bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novel prognostic nomogram for hepatitis B virus-related acute-on-chronic liver failure patients receiving artificial liver therapy
Authors: Wang Xiaofang , Yang Ziyue , Pu Zhangya , Zheng Yixiang , Chen Haiou , Huang Yan , Fan Xuegong , Yi Panpan 
Published: July 2024

Abstract

Background
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is frequently accompanied by short-term morbidity and mortality. However, there have been no studies on the associations between baseline clinicopathologic characteristics at hospital admission and clinical prognosis after receiving artificial liver therapy. Therefore, the current study aimed to develop a prognostic nomogram for predicting the outcomes of patients with HBV-ACLF following artificial liver support.
Methods
A retrospective study of 110 consecutive patients who were diagnosed with HBV-ACLF between January 2018 and August 2022 was conducted. First, univariate and multivariate logistic regression analyses were performed to determine the independent prognostic factors significantly associated with patient outcomes. Moreover, a predictive nomogram model underlying the prognostic factors was established and further evaluated. The area under the curve (AUC) was used to gauge the predictive accuracy. The calibration curve and decision curve analysis (DCA) were employed to assess the discriminability and clinical effectiveness, respectively.
Results
In patients with HBV-ACLF, multivariate logistic analysis revealed that age ≥ 40 years (OR 6.76, p = 0.025), middle-stage liver failure (OR 49.96, p < 0.001), end-stage liver failure (OR 19.27, p = 0.002), hepatic encephalopathy (OR 7.06, p = 0.032), upper gastrointestinal hemorrhage (OR 47.24, p = 0.047), and artificial liver therapy consisting of plasma exchange (PE) + plasma exchange double plasma molecular adsorption system (DPMAS) (OR 0.26, p = 0.04) were identified as prognostic factors. Then, we established and evaluated a predictive nomogram with an area under the curve (AUC) of 0.885, which showed better predictive accuracy than the model for end-stage liver disease (MELD) score (AUC of 0.634) and the Child‒Pugh score (AUC of 0.611). Moreover, the calibration curve showed good agreement between the ideal and bias-corrected curves. Decision curve analysis confirmed the better clinical utility of this approach.
Conclusion
We developed and evaluated a unique nomogram that was more accurate than conventional prognostic models for predicting the clinical prognosis of HBV-ACLF patients receiving artificial liver therapy. As a result, the nomogram may be a helpful tool in clinical decision-making to predict the outcomes of patients with HBV-ACLF.
Engineering Synthetic and Recombinant Human Lysosomal b-Glucocerebrosidase for Enzyme Replacement Therapy for Gaucher Disease
Authors: Figueiredo Lílian Louise Souza , Júnior Wilson Lau , Gonçalves Victor Wendel da Silva , Ramos Ester Silveira , D’Almeida Vania , de Souza Lucas Eduardo Botelho , Orellana Maristela Delgado , Abraham Kuruvilla Joseph , Lichtenstein Flávio , Bleicher Lucas , Azevedo Vasco , Chaves Rigoberto Gadelha , Bonfá Giuliano , Siciliano Velia Siciliano , Weiss Ron , Gerson Stanton , Fontes Aparecida Maria Fontes 
Published: July 2024

Abstract

Gaucher Disease (GD) is an autosomal recessive, lysosomal storage disease caused by pathogenic variants in the glucocerebrosidase gene, leading to the loss of b-glucocerebrosidase (GCase) enzymatic activity. Enzyme replacement therapy (ERT) with recombinant GCase is the standard of care in GD patients. Our study investigates the combined use of in silico molecular evolution, synthetic biology and gene therapy approaches to develop a new synthetic recombinant enzyme. We engineered four GCases containing missense mutations in the signal peptide (SP) from four selected mammalian species, and compared them with human GCase without missense mutations in the SP. We investigated transcriptional regulation with CMV and hEF1a promoters alongside a GFP control construct in 293-FT human cells. One hEF1a-driven mutant GCase shows a 5.2-fold higher level of transcription than control GCase. In addition, this mutant exhibits up to a 6-fold higher activity compared with the mock-control, and the predicted tertiary structure of this mutant GCase aligns with human GCase. We also evaluated conserved and coevolved residues mapped to functionally important positions. Further studies are needed to assess its functionality in a GD animal model. Altogether, our findings provide in vitro evidence of the potential of this engineered enzyme for improved therapeutic effects for GD.
Endodontic Emergency Patients’ Profile and Treatment Outcome – A Prospective Cohort Study
Authors: Haug Sivakami Rethnam , Røegh Margrethe , Fristad Inge 
Published: July 2024

Abstract

Background
Toothache is a debilitating condition, often with mild to excruciating pain, swelling, eating difficulties and insomnia. This study aims to delineate the profiles of patients seeking emergency dental care, focusing on the diagnosis, treatment, and outcomes following non-surgical root canal treatment.
Methods
This prospective cohort study was conducted from 2012 to 2021 at the Section for Endodontics, Department of Clinical Dentistry, University of Bergen, Norway. A total of 281 emergency patient forms were analyzed. Data registered included patient demographics, dental history, chief complaints, medications used, diagnostic results, treatments provided and outcome.
Results
A total of 272 patients (272 teeth) were included in the study. Pain was the predominant complaint (98.5%), where only 57.4% of the patients managed to localize pain to a specific tooth. The mean age of patients was 51.2 years with no significant gender differences. The maxillary right first molar (41.9%) was the most frequent tooth needing treatment. The majority of the patients had experienced pain for three days before they attended the emergency appointment. The most frequently used drug for pain management was paracetamol which was stated to have little effect. Teeth that needed endodontic treatment often had fillings rather than caries. The most frequent diagnoses were pulpitis (26.8%) followed by necrotic pulp (25.2%) and previously root-filled teeth (22.8%). Root canal treatment was performed on 62.5% of the teeth and a success rate of 95% was registered at one-year recall.
Conclusions
There was no singular diagnostic cause leading patients to seek an emergency appointment, highlighting the necessity of a thorough diagnostic procedure. Over the counter pain medications have little effect on alleviating dental pain, often resulting in desperate measures of self-medication. Restorative treatments, such as fillings or crowns, do not appear to protect against future pulpal disease. The good prognosis of root canal treatment for teeth with acute symptoms supports recommending dentists to attempt root canal treatment rather than opting for tooth extraction.
High-dose methylprednisolone mediates YAP/TAZ-TEAD in vocal fold fibroblasts with macrophages
Authors: Nakamura Ryosuke , Bing Renjie , Gartling Gary J. , Garabedian Michael J. , Branski Ryan C. 
Published: July 2024

Abstract

The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Targeting macrophage-fibroblast interactions is an interesting therapeutic strategy; macrophages alter their phenotype to mediate both inflammation and fibrosis. In the current study, we investigated concentration-dependent effects of methylprednisolone on the fibrotic response, with an emphasis on YAP/TAZ-TEAD signaling, and inflammatory gene expression in VF fibroblasts in physical contact with macrophages. We sought to provide foundational data to optimize therapeutic strategies for millions of patients with voice/laryngeal disease-related disability. Following induction of inflammatory (M(IFN/LPS)) and fibrotic (M(TGF)) phenotypes, THP-1-derived macrophages were seeded onto HVOX vocal fold fibroblasts. Cells were co-cultured +/-0.3-3000nM methylprednisolone +/- 3µM verteporfin, a YAP/TAZ inhibitor. Inflammatory (CXCL10, TNF, PTGS2) and fibrotic genes (ACTA2, CCN2, COL1A1) in fibroblasts were analyzed by real-time polymerase chain reaction after cell sorting. Ser211-phosphorylated glucocorticoid receptor (S211-pGR) was assessed by Western blotting. Nuclear localization of S211-pGR and YAP/TAZ was analyzed by immunocytochemistry. Methylprednisolone decreased TNF and PTGS2 in fibroblasts co-cultured with M(IFN/LPS) macrophages and increased ACTA2 and CCN2 in fibroblasts co-cultured with M(IFN/LPS) and M(TGF). Lower concentrations were required to decrease TNF and PTGS2 expression and to increase S211-pGR than to increase ACTA2 and CCN2 expression and nuclear localization of S211-pGR. Methylprednisolone also increased YAP/TAZ nuclear localization. Verteporfin attenuated upregulation of CCN2, but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation.
Effect of Air Injection Technique on the Emission Characteristics of a CI Engine During Transient Operation
Authors: Saad Syed Mohammad , Rummana Asiya 
Published: July 2024

Abstract

The performance of turbocharged diesel engine deteriorates during transient operating conditions. Air injection is an effective technique in improving the transient response of the engine. However, the technique is not evaluated for exhaust emissions. To meet the stringent emission regulations, it is important to improve the emission performance of the diesel engine. Present study deals with the effect of air injection technique on exhaust emissions (CO, HC and NOx) under speed and load transients. Optimization of injection pressure based on orifice diameter is performed to ensure that the application of the technology comply with Euro VI standard. The results of the simulation were evaluated for Euro VI standard and 3 bar air injection at 10 mm orifice diameter was found to be the optimum injection pressure for speed transients which brings slight reduction in CO and HC emissions and significant reduction in NOxemissions. For load transients, Emissions werefound to be below Euro VI standard for all the injection pressures and orifice diameters.Quantification of emissions were done and 1.2 bar injection pressure at 10 mm orifice diameter was found to reduce all the three emissions as compared to no air injection.
Association between visceral adiposity index and chronic diarrhea: A cross-sectional study of the NHANES 2005-2010
Authors: Chen Rongpeng , Fu Zexin , Feng Manting , Feng Zhicheng , Xiao Feng , Wang Guoqiang 
Published: July 2024

Abstract

Background
Obesity is recognised as a significant risk factor for chronic diarrhoea (CD). Moreover, the use of body mass index (BMI) as an indicator of obesity in relation to CD remains controversial. Furthermore, the relationship between visceral adiposity index (VAI) and the risk of CD has not been reported. The aim of this study was to investigate the relationship between VAI and the risk of CD.
Methods
A cross-sectional study was conducted using data from the 2005–2010 National Health and Nutrition Examination Survey (NHANES). Multiple linear regression analyses were used to examine the association between VAI and CD. In addition, a smooth curve-fitting algorithm was used to assess the possible non-linear dose-response relationship between VAI and CD, and subgroup analyses were also performed.
Results
Among the 5,699 participants in this study (mean age, 49.2 [17.9] years; 2,798 [49.1%] men), 424 (7.4%) reported CD, while 5,275 (92.6%) did not. After adjustment for potential confounders, VAI was associated with CD (OR, 1.12; 95%CI, 1.05–1.2; P = 0.001). Participants in the highest quartile (Q4; 2.44 to 12.73) of VAI had an adjusted OR for CD of 1.64 (95% CI, 1.2–2.24; P = 0.002) compared to those in the lowest quartile (Q1; 0.09 to 0.92). Multivariable restricted cubic spline analysis showed a linear relationship between VAI and CD (P for non-linearity = 0.762).
Conclusions
The results of this study demonstrated that the visceral adiposity index (VAI) is independently associated with the risk of chronic diarrhea (CD). VAI may serve as a promising indicator for assessing the risk of CD, offering valuable insights for its prevention and treatment guidance.
Barriers and facilitators of healthcare access for long COVID-19 patients in a universal healthcare system: Qualitative evidence from Austria
Authors: Gamillscheg Peter , Łaszewska Agata , Kirchner Stefanie , Hoffmann Kathryn , Simon Judit , Mayer Susanne 
Published: July 2024

Abstract

Background: Long COVID-19 challenges health and social systems globally. International research finds major inequalities in prevalence and healthcare utilization as patients describe difficulties with accessing health care. In order to improve long-term outcomes it is vital to understand any underlying access barriers, for which relevant evidence on long COVID-19 is thus far lacking in a universal healthcare system like Austria. This study aims to comprehensively identify access barriers and facilitators faced by long COVID-19 patients in Austria and explore potential socioeconomic and demographic drivers in health and social care access.
Methods: Applying an exploratory qualitative approach, we conducted semi-structured interviews with 15 experts including medical professionals and senior health officials as well as focus groups with 18 patients with confirmed long COVID-19 diagnosis reflecting varying participant characteristics (age, gender, urbanicity, occupation, education, insurance status) (July-Nov 2023). Data were analysed following a thematic framework approach, drawing on a comprehensive ‘access to health care’ model.
Results: Based on expert and patient experiences, several access barriers and facilitators emerged along all dimensions of the model. Main themes included scepticism and stigma by medical professionals, difficulties in finding knowledgeable doctors, limited specialist capacities in the ambulatory care sector, long waiting times for specialist care, and limited statutory health insurance coverage of treatments resulting in high out-of-pocket payments. Patients experienced constant self-organization of their patient pathway as stressful, emphasizing the need for multidisciplinary care and centralized coordination. Facilitators included supportive social environments, telemedicine, and informal information provided by a nationwide patient-led support group. Differences in patient experiences emerged, among others, as women and younger patients faced gender- and age-based stigmatization. Complementary health insurance reduced the financial strain, however, did not ease capacity constraints, which were particularly challenging for those living in rural areas.
Conclusions: The findings of this study indicate a call for action to improve the long COVID-19 situation in Austria by empowering both providers and patients via increased information offerings, strengthened interdisciplinary treatment structures and insurance coverage as well as research funding. Our insights on potentially relevant socioeconomic and demographic drivers in access barriers lay the necessary foundation for future quantitative inequality research.
Different Feeding and Delivery Modes on Otitis Media with Effusion in Children: A Correlational Study
Authors: Wang Yan , Hu Yuanjia , Lin Hong , Pan Yunyun , Zhou Zhaoyi , Zhu Chenyu , Wang Jiacheng , Wang Yaowen 
Published: July 2024

Abstract

Background:
Otitis media with effusion (OME) is predominantly observed in children under six years of age and can lead to hearing loss or even severe complications, impacting speech and cognitive development. While the benefits of breastfeeding and natural birth in enhancing infant immunity and cognitive abilities are globally recognized, their effects on OME have been scarcely reported.
Objective:
To investigate the relationship between feeding methods and deliverymodes with OME in children, providing a basis for targeted prevention of OME.
Methods:
A total of 81 children diagnosed with OME, aged ≤6 years, from May 2022 to May 2023, were selected as the experimental group. Another 81 children without a history of OME served as the control group. A questionnaire was used to inquire about the feeding methods and delivery modes at birth, as reported by the guardians. Statistical analysis was performed using SPSS 20.0 software.
Results:
Formula feeding and cesarean section are positively correlated with the incidence of OME (r > 0, p < 0.001), indicating that these factors contribute to an increased prevalence of the condition. A combined analysis of feeding and birth modes reveals that the incidence of OME is significantly higher in the group formula feeding is combined with cesarean section, suggesting that these effects are additive.
Conclusions:
Compared to formula feeding, breastfeeding significantly reduces the risk of OME infections; similarly, natural birth is more effective than cesarean section in lowering the incidence of OME. When both feeding and delivery modes are considered together, breastfeeding can mitigate the risk of OME in children born via cesarean section, while natural birthcan decrease the risk associated with formula feeding children. Therefore, the methods of feeding and delivery modes are closely linked to the early incidence of OME in children, and continued promotion of breastfeeding and encouragement of natural birth should be prioritized in the future .
Clinical Pathological Significance and Biological Function of PLIN1 in Hepatocellular Carcinoma: bioinformatics analysis and in vitro experiment
Authors: Huang Jiang-hua , Wei Yan , Yu Cong , Zhang Rui , Feng Zhen‑Bo , Zeng Li-Ping 
Published: July 2024

Abstract

Background & aims: Perilipin1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to have a close relationship with the development of numerous tumor types. The purpose of this work is to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and investigate possible mechanisms.
Methods: Public high-throughput RNA microarray and RNA sequencingwere collected to examine PLIN1 levels and clinical significance in HCC. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to assess PLIN1 expression levels and clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressed PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC base on HCC differentially expressed genes and PLIN1 co-expressed genes.
Results: PLIN1 was markedly down-regulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion in SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signaling pathways were the three most concentrated molecular mechanisms.
Conclusion: The current study found that down-regulated PLIN1 is associated with a poor prognosis in HCC patients and prevented HCC progression by inhibiting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.
Molecular dynamics study of supramolecular complexes to the carbohydrate- cation system
Authors: Kafi Dhaidan Khalaf , Mohi Ali Taher 
Published: July 2024

Abstract

It is known that calcium ions lead to aggregation of disaccharides, while magnesium ions do not. In this study, simulation results indicated that the cations primarily bind to the sulfate groups of the disaccharides. Moreover, results in the formation of carbohydrate-cation-carbohydrate complexes, with the disaccharides primarily binding to the glucose unit, which is attached to the sulfate group. If the cation is not present, the sulfate groups repel each other and complex formation is not possible. From molecular dynamics simulations, the differences between the two cation systems can be explained as follows: Magnesium ions bind much weaker to the disaccharide than calcium ions. The reason is that magnesium ions bind more strongly to the hydration shell due to their smaller ion radius compared to calcium ions. This is energetically more expensive in the case of magnesium ions, which leads to a kinetic hindrance of complex formation compared to the calcium system. Additionally, when a modified water model is used in the case of the magnesium system, in which the charges of the water atoms are reduced, the magnesium ions bind the hydration shell less strongly than in the 'normal' water model, which facilitates complex formation with the disaccharides. The other significant difference between the two cation complexes is that in the case of calcium ions, both disaccharides bind directly to the cation through the sulfate groups. To verify whether the stability differences between the two saccharides are also observed in the simulations, the simulations of the calcium system were repeated with the monosaccharide. As expected, the binding energy of the monosaccharide complex was found to be lower than that of the disaccharide complex (6 kJ/mol). The difference in binding energies between the two complexes was relatively small. A significantly lower rupture force was found in the simulations for an individual complex.
Predicting Contrast Sensitivity Functions with Digital Twins
Authors: Zhao Yukai , Lesmes Luis Andres , Dorr Michael , Lu Zhong-Lin 
Published: July 2024

Abstract

We developed and validated digital twins (DTs) for contrast sensitivity function (CSF), using a data-driven, generative model approach based on a Hierarchical Bayesian Model (HBM). The HBM was trained with the trial-by-trial responses obtained from quantitative CSF (qCSF) testing of an observer population across three luminance conditions (N = 112). HBM analysis yielded the joint posterior probability distribution of CSF hyperparameters and parameters at the population, condition, subject, and test levels. A generative model, which combines this joint posterior distribution with newly available data, yields DTs that predict CSFs for new or existing observers in unmeasured conditions. The DTs were tested and validated across 12 prediction tasks. In addition to their accuracy and precision, these predictions were evaluated for their potential as informative priors that enable generation of synthetic qCSF data or rescore existing qCSF data. The HBM captured covariances at all three levels of the hierarchy, which enabled the DTs to make highly accurate predictions for individuals and group. DT predictions could save more than 50% of the data collection burden in qCSF testing. DTs hold promise for revolutionizing the quantification of vision, which can better serve assessment and personalized medicine, offering efficient and effective patient care solutions.