiara , Cusano Andrea 
Published: January 2024

Abstract

Background
Breast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy.
Results
In this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison.
The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids.
We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analyzed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression.
Conclusions
Our results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients’ outcome.
NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells
Authors: Bottoni Laura , Minetti Alberto , Realini Giulia , Pio Elena , Giustarini Daniela , Rossi Ranieri , Rocchio Chiara , Franci Lorenzo , Salvini Laura , Catona Orazio , D’Aurizio Romina , Rasa Mahdi , Giurisato Emanuele , Neri Francesco , Orlandini Maurizio , Chiariello Mario , Galvagni Federico 
Published: January 2024

Abstract
Triple-negative breast cancer (TNBC) is a very aggressive and heterogeneous group of tumors. In order to develop effective therapeutic strategies, it is therefore essential to identify the subtype-specific molecular mechanisms underlying disease progression and resistance to chemotherapy. TNBC cells are highly dependent on exogenous cystine, provided by overexpression of the cystine/glutamate antiporter SLC7A11/xCT, to fuel glutathione synthesis and promote an oxidative stress response consistent with their high metabolic demands. Here we show that TNBC cells of the mesenchymal stem-like subtype (MSL) utilize forced cystine uptake to induce activation of the transcription factor NRF2 and promote a glutathione-independent mechanism to defend against oxidative stress. Mechanistically, we demonstrate that NRF2 activation is mediated by direct cysteinylation of the inhibitor KEAP1. Furthermore, we show that cystine-mediated NRF2 activation induces the expression of important genes involved in oxidative stress response, but also in epithelial-to-mesenchymal transition and stem-like phenotype. Remarkably, in survival analysis, four upregulated genes (OSGIN1, RGS17, SRXN1, AKR1B10) are negative prognostic markers for TNBC. Finally, expression of exogenous OSGIN1, similarly to expression of exogenous NRF2, can prevent cystine depletion-dependent death of MSL TNBC cells. The results suggest that the cystine/NRF2/OSGIN1 axis is a potential target for effective treatment of MSL TNBCs.
LncRNA H19 induces vascular calcification by suppressing the dual-specificity phosphatase 1/optic atrophy protein 1 pathway
Authors: chen wei ren , wu xue ping , sha yuan , zhou yu jie , qian geng , she fei , zhang ping 
Published: January 2024

Abstract

LncRNA H19 was first discovered to be involved in vascular calcification (VC). Our previous research found that VC inhibits dual specific phosphatase 1 (DUSP1) and optic atrophy protein 1 (OPA1) proteins, increases calcium deposition, runt related transcription factor 2 (Runx-2), bone morphogenetic protein 2 (BMP-2) expression, and apoptosis. This study sought to explore whether H19 induces VC and promotes calcium deposition, osteogenic differentiation, and apoptosis through the DUSP1/OPA1 pathway. The cell and animal calcification model were used to explore the effects of H19 on DUSP1/OPA1 pathways. β-glycerophosphate was used to establish vascular smooth muscle cells (VSMCs) calcification model. ApoE −/− diabetes mice were fed with high-fat diet for 32 weeks to establish animal calcification model. Calcium deposition was detected by Alizarin Red S staining and von Kossa staining. To observe osteogenic differentiation, the expression of Runx-2 and BMP-2 were measured by Western blotting. And apoptosis was evaluated by TUNEL staining and cleaved caspase-3 detection. The expression of H19 significantly increased, while the expression of DUSP1 and OPA1 significantly decreased in VC. H19 knockdown could significantly increase the expression of DUSP1 and OPA1 proteins. When DUSP1 was deleted, OPA1 was decreased again (P < 0.001). H19 knockdown inhibits calcified nodules, and reduces calcium content, Runx-2, BMP-2, cleaved caspase-3 expression, and apoptosis rate (P < 0.001). The inhibition of DUSP1 or OPA1 under H19 knockdown promotes the formation of calcified nodules, and increases the calcium content, Runx-2, BMP-2, expression of cleaved caspase-3, and apoptosis rate (P < 0.001). H19 induces VC by inhibiting the DUSP1/OPA1 protein pathway, which may be related to the increasing calcium deposition, osteogenic differentiation, and apoptosis.
An Imidazole-Copper(I) Metallacycle Complex Exhibiting Thermochromic Fluorescence
Authors: yu zongsu , wu dayu 
Published: January 2024

Abstract

In this paper, a new discrete coordination metallacycle complex, [CuI(bipy)]2 (1), is synthesized by solvothermal method using 2,6-bisimdazol pyridine and cuprous iodide as starting materials. The X-ray diffraction structure, temperature-dependent electronic absorption and photoluminescence spectra have been investigated. The solid-state fluorescence at variable temperatures shows that complex 1 exhibits an obvious thermochromic fluorescence. At low temperature, the dual fluorescence with peak at 590 and 694 nm was observed. The emission color significantly changes from red at 77 K to yellow at 200 K and blue-green at 330 K. The thermochromic fluorescent molecular materials shows great potential as temperature sensing.
The corrosion behavior of electroless Ni-P coatings in concentrated KOH electrolyte
Authors: He Anqiang , Hu Hang , Aasen Drew , Ivey Douglas Gordon 
Published: January 2024

Abstract

Ni-P has been widely used as a protective coating for many substrates. The corrosion resistance of Ni-P in neutral solutions such as NaCl, or acidic electrolytes such as HCl and H2SO4, has been extensively studied. However, the corrosion behavior of Ni-P coatings in caustic media, such as KOH, has received much less attention. Typically, corrosion behavior is studied through the use of electrochemical methods with corrosion rates determined from corrosion currents and potentials measured from Tafel curves. In this work, the corrosion rates of Ni-P coatings, with P concentrations varying from 2 to 11 wt%, in highly alkaline KOH (11 M) are obtained directly through electron microscopy measurements of cross sections and subsequent correlation with electrochemical data. Phosphorus concentration affects the corrosion rate; corrosion rate increases with increasing P content, peaks out at about 6–8 wt% P, and then decreases with any further increase in P content. This behavior is correlated to internal stress levels developed in the coatings.
Nanofluidic platform for studying the first-order phase transitions in superfluid helium-3
Authors: Heikkinen Petri J. , Eng Nathan , Levitin Lev V. , Rojas Xavier , Singh Angadjit , Autti Samuli , Haley Richard P. , Hindmarsh Mark , Zmeev Dmitry E. , Parpia Jeevak M. , Casey Andrew , Saunders John 
Published: January 2024

Abstract

The symmetry-breaking first-order phase transition between superfluid phases 3 He-A and 3 He-B can be triggered extrinsically by ionising radiation or heterogeneous nucleation arising from the details of the sample cell construction. However, the role of potential homogeneous intrinsic nucleation mechanisms remains elusive. Discovering and resolving the intrinsic processes may have cosmological consequences, since an analogous first-order phase transition, and the production of gravitational waves, has been predicted for the very early stages of the expanding Universe in many extensions of the Standard Model of particle physics. Here we introduce a new approach for probing the phase transition in superfluid 3 He. The setup consists of a novel stepped-height nanofluidic sample container with close to atomically smooth walls. The 3 He is confined in five tiny nanofabricated volumes and assayed non-invasively by NMR. Tuning of the state of 3 He by confinement is used to isolate each of these five volumes so that the phase transitions in them can occur independently and free from any obvious sources of heterogeneous nucleation. The small volumes also ensure that the transitions triggered by ionising radiation are strongly suppressed. Here we present the preliminary measurements using this setup, showing both strong supercooling of 3 He-A and superheating of 3 He-B, with stochastic processes dominating the phase transitions between the two. The objective is to study the nucleation as a function of temperature and pressure over the full phase diagram, to both better test the proposed extrinsic mechanisms and seek potential parallel intrinsic mechanisms.
Genome-wide Identification and Expression Analysis of the Universal Stress Protein (USP) Gene Family in Arabidopsis thaliana, Zea mays, and Oryza sativa
Authors: Fan Mingxia , Gao Song , Yang Yating , Yang Shuang , Wang He , Shi Lei 
Published: January 2024

Abstract

The Universal Stress Protein (USP) primarily participates in cellular responses to biotic and abiotic stressors, playing a pivotal role in plant growth, development, and Stress responses to adverse environmental conditions. Totals of 23, 26 and 26 USP genes were recognized in Arabidopsis thaliana, Zea mays, and Oryza sativa, respectively. According to USP genes physicochemical properties, proteins from USP Ⅰ class were identified as hydrophilic proteins with high stability. Based on phylogenetic analysis, USP genes family were classified into six groups, USP Ⅲ and USP Ⅴ showed more diversity. Additionally, members of the same subgroup exhibited similar numbers of introns/exons, and shared conserved domains, indicating close evolutionary relationships. Motif analysis results demonstrated a high degree of conservation among USP genes. Chromosomal distribution suggested that USP genes might have undergone gene expansion through segmental duplication in Arabidopsis thaliana, Zea mays, and Oryza sativa. Most Ka/Ks ratios were found to be less than 1, suggesting that USP genes in Arabidopsis thaliana, Zea mays, and Oryza sativa have experienced purifying selection. Expression profile analysis revealed that USP genes primarily respond to drought stress in Oryza sativa, temperature, and drought stress in Zea mays, and cold stress in Arabidopsis thaliana. Gene collinearity analysis can reveal correlations between genes, aiding subsequent in-depth investigations. This study sheds new light on the evolution of USP genes in monocots and dicots and lays the foundation for a better understanding of the biological functions of the USP genes family, can be used in programs related to Cucurbitaceae breeding.