bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in chronic inflammation in 3T3‐L1 adipose model
Authors: Gutiérrez Rojas Rocío A. , Aguayo‐Cerón Karla A. , De León‐Vargas Cruz , Villafaña Santiago , Romero‐Nava Rodrigo 
Published: May 2022

AbstractIntroduction Chronic or low‐level inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localized inflammations, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. Objective To analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3‐L1 cells. Methods the cell culture of 3T3‐L1 was made in 6 wells plate (4 x105 cell per well) in DMEM/F12 medium. The 3T3‐L1 cell were stimulated with TNF‐α (10mM) during 30 minutes as an inflammatory model in the cells. The gene expression was measured by RT‐qPCR. Results our result showed that the inflammatory stimulus with TNF‐α in adipocytes decrease the expression of the orphan receptor GPR21 GPR26, GPR39, GPR82 and GPR6 that are related with low grade inflammation. Conclusion the orphan receptors expressed in adipocytes have a main role in the TNF‐α induces inflammation process, and they could be a therapeutic target to decrease the inflammation in some diseases related to low grade inflammation as diabetes, obesity and metabolic syndrome.
Differential Expression of Adipokines in Mechanically Stretched‐ Endothelial cells
Authors: Al Ashmar Sarah , Kamareddine Layla , Zeidan Asad 
Published: May 2022

IntroductionHypertension is considered as the major risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality worldwide. This disease can develop mainly due to the mechanical forces exerted by the blood on the vessels wall. The endothelium, lining the blood vessel, responds to these hemodynamic mechanical forces such as mechanical stretch leading to endothelial dysfunction. Leptin and adiponectin (APN) are two adipokines that are known to be associated with the pathogenesis of hypertension. However, how the level of these hormones is elevated in response to mechanical stretch in endothelial cells is yet to be elucidated.AimIn the present study, we investigated the expression of leptin and adiponectin in endothelial cells exposed to mechanical stretch.MethodsImmortalized human umbilical vein endothelial cells (EA. hy926) were subjected to mechanical stretch (15%, 60 cycle/min and 1Hz) using STREX cell stretching system (STREX Inc., California, USA) for 6, 16 and 24 h. Cultured cells not subjected to stretch (static condition) where used as controls. The mRNA expression of leptin and its receptor (OB‐Rb) as well as APN and adiponectin receptor 2 (APN‐R2) were assessed at different time points using real‐time PCR.ResultsMechanical stretch induced changes in cell morphology in which the cells were elongated and aligned perpendicular to the stretch axis. Stretching of endothelial cells significantly upregulated the expression of leptin after 16 h (0.9515 ± 0.4238‐fold, n=6, p<0.05) and after 24 h (1.577 ± 0.4503‐fold, n=6, p<0.05) of stretching but without affecting the expression of its receptor (OB‐Rb). The mRNA expression of APN also increased significantly in response to 6 h stretching (0.5457 ± 0.1890‐fold, n=6, p<0.05), 16 h stretching (0.9487 ± 0.4058‐fold, n=6, p<0.05) and 24 h stretching (2.664 ± 0.3447, n=6, p<0.0001) compared to unstretched cells, however no change in the expression of APN‐R2 was observed.ConclusionOur findings suggesting that the exposure of endothelial cells to mechanical stretch can result in changes in the expression of adipokines, leptin and adiponectin, will result in better understanding of how vascular biology is affected by mechanical forces and how these molecules can modulate endothelial function in cardiovascular diseases.
Chloride Intracellular Channel Protein 1 (CLIC1) Inhibitor (IAA94) Decreases Contractile Force in Rat Uterine Arteries
Authors: Wilczynski Stephanie , Arishe Olufunke , Priviero Fernanda , Webb R. C. 
Published: May 2022

ObjectiveThe objective of this study was to determine the effects of the Chloride Intracellular Channel Protein 1 (CLIC1) inhibitor, IAA94, on uterine arteries in rats.HypothesisThis study tested the hypothesis that the inhibition of CLIC1 with IAA94 decreases contractility of the uterine artery.MethodsUterine arteries were harvested from 12‐week‐old female Wistar Rats. The arterial rings were mounted in a wire myograph and kept at 37ºC in Krebs solution, constantly aerated with a 95% O2+ 5% CO2 gas mix. Concentration‐response curves to Phenylephrine (PE, ‐9M to ‐4.5M). After washout, the arterial rings were incubated with the CLIC1 inhibitor (IAA94, 50 µM) for 30 minutes and then, concentration‐responses curves to PE were repeated. The curves were analyzed using nonlinear regression analysis and pEC50 and Emax were calculated with an N=8 for both groups. Data was analyzed by GraphPad Prism 9.2.0., and is presented as Mean ± SEM (n=8).Summary of ResultsIn the Wistar uterine arterial rings, the potency of PE was decreased in the presence of the CLIC1 inhibitor IAA94 (pEC50: 5.64 ± 0.28 vs. 6.59 ± 0.30 for IAA94 vs control, respectively; p <0.0001). Similarly, Emax to PE was decreased after incubation with IAA94 (105 ± 2% vs 128 ± 5%, for IAA94 vs control, respectively; p <0.001). These data show that the inhibition of CLIC1 plays a role in the contraction induced by PE. Further experiments are necessary to understand the mechanisms underlying this effect.ConclusionThe addition of the CLIC1 inhibitor, IAA94, elicits a decreased contractile response to PE. CLIC1 has been identified to be dysregulated in certain cancer types and aging. There are numerous overlaps between cell senescence/cancer morphology and the pathophysiology of preeclampsia. These preliminary experiments shed light on the uterine artery’s reactivity to a CLIC1 inhibitor and would be an interesting topic to pursue in pregnant rats in both SHR and Wistar strains. With hypertensive patients, we see an increase in peripheral contractility and a decrease in responsiveness to vasodilators. CLIC1 could be a possible target in vasoconstrictive pathways, especially those that occur during pregnancy and in preeclamptic patients.
Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children
Authors: Li Bi L. , Guan Yan P. , Yuen Vivian M. , Wei Wei , Huang Min , Zhang Ma Z. , Li Ai W. , Standing Joseph F. , Zhong Guo P. , Song Xing R. 
Published: May 2022

Background
Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old.

Methods
Intranasal dexmedetomidine 2 µg · kg−1 was administered to children with simple vascular malformations undergoing interventional radiological procedures. A population pharmacokinetic analysis with data from an optimized sparse-sampling design was performed using nonlinear mixed-effects modeling. Clearance was modeled using allometric scaling and a sigmoid postmenstrual age maturation model. Monte Carlo simulations were performed to assess the different dosing regimens.

Results
A total of 586 samples from 137 children aged 3 to 36 months were included in the trial. The data were adequately described by a two-compartment model with first-order elimination. Body weight with allometric scaling and maturation function were significant covariates of dexmedetomidine clearance. The pharmacokinetic parameters for the median subjects (weight 10 kg and postmenstrual age 101 weeks) in the authors’ study were apparent central volume of distribution 7.55 l, apparent clearance of central compartment 9.92 l · h−1, apparent peripheral volume of distribution 7.80 l, and apparent intercompartmental clearance 61.7 l · h−1. The simulation indicated that at the dose of 2 µg · kg−1, 95% of simulated individuals could achieve a target therapeutic concentration of 0.3 ng · ml−1 within 20 min, and the average peak concentration of 0.563 ng · ml−1 could be attained at 61 min.

Conclusions
The pharmacokinetic characteristics of intranasal dexmedetomidine were evaluated in Chinese pediatric patients aged between 3 and 36 months. An evidence-based dosing regimen at 2 µg · kg−1 could achieve a preset therapeutic threshold of mild to moderate sedation that lasted for up to 2 h.

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Specificity of cortical area and thickness as biomarkers for comorbid internalizing and externalizing mental disorders in pre-adolescence
Authors: Kuang Nanyu , Liu Zhaowen , Yu Gechang , Zhang Kai , Wu Xinran , Becker Ben , Fan Huaxin , Zhao Jiajia , Kang Jujiao , Dong Guiying , Zhao Xingming , Feng Jianfeng , Sahakian Barbara J. , Robbins Trevor W. , Schumann Gunter , Palaniyappan Lena , Zhang Jie 
Published: May 2022

AbstractBackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical changes represent a simple aggregate of the effects on each disorder, and if comorbidity-related cortical surface changes relate to a distinct genetic underpinning.MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (Dysthymia, Major Depressive Disorder, Disruptive Mood Dysregulation Disorder, Agoraphobia, Panic Disorder, Specific Phobia, Separation Anxiety Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post-Traumatic Stress Disorder), externalizing diagnostic groups (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct disorder) a group with comorbidity of the two and a healthy control group. Genome-wide association analysis and cell type specificity analysis were performed on 4,716 unrelated European participants from this cohort.ResultsReduced cortical surface area but increased thickness occurs across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT changes, while those patient groups without comorbidity had significant thickness increases. Distinct biological pathways were implicated for regional SA and CT changes. Specifically, CT changes were associated with immune-related processes implicating microglia, while SA-related changes related mainly to excitatory neurons.ConclusionsThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be a simple additive neurobiological effect. Distinct risk-adaptation processes, with unique genetic and cell-specific factors may underlie SA and CT changes. Children with highest risk but lowest resilience, both captured in their developmental morphometry, develop a comorbid illness pattern.
An intermediate step in bridging the gap between evidence and practice: developing and applying a methodology for “general good practices”
Authors: Safadi Heléna , Lám Judit , Baranyi Ivett , Belicza Éva 
Published: May 2022

AbstractThe gap between evidence and clinical practice has been in the focus of researches for decades. Although successful implementation means the new knowledge must work in particular environments, it doesn’t mean that the entire process should exclusively be executed by the individual institutes. This is the point where we assumed that an intermediate step, the “general good practice”, could help to ensure that translation is done in a more professional way.The development of the general good practice methodology was based on our infinitE model, which organized the factors of successful translation into an evidence-editing-embedding-effect on practice framework, using tools from the disciplines of Evidence-Based Medicine, Quality Improvement and Change Management.The methodology organised the editing and embedding part of the development into a process involving three full-day sessions carried out with different health professionals, experts and moderators. After pilot testing, it was finalized and applied to other topics as well.The methodology presented in detail in this paper, centred on flow chart, process analysis, failure mode identification and Kotter’s 8-step model. Beside the pilot topic of the institutional process of resuscitation, the methodology has also proved applicable to more than ten other topics, meaning that at least all the core elements of the proposed bundle of general good practice have been produced in the development process.Compared to the guidelines, general good practices demonstrate the evidence in operation, helping to develop workflows, responsibilities, documentation, trainings, etc. and can also be a starting point for the digitalisation of care processes.The next step is to examine how healthcare institutions can build on these in their own editing and embedding activities, and what the results will be. Further studies could explore the applicability of the development methodology in different healthcare systems or at different levels of maturity in terms of quality.
Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity
Authors: Kedl Ross M. , Hsieh Elena , Morrison Thomas E. , Samayoa-Reyes Gabriela , Flaherty Siobhan , Jackson Conner L. , Rochford Rosemary 
Published: May 2022

AbstractDespite the obvious knowledge that infectious particles can be shared through respiration, whether other constituents of the nasal/oral fluids can be passed between hosts has surprisingly never even been postulated, let alone investigated. The circumstances of the present pandemic facilitated a unique opportunity to fully examine this provocative idea. The data we show provides evidence for a new mechanism by which herd immunity may be manifested, the aerosol transfer of antibodies between immune and non-immune hosts.
Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Organ Dysfunction in Major Abdominal Surgery: A Retrospective Cohort Study
Authors: Dong Li , Takeda Chikashi , Kamitani Tsukasa , Hamada Miho , Hirotsu Akiko , Yamamoto Yosuke , Mizota Toshiyuki 
Published: May 2022

AbstractBackgroundData on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia.MethodsWe conducted a retrospective cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery.ResultsOf the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03–1.20;p= 0.006). Additionally, long-term exposure to EtCO2values of less than 35 mmHg (≥224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06–1.32;p= 0.003) and low EtCO2severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02–1.26;p= 0.018).ConclusionsIntraoperative low EtCO2of below 35 mmHg was associated with increased postoperative organ dysfunction.
Genetic Risk Factors for Postoperative Atrial Fibrillation – a Nationwide Genome-Wide Association Study (GWAS)
Authors: Christensen Mathias A , Bonde Alexander , Sillesen Martin 
Published: May 2022

AbstractBackgroundAtrial fibrillation (AF) is a major cause of morbidity with a high prevalence among the elderly and has an established genetic disposition. Surgery is a well-known risk factor for AF; however, it is currently not recognized how much common genetic variants influence the postoperative risk. The purpose of this study was to identify Single Nucleotide Polymorphisms associated with postoperative AF.MethodsThe UK Biobank was utilized to conduct a Genome-Wide Association Study (GWAS) to identify variants associated with AF after surgery. An initial discovery GWAS was performed in patients that had undergone surgery with subsequent replication in a unique non-surgical cohort. In the surgical cohort, cases were defined as newly diagnosed AF within 30 days after surgery. The threshold for significance was set at 5 × 10−8.ResultsAfter quality control, 144,196 surgical patients with 254,068 SNPs were left for analysis. Two variants (rs17042171 (p = 4.86 × 10−15) and rs17042081 (p = 7.12 × 10−15)) near the PITX2-gene reached statistical significance. These variants were replicated in the non-surgical cohort (1.39 × 10−101 and 1.27 × 10−93, respectively). Several other loci were significantly associated with AF in the non-surgical cohort.ConclusionIn this GWAS-analysis of a large national biobank, we identified 2 variants that were significantly associated with postoperative AF. These variants were subsequently replicated in a unique non-surgical cohort. These findings bring new insight in the genetics of postoperative AF and may help identify at-risk patients and guide management.
Trends in diabetes incidence and associated risk factors among people living with HIV in the current treatment era, 2008-2018
Authors: Spieler Gabriel , Westfall Andrew O. , Long Dustin M. , Cherrington Andrea , Burkholder Greer A. , Funderburg Nicholas , Raper James L. , Overton Edgar T. , Willig Amanda L. 
Published: May 2022

ABSTRACTPeople with HIV (PWH) have an increased risk for diabetes mellitus. Our objectives were to characterize the prevalence and incidence of diabetes in a cohort of people with HIV (PWH), and to evaluate both traditional and HIV-specific risk factors contributing to incident diabetes diagnoses. We conducted a retrospective study of a Southeastern US academic HIV clinic. All PWH age > 18 years of age who attended at least two clinic visits between 2008 and 2018 were evaluated to assess time to diabetes incidence. Laboratory, demographic, clinical, medication and diagnoses data were extracted from the Clinic EMR. Diabetes was defined when at least two of the following three criteria were met: (1) laboratory data consistent with a diagnosis as defined by the ADA SOC (Hgb A1C ≥ 6.5% and/or 2 glucose results >200 mg/dl (at least 30 days apart)), (2) diagnosis of diabetes in the EMR, or (3) exposure to diabetes medication. Time to Diabetes incidence was computed from the entire clinic population for each study year. Univariate Cox proportional hazard models were developed to evaluate associations between each baseline factor and time to DM. Multivariable Cox proportional hazard regression models with time-dependent covariates were created to evaluate the independent association between significant parameters from univariate analyses and time to incident DM. From 4113 PWH included in the analysis, we identified 252 incident cases of diabetes. In multivariable analysis, BMI classification, liver disease, steroid exposure, and use of Integrase Inhibitors were associated with incident diabetes. Additional associated factors included lower CD4 cell counts, duration of HIV infection, exposure to non-statin lipid lowering therapy, and dyslipidemia. Incident diabetes rates are increasing at an alarming rate among PWH. Diabetes prevalence increased from 8.8% in 2008 to 14% in 2018. Both traditional and HIV-related risk factors, particularly body weight, steroid exposure, and use of Integrase Inhibitors, were associated with incident diabetes. Notably, several of the risk factors identified are modifiable and should be targeted for intervention.
Medical text prediction and suggestion using generative pre-trained transformer models with dental medical notes
Authors: Sirriani Joseph , Sezgin Emre , Claman Daniel , Linwood Simon L 
Published: May 2022

AbstractBackgroundGenerative pre-trained transformer (GPT) models are one of the latest large pre-trained natural language processing (NLP) models, which enables model training with limited datasets, and reduces dependency on large datasets which are scarce and costly to establish and maintain. There is a rising interest to explore the use of GPT models in healthcare.ObjectiveWe investigate the performance of GPT-2 and GPT-Neo models for medical text prediction using 374,787 free-text dental notes.MethodsWe fine-tune pre-trained GPT-2 and GPT-Neo models for next word prediction on a dataset of over 374,000 manually written sections of dental clinical notes. Each model was trained on 80% of the dataset, validated on 10%, and tested on the remaining 10%. We report model performance in terms of next word prediction accuracy and loss. Additionally, we analyze the performance of the models on different types of prediction tokens for categories. We annotate each token in 100 randomly sampled notes by category (e.g. Names, Abbreviations, Clinical Terms, Punctuation, etc.) and compare the performance of each model by token category.ResultsModels present acceptable accuracy scores (GPT-2: 76%, GPT-Neo: 53%), and the GPT-2 model also performs better in manual evaluations, especially for names, abbreviations, and punctuation. The results suggest that pre-trained models have the potential to assist medical charting in the future. We share the lessons learned, insights, and suggestions for future implementations.ConclusionThe results suggest that pre-trained models have the potential to assist medical charting in the future. Our study presented one of the first implementations of the GPT model used with medical notes.