bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive urinary protein signatures combined clinical information associated with microvascular invasion risk in HCC patients
Authors: Wang Yaru , Meng Bo , Wang Xijun , Wu Anke , Li Xiaoyu , Qian Xiaohong , Wu Jianxiong , Ying Wantao , Xiao Ting , Rong Weiqi 
Published: December 2023

Abstract
Background
Microvascular invasion (MVI) is the main factor affecting the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify accurate diagnostic biomarkers from urinary protein signatures for preoperative prediction.

Methods
We conducted label-free quantitative proteomic studies on urine samples of 91 HCC patients and 22 healthy controls. We identified candidate biomarkers capable of predicting MVI status and combined them with patient clinical information to perform a preoperative nomogram for predicting MVI status in the training cohort. Then, the nomogram was validated in the testing cohort (n = 23). Expression levels of biomarkers were further confirmed by enzyme-linked immunosorbent assay (ELISA) in an independent validation HCC cohort (n = 57).

Results
Urinary proteomic features of healthy controls are mainly characterized by active metabolic processes. Cell adhesion and cell proliferation-related pathways were highly defined in the HCC group, such as extracellular matrix organization, cell–cell adhesion, and cell–cell junction organization, which confirms the malignant phenotype of HCC patients. Based on the expression levels of four proteins: CETP, HGFL, L1CAM, and LAIR2, combined with tumor diameter, serum AFP, and GGT concentrations to establish a preoperative MVI status prediction model for HCC patients. The nomogram achieved good concordance indexes of 0.809 and 0.783 in predicting MVI in the training and testing cohorts.

Conclusions
The four-protein-related nomogram in urine samples is a promising preoperative prediction model for the MVI status of HCC patients. Using the model, the risk for an individual patient to harbor MVI can be determined.
Enhancement of phycocyanin productivity and thermostability from Arthrospira platensis using organic acids
Authors: Gomaa Mohamed , Ali Shimaa Abdelmohsen , Hifney Awatief F. 
Published: December 2023

AbstractIntracellular hyperaccumulation of phycocyanin (PC) and its high susceptibility to degradation at higher temperatures are major challenging problems associated with its production from cyanobacteria. The present study evaluated different concentrations of organic acids (1, 2, and 3 mM) (citric acid, acetic acid, succinic acid, fumaric acid, and oxalic acid) under fed-batch mode on the biomass and phycobiliproteins’ production from Arthrospira platensis. Besides they were evaluated at 2.5–7.5 mM as preservative to stabilize PC at high temperatures. The incorporation of 3 mM of succinic acid into the cultivation medium enhanced the biomass and PC productivity to 164.05 and 26.70 mg L−1 day−1, which was ~ 2- and threefold higher than control, respectively. The produced PC in this treatment was food-grade with a 2.2 purity ratio. The use of organic acids also enhanced the thermal stability of PC. Citric acid (7.5 mM) markedly promoted the half-life values of PC to 189.44 min compared to 71.84 min in the control. The thermodynamic analysis confirmed higher thermostability of PC in the presence of organic acids and indicated the endothermic and non-spontaneity of the thermal denaturation process. The findings of the present study confirmed that organic acids could be utilized as cost effective and sustainable compounds for promoting not only phycobiliproteins’ production but also the thermostability of PC for potential application in food industry.
Polysaccharides from Spirulina platensis (PSP): promising biostimulants for the green synthesis of silver nanoparticles and their potential application in the treatment of cancer tumors
Authors: Al-Badwy Asmaa H. , Khalil Ahmed M. , Bashal Ali H. , Kebeish Rashad 
Published: December 2023

AbstractPhotosynthetic cyanobacterial components are gaining great economic importance as prospective low-cost biostimulants for the green synthesis of metal nanoparticles with valuable medical and industrial applications. The current study comprises the biological synthesis of silver nanoparticles (Ag-NPs) using soluble polysaccharides isolated from Spirulina platensis (PSP) as reducing and capping agents. FTIR spectra showed major functional groups of PSP and biogenic silver nanoparticles including O–H, C–H (CH2), C–H (CH3), C=O, amide, and COO– groups. The UV/Vis spectroscopy scan analyses of the extracted PSP showed absorption spectra in the range of 200–400 nm, whereas the biogenic Ag-NPs showed a maximum spectrum at 285 nm. Transmission electron microscopy (TEM) analysis of the synthesized Ag-NPs showed spherical nanoparticles with mean size between 12 and 15.3 nm. The extracted PSP and Ag-NPs exhibited effective cytotoxic activity against Hep-G2 (human hepatocellular carcinoma). The IC50 for PSP and Ag-NPs were 65.4 and 24.5 µg/mL, respectively. Moreover, cell apoptosis assays for PSP and Ag-NPs against the growth of Hep-G2 cells revealed superior growth inhibitory effects of the green synthesized Ag-NPs that encouraged tracing the apoptotic signalling pathway. In conclusion, the current study demonstrated an unprecedented approach for the green synthesis of silver nanoparticles (NPs), using the polysaccharide of Spirulina platensis as reducing and capping agents, with superior anticancer activity against a hepatocellular carcinoma cell line.
The function and mechanism of PSMD14 in promoting progression and resistance to anlotinib in osteosarcoma
Authors: Liu Zhiyong , Wang Xin , Li Chao , Zhao Ruina 
Published: December 2023

Abstract
Background
Osteosarcoma is a rare bone malignancy that frequently affects adolescents and poses formidable obstacles in its advanced stages. Studies revealed that PSMD14 may be a viable osteosarcoma treatment target. However, PSMD14’s function and mechanism in osteosarcoma remain unknown. This study aimed to examine the function and mechanism of PSMD14 in the biological behavior of osteosarcoma and its role in anlotinib resistance.

Methods
Western blotting, qRT-PCR, and immunohistochemistry (IHC) studies were used to examine PSMD14 levels. The role of PSMD14 in the malignant phenotype of osteosarcoma and its molecular pathway was explored by a series of studies, including Western blotting, cell amplification assay, transwell assay, and tumor growth. Furthermore, a series of in vitro investigations were done to determine the effect of PSMD14 on anlotinib-resistant osteosarcoma cell lines.

Results
PSMD14 expression was elevated in osteosarcoma tissues compared to normal tissues. Overexpression of PSMD14 was associated with osteosarcoma patients’ pathological grade and clinical stage, and PSMD14 was an independent poor prognostic factor. PSMD14 knockdown inhibits in vitro cell proliferation, migration, invasion, and in vivo tumor growth. PSMD14 knockdown has the potential to downregulate the PI3K/Akt/mTOR pathway, which was regarded as one of the key mechanisms promoting tumor growth. PSMD14 was likewise overexpressed in anlotinib-resistant OS cell lines, and its knockdown not only reduced the proliferation, migration, and invasion of subline cells and triggered cell apoptosis. Importantly, combination therapy with anlotinib enhanced these effects.

Conclusions
PSMD14 is substantially expressed in osteosarcoma and may be an independent risk factor associated with poor prognosis. It can promote tumor progression and anlotinib resistance in osteosarcoma and may promote osteosarcoma progression by modulating PI3K/AKT/mTOR signaling pathway.
25(OH)D3 improves granulosa cell proliferation and IVF pregnancy outcomes in patients with endometriosis by increasing G2M+S phase cells
Authors: Hu Rui , Li Leilei , Liang Lanlan , Qi YuXin , Ma Xiaoling , Yang Yuan 
Published: December 2023

AbstractBackgroundThe 25-hydroxyvitamin D3 (25 (OH) D3) is crucial for follicular development. This study aimed to investigate the relationship between the level of 25 (OH) D3 in endometriosis patients, pregnancy outcomes of in vitro fertilization (IVF), and the underlying mechanism.MethodsThe 25 (OH) D3 levels in serum and follicular Fluid (FF) samples were detected using enzyme-linked immunosorbent assay (ELISA). Clinical features and pregnancy outcomes of endometriosis patients were also compared between the deficient group (< 20 ug/ml) and the adequate group (≥ 20 ug/ml). The effects of 25 (OH) D3 on the proliferation and cell cycle of human ovarian granulosa cells were respectively detected by CCK-8 assay and flow cytometry (FCM). The differentially expressed genes (DEGs) in granulosa cells of endometriosis and tubal infertility patients were screened from GEO database. The effects of 25 (OH) D3 on the expressions of CDKN2D, PPARA, TGFB2 and THBD were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot.ResultsThe levels of 25 (OH) D3 in serum and FF samples were decreased in endometriosis patients. The deficient group had fewer embryos that can be transferred, lower quality embryos and lower clinical pregnancy rates. Adequate 25 (OH) D3 levels in FF samples was a protective factor for live birth outcome in endometriosis patients. 25 (OH) D3 enhanced the proliferation capacity of granulosa cells (the concentration of 10 nM was the most significant) and increased the proportion of G2M + S phase cells. The expression of CDKN2D was decreased and TGFB2 and THBD were significantly upregulated.Conclusions25 (OH) D3 deficiency may be associated with poor IVF pregnancy outcomes in endometriosis patients. 25 (OH) D3 promotes ovarian granulosa cell proliferation by promoting the ability of cells to divide, and may accelerate cell cycle progression by up-regulating THBD and down-regulating CDKN2D expression.
Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus
Authors: Ijima Shogo , Saito Yuki , Yamamoto Sena , Nagaoka Kentaro , Iwamoto Taiki , Kita Arisa , Miyajima Maki , Sato Tsukasa , Miyazaki Akihiro , Chikenji Takako S. 
Published: December 2023

AbstractOral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients’ tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.
Challenges in international health financing and implications for the new pandemic fund
Authors: Brown Garrett Wallace , Rhodes Natalie , Tacheva Blagovesta , Loewenson Rene , Shahid Minahil , Poitier Francis 
Published: December 2023

AbstractBackgroundThe failures of the international COVID-19 response highlighted key gaps in pandemic preparedness and response (PPR). The G20 and WHO have called for additional funding of $10.5 billion per year to adequately strengthen the global PPR architecture. In response to these calls, in 2022 the World Bank announced the launch of a new Financial Intermediary Fund (The Pandemic Fund) to catalyse this additional funding. However, there is considerable unclarity regarding the governance makeup and financial modalities of the Pandemic Fund, and divergence of opinion about whether the Fund has been successfully designed to respond to key challenges in global health financing.Methods/ResultsThe article outlines eight challenges associated with global health financing instruments and development aid for health within the global health literature. These include misaligned aid allocation; accountability; multistakeholder representation and participation; country ownership; donor coherency and fragmentation; transparency; power dynamics, and; anti-corruption. Using available information about the Pandemic Fund, the article positions the Pandemic Fund against these challenges to determine in what ways the financing instrument recognizes, addresses, partially addresses, or ignores them. The assessment argues that although the Pandemic Fund has adopted a few measures to recognise and address some of the challenges, overall, the Pandemic Fund has unclear policies in response to most of the challenges while leaving many unaddressed.ConclusionIt remains unclear how the Pandemic Fund is explicitly addressing challenges widely recognized in the global health financing literature. Moreover, there is evidence that the Pandemic Fund might be exacerbating these global financing challenges, thus raising questions about its potential efficacy, suitability, and chances of success. In response, this article offers four sets of policy recommendations for how the Pandemic Fund and the PPR financing architecture might respond more effectively to the identified challenges.
Alarm with care—a de-implementation strategy to reduce fall prevention alarm use in US hospitals: a study protocol for a hybrid 2 effectiveness-implementation trial
Authors: Turner Kea , McNett Molly , Potter Catima , Cramer Emily , Al Taweel Mona , Shorr Ronald I. , Mion Lorraine C. 
Published: December 2023

Abstract
Background
Fall prevention alarms are commonly used among US hospitals as a fall prevention strategy despite limited evidence of effectiveness. Further, fall prevention alarms are harmful to healthcare staff (e.g., alarm fatigue) and patients (e.g., sleep disturbance, mobility restriction). There is a need for research to develop and test strategies for reducing use of fall prevention alarms in US hospitals.

Methods
To address this gap, we propose testing the effectiveness and implementation of Alarm with Care, a de-implementation strategy to reduce fall prevention alarm use using a stepped-wedge randomized controlled trial among 30 adult medical or medical surgical units from nonfederal US acute care hospitals. Guided by the Choosing Wisely De-Implementation Framework, we will (1) identify barriers to fall prevention alarm de-implementation and develop tailored de-implementation strategies for each unit and (2) compare the implementation and effectiveness of high- versus low-intensity coaching to support site-specific de-implementation of fall prevention alarms. We will evaluate effectiveness and implementation outcomes and examine the effect of multi-level (e.g., hospital, unit, and patient) factors on effectiveness and implementation. Rate of fall prevention alarm use is the primary outcome. Balancing measures will include fall rates and fall-related injuries. Implementation outcomes will include feasibility, acceptability, appropriateness, and fidelity.

Discussion
Findings from this line of research could be used to support scale-up of fall prevention alarm de-implementation in other healthcare settings. Further, research generated from this proposal will advance the field of de-implementation science by determining the extent to which low-intensity coaching is an effective and feasible de-implementation strategy.

Trial registration
ClinicalTrials.gov identifier: NCT06089239. Date of registration: October 17, 2023.
Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study
Authors: Li Hui , Pan Xiaojun , Zhang Sheng , Shen Xuan , Li Wan , Shang Weifeng , Wen Zhenliang , Huang Sisi , Chen Limin , Zhang Xu , Chen Dechang , Liu Jiao 
Published: December 2023

Abstract
Background
Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.

Methods
In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis.

Results
In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023–1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058–1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002–1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044–1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040–1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11–1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03–1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis.

Conclusion
Both in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.
A large-scale genomically predicted protein mass database enables rapid and broad-spectrum identification of bacterial and archaeal isolates by mass spectrometry
Authors: Sekiguchi Yuji , Teramoto Kanae , Tourlousse Dieter M. , Ohashi Akiko , Hamajima Mayu , Miura Daisuke , Yamada Yoshihiro , Iwamoto Shinichi , Tanaka Koichi 
Published: December 2023

AbstractMALDI-TOF MS-based microbial identification relies on reference spectral libraries, which limits the screening of diverse isolates, including uncultured lineages. We present a new strategy for broad-spectrum identification of bacterial and archaeal isolates by MALDI-TOF MS using a large-scale database of protein masses predicted from nearly 200,000 publicly available genomes. We verify the ability of the database to identify microorganisms at the species level and below, achieving correct identification for > 90% of measured spectra. We further demonstrate its utility by identifying uncultured strains from mouse feces with metagenomics, allowing the identification of new strains by customizing the database with metagenome-assembled genomes.
Integration of datasets for individual prediction of DNA methylation-based biomarkers
Authors: Merzbacher Charlotte , Ryan Barry , Goldsborough Thibaut , Hillary Robert F. , Campbell Archie , Murphy Lee , McIntosh Andrew M. , Liewald David , Harris Sarah E. , McRae Allan F. , Cox Simon R. , Cannings Timothy I. , Vallejos Catalina A. , McCartney Daniel L. , Marioni Riccardo E. 
Published: December 2023

Abstract
Background
Epigenetic scores (EpiScores) can provide biomarkers of lifestyle and disease risk. Projecting new datasets onto a reference panel is challenging due to separation of technical and biological variation with array data. Normalisation can standardise data distributions but may also remove population-level biological variation.

Results
We compare two birth cohorts (Lothian Birth Cohorts of 1921 and 1936 — nLBC1921 = 387 and nLBC1936 = 498) with blood-based DNA methylation assessed at the same chronological age (79 years) and processed in the same lab but in different years and experimental batches. We examine the effect of 16 normalisation methods on a novel BMI EpiScore (trained in an external cohort, n = 18,413), and Horvath’s pan-tissue DNA methylation age, when the cohorts are normalised separately and together. The BMI EpiScore explains a maximum variance of R2=24.5% in BMI in LBC1936 (SWAN normalisation). Although there are cross-cohort R2 differences, the normalisation method makes a minimal difference to within-cohort estimates. Conversely, a range of absolute differences are seen for individual-level EpiScore estimates for BMI and age when cohorts are normalised separately versus together. While within-array methods result in identical EpiScores whether a cohort is normalised on its own or together with the second dataset, a range of differences is observed for between-array methods.

Conclusions
Normalisation methods returning similar EpiScores, whether cohorts are analysed separately or together, will minimise technical variation when projecting new data onto a reference panel. These methods are important for cases where raw data is unavailable and joint normalisation of cohorts is computationally expensive.