bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology and molecular docking to elucidate the common mechanism of hydroxychloroquine treatment in lupus nephritis and IgA nephropathy
Authors: Chen Yixuan , Lu Meiqi , Lin Mengshu , Gao Qing 
Published: January 2024

Objective Hydroxychloroquine (HCQ), characterized by a broad effect on immune regulation, has been widely used in the treatment of autoimmune glomerulonephritis such as lupus nephritis (LN) and immunoglobulin A nephropathy (IgAN). The current research investigates whether HCQ plays a role in the treatment of LN and IgAN through common mechanisms since the pathogenesis of both LN and IgAN is closely related to immune complex deposition, complement activation, and ultimately inflammation. Methods Seventy-two common targets were obtained related to the common mechanism of HCQ treatment of LN and IgAN. Targets associated with LN and IgAN were collected based on DisGeNET, GeneCards, and OMIM databases. Possible HCQ targets were obtained from the PubChem database and PharmMapper databases. The overlapping targets of HCQ ingredients, IgAN, and LN were discovered via the Venn 2.1.0 online platform. Through the DAVID database, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Cytoscape (v3.9.1) was used to build a protein–protein interaction (PPI) network. Molecular docking was performed by using AutoDockTools 1.5.6 software and PyMol software to match the binding activity between HCQ and the 10 core targets. Results The results showed that core targets (including MMP 2, PPARG, IL-2, MAPK14, MMP 9, and SRC), three signaling pathways (including the PI3K-Akt, AGE-RAGE, and MAPK), and cell differentiation (including Th1, Th2, and Th17) might be related to the body’s immunity and inflammation. These results suggested that HCQ might act on targets and pathways involved in inflammation and immune regulation to exert a common effect on the treatment of LN and IgAN. Conclusions The current study provided new evidence for the protective mechanism and clinical utility of HCQ against LN and IgAN.
Insights into the multi-chromosomal mitochondrial genome structure of the xero-halophytic plant Haloxylon Ammodendron (C.A.Mey.) Bunge ex Fenzl
Authors: Yang Lulu , Liu Jia , Guo Wenjun , Zheng Zehan , Xu Yafei , Xia Houjun , Xiao Tian 
Published: January 2024

Abstract
Background
Haloxylon ammodendron holds significance as an ecological plant, showcasing remarkable adaptability to desert conditions, halophytic environments, and sand fixation. With its potential for carbon sequestration, it emerges as a promising candidate for environmental sustainability. Furthermore, it serves as a valuable C4 plant model, offering insights into the genetic foundations of extreme drought tolerance. Despite the availability of plastid and nuclear genomes, the absence of a mitochondrial genome (mitogenome or mtDNA) hinders a comprehensive understanding of its its mtDNA structure, organization, and phylogenetic implications.

Results
In the present study, the mitochondrial genome of H. ammodendron was assembled and annotated, resulting in a multi-chromosomal configuration with two circular chromosomes. The mtDNA measured 210,149 bp in length and contained 31 protein-coding genes, 18 tRNA and three rRNA. Our analysis identified a total of 66 simple sequence repeats along with 27 tandem repeats, 312 forward repeats, and 303 palindromic repeats were found. Notably, 17 sequence fragments displayed homology between the mtDNA and chloroplast genome (cpDNA), spanning 5233 bp, accounting for 2.49% of the total mitogenome size. Additionally, we predicted 337 RNA editing sites, all of the C-to-U conversion type. Phylogenetic inference confidently placed H. ammodendron in the Amaranthacea family and its close relative, Suaeda glacum.

Conclusions
H. ammodendron mtDNA showed a multi-chromosomal structure with two fully circularized molecules. This newly characterized mtDNA represents a valuable resource for gaining insights into the basis of mtDNA structure variation within Caryophyllales and the evolution of land plants, contributing to their identification, and classification.
Chrysanthemum (Chrysanthemum morifolium) CmHRE2-like negatively regulates the resistance of chrysanthemum to the aphid (Macrosiphoniella sanborni)
Authors: Wang You , Zhang Wanwan , Hong Chaojun , Zhai Lisheng , Wang Xinhui , Zhou Lijie , Song Aiping , Jiang Jiafu , Wang Likai , Chen Fadi , Chen Sumei 
Published: January 2024

Abstract
Background
The growth and ornamental value of chrysanthemums are frequently hindered by aphid attacks. The ethylene-responsive factor (ERF) gene family is pivotal in responding to biotic stress, including insect stress. However, to date, little is known regarding the involvement of ERF transcription factors (TFs) in the response of chrysanthemum to aphids.

Results
In the present study, CmHRE2-like from chrysanthemum (Chrysanthemum morifolium), a transcription activator that localizes mainly to the nucleus, was cloned. Expression is induced by aphid infestation. Overexpression of CmHRE2-like in chrysanthemum mediated its susceptibility to aphids, whereas CmHRE2-like-SRDX dominant repressor transgenic plants enhanced the resistance of chrysanthemum to aphids, suggesting that CmHRE2-like contributes to the susceptibility of chrysanthemum to aphids. The flavonoids in CmHRE2-like-overexpression plants were decreased by 29% and 28% in two different lines, whereas they were increased by 42% and 29% in CmHRE2-like-SRDX dominant repressor transgenic plants. The expression of Chrysanthemum-chalcone-synthase gene(CmCHS), chalcone isomerase gene (CmCHI), and flavonoid 3′-hydroxylase gene(CmF3’H) was downregulated in CmHRE2-like overexpression plants and upregulated in CmHRE2-like-SRDX dominant repressor transgenic plants, suggesting that CmHRE2-like regulates the resistance of chrysanthemum to aphids partially through the regulation of flavonoid biosynthesis.

Conclusion
CmHRE2-like was a key gene regulating the vulnerability of chrysanthemum to aphids. This study offers fresh perspectives on the molecular mechanisms of chrysanthemum-aphid interactions and may bear practical significance for developing new strategies to manage aphid infestation in chrysanthemums.
The relationship between dysphagia and frailty among Chinese hospitalized older patients: a serial mediation model through self-perceived oral health and self-reported nutritional status
Authors: Yu Jianjiao , Zhu Huolan , Zhang Yulian , Wang Dan , Guo Hua , Liu Xiaomei , Lai Jin , Zhang Huiying , Xu Huanhuan , Bai Bingyue 
Published: January 2024

Abstract
Background
Frailty contributes to adverse outcomes in older adults and places a heavy burden on healthcare resources. Dysphagia is associated with frailty, but the mechanisms by which dysphagia affects frailty in older adults are unclear. This study aimed to investigate a serial mediating effect of self-perceived oral health and self-reported nutritional status in the relationship between dysphagia and frailty among hospitalized older patients in China.

Methods
This cross-sectional study included 1200 patients aged ≥ 65 years in the Department of Geriatrics, Shaanxi Provincial People’s Hospital. A structured face-to-face interview was used to survey the following questionnaires: General Information Questionnaire, Tilburg Frailty Indicators (TFI), Eating Assessment Tool-10 (EAT-10), 30mL Water Swallow Test (WST), Geriatric Oral Health Assessment Index (GOHAI), and Short-Form Mini-Nutritional Assessment (MNA-SF). A total of 980 participants with complete data were included in the analysis. Statistical analysis was performed using SPSS 26.0 and Amos 28.0 software. Spearman’s correlation analysis was used for correlation analysis of study variables. The results of the multivariate linear regression analysis for frailty were used as covariates in the mediation analysis, and the structural equation model (SEM) was used to analyze the mediating effects among the study variables.

Results
Dysphagia, self-perceived oral health, self-reported nutritional status, and frailty were significantly correlated (P<0.001). Dysphagia was found to directly affect frailty (β = 0.161, 95%CI = 0.089 to 0.235) and through three significant mediation pathways: (1) the path through self-perceived oral health (β = 0.169, 95%CI = 0.120 to 0.221), accounting for 36.98% of the total effect; (2) the path through self-reported nutritional status (β = 0.050, 95%CI = 0.023 to 0.082), accounting for 10.94% of the total effect; (3) the path through self-perceived oral health and self-reported nutritional status (β = 0.077, 95%CI = 0.058 to 0.102), accounting for 16.85% of the total effect. The total mediation effect was 64.77%.

Conclusions
This study indicated that dysphagia was significantly associated with frailty. Self-perceived oral health and self-reported nutritional status were serial mediators of this relationship. Improving the oral health and nutritional status of hospitalized older patients may prevent or delay the frailty caused by dysphagia.
Testing, diagnosis, and treatment following the implementation of a program to provide dried blood spot testing for HIV and hepatitis C infections: the NSW DBS Pilot
Authors: Carrington Nigel , Conway Anna , Grebely Jason , Starr Mitchell , Catlett Beth , Stevens Annabelle , Prain Bianca , McGrath Colette , Causer Louise , Guy Rebecca , Holden Joanne , Keen Phillip , Kingsland Melanie , Lu Heng , Power Cherie , Read Phillip , Murray Carolyn , McNulty Anna , Cunningham Philip ,   on behalf of the NSW DBS Pilot Study Group
Published: January 2024

Abstract
Background
Dried blood spot (DBS) testing provides an alternative to phlebotomy and addresses barriers to accessing healthcare experienced by some key populations. Large-scale evaluations of DBS testing programs are needed to understand their feasibility. This study evaluated the implementation of a state-wide DBS HIV and hepatitis C virus (HCV) testing pilot.

Methods
The New South Wales (NSW) DBS Pilot is an interventional cohort study of people testing for HIV antibody and/or HCV RNA from DBS samples in NSW, Australia. Participants at risk of HIV/HCV participated in testing via: 1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or 2) assisted DBS sample collection at 36 community health sites (including drug treatment and harm-minimisation services) and prisons. Participants received results by text (HIV antibody/ HCV RNA not detected) or a healthcare provider (HIV antibody/ HCV RNA detected). The RE-AIM framework was used to evaluate reach, effectiveness, adoption, and implementation.

Results
Reach: Between November 2016 and December 2020, 7,392 individuals were tested for HIV and/or HCV (21% self-registration, 34% assisted in community, and 45% assisted in prison). Effectiveness: Of 6,922 people tested for HIV (19% men who have sex with men, 13% living outside major cities, 21% born outside Australia), 51% (3,521/6,922) had no HIV test in the past two years, 0.1% (10/6,922) were newly diagnosed with HIV, and 80% (8/10) initiated HIV treatment within six months. Of 5,960 people tested for HCV (24% women, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs), 15% had detectable HCV RNA (878/5,960), and 45% (393/878) initiated treatment within six months. Adoption: By the end of 2020, DBS via assisted registration was available at 36 community sites and 21 prisons. Implementation: 90% of DBS cards arriving at the laboratory had the three full spots required for testing; the proportion was higher in assisted (94%) compared to online (76%) registration.

Conclusions
This study demonstrated the feasibility of DBS testing for HIV and HCV in key populations including Aboriginal and Torres Strait Islander peoples, men who have sex with men, people who inject drugs, and demonstrated the utility of DBS in the prison setting.
Bivalent mRNA vaccine effectiveness against COVID-19 among older adults in Japan: a test-negative study from the VENUS study
Authors: Tamada Yudai , Takeuchi Kenji , Kusama Taro , Maeda Megumi , Murata Fumiko , Osaka Ken , Fukuda Haruhisa 
Published: January 2024

Abstract
Background
Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan.

Methods
We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 − odds ratio) × 100%.

Results
A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14–20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults.

Conclusions
Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.
Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen
Authors: Tamaki Ryo , Noshiro Kiwamu , Furugen Ayako , Nishimura Ayako , Asano Hiroshi , Watari Hidemichi , Kobayashi Masaki , Umazume Takeshi 
Published: January 2024

Abstract
Background
Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques.

Methods
We conducted a study on 20 postpartum mothers from August 2019–March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach.

Results
For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093.

Conclusions
While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.
The role of adenocarcinoma subtypes and immunohistochemistry in predicting lymph node metastasis in early invasive lung adenocarcinoma
Authors: Xue Mengchao , Liu Junjie , Li Zhenyi , Lu Ming , Zhang Huiying , Liu Wen , Tian Hui 
Published: January 2024

Abstract
Background
Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma.

Methods
In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA).

Results
The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P < 0.001), serum amyloid (SA) (P = 0.008); carcinoma antigen 125 (CA125) (P = 0. 042); mucus composition (P = 0.003); novel aspartic proteinase of the pepsin family A (Napsin A) (P = 0.007); and cytokeratin 5/6 (CK5/6) (P = 0.042). The area under the ROC curve (AUC) was 0.843 (95% CI: 0.779–0.908) in the training cohort and 0.838 (95% CI: 0.748–0.927) in the validation cohort. the P-value of the Hosmer–Lemeshow test was 0.0613 in the training cohort and 0.8628 in the validation cohort. the bias of the training cohort corrected C-index was 0.8444 and the bias-corrected C-index for the validation cohort was 0.8375. demonstrating that the prediction model has good discriminative power and good calibration.

Conclusions
The column line graphs created showed excellent discrimination and calibration to predict lymph node status in patients with ≤ 2 cm invasive lung adenocarcinoma. In addition, the predictive model has predictive potential before the end of surgery and can inform clinical decision making.
The macrophage-associated prognostic gene ANXA5 promotes immunotherapy resistance in gastric cancer through angiogenesis
Authors: Hong Zhijun , Wen Peizhen , Wang Kang , Wei Xujin , Xie Wen , Rao Shihao , Chen Xin , Hou Jingjing , Zhuo Huiqin 
Published: January 2024

AbstractGastric cancer (GC) remains a predominant form of malignant tumor globally, necessitating innovative non-surgical therapeutic approaches. This investigation aimed to delineate the expression landscape of macrophage-associated genes in GC and to evaluate their prognostic significance and influence on immunotherapeutic responsiveness. Utilizing the CellMarker2.0 database, we identified 69 immune cell markers with prognostic relevance in GC, including 12 macrophage-specific genes. A Weighted Gene Co-Expression Network Analysis (WGCNA) isolated 3,181 genes correlated with these macrophage markers. The Cancer Genome Atlas (TCGA-STAD) dataset was employed as the training set, while data from the GSE62254 served as the validation cohort. 13 genes were shortlisted through LASSO-Cox regression to formulate a prognostic model. Multivariable Cox regression substantiated that the calculated risk score serves as an imperative independent predictor of overall survival (OS). Distinct macrophage infiltration profiles, pathway associations, treatment susceptibilities, and drug sensitivities were observed between high- and low-risk groups. The preliminary validation of ANXA5 in predicting the survival rates of GC patients at 1 year, 3 years, and 5 years, as well as its expression levels were higher and role in promoting tumor angiogenesis in GC through immunohistochemistry and angiogenesis experiments. In summary, macrophage-related genes were potentially a novel crosstalk mechanism between macrophages and endothelial cells in the tumor microenvironment, and the interplay between inflammation and angiogenesis might have also offered new therapeutic targets, providing a new avenue for personalized treatment interventions.
Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension
Authors: Kim Yoo-Jin , Shin Seung Han , Kim Ee-Kyung , Kim Han-Suk 
Published: January 2024

Abstract
Background
Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil.

Methods
This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment.

Results
During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil.

Conclusion
Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.