bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation
Authors: Jiao Juying , Ruan Linjie , Cheng Chien-shan , Wang Fengjiao , Yang Peiwen , Chen Zhen 
Published: April 2023

Abstract
Background
Protein kinases play a pivotal role in the malignant evolution of pancreatic cancer (PC) through mediating phosphorylation. Many kinase inhibitors have been developed and translated into clinical use, while the complex pathology of PC confounds their clinical efficacy and warrants the discovery of more effective therapeutic targets.

Methods
Here, we used the Gene Expression Omnibus (GEO) database and protein kinase datasets to map the PC-related protein kinase-encoding genes. Then, applying Gene Expression and Profiling Interactive Analysis (GEPIA), GEO and Human Protein Atlas, we evaluated gene correlation, gene expression at protein and mRNA levels, as well as survival significance. In addition, we performed protein kinase RIPK2 knockout and overexpression to observe effects of its expression on PC cell proliferation, migration and invasion in vitro, as well as cell apoptosis, reactive oxygen species (ROS) production and autophagy. We established PC subcutaneous xenograft and liver metastasis models to investigate the effects of RIPK2 knockout on PC growth and metastasis. Co-immunoprecipitation and immunofluorescence were utilized to explore the interaction between protein kinases RIPK2 and PRKCI. Polymerase chain reaction and immunoblotting were used to evaluate gene expression and protein phosphorylation level.

Results
We found fourteen kinases aberrantly expressed in human PC and nine kinases with prognosis significance. Among them, RIPK2 with both serine/threonine and tyrosine activities were validated to promote PC cells proliferation, migration and invasion. RIPK2 knockout could inhibit subcutaneous tumor growth and liver metastasis of PC. In addition, RIPK2 knockout suppressed autophagosome formation, increased ROS production and PC cell apoptosis. Importantly, another oncogenic kinase PRKCI could interact with RIPK2 to enhance the phosphorylation of downstream NF-κB, JNK and ERK.

Conclusion
Paired protein kinases PRKCI-RIPK2 with multiple phosphorylation activities represent a new pathological mechanism in PC and could provide potential targets for PC therapy.
Gonadal transcriptomes reveal sex-biased expression genes associated with sex determination and differentiation in red-tail catfish (Hemibagrus wyckioides)
Authors: Wei Wen-Yu , Gong Yi , Guo Xin-Fen , Liu Min , Zhou Yu-Lin , Li Zhi , Zhou Li , Wang Zhong-Wei , Gui Jian-Fang 
Published: April 2023

Abstract
Background
Red-tail catfish (Hemibagrus wyckioides) is an important commercially farmed catfish in southern China. Males of red-tail catfish grow faster than females, suggesting that all-male catfish will produce more significant economic benefits in aquaculture practice. However, little research has been reported on sex determination and gonadal development in red-tail catfish.

Results
In this study, we performed the first transcriptomic analysis of male and female gonads at four developmental stages at 10, 18, 30, and 48 days post hatching (dph) using RNA-seq technology. A total of 23,588 genes were screened in 24 sequenced samples, of which 28, 213, 636, and 1381 differentially expressed genes (DEGs) were detected at four developmental stages, respectively. Seven candidate genes of sex determination and differentiation were further identified. Real-time quantitative PCR (RT-qPCR) further confirmed that anti-Mullerian hormone (amh), growth differentiation factor 6a (gdf6a), testis-specific gene antigen 10 (tsga10), and cytochrome P450 family 17 subfamily A (cyp17a) were highly expressed mainly in the male, while cytochrome P450 family 19 subfamily A polypeptide 1b (cyp19a1b), forkhead box L2 (foxl2), and hydroxysteroid 17-beta dehydrogenase 1 (hsd17b1) were highly expressed in the female. The KEGG pathway enrichment data showed that these identified DEGs were mainly involved in steroid hormone biosynthesis and TGF-β signaling pathways.

Conclusions
Based on RNA-seq data of gonads at the early developmental stages, seven DEGs shared by the four developmental stages were identified, among which amh and gdf6a may be the male-biased expression genes, while foxl2, cyp19a1b and hsd17b1 may be the female-biased expression genes in red-tail catfish. Our study will provide crucial genetic information for the research on sex control in red-tail catfish, as well as for exploring the evolutionary processes of sex determination mechanisms in fish.
Intercellular crosstalk in adult dental pulp is mediated by heparin-binding growth factors Pleiotrophin and Midkine
Authors: Jiravejchakul Natnicha , Abe Gabriela L. , Loza Martin , Park Soyoung , Matangkasombut Ponpan , Sasaki Jun-Ichi , Imazato Satoshi , Diez Diego , Standley Daron M. 
Published: April 2023

AbstractBackgroundIn-depth knowledge of the cellular and molecular composition of dental pulp (DP) and the crosstalk between DP cells that drive tissue homeostasis are not well understood. To address these questions, we performed a comparative analysis of publicly available single-cell transcriptomes of healthy adult human DP to 5 other reference tissues: peripheral blood mononuclear cells, bone marrow, adipose tissue, lung, and skin.ResultsOur analysis revealed that DP resident cells have a unique gene expression profile when compared to the reference tissues, and that DP fibroblasts are the main cell type contributing to this expression profile. Genes coding for pleiotrophin (PTN) and midkine (MDK), homologous heparin-binding growth-factors, possessed the highest differential expression levels in DP fibroblasts. In addition, we identified extensive crosstalk between DP fibroblasts and several other DP resident cells, including Schwann cells, mesenchymal stem cells and odontoblasts, mediated byPTNandMDK.ConclusionsDP fibroblasts emerge as unappreciated players in DP homeostasis, mainly through their crosstalk with glial cells. These findings suggest that fibroblast-derived growth factors possess major regulatory functions and thus have a potential role as dental therapeutic targets.
The adjustment of China endemic Heptacodium miconioides Rehd. to temperate zone of Poland
Authors: Monder Marta Joanna , Bąbelewski Przemysław , Szperlik Jakub , Kościelak Agnieszka 
Published: April 2023

AbstractHeptacodium miconioidesis an increasingly popular ornamental plant, originally being endemic to China. The late and long flowering determines its ecological and ornamental value in cultivation. The aims of this research were to define and distinguish phenological phases of the development ofHeptacodium miconioidesin the temperate zone region and identification of anatomical changes within the stem during autumn in relation to phenological phases and climatic conditions. Phenological observations were carried out in Wrocław during 2012–2013, as well as in Warsaw (Poland, 52.6°N, 20.5°E) during 2018–2021. During the last year of research an analysis of the anatomical structure was carried out for young stems that bore flowers that year, as well as older, 2- to 6-year-old ones. The material was collected H1 – 10.09., H2 – 28.09., H3 – 16.10., H4 – 3.11., H5 – 21.11. The width of annual increments in subsequent years was determined; length, width and vessel density in early and latewood for subsequent rings of annual growth was measured, as well as the width of the phloem in 1–6-year-old stems (2016–2021). In the vegetative stage three main stages of development were distinguished (leaf buds have the green tips; full autumn discoloration of leaves; leaves falling). In the generative phase, which lasted on average from August 22ndto January the 7thfive main phases of development were distinguished (flowering, unripe fruits, ripe fruits, spreading of seeds). Increased average temperature during winter and spring had an effect on the growth pattern: early phenological stages occurred sooner and foliage development lasted 44 days longer. Flowering occurred at a similar date at both observed locations and climatic conditions. This year’s shoots flowering on a radial section with axial symmetry, were slightly flattened and in clusters arranged regularly to match the shape.Heptacodiumdevelops 2–6 years old shoots with radial symmetry. The growth ring boundaries are distinct, the wood semi-rings porous, with marked differences in the structure of the primary and secondary shoot. Lignification of tissues before winter ends during late leaf-fall phase. The research indicated the adaptive potential ofHeptacodiumin response to climatic conditions of temperate zone.
Association between different MAP levels and 30-day mortality in sepsis patients: a propensity-score-matched, retrospective cohort study
Authors: Zhong Xiaoxin , Li Haifeng , Chen Qian , Hao Peng , Chen Tong , Mai Hantao , Zhang Kelin , Zhong Guifang , Guo Ruilian , Cheng Huihua , Jiang Benhua , Zhu Sicong , Zhuang Suyuan , Li Haoran , Chen Yantao , He Qing 
Published: April 2023

Abstract
Background
Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients.

Methods
We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60–65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results.

Results
A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60–65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60–0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission.

Conclusions
After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.
Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis
Authors: Li Qiang , Bu Yanling , Shao Haifeng , Li Wenhua , Zhao Di , Wang Jian 
Published: April 2023

Abstract
Background
The exosomes (exos) of bone marrow mesenchymal stem cells (BMSCs) play an important therapeutic role in repairing myocardial injury. The purpose of this study was to explore how the exos of BMSCs can alleviate the myocardial cell injury caused by hypoxia/reoxygenation (H/R) through HAND2-AS1/miR-17-5p/Mfn 2 pathway.

Methods
Cardiomyocytes H9c2 were damaged by H/R to mimic myocardial damage. Exos were gained from BMSC. The content of HAND2-AS1 and miR-17-5p was assessed by RT-qPCR. Cell survival rate and apoptosis were estimated by MTT assay and flow cytometry. Western blotting was used to detect the expression of protein. The contents of LDH, SOD, and MDA in the cell culture were detected by commercial kits. The luciferase reporter gene method confirmed the targeted relationships.

Results
In H9c2 cells induced by H/R, the level of HAND2-AS1 declined and the expression of miR-17-5p was elevated, but their expression was reversed after exo treatment. Exos improved the cell viability, declined cell apoptosis, controlled the oxidative stress, and repressed inflammation, thus attenuating the damage of H9c2 induced by H/R, whereas, the knockdown of HAND2-AS1 partly alleviated the impacts of exos. MiR-17-5p played the opposite role to HAND2-AS1 on H/R-injured myocardial cells.

Conclusion
Exos derived from BMSC could alleviate H/R-induced myocardial injury by activating HAND2-AS1/miR-17-5p/Mfn2 pathway.
Effect of C-reactive protein on the risk of Heart failure: a mendelian randomization study
Authors: Habibi Danial , Daneshpour Maryam S , Asgarian Sara , Kohansal Karim , Hadaegh Farzad , Mansourian Marjan , Akbarzadeh Mahdi 
Published: April 2023

Abstract
Background
Traditional observational studies have shown positive associations between c-reactive protein (CRP) and heart failure (HF) risk. However, this association has not been fully elucidated. Therefore, Mendelian randomization was used to examine CRP’s possible etiological roles with HF.

Methods
We implemented a two-sample Mendelian randomization framework to examine the causality of the association between CRP and HF based on summary statistics by large-scale genome-wide association studies (GWAS) datasets of European ancestry through inverse-variance weighted, weighted median, MREgger regression, and MR-PRESSO methods. The summary statistics dataset on the association of genetic variants with CRP was used from the published GWAS of European descent in UK Biobank participants (N = 427,367) and the CHARGE consortium (N = 575,531). The GWAS dataset used to identify genetic variants underlying HF from the HERMES consortium includes 977,323 participants (47,309 cases and 930,014 controls). The odds ratio (OR) with 95% confidence intervals (CIs) was employed to examine this association.

Results
The results of our IVW indicated that CRP was strongly associated with HF (OR = 4.18, 95% CI = 3.40–5.13, p < 0.001). The Cochran heterogeneity test showed significant heterogeneity among SNPs of CRP (Q = 317.55, p < 0.001; I2 = 37.6%), and no considerable pleiotropy was detected for the association of CRP with HF [intercept = 0.003; p = 0.234]. This finding remained consistent using different Mendelian randomization methods and sensitivity analyses.

Conclusion
Our MR study did identify convincing evidence to support CRP associated with HF risk. Human genetic data suggest that CRP is a causative factor in HF. Hence, CRP assessment may offer additional prognostic information as an adjuvant to overall risk assessment in HF patients. These findings prompt significant questions about the function of inflammation in the progression of HF. More research into the role of inflammation in HF is needed to guide trials of anti-inflammation management.
The conceptualization of acute bronchitis in general practice – a fuzzy problem with consequences? A qualitative study in primary care
Authors: Schubert Nadine , Kühlein Thomas , Burggraf Larissa 
Published: April 2023

Abstract
Background
Acute bronchitis is one of the most frequent diagnoses in primary care. Scientifically, it is conceptualized as a viral infection. Still, general practitioners (GPs) often prescribe antibiotics for acute bronchitis. The explanation for this discrepancy may lie in a different conceptualization of acute bronchitis. Therefore, we wanted to know, how GPs conceptualize acute bronchitis, and how they differentiate it from common cold and pneumonia. Furthermore, we tried to find out the GPs’ reasons for prescribing antibiotics in those cases.

Methods
To answer our study questions, we conducted a qualitative study with GPs in Bavaria, Germany, by using semi-structured guided interviews. The analysis of the data was conducted using the documentary method according to Ralf Bohnsack. The transcripts were subdivided into categories. Analyzing each part by reflective interpretation, first manually, secondly with the help of RQDA, we extracted the most representative citations and main messages from the interviews.

Results
The term acute bronchitis seems to be applied when there is neither certainty of the diagnosis common cold, nor of pneumonia. It seems it bridges the gap of uncertainty between supposedly harmless clinical pictures (common cold/viral), to the more serious ones (pneumonia/bacterial). The conceptual transitions between common cold and acute bronchitis on the one side, and acute bronchitis and pneumonia on the other are fluid. The diagnosis acute bronchitis cannot solve the problem of uncertainty but seems to be a label to overcome it by offering a way to include different factors such as severity of symptoms, presumed signs of bacterial secondary infection, comorbidities, and presumed expectations of patients. It seems to solve the pathophysiologic riddle of bacterial or viral and of decision making in prescribing antibiotics.

Conclusion
Acute bronchitis as an "intermediate category" proved difficult to define for the GPs. Applying this diagnosis leaves GPs in abeyance of prescribing an antibiotic or not. As a consequence of this uncertainty in pathophysiologic reasoning (viral or bacterial) other clinical and social factors tip the balance towards antibiotic prescribing. Teaching physicians to better think in probabilities of outcomes instead of pathophysiologic reasoning and to deal with uncertainty might help reducing antibiotic overprescribing.
Change in functional disability and its trends among older adults in Korea over 2008–2020: a 4-year follow-up cohort study
Authors: Nguyen Van Cuong , Hong Gwi-Ryung Son 
Published: April 2023

Abstract
Background
The prevalence of functional disabilities, including difficulties in performing activities of daily living (ADLs) and instrumental activities of daily living (IADLs), increased significantly in recent years and burdened the healthcare system.

Methods
We analysed data from Korean Longitudinal Study of Aging (KLOSA) surveys, including participants aged 65 or older at baseline (2008), and participated in all 4-year follow-up periods in 2012, 2016, and 2020. A 4-year follow-up cohort study was applied to specify the change in functional disability and its trend over time among older adults. The generalized estimation equation (GEE) model was used to verify the uptrend of functional disability. Logistic regression analyses were applied to examine the influence of demographic and health parameters on the change in functional disability.

Results
The prevalence of ADL disability was 2.24% at baseline, increased to 3.10% after four years, 6.42% after eight years, and reached 11.12% after 12 years, five times higher than that at baseline. For IADL disability, they were 10.67%, 10.61%, 18.18%, and 25.57%, respectively. The uptrend of ADL disability in persons aged 65–74 (1.77% at baseline, increased to 7.65% in 2020, 12-year change of 5.88%) was slower than in those aged 75 or older (4.22% at baseline, increased to 25.90% in 2020, 12-year change of 21.68%). IADL disability were consistent with this. The high ADL/IADL disability rate was also present among persons with poor health status, physical inactivity, depression, dementia, and multiple chronic diseases. The relative risk of ADL/IADL disability in persons with a history of functional disability was significantly higher than in those without historical disabilities.

Conclusion
The study verified the change in functional disability and its upward trend over time by older adults’ demographic and health parameters. Functional disability was relatively flat tending to increase slowly during the early years but increased rapidly in the following years. Factors that strongly influenced the change in prevalence and the uptrend of functional disability were advanced age, living alone, being underweight or obese, poor health status, physical inactivity, depression, dementia, having multiple chronic diseases, and especially having a historical disability.
Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study
Authors: Eletreby Rasha , Abdelaziz Rasha , Shousha Hend Ibrahim , Hammam Zeinab , Hany Ayman , Sabry Dina , Elawady Basma , Zayed Naglaa , Yosry Ayman , Alem Shereen Abdel 
Published: April 2023

Abstract
Background
Cytomegalovirus (CMV) infection among pregnant females could induce CMV hepatitis with possible changes in liver stiffness measurement (LSM) which could be reversibly increased during normal pregnancies, particularly in the third trimester. This study aimed to detect the prevalence of CMV infection among pregnant females with and without chronic liver disease and to evaluate the effects of CMV infection on LSM and pregnancy outcomes in comparison to non-CMV-infected pregnant females.

Methods
This is an observational prospective study that included 201 pregnant ladies presented to the liver disease with pregnancy clinic, Cairo University from March 2018 to April 2019. We assessed the laboratory results, abdominal ultrasonography, LSM using ARFI elastography, and pregnancy outcomes.

Results
Two hundred and one pregnant ladies were divided into ; group 1: pregnant ladies with normal pregnancy (n = 128), group 2: pregnant ladies with chronic liver diseases not related to pregnancy (n = 35), and group 3: pregnant ladies with pregnancy-related liver diseases (n = 38). Positive CMV serology (either/or, +ve CMV-IgM, IgG) was detected in 106/201 patients (52.74%), and fifteen of them had an active infection (IgG +, IgM+, PCR+). Pregnant females with chronic liver diseases not related to pregnancy had significantly higher serum levels of CMV IgM, IgG, and PCR. Moreover, LSM had a significant correlation with CMV IgG and CM_PCR in normal pregnant ladies. Maternal mortality occurred only in pregnant females with chronic liver diseases in 5.7% (2/35).

Conclusion
Maternal CMV infection carries a significant risk to pregnant females with chronic liver disease. Routine CMV screening for women planning to be pregnant, especially those with chronic liver disease could help to avoid bad maternal and fetal outcomes.