bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the creatinine clearance predictor machine learning models in critically ill adults
Authors: Huang Chao-Yuan , Güiza Fabian , Wouters Pieter , Mebis Liese , Carra Giorgia , Gunst Jan , Meersseman Philippe , Casaer Michael , Van den Berghe Greet , De Vlieger Greet , Meyfroidt Geert 
Published: July 2023

Abstract
Background
In critically ill patients, measured creatinine clearance (CrCl) is the most reliable method to evaluate glomerular filtration rate in routine clinical practice and may vary subsequently on a day-to-day basis. We developed and externally validated models to predict CrCl one day ahead and compared them with a reference reflecting current clinical practice.

Methods
A gradient boosting method (GBM) machine-learning algorithm was used to develop the models on data from 2825 patients from the EPaNIC multicenter randomized controlled trial database. We externally validated the models on 9576 patients from the University Hospitals Leuven, included in the M@tric database. Three models were developed: a “Core” model based on demographic, admission diagnosis, and daily laboratory results; a “Core + BGA” model adding blood gas analysis results; and a “Core + BGA + Monitoring” model also including high-resolution monitoring data. Model performance was evaluated against the actual CrCl by mean absolute error (MAE) and root-mean-square error (RMSE).

Results
All three developed models showed smaller prediction errors than the reference. Assuming the same CrCl of the day of prediction showed 20.6 (95% CI 20.3–20.9) ml/min MAE and 40.1 (95% CI 37.9–42.3) ml/min RMSE in the external validation cohort, while the developed model having the smallest RMSE (the Core + BGA + Monitoring model) had 18.1 (95% CI 17.9–18.3) ml/min MAE and 28.9 (95% CI 28–29.7) ml/min RMSE.

Conclusions
Prediction models based on routinely collected clinical data in the ICU were able to accurately predict next-day CrCl. These models could be useful for hydrophilic drug dosage adjustment or stratification of patients at risk.
Trial registration. Not applicable.
A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling
Authors: Damavandi Sedigheh , Shiri Fereshteh , Emamjomeh Abbasali , Pirhadi Somayeh , Beyzaei Hamid 
Published: July 2023

AbstractLactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometrics does not require knowledge of the protein's three-dimensional structure, but rather depends on the amino acid sequence and protein descriptors. Here, we applied this methodology to model a set of LDHA and LDHB isoenzyme inhibitors. To implement the proteochemetrics method, the camb package in the R Studio Server programming environment was used. The activity of 312 compounds of LDHA and LDHB isoenzyme inhibitors from the valid Binding DB database was retrieved. The proteochemometrics method was applied to three machine learning algorithms gradient amplification model, random forest, and support vector machine as regression methods to find the best model. Through the combination of different models into an ensemble (greedy and stacking optimization), we explored the possibility of improving the performance of models. For the RF best ensemble model of inhibitors of LDHA and LDHB isoenzymes, and were 0.66 and 0.62, respectively. LDH inhibitory activation is influenced by Morgan fingerprints and topological structure descriptors.
MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection
Authors: Li Juanfeng , Sun Lulu , Xie Fujie , Shao Tianren , Wu Shanbo , Li Xiaoying , Zhang Longxian , Wang Rongjun 
Published: July 2023

Abstract
Background
Cryptosporidium is second only to rotavirus as a cause of moderate-to-severe diarrhea in young children. There are currently no fully effective drug treatments or vaccines for cryptosporidiosis. MicroRNAs (miRNAs) are involved in regulating the innate immune response to Cryptosporidium parvum infection. In this study, we investigated the role and mechanism of miR-3976 in regulating HCT-8 cell apoptosis induced by C. parvum infection.

Methods
Expression levels of miR-3976 and C. parvum burden were estimated using real-time quantitative polymerase chain reaction (RT-qPCR) and cell apoptosis was detected by flow cytometry. The interaction between miR-3976 and B-cell lymphoma 2-related protein A1 (BCL2A1) was studied by luciferase reporter assay, RT-qPCR, and western blotting.

Results
Expression levels of miR-3976 were decreased at 8 and 12 h post-infection (hpi) but increased at 24 and 48 hpi. Upregulation of miR-3976 promoted cell apoptosis and inhibited the parasite burden in HCT-8 cells after C. parvum infection. Luciferase reporter assay indicated that BCL2A1 was a target gene of miR-3976. Co-transfection with miR-3976 and a BCL2A1 overexpression vector revealed that miR-3976 targeted BCL2A1 and suppressed cell apoptosis and promoted the parasite burden in HCT-8 cells.

Conclusions
The present data indicated that miR-3976 regulated cell apoptosis and parasite burden in HCT-8 cells by targeting BCL2A1 following C. parvum infection. Future study should determine the role of miR-3976 in hosts’ anti-C. parvum immunity in vivo.

Graphical Abstract
Metabolomics analysis reveals changes related to pseudocyst formation induced by iron depletion in Trichomonas vaginalis
Authors: Cheng Wei-Hung , Huang Po-Jung , Lee Chi-Ching , Yeh Yuan-Ming , Ong Seow-Chin , Lin Rose , Ku Fu-Man , Chiu Cheng-Hsun , Tang Petrus 
Published: July 2023

Abstract
Background
Iron is an essential element for cellular functions, such as energy metabolism. Trichomonas vaginalis, a human urogenital tract pathogen, is capable of surviving in the environment without sufficient iron supplementation. Pseudocysts (cyst-like structures) are an environmentally tolerated stage of this parasite while encountering undesired conditions, including iron deficiency. We previously demonstrated that iron deficiency induces more active glycolysis but a drastic downregulation of hydrogenosomal energy metabolic enzymes. Therefore, the metabolic direction of the end product of glycolysis is still controversial.

Methods
In the present work, we conducted an LC‒MS-based metabolomics analysis to obtain accurate insights into the enzymatic events of T. vaginalis under iron-depleted (ID) conditions.

Results
First, we showed the possible digestion of glycogen, cellulose polymerization, and accumulation of raffinose family oligosaccharides (RFOs). Second, a medium-chain fatty acid (MCFA), capric acid, was elevated, whereas most detected C18 fatty acids were reduced significantly. Third, amino acids were mostly reduced, especially alanine, glutamate, and serine. Thirty-three dipeptides showed significant accumulation in ID cells, which was probably associated with the decrease in amino acids. Our results indicated that glycogen was metabolized as the carbon source, and the structural component cellulose was synthesized at same time. The decrease in C18 fatty acids implied possible incorporation in the membranous compartment for pseudocyst formation. The decrease in amino acids accompanied by an increase in dipeptides implied incomplete proteolysis. These enzymatic reactions (alanine dehydrogenase, glutamate dehydrogenase, and threonine dehydratase) were likely involved in ammonia release.

Conclusion
These findings highlighted the possible glycogen utilization, cellulose biosynthesis, and fatty acid incorporation in pseudocyst formation as well as NO precursor ammonia production induced by iron-depleted stress.

Graphical Abstract
Effect of bromocriptine on glycemic control, risk of cardiovascular diseases and weight in patients with type 2 diabetes: a systematic review
Authors: Birhan Mulualem Tesfaye , Ayele Teklie Mengie , Abebe Fikire Wondimu , Dgnew Fiseha Nigussie 
Published: July 2023

Abstract
Background
Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control with drugs may reduce long-term CVD risk. Bromocriptine has been in clinical use for over 30 years, but the utility of bromocriptine in the treatment of diabetes patients has been proposed more recently.

Objective
To summarize the available data regarding the effect of bromocriptine in T2DM management.

Method
A systematic literature search was conducted in the electronic databases, including Google Scholar, PubMed, Medline, and Science Direct, to locate studies that meet the objectives of this systematic review. Additional articles were included by conducting direct Google searches of the references cited by eligible articles located by the database search. The following search terms were used on PubMed “bromocriptine OR dopamine agonist AND diabetes mellitus OR hyperglycemia OR obese”.

Result
Eight studies were included in the final analysis. 6210 of the 9391 study participants received bromocriptine treatment, while 3183 received a placebo. The studies demonstrated that patients who took bromocriptine treatment had significantly reduced blood glucose and BMI, which is the main cardiovascular risk factor in T2DM patients.

Conclusion
Based on this systematic review, bromocriptine may be used for T2DM treatment for its cardiovascular risk reduction effect, especially body weight reduction. However, advanced study designs might be warranted.
Epigenetic marks associated with gestational diabetes mellitus across two time points during pregnancy
Authors: Linares-Pineda Teresa , Peña-Montero Nerea , Fragoso-Bargas Nicolás , Gutiérrez-Repiso Carolina , Lima-Rubio Fuensanta , Suarez-Arana María , Sánchez-Pozo Antonio , Tinahones Francisco J. , Molina-Vega María , Picón-César María José , Sommer Christine , Morcillo Sonsoles 
Published: July 2023

AbstractAn adverse intrauterine or periconceptional environment, such as hyperglycemia during pregnancy, can affect the DNA methylation pattern both in mothers and their offspring. In this study, we explored the epigenetic profile in maternal peripheral blood samples through pregnancy to find potential epigenetic biomarkers for gestational diabetes mellitus (GDM), as well as candidate genes involved in GDM development. We performed an epigenome-wide association study in maternal peripheral blood samples in 32 pregnant women (16 with GDM and 16 non-GDM) at pregnancy week 24–28 and 36–38. Biochemical, anthropometric, and obstetrical variables were collected from all the participants. The main results were validated in an independent cohort with different ethnic origin (European = 307; South Asians = 165). Two hundred and seventy-two CpGs sites remained significantly different between GDM and non-GDM pregnant women across two time points during pregnancy. The significant CpG sites were related to pathways associated with type I diabetes mellitus, insulin resistance and secretion. Cg01459453 (SELP gene) was the most differentiated in the GDM group versus non-GDM (73.6 vs. 60.9, p = 1.06E−11; FDR = 7.87E−06). Three CpG sites (cg01459453, cg15329406, and cg04095097) were able to discriminate between GDM cases and controls (AUC = 1; p = 1.26E−09). Three differentially methylated positions (DMPs) were replicated in an independent cohort. To conclude, epigenetic marks during pregnancy differed between GDM cases and controls suggesting a role for these genes in GDM development. Three CpGs were able to discriminate GDM and non-GDM groups with high specificity and sensitivity, which may be biomarker candidates for diagnosis or prediction of GDM.
Fifty years of artisan entrepreneurship: a systematic literature review
Authors: Hasanah Uswatun , Sukoco Badri Munir , Supriharyanti Elisabeth , Wu Wann-Yih 
Published: July 2023

AbstractCulturally based products and businesses have become increasingly common, drawing attention to artisan entrepreneurship. A small number of studies have comprehensively reviewed artisan entrepreneurship in terms of its antecedents and consequences, as is examined in this study. Specifically, this research looked at the factors that contribute to successful artisan entrepreneurship, managing environmental dynamism, markets, and institutional pressures. This study focuses on developing antecedents and consequences that may be used as a reference for the development of artisan entrepreneurship. A systematic literature review was conducted on 72 papers from the last 50 years from the first quartile of the Scopus database. This study identified that environmental, social, organizational, and individual factors could determine the development of artisan entrepreneurship and have consequences on social, organizational, and individual levels. This framework may aid artisan entrepreneurship and stakeholders in identifying the factors needed in the development of artisan entrepreneurship. The main elements of the resulting research agenda include suggestions for theory development, methodology, antecedents, and consequences.
The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications
Authors: Gu Yunru , Fang Yuan , Wu Xi , Xu Tingting , Hu Tong , Xu Yangyue , Ma Pei , Wang Qiang , Shu Yongqian 
Published: July 2023

AbstractTumor initiation, progression, and response to therapies depend to a great extent on interactions between malignant cells and the tumor microenvironment (TME), which denotes the cancerous/non-cancerous cells, cytokines, chemokines, and various other factors around tumors. Cancer cells as well as stroma cells can not only obtain adaption to the TME but also sculpt their microenvironment through a series of signaling pathways. The post-translational modification (PTM) of eukaryotic cells by small ubiquitin-related modifier (SUMO) proteins is now recognized as a key flexible pathway. Proteins involved in tumorigenesis guiding several biological processes including chromatin organization, DNA repair, transcription, protein trafficking, and signal conduction rely on SUMOylation. The purpose of this review is to explore the role that SUMOylation plays in the TME formation and reprogramming, emphasize the importance of targeting SUMOylation to intervene in the TME and discuss the potential of SUMOylation inhibitors (SUMOi) in ameliorating tumor prognosis.
Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion
Authors: Ho Yi-Ju , Cheng Hsiang-Lung , Liao Lun-De , Lin Yu-Chun , Tsai Hong-Chieh , Yeh Chih-Kuang 
Published: July 2023

Abstract

Background
Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.

Methods

The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO
2
), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.

Results

The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO
2
level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

Graphical Abstract
Cracking the code: unveiling the specific and shared mechanisms behind musculoskeletal interventions
Authors: McDevitt Amy W. , O’Halloran Bryan , Cook Chad E. 
Published: July 2023

Abstract
Background
Mechanisms reflect the steps or processes through which an intervention unfolds and produces change in a specified outcome variable. Mechanisms are responsible for determining “how treatments work” which has emerged as a critical question for both developing theory and enhancing treatment efficacy. Studies that evaluate “how” treatments work, not just “if” treatments work are of considerable importance.

Discussion
Specific and shared mechanisms research is a promising approach which aims to improve patient outcomes by tailoring treatments to the specific needs of each patient. Mechanisms research is an underexplored area of research requiring a unique research design.

Conclusion
Although mechanisms research is still in its infancy, prioritizing the study of the mechanisms behind manual therapy interventions can provide valuable insight into optimizing patient outcomes.
Comparison of survival for super high-flux hemodialysis (SHF-HD) with high albumin leakage versus online hemodiafiltration or SHF-HD with low albumin leakage: the SUPERB study
Authors: Okada Kazuyoshi , Tashiro Manabu , Michiwaki Hiroyuki , Inoue Tomoko , Shima Hisato , Minakuchi Jun , Kawashima Shu 
Published: July 2023

Abstract
Background
Survival is equivalent between super high-flux hemodialysis (SHF-HD) and online hemodiafiltration (OHDF) with similar albumin leakage. According to the 2013 Japanese dialyzer performance classification, survival on HD is optimal when a type II dialyzer (β2-microglobulin clearance ≥ 70 mL/min) is used. Here, we investigated whether survival could be improved by SHF-HD using a type II-b dialyzer (sieving coefficient for albumin ≥ 0.03) with high albumin leakage compared with OHDF or SHF-HD using a type II-a dialyzer (sieving coefficient for albumin < 0.03) with low albumin leakage.

Methods
This 3-year retrospective observational propensity score-matched study included 738 patients receiving SHF-HD (n = 310) or OHDF (n = 428) with a type II dialyzer at our institution between April 1 and July 1, 2017. Three-year all-cause mortality was compared for SHF-HD with high estimated albumin leakage (EAL) versus OHDF and SHF-HD with low EAL. Kaplan–Meier survival curves were compared using the log-rank test and hazard ratios were calculated by Cox regression analysis.

Results
Mortality in SHF-HD with high EAL was significantly lower than OHDF with low EAL (each n = 52 after matching; P = 0.007, log-rank test). All the dialyzers used a polyethersulfone (PES) membrane, whereas none of the hemodiafilters had a PES membrane. In SHF-HD, mortality was significantly lower when EAL was ≥ 3.0 g/session than when EAL was < 3.0 g/session (each n = 115 after matching, P = 0.004, log-rank test) and when the dialyzer used was type II-b rather than type II-a (each n = 133 after matching, P = 0.001, log-rank test).

Conclusions
These findings suggest that survival is better on SHF-HD using a type II-b dialyzer with high albumin leakage than on OHDF with low albumin leakage or SHF-HD using a type II-a dialyzers. The PES used in the type II-b dialyzer may also have a beneficial effect on survival.
Clinical impact of 99mTc-MAA SPECT/CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients
Authors: Bucalau Ana-Maria , Collette Benoît , Tancredi Illario , Vouche Michael , Pezzullo Martina , Bouziotis Jason , Moreno-Reyes Rodrigo , Trotta Nicola , Levillain Hugo , Van Laethem Jean Luc , Verset Gontran 
Published: July 2023

Abstract
Background
Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC).

Aim
We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry.

Methods
This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach.

Results
Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3–55) in group A and 21 months (range 4–39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity.

Conclusions
Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.