bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the anti-hypertensive mechanism of α-mangostin based on network pharmacology, molecular docking and experimental validation
Authors: Xue Qi-Qi , Liu Chu-Hao , Li Yan 
Published: November 2024

Abstract
Background
Hypertension is a leading risk factor for disability and deaths worldwide. Evidence indicates that alpha-mangostin(α-MG) can reduce blood pressure and improve target organ damage. Nonetheless, its pharmacological targets and potential mechanisms of action remain inadequately elucidated.

Method
We used SwissTargetPrediction to identify α-MG’s drug targets and DisGeNET, GeneCards, CTD, and GEO databases for hypertension-related targets, and then determined antihypertensive therapeutic targets of α-MG by intersecting these targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were conducted using the DAVID database and R package “clusterprofile”, visualized with Cytoscape software. The binding affinity of α-MG to identified targets was confirmed through molecular docking using Autodock Vina v.1.2.2 software. The impact of α-MG on target genes was validated using an Angiotensin II-induced hypertensive mouse model and RT-qPCR.

Results
A total of 51 potential antihypertensive therapeutic targets for α-MG were identified by intersecting 109 drug targets with 821 disease targets. Furthermore, 10 cellular component terms, 10 disease terms, and the top 20 enriched biological processes, molecular functions, and KEGG pathways related to α-MG’s antihypertensive effects were documented. Molecular docking studies indicated a strong binding affinity of α-MG with the HSP90AA1 domain. In Ang II-induced hypertensive mice aorta, treatment with α-MG effectively reversed the aberrant mRNA expression of TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA.

Conclusion
Our analyses showed that TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA might be α-MG’s potential therapeutic targets for hypertension, laying groundwork for further investigation into its pharmacological mechanisms and clinical uses.
Human limits in machine learning: prediction of potato yield and disease using soil microbiome data
Authors: Aghdam Rosa , Tang Xudong , Shan Shan , Lankau Richard , Solís-Lemus Claudia 
Published: November 2024

Abstract
Background
The preservation of soil health is a critical challenge in the 21st century due to its significant impact on agriculture, human health, and biodiversity. We provide one of the first comprehensive investigations into the predictive potential of machine learning models for understanding the connections between soil and biological phenotypes. We investigate an integrative framework performing accurate machine learning-based prediction of plant performance from biological, chemical, and physical properties of the soil via two models: random forest and Bayesian neural network.

Results
Prediction improves when we add environmental features, such as soil properties and microbial density, along with microbiome data. Different preprocessing strategies show that human decisions significantly impact predictive performance. We show that the naive total sum scaling normalization that is commonly used in microbiome research is one of the optimal strategies to maximize predictive power. Also, we find that accurately defined labels are more important than normalization, taxonomic level, or model characteristics. ML performance is limited when humans can’t classify samples accurately. Lastly, we provide domain scientists via a full model selection decision tree to identify the human choices that optimize model prediction power.

Conclusions
Our study highlights the importance of incorporating diverse environmental features and careful data preprocessing in enhancing the predictive power of machine learning models for soil and biological phenotype connections. This approach can significantly contribute to advancing agricultural practices and soil health management.
Effect of low-dose dexmedetomidine to prolong spinal anesthesia in elderly patients: a prospective randomized controlled study
Authors: Sangkum Lisa , Termpornlert Sivaporn , Tunprasit Choosak , Rathanasutthajohn Chatchayapa , Komonhirun Rojnarin , Dusitkasem Sasima 
Published: November 2024

Abstract
Background
Spinal anesthesia for transurethral resection of the prostate (TURP) has a short duration, which poses challenges for postoperative pain management. The present study aimed to investigate the effects of intravenous (IV) dexmedetomidine at a dosage of 0.4 µg/kg in prolonging the duration of spinal anesthesia and minimizing postoperative pain in elderly patients undergoing TURP.

Methods
This prospective randomized controlled trial enrolled 38 patients aged 60–80 years who underwent elective TURP with spinal anesthesia. The patients were randomly assigned to two treatment groups: Group D received IV 0.4 µg/kg dexmedetomidine, whereas Group C received IV normal saline after spinal anesthesia administration. The primary outcome was the time to 2-dermatome regression.

Results
The 2-dermatome regression time was longer in Group D than in Group C (104.44 ± 16.97 min vs. 80.63 ± 15.59 min, p < 0.05). The peak sensory block levels were significantly higher in Group D [T7 (T6–T8)] than in Group C [T10 (T7–T10)] (p = 0.017). The incidence of hypotension and bradycardia and postoperative pain at 0, 6, 12, and 24 h were not different between two groups.

Conclusion
Intravenous dexmedetomidine at a dosage of 0.4 µg/kg significantly prolongs the duration of spinal sensory blockade. Although postoperative analgesia was not different, it provided hemodynamic stability without increasing the side effects.
Evaluating plasma antinuclear autoantibody profile as a prognostic biomarker in lymphoma
Authors: Zheng Cuiling , Gao Ruyun , Wang Yanrong , Han Xiaohong 
Published: November 2024

Abstract
Background
Research on the antinuclear antibodies (ANA) profile across different pathological subtypes of lymphoma was limited. Our study aimed to assess ANA profile and investigate its potential prognostic value in lymphoma.

Method
We collected plasma samples from 139 lymphoma patients and analyzed the expression of plasma ANA, SSA, and SSB using the enzyme-linked immunosorbent assay (ELISA). Additionally, we focused on B-cell non-Hodgldn’s lymphoma (B-NHL) for survival analysis.

Results
Influencing factors for ANA profile levels included age (ANA: P = 0.0035, SSA: P = 0.0553, SSB: P = 0.0025), gender (SSA: P = 0.0436), serum IgG (ANA, P = 0.0385; SSA, P = 0.0175; SSB, P = 0.0291), and erythrocyte sedimentation rate (ESR) (SSA: P = 0.0380). In subtype comparisons, ANA and SSB levels were significantly lower in low-grade B-NHL compared to Hodgkin lymphoma (HL) (low-grade B-NHL vs. NHL: ANA, P = 0.0107; SSB, P = 0.0126). Aggressive NHL exhibited a higher ANA profile compared to indolent NHL (aggressive NHL vs. indolent NHL: ANA, P = 0.0262; SSA, P = 0.0136; SSB, P = 0.0280). Kaplan–Meier analyses identified SSA and SSB as potential prognostic biomarkers in patients with B-NHL undergoing chemotherapy.

Conclusion
Our study evaluated ANA profile in various subtypes of lymphoma and demonstrated the prognostic value of autoantibodies in predicting clinical outcomes. The results highlight the potential of incorporating ANA profile into the prognostic assessment of lymphoma.
Organosolv-derived lipids from hemicellulose and cellulose, and pre-extracted tannins as additives upon hydrothermal liquefaction (HTL) of spruce bark lignins to bio-oil
Authors: Thoresen Petter Paulsen , Fahrni Jonas , Patel Alok , Enman Josefine , Gustafsson Tomas , Rova Ulrika , Christakopoulos Paul , Matsakas Leonidas 
Published: November 2024

AbstractThe rise in global temperature and accumulation of petroleum-based wastes in the environment forces the scientific focus towards renewable alternatives. In the present work, an under-exploited resource – spruce bark – is investigated as a raw material for production of bio-oil as a liquid energy carrier. To enhance the energy-content of the produced bio-crude, ultimately being produced through hydrothermal liquefaction, the polysaccharides were extracted through organosolv fractionation and converted to lipids by oleaginous microorganisms. The effect originating from tannins was also investigated by performing a pre-extraction before the organosolv fractionation. It was found that performing the organosolv fractionation and upgrading the isolated organosolv lignin to bio-oil greatly reduced the oxygen content of the oil fraction thereby improving its energy content, and introducing upgraded polysaccharides in the form of lipids, as well as pre-extracted tannins, caused clear changes in the product distribution of the final bio-oil and kept a final product with low oxygen content. The other factor largely influencing the product distribution originated from the various heating rates tested by altering operational mode of the HTL process between batch and semi-continuous. Ultimately, performing the organosolv fractionation and individual upgrading of the polysaccharides had a beneficial effect on reducing the final solids content and enhancing the liquid oil yield.
Estimating the cost of chronic kidney disease in Australia
Authors: Randall Sean , Lee Crystal M. Y. , Thomas Elizabeth , Chakera Aron , Chai Kevin E. K. , Varhol Richard , Mehta Kanika , Irish Ashley , Conradie Johan , Hadlow Narelle , Hendrie Delia , Boyd James H. , Robinson Suzanne 
Published: November 2024

Abstract
Introduction
Chronic kidney disease (CKD) is a significant burden on health systems globally, with limited up-to-date information on health system costs, particularly for non-dialysis patients. This study estimates the direct healthcare costs of CKD within Australia.

Methods
The study utilised the CKD.WA dataset, a linked repository for the state of Western Australia, containing public and private pathology, hospital, emergency and mortality data for over 2 million people, along with a secondary dataset of general practice records. Costs were calculated for individuals with CKD in 2019 and compared to controls without CKD to identify costs attributable to CKD. Cost items included hospital, emergency, medication, general practice, pathology, dialysis and outpatient services. Costs were expressed in 2023 AUD.

Results
There were 114,899 individuals with CKD in 2019. Average yearly costs attributable to CKD were $3,367 for Stage 1, $4,114 for Stage 2, $3,607 for Stage 3a, $6,572 for Stage 3b, $11,456 for Stage 4 and $62,558 for Stage 5. Non-dialysis hospital costs were the biggest contributor, followed by dialysis costs. The estimated total cost of CKD to Australia was $8.3 billion for 2019.

Conclusion
These findings highlight the significant cost burden of CKD. While CKD costs per individual are highest in later stages, the greater number of early-stage CKD cases means the majority of the cost burden is located among early-stage cases. Primary and secondary prevention strategies are likely key to reducing costs.
Serological evidence of sarbecovirus exposure along Sunda pangolin trafficking pathways
Authors: Worthington Brian M. , Wong Portia Y.-H. , Kumaree Kishoree K. , Prigge Tracey-Leigh , Ng Kar Hon , Liao Yunshi , Martelli Paolo , Churgin Sarah , Lee Foo K. , Perkins Chris , Bradley Michael , Pierce Mac P. , Shum Marcus H.-H. , Miot Elliott F. , Cheung William Y.-M. , McIlroy Shelby E. , Nash Helen C. , Wirdateti  , Semiadi Gono , Tan Chee-Wah , Wang Lin-Fa , Ades Gary , Baker David M. , Dingle Caroline , Pybus Oliver G. , Holmes Edward C. , Leung Gabriel M. , Guan Yi , Zhu Huachen , Bonebrake Timothy C. , Lam Tommy T. Y. 
Published: November 2024

Abstract
Background
Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential.

Results
Using a combination of virological and wildlife forensics tools, we investigated 89 Sunda pangolin carcasses seized by Hong Kong authorities during anti-smuggling operations in the territory conducted in 2013 (n = 1) and 2018 (n = 88). Swabs, organ tissues, blood, and other body fluids were collected during post-mortem examination. Two enzyme-linked immunosorbent assays (ELISAs), which employ a double-antigen sandwich format, were used to detect antibodies reactive against SARSr-CoVs. One individual was found to be seropositive with support from both methods, while five individuals exhibited a putatively seropositive result from one ELISA method. Polymerase chain reaction (PCR) screening for coronavirus and paramyxovirus ribonucleic acid (RNA) did not yield any positives. Based on genomic data, the seropositive individual was determined to have likely originated from Java, while the putatively seropositive individuals were determined to have originated from populations in Borneo, Java, and Singapore/Sumatra.

Conclusions
While the role of pangolins in the evolution and ecology of SARS-CoV-2 is uncertain, our results suggest susceptibility and potential exposure of pangolins to SARSr-CoVs, occurring naturally or associated with the illegal trafficking of these animals. Complex dynamics between natural populations, traded individuals, and pathogen susceptibility complicate conclusions about the role of pangolins, as well as other host species, in the ecology of SARSr-CoVs and potentially zoonotic viruses with risk of future emergence.
Carrageenan and insulin resistance in humans: a randomised double-blind cross-over trial
Authors: Wagner Robert , Buettner Janine , Heni Martin , Fritsche Louise , Kullmann Stephanie , Wagmüller Moritz , Peter Andreas , Preissl Hubert , Machann Jürgen , Jumpertz von Schwartzenberg Reiner , Birkenfeld Andreas L. , Pape Ulrich-Frank , van Hall Gerrit , Plomgaard Peter , Häring Hans-Ulrich , Fritsche Andreas , Thompson Kelsey N. , Klein Reinhild , Stefan Norbert 
Published: November 2024

Abstract
Background
The potential impact of specific food additives, common in Western diets, on the risk of developing type 2 diabetes is not well understood. This study focuses on carrageenan, a widely used food additive known to induce insulin resistance and gut inflammation in animal models, and its effects on human health.

Methods
In a randomised, double-blind, placebo-controlled, cross-over trial conducted at a university hospital metabolic study centre, 20 males (age 27.4 ± 4.3 years, BMI 24.5 ± 2.5 kg/m2) participated. The intervention involved oral intake of carrageenan (250 mg) or placebo in the morning and in the evening and each intervention lasted 2 weeks. The primary outcome measured was insulin sensitivity (using oral glucose tolerance test [OGTT] and hyperinsulinaemic-euglycaemic clamp). Additional end-points included whole body and hepatic insulin sensitivity, MRI-measured brain inflammation and insulin resistance, intestinal permeability (via lactulose-mannitol test and plasma zonulin levels), and gut microbiome composition. Immune-cell activation and pro-inflammatory cytokine release from peripheral blood mononuclear cells were measured.

Results
Overall insulin sensitivity did not show significant differences between the treatments. However, interactions between BMI and treatment were observed (OGTT-based insulin sensitivity index: p=0.04, fasting insulin resistance:
p=0.01, hepatic insulin sensitivity index: p=0.04). In overweight participants, carrageenan exposure resulted in lower whole body and hepatic insulin sensitivity, a trend towards increased brain inflammation, and elevated C-reactive protein (CRP) and IL-6 levels compared to placebo. Additionally, carrageenan was associated with increased intestinal permeability. In vitro natural killer (NK-)cell activation and increased pro-inflammatory cytokine release were found after carrageenan exposure in the participant’s peripheral blood mononuclear cells.

Conclusions
These findings suggest that carrageenan, a common food additive, may contribute to insulin resistance and subclinical inflammation in overweight individuals through pro-inflammatory mechanisms in the gut. Further investigation into the long-term health impacts of carrageenan and other food additives is warranted.

Trial registration
NCT02629705.
Prognostic value of glycaemic variability for mortality in critically ill atrial fibrillation patients and mortality prediction model using machine learning
Authors: Chen Yang , Yang Zhengkun , Liu Yang , Gue Ying , Zhong Ziyi , Chen Tao , Wang Feifan , McDowell Garry , Huang Bi , Lip Gregory Y. H. 
Published: November 2024

Abstract
Background
The burden of atrial fibrillation (AF) in the intensive care unit (ICU) remains heavy. Glycaemic control is important in the AF management. Glycaemic variability (GV), an emerging marker of glycaemic control, is associated with unfavourable prognosis, and abnormal GV is prevalent in ICUs. However, the impact of GV on the prognosis of AF patients in the ICU remains uncertain. This study aimed to evaluate the relationship between GV and all-cause mortality after ICU admission at short-, medium-, and long-term intervals in AF patients.

Methods
Data was obtained from the Medical Information Mart for Intensive Care IV 3.0 database, with admissions (2008–2019) as primary analysis cohort and admissions (2020–2022) as external validation cohort. Multivariate Cox proportional hazards models, and restricted cubic spline analyses were used to assess the associations between GV and mortality outcomes. Subsequently, GV and other clinical features were used to construct machine learning (ML) prediction models for 30-day all-cause mortality after ICU admission.

Results
The primary analysis cohort included 8989 AF patients (age 76.5 [67.7–84.3] years; 57.8% male), while the external validation cohort included 837 AF patients (age 72.9 [65.3–80.2] years; 67.4% male). Multivariate Cox proportional hazards models revealed that higher GV quartiles were associated with higher risk of 30-day (Q3: HR 1.19, 95%CI 1.04–1.37; Q4: HR 1.33, 95%CI 1.16–1.52), 90-day (Q3: HR 1.25, 95%CI 1.11–1.40; Q4: HR 1.34, 95%CI 1.29–1.50), and 360-day (Q3: HR 1.21, 95%CI 1.09–1.33; Q4: HR 1.33, 95%CI 1.20–1.47) all-cause mortality, compared with lowest GV quartile. Moreover, our data suggests that GV needs to be contained within 20.0%. Among all ML models, light gradient boosting machine had the best performance (internal validation: AUC [0.780], G-mean [0.551], F1-score [0.533]; external validation: AUC [0.788], G-mean [0.578], F1-score [0.568]).

Conclusion
GV is a significant predictor of ICU short-term, mid-term, and long-term all-cause mortality in patients with AF (the potential risk stratification threshold is 20.0%). ML models incorporating GV demonstrated high efficiency in predicting short-term mortality and GV was ranked anterior in importance. These findings underscore the potential of GV as a valuable biomarker in guiding clinical decisions and improving patient outcomes in this high-risk population.
Advancing implementation science in community settings: the implementation strategies applied in communities (ISAC) compilation
Authors: Balis Laura E. , Houghtaling Bailey , Clausen Whitney , Lane Hannah , Wende Marilyn E. , Pereira Emiliane , McLoughlin Gabriella M. , Harden Samantha M. 
Published: November 2024

Abstract
Background
Implementation strategies have predominantly been operationalized and studied in clinical settings. Implementation strategies are also needed to improve evidence-based intervention (EBI) integration in community settings, but there is a lack of systematic characterization of their use, which limits generalizability of findings. The goals of this study were to determine which implementation strategies are most used to deliver primary prevention EBIs in community settings, develop a compilation and pragmatic strategy selection process with accompanying guidance tools, and understand practitioners’ preferences for dissemination.

Methods
Purposive and snowball sampling was used to recruit community setting researchers and practitioners delivering primary prevention EBIs (nutrition, physical activity, tobacco prevention) in community settings: education, social services, city planning and transportation, workplaces, recreation/sport, faith-based, and other public health organizations. Semi-structured interviews were conducted using a guide based on the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. Participants were asked to describe barriers experienced and strategies used to overcome them within each RE-AIM dimension. Practitioners were also asked about preferred dissemination strategies, prompted by Diffusion of Innovations theory concepts of sources (who provides information) and channels (how information is provided). A rapid deductive approach was used to analyze findings with a coding matrix aligned with the interview guide.

Results
Researchers (n = 10) and practitioners (n = 8) across all targeted settings and intervention outcomes completed interviews. Interviewees shared unique implementation strategies (N = 40) which were used to overcome barriers related to multiple RE-AIM dimensions, most commonly implementation (n = 29) and adoption (n = 27). Most frequently mentioned implementation strategies were conduct pragmatic evaluation (n = 31), provide training (n = 26), change adaptable program components (n = 26), and leverage funding sources (n = 21). Webinars (n = 6) and listservs/newsletters (n = 5) were the most mentioned dissemination channels; national public health organizations (n = 13) were the most mentioned sources.

Conclusions
Results reflect commonly used implementation strategies in community settings (e.g., training, technical assistance) and add novel strategies not reflected in current taxonomies. Dissemination preferences suggest the need to involve broad-reaching public health organizations. The resultant compilation (Implementation Strategies Applied in Communities) and strategy selection process provide resources to assist researchers and practitioners in applying strategies and improving EBI delivery in community settings.